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1. |
Bile acid transport systems as pharmaceutical targets |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 715-732
W. KRAMER,
G. WESS,
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ISSN:0014-2972
DOI:10.1111/j.1365-2362.1996.tb02383.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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2. |
Apolipoprotein function in health and disease: insights from natural mutations |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 733-746
G. FRANCESCHINI,
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ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.2120536.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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3. |
Red blood cell aggregability is increased by aspirin and flow stress, whereas dipyridamole induces cell shape alterations: measurements by digital image analysis |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 747-754
J. Bozzo,
M. R. Hernández,
A. del Giorgio,
A. Ordinas,
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摘要:
We evaluated the influence of pretreatment with aspirinin vitro, alone or combined with dipyridamole, on red cell aggregability. Samples were tested before and after being exposed to well‐defined flow conditions. An aggregation rate was estimated through digital analysis of light microscopy images. Red cells of untreated blood that had been exposed to flow showed a higher aggregation rate (38.54 ± 1.63 vs. 27.52 ± 1.36;P < 0.05). This effect was not observed in the absence of platelets. Treatment with aspirin induced a high aggregation rate, with or without exposure to flow conditions. Dipyridamole alone or combined with aspirin provoked echinocytosis, disturbing the rouleaux arrangement (rates ranging from 11.25 ± 1.91–13.62 ± 1.62). Washing red cells after treatment restored about 90% of echinocytes to their biconcave shape, but aggregation rate did not recover in parallel. These results highlight the influence of red cell–platelet interactions in the regulation of haemostasis and show how therapeutic agents can interfe
ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.1960540.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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4. |
Utilization of myristic and palmitic acid in humans fed different dietary fats |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 755-762
D. E. MacDougall,
P. J. H. Jones,
J. Vogt,
P. T. Phang,
D. D. Kitts,
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摘要:
To assess the influence of dietary fat composition on the contribution of dietary myristic and palmitic acid to total fat oxidation and energy production, eight healthy men consumed diets containing 40% of total energy as fat, largely as either butter, tallow or corn oil, for 11 days. On days 8 and 11 of each diet, [1‐13C]‐myristic or [1‐13C]‐palmitic acid (20 mg kg–1body weight) was ingested mixed with the test breakfast meal. Respiratory gas exchange was measured before, and for 9 h after, consumption of the meal. Breath13CO2enrichments were determined hourly by isotope ratio mass spectrometry. Cumulative 9‐h percentage oxidation of dietary myristic acid exceeded that of palmitic acid (P < 0.01), but neither was influenced by fat treatment [n = 8, 7.1% (1.0) (SEM), 8.6% (0.9) and 8.9% (0.6) of dietary myristic acid and 3.3% (0.7), 3.0% (0.9), and 2.5% (0.6) of dietary palmitic acid from butter, tallow and corn oil meals respectively]. Net dietary myristic acid oxidation was greater (P <0.05) after consumption of the meal high in butter than after consumption of other fats. Net dietary palmitic acid oxidation was similar after consumption of all test meals. Precedent fat treatment had no measurable effect on net fat or carbohydrate oxidation or energy expenditure. The overall contribution of dietary myristic or palmitic acid to total fat oxidation did not exceed 1% over 9 h for any dietary fat. These results suggest that, although dietary fatty acid content is the principal determinant of net dietary fatty acid oxidation, dietary fat sources with moderate differences in fat composition do not measurably alter total energy or subst
ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.1980545.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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5. |
Effects of low‐ and conventional‐dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 763-771
C. A. Sharp,
S. F. Evans,
L. Risteli,
J. Risteli,
M. WORSFOLD,
M. W. J. Davies,
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摘要:
The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L–1. Our data suggest that low‐dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional‐dose HRT and is associated with decreased circulating markers of bone and connective tiss
ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.2000550.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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6. |
Direct vasodilator effects of physiological hyperinsulin‐aemia in human skeletal muscle |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 772-778
C. J. J. Tack,
A. E. P. Schefman,
J. L. Willems,
T. Thien,
J. A. Lutterman,
P. Smits,
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摘要:
Systemic hyperinsulinaemia induces vasodilatation in human skeletal muscle. This effect is gradual in onset, and at low insulin levels not maximal until at least 3 h. To investigate whether the vasodilator response to insulin results from adirectvascular effect, we infused insulin directly into the cannulated brachial artery (perfused forearm technique) in a total of 30 experiments in 20 healthy, lean, normotensive volunteers. Local, intra‐arterial, infusion of insulin (180 min, 0.3 mU dL−1forearm volume min−1,n = 15, forearm venous insulin concentration approximately 540 pmol L−1) induced a gradual increase in forearm blood flow (FBF; venous occlusion plethysmography) from 1.86 ± 0.17 to 3.64 ± 0.64 mL dL−1 min−1after 180 min (anovaP < 0.001). Percentage increases in FBF after 60, 120 and 180 min averaged 14.4 ± 5.9, 59.4 ± 25.5 and 124.6 ± 51.2% respectively. Forearm glucose uptake increased from 0.24 ± 0.05 to a maximum of 1.98 ± 0.28 μmol dL−1 min (P < 0.001). Furthermore, insulin infusion increased forearm lactate release and potassium uptake. In 10 out of these 15 individuals, the forearm glucose uptake was further increased in a second, separate, repeat experiment with concomitant intra‐arterial infusion of glucose 5% (0.2 mL dL−1 min−1), resulting in forearm venous glucose concentrations of approximately 15 mmol L−1. This combined infusion achieved a similar vasodilator response to the infusion of insulin alone. The individual vascular responses of the two paired experiments showed a strong correlation (r = 0.87,P < 0.01). In five subjects time and vehicle control experiments were performed, showing no changes in FBF or metabolism during the 180 min. We conclude that the slow vasodilator response to insulin (as observed during systemic infusion) can, at least partly, be explained by adirectvascular effect of insulin. Insuli
ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.2020551.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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7. |
A simple, rapid immunometric assay for determination of functional and growth hormone‐occupied growth hormone‐binding protein in human serum |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 779-785
S. FISKER,
J. FRYSTYK,
L. SKRIVER,
E. VESTBO,
K. K. Y. HO,
H. ØRSKOV,
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摘要:
We present a sensitive time‐resolved fluorometric immunofunctional assay (TR‐FIA) for direct quantitation of functional growth hormone‐binding protein (GHBP), using an immunoassay kit for growth hormone (GH‐DELFIA). In addition to the immobilized GH antibody, one monoclonal antibody against GHBP was used. This anti‐GHBP was labelled with the chelate of europium. The assay was performed in one step. The detection limit for GHBP was 0.044 nmol L–1(NBS + 3 SD). The calibration curve was linear in the interval 0.11–8.03 nmol L−1. Average intra‐assay coefficient of variation (CV) was 3.44%. Average interassay CV at GHBP concentrations 0.563 nmol L−1and 1.40 nmol L−1were 12% and 6.3% respectively. Analytical recovery in serum ranged from 76% to 127% with a mean of 101 ± 3.6%. Serum GHBP in 102 normal subjects ranged from 0.513 to 3.772 nmol L 1and was positively related to body mass index (P < 0.001). In growth hormone‐deficient sera GHBP was higher than in control subjects (1.751 ± 0.179 nmol L−1and 1.257 ± 0.140 nmol L−1respectively,P < 0.001). Acromegalic patients had lower levels of GHBP than controls (0.946 ± 0.251 and 1.234 ± 0.144 nmol L−1respectively,P = 0.005). This assay also allowed detection of GH‐complexed GHBP in serum. These results were in agreement with theoretical values calculated from the measured GH and the functional GHBP concentrations. Results were compared with data obtained by a recently reported, validated ligand immunofunctional assay (LIFA), which is fundamentally different. There was a significant linear relationship between the results from the two assays (r = 0.89,P = 0.001). The slope of the regression line was 0.65. In conclusion, this new convenient GHBP TR‐FIA provides a sensitive and precise method for det
ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.2010558.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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8. |
Complexes between proteinase 3, α1‐antitrypsin and proteinase 3 anti‐neutrophil cytoplasm autoantibodies: a comparison between α1‐antitrypsin PiZ allele carriers and non‐carriers with Wegener's granulomatosis |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 786-792
B. Baslund,
W. Szpirt,
S. Eriksson,
A.‐N. Elzouki,
A. Wiik,
J. Wieslander,
J. Petersen,
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摘要:
To test the hypothesis that anti‐neutrophil cytoplasm autoantibodies (ANCAs) interfere with the functions of proteinase 3 (PR3) (the Wegener autoantigen) and α1‐antitrypsin (α1AT), complexes of PR3/α1AT and PR3/PR3‐ANCA‐IgG were assayed. Plasma samples were obtained from 44 patients with Wegener's granulomatosis (WG): 34 had active disease (88% ANCA positive) whereas 10 patients were in remission (20% ANCA positive). Plasma samples from 14 of the patients with active disease were also available at the time of remission. The complexes of PR3/α1AT and PR3/PR3‐ANCA‐IgG were detected by capture enzyme‐linked immunoassays (ELISAs). α1AT deficiency was evaluated by determining PiZ alleles by ELISA. Eight (18%) of the patients were PiZ positive. The frequency of this α1‐antitrypsin phenotype in the Scandinavian population is 4.7% (P < 0.001). The median PR3/α1AT complex level in the PiZ‐positive group with active disease (n = 5) was similar to the level in the PiZ‐negative group with active disease. During remission the median level for the PR3/α1AT complex was significantly higher than in the acute group (P < 0.001) including both PiZ‐positive and PiZ‐negative patients. No difference between PiZ positivity and PiZ negativity could be found in the remission group. PR3/PR3‐ANCA‐IgG complexes were found in patients with acute disease as well as in patients in remission, in almost equal frequency. This complex was also present in 13/18 ANCA‐negative samples from patients in remission. Finally, purified IgG fractions from WG patients were examined for their capacity to inhibit binding between PR3 and α1AT. An effect on the binding between PR3 and α1AT by PR3‐ANCA could not be demonstrated. Thus, our results do not support the hypothesis that PR3‐ANCA interferes with the binding between PR3 and α1AT. However, the high prevalence of the PiZ alleles among WG patients suggests that an imbalance between proteinases and α1AT may be of importance in this disease. The clinical usefulness of both the PR3/α1AT and the PR3/PR3‐ANCA‐IgG complexes and the possible influence on ANCA det
ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.2070553.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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9. |
Vitamin D receptor genotypes are related to bone size and bone density in men |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 793-796
A. G. Need,
M. Horowitz,
A. Stiliano,
F. Scopacasa,
H. A. Morris,
B. E. Chatterton,
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摘要:
Three restriction fragment length polymorphisms in the vitamin D receptor gene have been associated with a low bone density in twin and female population studies, but no studies have been conducted exclusively in men. We studied 146 normal men aged 20–83 years. Bone density was measured in the spine, hip, whole body and forearm, and the Bsm polymorphism for the vitamin D receptor was detected by the polymerase chain reaction. Men with genotype BB tended to have a lower bone density at all but one site than the other genotypes. In the men ≤50 years of age bone density in the forearm was 7% lower in the BB than the Bb and bb groups (P = 0.030) but bone mineral content did not differ between the groups. Bone area was greater in the BB genotype at all sites. This was statistically significant in the forearm (P = 0.026). We conclude that BB genotype is associated with lower bone density in men, which may be due to larger bone size rather tha
ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.2080554.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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10. |
Synthesis and release of phosphatidylcholine by isolated porcine gastric mucous cells in primary culture |
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European Journal of Clinical Investigation,
Volume 26,
Issue 9,
1996,
Page 797-802
W. Bernhard,
H. Schulte,
M. Piller,
K.‐F. Sewing,
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摘要:
Phosphatidylcholine (PC) is the major phospholipid of the hydrophobic gastric mucosal barrier and is chiefly released from mucous cells into the gastric mucus. Whereas the mucosa contains highly unsaturated PC, gastric mucus predominantly contains palmitoyl‐oleoyl‐PC and palmitoyl‐linoleoyl‐PC, indicating a selective release of these PC species into the gastric lumen. In order to understand gastric PC metabolism, we investigated synthesis and release of PC in cultivated porcine gastric mucous cells, using dual labelling with [methyl‐3H]‐choline and [1‐14C]‐palmitate, in the presence of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), indomethacin and prostaglandin E2(PGE2). Linear incorporation of [methyl‐3H]‐choline and [1‐14C]‐palmitate into PC was achieved for at least 8 h. In contrast to type II pneumocytes TPA increased PC synthesis in gastric mucous cells but not its release. Indomethacin did not influence PC synthesis, but it decreased the release of newly synthesized PC. PGE2antagonized the effect of indomethacin on PC release. We conclude that PC release by isolated porcine gastric mucous cells is regulated in a manner different from type II pneumocytes. PC release is impaired by indomethacin and th
ISSN:0014-2972
DOI:10.1046/j.1365-2362.1996.2100556.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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