| 1. |
- Mahdavi, Jafar, et al.
(författare)
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Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation
- 2002
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 297:5581, s. 573-578
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.
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| 2. |
- Knutsson, Anders, et al.
(författare)
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Postprandial responses of glucose, insulin and triglycerides : Influence of the timing of meal intake during night work
- 2002
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Ingår i: Nutrition and Health. - : SAGE Publications. - 0260-1060 .- 2047-945X. ; 16, s. 133-141
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to study the postprandial responses of glucose, insulin and triglycerides to meal intake at different clock times during night work. Eleven night shift working nurses participated. Identical test meals were ingested at 19:30, 23:30 and 03:30, and contained 440 kcal/ 1860 kJ of energy (33 E% fat, 51 E% carbohydrate, 16 E% protein). The food intake was standardized three days before the first test meal. Blood samples were drawn just before the test meals were ingested and thereafter at 30, 60, 90, 120, 180 and 240 minutes. The postprandial responses were estimated as the total area under the curve (AUC) and significance testing was done using repeated measures ANOVA. The highest insulin level was found after meal intake at 23:30, and the lowest after meal intake 03:30. The glucose response showed the same pattern. The insulin response to food intake in night working nurses is more pronounced in the night compared with morning and evening. The results would have implications for metabolic and cardiovascular disorders in night workers.
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| 3. |
- Naumburg, Estelle, et al.
(författare)
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Perinatal exposure to infection and risk of childhood leukemia
- 2002
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Ingår i: Medical and Pediatric Oncology. - : Wiley. - 0098-1532 .- 1096-911X. ; 38, s. 391-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A population-based case-control study was conducted to investigate the association between childhood leukemia and infectious exposures during pregnancy and early neonatal period.PROCEDURE: Children born and diagnosed with leukemia between 1973 and 1989 in Sweden (578 lymphatic, 74 myeloid) were selected as cases. One control was randomly selected for each case and individually matched by sex, month, and year of birth. Children with Down's syndrome were excluded. Exposure data were blindly abstracted from antenatal, obstetric, and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression.RESULTS: A history of maternal infection was not significantly associated with childhood leukemia, OR = 1.25 (95% CI 0.95-1.65). Maternal lower genital tract infection significantly increased the risk of childhood leukemia, OR = 1.78 (95% CI 1.17-2.72), and especially for children over 4 years of age at diagnosis, OR = 2.01 (95% CI 1.12-3.80). Neonatal infection was not associated with the risk of leukemia. The results remained unaltered after adjustment for potential confounders, and separate analyses for myeloid and lymphoid leukemia.CONCLUSIONS: We could document an association between exposure to maternal lower genital tract infection in utero, and a subsequent risk for childhood leukemia, which indicate the importance of an early exposure.
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| 4. |
- Sköld, Camilla, et al.
(författare)
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Effects of functional electrical stimulation training for six months on body composition and spasticity in motor complete tetraplegic spinal cord-injured individuals.
- 2002
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 34:1, s. 25-32
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Tidskriftsartikel (refereegranskat)abstract
- The effect of functional electrical stimulation (FES) training on body composition, assessed by computed tomography, and the effect of spasticity, assessed by both objective and subjective measures, are evaluated. Fifteen motor-complete spinal-cord-injured men participated in the study. Eight of the 15 subjects undertook FES cycling 3 times weekly for 6 months. Whole body computed tomography scans evaluated changes in body composition. Simultaneous Modified Ashworth Scale and electromyography (EMG) measurements, resistive torque (Kin-Com) and EMG measurements, and self-ratings with Visual Analogue Scale during four consecutive days were used to evaluate changes in spasticity. Lower extremity muscle volume increased by an average of 1300 cm3 (p < 0.001) in the training group compared to the control group, who experienced no change. Otherwise no changes in body composition were seen. Significant correlations (Spearman) were found between individual EMG activity recordings and movement-provoked Modified Ashworth Scale ratings in 26% of the test situations, irrespective of group and time. The objective and subjective evaluation of movement-provoked passive (viscoelastic) and active (spasticity-related) resistance remained unchanged.
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| 5. |
- Carlsson, Lena, et al.
(författare)
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Cytoskeletal derangements in hereditary myopathy with a desmin L345P mutation
- 2002
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Ingår i: Acta Neuropathologica. - : Springer. - 0001-6322 .- 1432-0533. ; 104:5, s. 493-504
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Tidskriftsartikel (refereegranskat)abstract
- Patients with abnormal accumulations of desmin have been described in myopathies with or without cardiac involvement. Desmin deposits were sometimes associated with abnormal aggregates of other cytoskeletal proteins. In the present study we present how the cytoskeletal organisation of desmin, nestin, synemin, paranemin, plectin and alphaB-crystallin is altered in skeletal muscles from a patient with a L345P mutation in the desmin gene. In general, accumulations of desmin together with synemin, nestin, plectin and alphaB-crystallin were present between myofibrils and beneath the sarcolemma. However, as the biopsy samples were very myopathic, large variability in fibre size and fibre maturation was seen, thus the myofibrillar content and the cytoskeletal organisation varied considerably. In cultured satellite cells from the patient, desmin aggregates were not observed in initial passages, but occurred over time in culture in the form of perinuclear, peripheral or cytoplasmic deposits. Nestin colocalised to the abnormal desmin deposits to a larger extent than did vimentin. alphaB-Crystallin was only present in cells with a disrupted desmin network. Plectin was altered in a subset of cells with a disrupted desmin network, whereas synemin and paranemin were not detected. We conclude that the L345P desmin mutation has a profound influence on the cytoskeletal organisation both in vivo and in vitro, which reflects the pathogenesis of the desmin myopathy.
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| 6. |
- Sahlin, Kent, et al.
(författare)
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No evidence of an intracellular lactate shuttle in rat skeletal muscle.
- 2002
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Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 541:Pt 2, s. 569-74
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Tidskriftsartikel (refereegranskat)abstract
- The concerted view is that cytosolic pyruvate is transferred into mitochondria and after oxidative decarboxylation further metabolized in the tricarboxylic acid cycle. Recently this view has been challenged. Based on experimental evidence from rat skeletal muscle it has been concluded that mitochondria predominantly oxidize lactate in vivo and that this constitutes part of an 'intracellular lactate shuttle'. This view appears to be gaining acceptance in the scientific community and due to its conceptual importance, confirmation by independent experiments is required. We have repeated the experiments in mitochondria isolated from rat soleus muscle. Contrary to the previously published findings we cannot find any mitochondrial respiration with lactate. Analysis of lactate dehydrogenase (LDH) by spectrophotometry demonstrated that the activity in the mitochondrial fraction was only 0.7 % of total activity. However, even when external LDH was added to mitochondria, there were no signs of respiration with lactate. In the presence of conditions where lactate is converted to pyruvate (external additions of both LDH and NAD(+)), mitochondrial oxygen consumption increased. Furthermore, we provide theoretical evidence that direct mitochondrial lactate oxidation is energetically unlikely. Based on the present data we conclude that direct mitochondrial lactate oxidation does not occur in skeletal muscle. The presence of an 'intracellular lactate shuttle' can therefore be questioned.
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| 7. |
- Ullenhag, Gustav J, et al.
(författare)
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Induction of IgG subclass responses in colorectal carcinoma patients vaccinated with recombinant carcinoembryonic antigen.
- 2002
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 62, s. 1364-
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Tidskriftsartikel (refereegranskat)abstract
- There is scanty information on the IgG subclass response after vaccination against cancer antigens. The induction and development of the IgG subclass responses in 18 colorectal carcinoma patients vaccinated s.c. seven times with recombinant human carcinoembryonic antigen (rhCEA) over a 12-month period were analyzed by ELISA. The patients were followed for 3 years. Four rhCEA doses were used, and half of the patients also received granulocyte macrophage-colony stimulating factor (GM-CSF) as an adjuvant. Anti-rhCEA-specific IgG1 and IgG4 responses and, to a lesser degree, IgG2 responses were markedly enhanced by concomitant GM-CSF administration, whereas the antigen dose was of minor importance. Almost no IgG3 response was observed. A significant antibody response was noted within the first weeks for IgG1 and IgG2 but noted several months later for IgG4. The responses gradually increased by repeated immunizations and peaked around 12 months for IgG1 and a few months later for IgG2 and IgG4. A sustained but reduced response was noted for these three subclasses at 24 and 36 months. Interestingly, there was a gradual shift from a predominant IgG1 response at 6 months to an IgG4 response at 15 months. No significant change in total concentrations of the four IgG subclasses was observed comparing prevaccination concentrations with concentrations at 12 months, indicating an antigen-specific effect of GM-CSF administration on the anti-rhCEA response. The clinical significance of the individual IgG subclass antibodies for tumor response is not clear and requires additional studies.
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| 8. |
- Rask, Eva, 1958-, et al.
(författare)
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Tissue-specific changes in peripheral cortisol metabolism in obese women : increased adipose 11beta-hydroxysteroid dehydrogenase type 1 activity
- 2002
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Williams & Wilkins Co.. - 0021-972X .- 1945-7197. ; 87:7, s. 3330-6
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Tidskriftsartikel (refereegranskat)abstract
- Cushing's syndrome and the metabolic syndrome share clinical similarities. Reports of alterations in the hypothalamic-pituitary-adrenal (HPA) axis are inconsistent, however, in the metabolic syndrome. Recent data highlight the importance of adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which regenerates cortisol from cortisone and, when overexpressed in fat, produces central obesity and glucose intolerance. Here we assessed the HPA axis and 11beta-HSD1 activity in women with moderate obesity and insulin resistance. Forty women were divided into tertiles according to body mass index (BMI; median, 22.0, 27.5, and 31.4, respectively). Serum cortisol levels were measured after iv CRH, low dose dexamethasone suppression, and oral cortisone administration. Urinary cortisol metabolites were measured in a 24-h sample. A sc abdominal fat biopsy was obtained in 14 participants for determination of 11beta-HSD type 1 activity in vitro. Higher BMI was associated with higher total cortisol metabolite excretion (r = 0.49; P < 0.01), mainly due to increased 5alpha- and, to a lesser extent, 5beta-tetrahydrocortisol excretion, but no difference in plasma cortisol basally, after dexamethasone, or after CRH, and only a small increase in the ACTH response to CRH. Hepatic 11beta-HSD1 conversion of oral cortisone to cortisol was impaired in obese women (area under the curve, 147,736 +/- 28,528, 115,903 +/- 26,032, and 90,460 +/- 18,590 nmol/liter.min; P < 0.001). However, 11beta-HSD activity in adipose tissue was positively correlated with BMI (r = 0.55; P < 0.05). In obese females increased reactivation of glucocorticoids in fat may contribute to the characteristics of the metabolic syndrome. Increased inactivation of cortisol in liver may be responsible for compensatory activation of the HPA axis. These alterations in cortisol metabolism may be a basis for novel therapeutic strategies to reduce obesity-related complications.
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| 9. |
- Tajsharghi, Homa, 1968, et al.
(författare)
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Myosin heavy chain IIa gene mutation E706K is pathogenic and its expression increases with age.
- 2002
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 58:5, s. 780-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The authors recently described a new autosomal dominant myopathy (OMIM 605637 inclusion body myopathy 3) associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene (MyHC IIa, Human Gene Map [HGM] locus MYH2). Young patients showed minor changes in their muscle biopsies, although dystrophic alterations and rimmed vacuoles with 15- to 20-nm tubulofilaments identical to those in sporadic inclusion body myositis (s-IBM) were observed in some of the adult (especially older) patients. The current study was undertaken to investigate the relation between expression of the mutant MyHC IIa and pathologic changes in muscle. METHODS: The expression of MyHC IIa in nine muscle specimens from six individuals carrying the mutation was analyzed by immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a new reverse transcriptase--PCR method to measure the relative abundance of the various MyHC transcripts. RESULTS: Young patients with muscle weakness and minor pathologic changes in muscle expressed MyHC IIa at undetectable levels. MyHC IIa was expressed at high levels in adults with a progressive clinical course and dystrophic muscle changes. In these cases, a large number of muscle fibers were hybrids with expression of more than one MyHC isoform. Both MyHC IIa alleles were equally expressed. The relative level of MyHC IIa transcripts exceeded that of the corresponding protein, indicating an increased turnover of mutated protein. MyHC IIa expression was a consistent finding in muscle fibers with rimmed vacuoles. CONCLUSIONS: The clear correlation between pathologic changes and expression of MyHC IIa indicates that defects in MyHC may lead not only to muscle weakness but also to muscle degeneration. The consistent expression of MyHC IIa in muscle fibers with rimmed vacuoles indicates that the breakdown of sarcomeric proteins is a key element in the pathogenesis of rimmed vacuoles of s-IBM type.
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| 10. |
- McGlone, Francis, et al.
(författare)
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Functional neuroimaging studies of human somatosensory cortex
- 2002
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Ingår i: Behavioural Brain Research. - : Elsevier. - 0166-4328 .- 1872-7549. ; 135:1-2, s. 147-158, PII S0166-4328(02)00144-4
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Tidskriftsartikel (refereegranskat)abstract
- Two studies were carried out to assess the applicability of echoplanar fMRI at 3.0 T to the analysis of somatosensory mechanisms in humans. Vibrotactile stimulation of the tips of digits two and five reliably generated significant clusters of activation in primary (SI) and secondary (SII) somatosensory cortex, area 43, the pre-central gyrus, posterior insula, posterior parietal cortex and posterior cingulate. Separation of these responses by digit in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study employed microneurographic techniques in which individual median-nerve mechanoreceptive afferents were isolated, physiologically characterized, and microstimulated in conjunction with fMRI. Hemodynamic responses, observed in every case, were robust, focal, and physiologically orderly. These techniques will enable more detailed studies of the representation of the body surface in human somatosensory cortex, the relationship of that organization to short-term plasticity in responses to natural tactile stimuli, and effects of stimulus patterning and unimodal/cross-modal attentional manipulations. They also present unique opportunities to investigate the basic physiology of the BOLD effect, and to optimize the operating characteristics of two important human functional neuroimaging modalities-high-field fMRI and high-resolution EEG-in an unusually specific and well-characterized neurophysiological setting.
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