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Biomedical subjects

S Johansson

Publications and source records attributed to S Johansson.

At least 37 records · Page 2Linked to original sources
PubMed2004

Serotypes and clinical manifestations of invasive group B streptococcal infections in western Sweden 1998-2001.

This study monitored the serotypes of Streptococcus agalactiae (group B streptococcus; GBS) isolated from invasive infections in western Sweden and investigated possible relationships between serotype, age and clinical manifestations. Invasive GBS isolates were collected prospectively during 1998-2001 at six laboratories, covering two counties with a population of 1.8 million, and were serotyped by coagglutination. Clinical data were obtained from hospital notes. In total, 161 invasive strains (50 from neonates and infants aged < 3 months, and 111 from adults) were serotyped. The commonest serotypes from neonates and infants were serotypes III (60%), V (22%) and Ia (10%), and from adults were serotypes V (42%) and III (25%). Serotype V had doubled in frequency among both children and adults compared to a previous study from the same area in 1988-1997. Most (80%) of the adults had an underlying medical condition. No relationship was found between serotype and clinical manifestations. However, the study demonstrated the importance of active surveillance of GBS serotypes and the difficulties of formulating a multivalent polysaccharide conjugate vaccine against GBS.

Adolescent↗
PubMed2003

Is there any association between myocardial infarction, gastro-oesophageal reflux disease and acid-suppressing drugs?

BACKGROUND: A link between gastro-oesophageal reflux disease and coronary heart disease has been suggested. AIM: To estimate the incidence of myocardial infarction in patients with newly diagnosed gastro-oesophageal reflux disease in comparison with that in the general population. METHODS: A population-based cohort study was performed in the UK. Patients aged 18-79 years with a first diagnosis of gastro-oesophageal reflux disease (n = 7084) were identified and a group of 10,000 patients free of gastro-oesophageal reflux disease were sampled. A nested case-control analysis was performed to assess the risk factors for myocardial infarction. RESULTS: The incidence of myocardial infarction in the general population was 4.0 per 1,000 person-years [95% confidence interval (CI), 3.2-4.9] and 5.1 per 1,000 person-years (95% CI, 4.1-6.4) in patients with gastro-oesophageal reflux disease. The relative risk of myocardial infarction in patients with gastro-oesophageal reflux disease was 1.4 (95% CI, 1.0-1.9). The increased risk of myocardial infarction was limited to the immediate days after the diagnosis of gastro-oesophageal reflux disease. Previous chest pain was an important predictor of myocardial infarction in patients free of gastro-oesophageal reflux disease. No association was found between the use of acid-suppressing drugs and the risk of myocardial infarction. CONCLUSION: Our results suggest that gastro-oesophageal reflux disease is not an independent predictor of myocardial infarction. Rather, the increased risk of myocardial infarction in patients with gastro-oesophageal reflux disease in the immediate days after diagnosis indicates that prodromal ischaemic symptoms were misinterpreted as reflux symptoms.

Adolescent↗
PubMed2003

Perinatal asphyxia impairs connectivity and dopamine neurite branching in organotypic triple culture from rat substantia nigra, neostriatum and neocortex.

The effect of perinatal asphyxia on brain development was studied with organotypic cultures from substantia nigra, neostriatum and neocortex. Asphyxia was induced by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Following asphyxia, the pups were nursed by a surrogate dam and sacrificed after 3 days to prepare organotypic cultures. Non-asphyxiated caesarean-delivered pups were used as controls. Morphological features were recorded during in vitro development. At day in vitro (DIV) 24, the cultures were treated for histochemistry using fast red for cell nucleus labelling and antibodies against tyrosine hydroxylase for dopaminergic neurons. Compared to controls, cultures from asphyxiated pups revealed a diminished integration quantified during 21 DIV. After immunocytochemistry and camera lucida reconstruction, tyrosine hydroxylase-positive neurons showed a decreased number of neurites from secondary and higher level branching, demonstrating a vulnerability of the dopaminergic systems after perinatal asphyxia.

Animals↗
PubMed2003

Radiative cycle with stimulated emission from atoms and ions in an astrophysical plasma.

We propose that a radiative cycle operates in atoms and ions located in a rarefied gas in the vicinity of a hot star. Besides spontaneous transitions the cycle includes a stimulated transition in one very weak intermediate channel. This radiative "bottleneck" creates a population inversion, which for an appropriate column density results in amplification and stimulated radiation in the weak transition. The stimulated emission opens a fast decay channel leading to a fast radiative cycle in the atom (or ion). We apply this model by explaining two unusually bright Fe II lines at 250.7 and 250.9 nm in the UV spectrum of gas blobs close to eta Carinae, one of the most massive and luminous stars in the Galaxy.

Journal Article↗
PubMed2003

Small, novel proteins from the mistletoe Phoradendron tomentosum exhibit highly selective cytotoxicity to human breast cancer cells.

Four novel proteins (phoratoxins C-F) have been isolated from the North American mistletoe Phoradendron tomentosum. The amino acid sequences of these phoratoxins were determined unambiguously using a combination of Edman degradation and trypsin enzymatic digestion, and by electrospray ionization tandem mass spectrometry sequencing. Phoratoxins C, E and F consist of 46 amino acid residues; and phoratoxin D of 41. All proteins had six cysteines, similar to the earlier described phoratoxins A and B, which are thionins. The cytotoxicity of each protein was evaluated in a human cell line panel that represented several cytotoxic drug-resistance mechanisms. For the half-maximal inhibitory concentrations (IC50 values) of the different cell lines in the panel, correlation with those of standard drugs was low. The most potent cytotoxic phoratoxin C was further tested on primary cultures of human tumor cells from patients. The solid tumor samples from breast cancer cells were 18 times more sensitive to phoratoxin C than the tested hematological tumor samples.

Amino Acid Sequence↗
PubMed2003

HLA associations in type 1 diabetes: DPB1 alleles may act as markers of other HLA-complex susceptibility genes.

Alleles at the HLA-DQB1, -DQA1 and -DRB1 loci are major determinants for susceptibility to develop type 1 diabetes (T1D). Increasing evidence supports that also other genes in, or near, the HLA complex contribute to the HLA-encoded risk. Alleles at the DPB1 locus have been suggested to directly influence the risk conferred by DQB1, DQA1 and DRB1 alleles, but the results are conflicting. We therefore genotyped 217 families from Norway, Denmark, Sweden and southern France to address the role of DPB1 alleles in T1D. After taking into account linkage disequilibrium (LD) with DQB1, DQA1 and DRB1 alleles, we found evidence that some DPB1 alleles are associated with modulating the risk of developing T1D. However, we show that the strong LD in the HLA complex, and the presence of extended haplotypes complicate the interpretation of the results. On DQ2-DR3 haplotypes, both allele 3 at microsatellite D6S2223 located 5.3-Mb telomeric of DPB1 and the extended DQ2-DR3-B18 haplotype display much stronger association than DPB1 alleles. When we exclude these effects, most of the apparent association of DPB1 alleles on DQ2-DR3 haplotypes disappear. Taken together, although we cannot completely rule out an effect of some DPB1 alleles, we propose that the statistically significant, albeit weak, DPB1 associations found are most likely the result of LD with another unidentified disease-susceptibility gene(s) in this region.

Alleles↗
PubMed2003

Evidence of at least two type 1 diabetes susceptibility genes in the HLA complex distinct from HLA-DQB1, -DQA1 and -DRB1.

Susceptibility to, and protection against development of type 1 diabetes (T1D) are primarily associated with the highly polymorphic exon 2 sequences of the HLA class II genes: DQB1, DQA1 and DRB1. However, several studies have also suggested that additional genes in the HLA complex influence T1D risk, albeit to a lesser degree than the class II genes. We have previously shown that allele 3 of microsatellite marker D6S2223, 4.9 Mb telomeric of DQ in the extended class I region, is associated with a reduction in risk conferred by the DQ2-DR3 haplotype. Here we replicate this finding in two populations from Sweden and France. We also show that markers in the HLA class II, III and centromeric class I regions contribute to the DQ2-DR3 associated risk of T1D, independently of linkage disequilibrium (LD) with both the DQ/DR genes and the D6S2223 associated gene. The associated marker alleles are carried on the DQ2-DR3-B18 haplotype in a region of strong LD. By haplotype mapping, we have located the most likely location for this second DQ2-DR3 haplotype-modifying locus to the 2.35 Mb region between HLA-DOB and marker D6S2702, located 970 kb telomeric of HLA-B.

Chi-Square Distribution↗
PubMed2002

Glutamate-induced currents reveal three functionally distinct NMDA receptor populations in rat dorsal horn - effects of peripheral nerve lesion and inflammation.

The importance of the N-methyl-D-aspartate (NMDA) receptor in various painful conditions is well established. The effects of peripheral nerve lesion or joint inflammation, as models of different pain states, on NMDA receptor-mediated currents and NMDA receptor subunit mRNA expression were therefore studied in acutely dissociated neurones from the rat spinal cord dorsal horn. In the neuronal population from control rats, all four NR2 subunits and both NR1 splice variants assayed were detected. A majority of neurones expressed mRNA for more than one NR2 subunit, and some neurones expressed all four NR2 subunits as well as both NR1 splice variants. The NR2B subunit was the most commonly expressed, while the NR2C was the rarest. Following nerve lesion, fewer neurones expressed NR2A compared to the control. The dose-response curve for glutamate-evoked NMDA receptor-mediated currents in the neurones was best described by a three-component fit, suggesting that three functionally distinct NMDA receptor populations are present in the dorsal horn. Minor changes in the dose-response curve after nerve lesion could not be ascribed with certainty to the lesion. Changes in other parameters of NMDA receptor-mediated currents were observed neither after nerve lesion nor after joint inflammation. In summary, the present work demonstrates that single dorsal horn neurones express mRNA for several NMDA receptor subunits. The glutamate dose-response curves indicate that there are three major types of NMDA receptors present in dorsal horn neurones. We also report a reduced expression of NR2A following peripheral nerve lesion.

Animals↗
PubMed2002

Subclinical hypervitaminosis A causes fragile bones in rats.

Excessive intake of vitamin A has been associated with an increased risk of hip fracture in humans. This finding has raised the question of whether long-term intake of relatively moderate doses ("subclinical" hypervitaminosis A) contributes to fracture risk. Although it has been known for more than half a century that toxic doses of vitamin A lead to spontaneous fractures in rats, the lowest intake that induces adverse effects is not known, and the result of exposure to excessive doses that do not cause general toxicity has been rarely investigated. In this study, mature female rats were fed a standard diet with 12 IU vitamin A/g pellet (control, C), or standard diet supplemented with either 120 IU ("10 x C") or 600 IU ("50 x C") vitamin A/g pellet for 12 weeks. Fifteen animals were included in each group. The supplemented diets correspond to a vitamin A intake of approximately 1800 IU/day and 9000 IU/day, respectively. The latter dose is about one third of that previously reported to cause skeletal lesions. At the end of the study, serum retinyl esters were elevated 4- (p < 0.01) and 20-fold (p < 0.001) and the total amount of liver retinoid had increased 3- (p < 0.001) and 7-fold (p < 0.001) in the 10 x C and 50 x C group, respectively. The animals showed no clinical signs of general toxicity, and there were no significant bone changes in the 10 x C group. However, in the 50 x C group, a characteristic thinning of the cortex (cortical area -6.5% [p < 0.001]) and reduction of the diameter of the long bones were evident (bone cross-sectional area -7.2% [p < 0.01] at the midshaft and -11.0% [p < 0.01] at the metaphysis), as measured by peripheral quantitative computed tomography. In agreement with these data and a decreased polar strength strain index (-14.0%, p < 0.01), the three-point bending breaking force of the femur was reduced by 10.3% (p < 0.01) in the 50 x C group. These data indicate that the negative skeletal effects appear at a subchronic vitamin A intake of somewhere between 10 and 50 times the standard diet. This level is considerably lower than previously reported. Our results suggest that long-term ingestion of modest excesses of vitamin A may contribute to fracture risk.

Animals↗
PubMed2002

Extra-intestinal manifestations associated with irritable bowel syndrome: a twin study.

BACKGROUND: Little is known about the role of genetic and environmental factors in irritable bowel syndrome. Various extra-intestinal manifestations are more prevalent in cases than in controls. Genetic effects may be important in the liability to develop functional bowel disorders. AIMS: To evaluate the associations of irritable bowel syndrome with several disorders co-morbid with the condition, using both a case-control design and a co-twin control design. METHODS: A sample of 850 Swedish twin pairs, aged 18-85 years, was contacted for a telephone interview. Through a diagnostic algorithm, 72 unrelated cases of irritable bowel syndrome and 216 age- and gender-matched controls were identified. Fifty-eight twin pairs discordant for irritable bowel syndrome were evaluated in co-twin analyses. RESULTS: Renal problems (odds ratio (OR)=3.3; confidence interval (CI), 1.3-8.2), obesity (OR=2.6; CI, 1.0-6.4), underweight in the past (OR=2.4; CI, 1.1-6.4), gluten intolerance (OR=9.0; CI, 1.4-60.1), rheumatoid arthritis (OR=3.2; CI, 1.1-9.4) and poor self-rated health (OR=1.8; CI, 1.0-3.2) were significantly associated with irritable bowel syndrome. In the co-twin analyses, the only factors maintaining significance were renal and recurrent urinary tract problems. CONCLUSIONS: The association between irritable bowel syndrome and renal and urinary tract problems does not reflect a genetic or familial mediation. Eating disorders in childhood represent a familial-environmental influence on irritable bowel syndrome, whereas the association with rheumatoid arthritis and perhaps gluten intolerance probably reflects genetic mediation.

Adult↗
PubMed2002

Perinatal water intoxication due to excessive oral intake during labour.

UNLABELLED: The increased body water in pregnant women and the birth-related activation of water-sparing systems contribute to a high risk of perinatal water intoxication if the mother drinks too much water during labour. This study reports on four newborn term infants and one mother presenting with life-threatening symptoms due to hyponatraemia from excessive oral intake during labour. Awareness of this diagnosis in the delivery unit is very important, because the clinical picture may mimic that of pre-eclampsia or dehydration. CONCLUSION: Guidelines are proposed to prevent and treat perinatal water intoxication due to excessive oral intake during labour.

Adult↗
PubMed2001

Association between oxidative stress and bone mineral density.

Free radicals have been shown to be involved in bone resorption in vitro and in rodents. We studied the effect of oxidative stress on bone mineral density (BMD) in 48 women and 53 men from a population-based study. The levels of 8-iso-PGF(2alpha) (a major F(2)-isoprostane and a biomarker of oxidative stress) and a control, 15-keto-dihydro-PGF(2alpha) (a biomarker of inflammatory response), were measured in urinary samples and their association with BMD and quantitative ultrasound (QUS) measurements were examined. In multivariate linear regression analyses, 8-iso-PGF(2alpha) levels were negatively associated with both BMD and QUS. In contrast, no association was found for 15-keto-dihydro-PGF(2alpha). Our findings establish a biochemical link between increased oxidative stress and reduced bone density and provide a rational for further studies investigating the role of pro- and antioxidants in osteoporosis.

Adult↗
PubMed2001

Evidence for target-specific outgrowth from subpopulations of grafted human dopamine neurons.

Clinical and experimental grafting in Parkinson's disease has shown the need for enhanced survival of dopamine neurons to obtain improved functional recovery. In addition, it has been suggested that a limited number of surviving dopamine neurons project to the dopamine-denervated host striatum. The aim of this study was to investigate if subpopulations of ventral mesencephalic dopamine neurons project to their normal targets, i.e., dorsal vs. ventral striatum. Following implantation of human ventral mesencepahlic tissue into the lateral ventricle of dopamine-depleted rats, human-derived dopamine reinnervation was achieved both in dorsal and ventral striatum. Treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) resulted in a degeneration of tyrosine hydroxylase (TH)-immunoreactive nerve fibers in dorsal striatum but not in ventral areas in some animals, while MPTP was without effect in other animals. TH-immunoreactive neurons were small and appeared shrunken in animals carrying grafts affected by the MPTP treatment. In conclusion, grafted dopamine neurons projected nerve fibers into areas that they normally innervate. Thus, when searching for factors that may enhance survival of grafted dopamine neurons it is important to study which subpopulation(s) of ventral mesencephalic dopamine neurons is affected, such that a proper reinnervation may be achieved.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

The functional role of a bicuculline-sensitive Ca2+-activated K+ current in rat medial preoptic neurons.

A Ca2+-activated K+ current was identified in neurons from the rat medial preoptic nucleus. Its functional role for the resting potential and for impulse generation was characterised by using the reversible blocking agent bicuculline methiodide. Acutely dissociated neurons were studied by perforated-patch recordings. The effect of bicuculline methiodide was investigated under voltage-clamp conditions to clearly identify the current affected. At membrane potentials > -50 mV, bicuculline methiodide rapidly (< 1 s) and reversibly blocked a steady outward current. Half-saturating concentration was 12 microM. The current amplitude increased with potential in the range -50 to 0 mV. The bicuculline-sensitive current was identified as an apamin-sensitive, Ca2+-dependent K+ current. It was neither affected by the GABAA receptor blocker picrotoxin (100 microM) nor by a changed pipette Cl- concentration, but was affected by substitution of extracellular K+ for Na+. The current was dependent on extracellular Ca2+ and was sensitive to 1 microM apamin but not to 200 nM charybdotoxin. A role for the Ca2+-dependent K+ current in setting the resting potential and controlling spontaneous firing frequency was observed under current-clamp conditions. Bicuculline methiodide (100 microM) induced a positive shift (5 +/- 1 mV; n = 18) of resting potential in all neurons tested. In the majority of spontaneously firing neurons, the firing frequency was reversibly affected, either increased or decreased depending on the cell, by bicuculline methiodide.

Animals↗
PubMed2001

Assembly of laminin polymers is dependent on beta1-integrins.

Recent reports suggest that laminin deposition is controlled by the cell via specific receptors, one of which is dystroglycan. In this study, the involvement of beta1-integrins in this process was investigated by comparing beta1-integrin-deficient cells of different phenotypes with their normal counterparts. Normal embryonic stem (ES) cells and embryoid bodies (EBs) derived from them were found to deposit cell-associated laminin into fibrillar networks, and in the EBs a basement membrane was assembled under the primitive endoderm. beta1-deficient ES cells and their EBs formed only small amounts of dot-like laminin deposits. Skeletal myotubes formed after prolonged differentiation in EBs were found to be surrounded by laminin, nidogen, and perlecan by immunofluorescent staining irrespective of the presence of beta1-integrins on the myotubes. However, at the electron microscope level only very thin sheet-like structures were detected close to the beta1-deficient myotubes, while the wt myotubes formed thick basement membranes. An epithelial cell line, GE11, derived from the beta1-integrin-deficient ES cells was also unable to assemble laminin on the cell surface, while transfection of the cells with the integrin beta1 subunit resulted in formation of a dense laminin network. Taken together, these results suggest that dystroglycan and beta1-integrins can both contribute to the recruitment of laminin to cell surfaces and that integrins are required at a subsequent step in the formation of basement membranes.

Animals↗
PubMed2001

Lifetime measurements of metastable states in Fe+.

The lifetime of two metastable levels in Fe+ has been measured by laser probing of a stored ion beam. In the dense spectrum of Fe+, the metastable levels a (6)S(5/2) and b (4)D(7/2) were selected and their lifetimes were determined to be 230 +/- 30 and 530 +/- 30 ms, respectively. The lifetimes are compared with previous theoretical results. Metastable lifetime measurements of Fe+ are of great importance for interpretation of spectra from astronomical objects. The present experiment opens for the possibilities to investigate lifetimes of metastable states in complex atomic ions, which have, so far, been unexplored.

Journal Article↗