| 1. |
- Herías, M V, et al.
(författare)
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Role of Escherichia coli P fimbriae in intestinal colonization in gnotobiotic rats.
- 1995
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Ingår i: Infection and immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 63:12, s. 4781-9
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Tidskriftsartikel (refereegranskat)abstract
- Adherence via P fimbriae is associated with long-term persistence of Escherichia coli in the human large intestine, but a causal relationship has not been proven. In the present study, germfree rats were colonized with a mixture of two isogenic E. coli strains, one P fimbriated and the other type 1 fimbriated. Both types of fimbriae conferred adherence to rat colonic epithelial cells. With two mutant strains from a pyelonephritogenic isolate of serotype O75:K5:H-, the P-fimbriated strain 824 attained much higher numbers than its type 1-fimbriated counterpart when colonized in vivo for 2 weeks (10(10) versus 10(6) bacteria per g, respectively; P < 0.0001). The expression of P fimbriae by 824 was also retained during colonization. With transformant isogenic strains obtained from a normal fecal isolate incapable of phase variation, no benefit of P fimbriae was seen and most bacteria lost their plasmids during in vivo colonization. When the pyelonephritogenic mutant and fecal transformant strains were combined, the former colonized at high levels while the latter were suppressed. In contrast, no suppression was seen when the transformant E. coli strains colonized in combination with Lactobacillus acidophilus or Peptostreptococcus sp. The results indicate that P fimbriae, but also other bacterial traits linked to uropathogeneicity, could play an important role for persistence in the gut normal microbiota. Neither P nor type 1 fimbriae seemed to contribute to the ability to translocate to the mesenteric lymph nodes.
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| 2. |
- Carlsson, Björn, 1958, et al.
(författare)
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Obese (ob) gene defects are rare in human obesity
- 1997
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 5:1, s. 30-5
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the role of the recently cloned ob-protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob-gene expression, with extreme overexpression in mice which lack bioactive ob-protein, have nonfunctional ob-receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob-gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot. The coding region of the ob-gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob-gene and ob-gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob-expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob-gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob-gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.
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| 3. |
- Axelsson, L., et al.
(författare)
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Study of the unbound nucleus 11N by elastic resonance scattering
- 1996
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813 .- 2469-9985 .- 2469-9993. ; 54:4, s. 1511-1514
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Tidskriftsartikel (refereegranskat)abstract
- Resonances in the unbound nucleus 11N have been studied, using the resonance scattering reaction 10C+p. The data give evidence for three states above the 10C+p threshold with energies 1.30, 2.04, and 3.72 MeV. These states can be interpreted, in a potential-model analysis, as the ground state and the first two excited states with spin-parity 1 / 2+, 1 / 2-, and 5 / 2+ arising from the shell-model orbitals 1s1 / 2, 0p1 / 2, and 0d5 / 2. A narrow state superposed on a broad structure found at higher energy could be interpreted as the mirror state of the 3 / 2- in 11Be shifted down in energy. This shift would suggest a large radius of the potential.
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| 4. |
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| 5. |
- Guron, Gregor, 1967, et al.
(författare)
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Cardiac insulin-like growth factor I and growth hormone receptor expression in renal hypertension
- 1996
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 27:3/Pt 2, s. 636-42
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the role of insulin-like growth factor I in the development of cardiac hypertrophy in two-kidney, one clip hypertension by relating growth hormone receptor and insulin-like growth factor I receptor mRNA levels to insulin-like growth factor I gene transcription using a solution hybridization/RNase protection assay. Two-kidney, one clip hypertension was induced in male Wistar rats, and experiments were performed 2, 4, 7, and 12 days after surgery. Systolic blood pressure was elevated 2, 7, and 12 days after clipping (P < .001). Left ventricular weights were increased 2, 4, 7, and 12 days after surgery (P < .01). Associated with the rise in blood pressure, left ventricular insulin-like growth factor I mRNA was increased 2, 7, and 12 days after surgery (P < .01). Furthermore, growth hormone receptor and insulin-like growth factor I receptor gene expression increased specifically in the left ventricle of renal hypertensive rats (P < .05 and P < .001, respectively). Left ventricular growth hormone receptor mRNA peaked 7 days after induction of renal artery stenosis. These results show that insulin-like growth factor I, growth hormone receptor, and insulin-like growth factor I receptor mRNA increase in the pressure-overloaded left ventricle of two-kidney, one clip rats, suggesting a role for insulin-like growth factor I and the growth hormone/insulin-like growth factor I axis in the development of cardiac hypertrophy.
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| 6. |
- Mikkola, Hanna, et al.
(författare)
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Four novel mutations in deficiency of coagulation factor XIII: Consequences to expression and structure of the A-subunit
- 1996
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Ingår i: Blood. - 1528-0020. ; 87:1, s. 141-151
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Tidskriftsartikel (refereegranskat)abstract
- The characterization of naturally occurring mutations is one way to approach functionally significant domains of polypeptides. About 10 mutations have been reported in factor XIII (FXIII) A-subunit deficiency, but very little is known about the effects of the mutations on the expression or the structure of this enzyme. In this study, the recent crystallization of FXIII A-subunit and determination of the three-dimensional model were used for the first time to pursue the structural consequences of mutations in the A- subunit. The molecular analysis of four families from Sweden, Germany, and Denmark revealed four previously unreported point mutations. Three of the mutations were missense mutations, Arg326 → Gln, Arg252 → Ile, and Leu498 → Pro, and one was a nonsense mutation, a deletion of thymidine in codon for Phe8 resulting in early frameshift and premature termination of the polypeptide chain. In the case of the nonsense mutation, delT Phe8, the steady-state mRNA level of FXIII A-subunit was reduced, as quantitated by reverse transcriptase-polymerase chain reaction and solid-phase minisequencing. In contrast, none of the missense mutations affected mRNA levels, indicating the possible translation of the mutant polypeptides. However, by enzyme-linked immunosorbent analysis and immunofluorescence, all the patients demonstrated a complete lack of detectable factor XIIIA antigen in their platelets. In the structural analysis, we included the mutations described in this work and the Met242 → Thr mutation reported earlier by us. Interestingly, in the three-dimensional model, all four missense mutations are localized in the evolutionarily conserved catalytic core domain. The substitutions are at least 15 Å away from the catalytic cleft and do not affect any of the residues known to be directly involved in the enzymetic reaction. The structural analyses suggest that the mutations are most likely interfering with proper folding and stability of the protein, which is in agreement with the observed absence of detectable FXIIIA antigen. Arg326, Arg252, and Met242 are all buried within the molecule. The Arg326 → Gln and Arg252 → Ile mutations are substitutions of smaller, neutral amino acids for large, charged residues. They disrupt the electrostatic balance and hydrogen- bonding interactions in structurally significant areas. The Met242 → Thr mutation is located in the same region of the core domain as the Arg252 → Ile site and is expected to have a destabilizing effect due to an introduction of a smaller, polar residue in a tightly packed hydrophobic pocket. The substitution of proline for Leu498 is predicted to cause unfavorable interatomic contacts and a disruption of the alpha-helix mainchain hydrogen-bonding pattern; it is likely to form a kink in the helix next to the dimer interface and is expected to impair proper dimerization of the A-subunits. In the case of all four missense mutations studied, the knowledge achieved from the three-dimensional model of crystallized FXIII A- subunit provides essential information about the structural significance of the specific residues and aids in understanding the biologic consequences of the mutations observed at the cellular level.
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| 7. |
- Herías, M V, et al.
(författare)
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Escherichia coli K5 capsule expression enhances colonization of the large intestine in the gnotobiotic rat.
- 1997
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Ingår i: Infection and immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 65:2, s. 531-6
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Tidskriftsartikel (refereegranskat)abstract
- The role of capsule expression in the capacity of Escherichia coli to colonize in the large intestinal environment was studied in a gnotobiotic rat model. The rats were given perorally a mixture of two mutant strains differing in K5 expression. After 2 weeks, the rats were sacrificed, and subsequently intestinal contents, intestinal mucosae, and mesenteric lymph nodes were homogenized and bacterial numbers were quantified. Two E. coli mutant pairs were used, the first pair (972-998) lacking the O-specific side chain and the second pair (973-997) carrying the O75 lipopolysaccharide. The K5+ mutants established themselves at a higher level than the K5- mutants (10(9) versus 10(6) CFU/g [P < 0.001] for the first pair and 10(9) versus 10(8) CFU/g [P < 0.01] for the second pair, respectively). The results were confirmed by serology showing a K5+ phenotype for practically all isolates. The bacterial population associated with the mucosa was similar to that in the luminal contents with respect to the proportions of the respective mutants, and translocation occurred in numbers proportional to the intestinal population densities of the respective mutants. All mutants were able to express type 1 as well as P fimbriae. After colonization, the expression of P fimbriae remained high whereas only a minority of the isolates expressed type 1 fimbriae. The results suggest that capsule expression and P fimbriae enhance intestinal colonization by E. coli and that these virulence factors, by increasing bacterial densities in the intestine, secondarily increase translocation.
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| 8. |
- Kiviranta, Ilkka, et al.
(författare)
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Effects of mechanical loading and immobilization on the articular cartilage
- 1997
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Ingår i: Bailliere's Clinical Orthopaedics. - 1074-8814. ; 2:1, s. 109-122
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Forskningsöversikt (refereegranskat)abstract
- Articular cartilage provides nearly frictionless surfaces for joint movemants and reduces contact pressures, protecting the underlying suchondral bone from excess stress. The unique properties of articular cartilage are based on the interaction of the main components of the extracellular matrix: proteoglycans (PGs), collagen and interstitial fluid. Animal experiments and in vitro studies demonstrate that one of the most important regulators of the extracellular matrix metabolism is mechanical loading acting on the joints. Unloading and immobilization leads to PG depletion and softening of articular cartilage, increasing the risk of permanent cartilage degeneration. Moderate running exercise and increased weight bearing increases cartilage thickness, PG concentration and improves biomechanical properties of articular cartilage. With further increase in training intensity this positive influence of exercise disappears and cartilage shows changes analogous to immobilization of the joint, i.e. PG depletion and softening of the tissue. In humans most epidemiological studies have failed to prove the connection between running training and cartilage degeneration, but there is evidence that sports activities exposing joints to impact loading might increase the risk of osteoarthrosis.
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| 9. |
- Ahrné, Siv, et al.
(författare)
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The normal Lactobacillus flora of healthy human rectal and oral mucosa.
- 1998
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Ingår i: Journal of applied microbiology. - 1364-5072. ; 85:1, s. 88-94
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Tidskriftsartikel (refereegranskat)abstract
- The Lactobacillus flora of the rectal and oral mucosa was sampled from 42 healthy volunteers. Species identification was carried out by numerically comparing API 50CH fermentation patterns with type strains, using an SJ-similarity cut-off level of 79%. For the largest groups, identity was further confirmed by DNA-DNA hybridizations against the type strain of the species. Seventeen lactobacilli clusters were defined, of which most were found both on rectal and oral mucosa. The largest taxa were Lactobacillus plantarum, Lact. rhamnosus and Lact. paracasei ssp. paracasei, which were isolated from 52%, 26% and 17% of the individuals, respectively. Most isolates were tested for their capacity to adhere to the human colonic cell line HT-29 in the absence and presence of methyl-alpha-D-mannoside. Mannose-sensitive adherence to HT-29 cells was encountered in two-thirds of the Lact. plantarum isolates, but infrequently among isolates of other taxa. The results suggest that Lact. plantarum is a major colonizer of the human gastrointestinal mucosa, and that its capacity to adhere to mannose-containing receptors may be of some ecological importance.
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| 10. |
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