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排序方式: 共有468条查询结果,搜索用时 15 毫秒
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Olaug K. Rødningen Oddveig Røshy Serena Tonstad Leiv Ose Kåre Berg Trond P. Leren 《Clinical genetics》1992,42(6):288-295
Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was performed in Norwegian subjects heterozygous for familial hypercholesterolemia (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and the restriction enzyme NcoI, showed that two out of 57 unrelated FH subjects had an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was due to a 9.6 kb deletion that included exons 16 and 17. The 5' deletion breakpoint was after 245 bp of intron 15, and the 3' deletion breakpoint was in exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane-spanning and cytoplasmatic domains of the receptor had been deleted. A polymerase chain reaction (PCR) method was developed to identify this deletion among other Norwegian FH subjects. As a result of this screening one additional subject was found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated Norwegian FH subject possessed this deletion. The deletion was found on the same haplotype in the three unrelated subjects, suggesting a common mutagenic event. The deletion is identical to a deletion (FH-Helsinki) that is very common among Finnish FH subjects. However, it is not yet known whether the mutations evolved separately in the two countries. 相似文献
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Summary The dose-response relationships between acutely established hyperglycaemia and the plasma C-peptide and insulin responses to i. v. stimulation with 1 mg of glucagon and a standard mixed meal were investigated in 10 patients with well-controlled Type 2 (non-insulin dependent) diabetes mellitus. Hyperglycaemia was maintained for 90 min before stimulation using a hyperglycaemic clamp technique. Each test was performed on different steady state blood glucose levels of 6 mmol/l, 12 mmol/l, and 20 mmol/l, respectively. The plasma C-peptide and insulin responses after glucagon and the meal were potentiated markedly at each level of prestimulatory hyperglycaemia. After glucagon injection, the relative glucose potentiation of the insulin response was significantly higher than the relative glucose potentiation of the C-peptide response at each level of hyperglycaemia (p<0.01). This difference may be explained by a higher fractional hepatic removal of insulin at normoglycaemia, since the molar ratio between the incremental C-peptide and insulin responses after glucagon stimulation was higher at prestimulatory normoglycaemia (4.85 (3.65–12.05)) than at the prestimulatory blood glucose concentrations 12 mmol/l (2.41 (2.05–4.09)) (p< 0.01) and 20 mmol/l (2.24 (1.37–3.62)) (p<0.01). In conclusion, the islet B-cell responses to glucagon and a standard mixed meal are potentiated to a high degree by acutely established prestirnulatory hyperglycaemia in patients with well-controlled Type 2 diabetes. Acute prestirnulatory hyperglycaemia is also associated with a markedly reduced incremental C-peptide/insulin ratio after glucagon stimulation in such patients. Measurement of the insulin response after i. v. glucagon injection at acute hyperglycaemia compared with the response at normoglycaemia therefore seriously overestimates the relative glucose potentiation of pancreatic B-cell responsiveness in patients with well-controlled Type 2 diabetes. 相似文献
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Swift F Franzini-Armstrong C Øyehaug L Enger UH Andersson KB Christensen G Sejersted OM Louch WE 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(10):3997-4001
Cardiomyocyte contraction and relaxation are controlled by Ca(2+) handling, which can be regulated to meet demand. Indeed, major reduction in sarcoplasmic reticulum (SR) function in mice with Serca2 knockout (KO) is compensated by enhanced plasmalemmal Ca(2+) fluxes. Here we investigate whether altered Ca(2+) fluxes are facilitated by reorganization of cardiomyocyte ultrastructure. Hearts were fixed for electron microscopy and enzymatically dissociated for confocal microscopy and electrophysiology. SR relative surface area and volume densities were reduced by 63% and 76%, indicating marked loss and collapse of the free SR in KO. Although overall cardiomyocyte dimensions were unaltered, total surface area was increased. This resulted from increased T-tubule density, as revealed by confocal images. Fourier analysis indicated a maintained organization of transverse T-tubules but an increased presence of longitudinal T-tubules. This demonstrates a remarkable plasticity of the tubular system in the adult myocardium. Immunocytochemical data showed that the newly grown longitudinal T-tubules contained Na(+)/Ca(2+)-exchanger proximal to ryanodine receptors in the SR but did not contain Ca(2+)-channels. Ca(2+) measurements demonstrated a switch from SR-driven to Ca(2+) influx-driven Ca(2+) transients in KO. Still, SR Ca(2+) release constituted 20% of the Ca(2+) transient in KO. Mathematical modeling suggested that Ca(2+) influx via Na(+)/Ca(2+)-exchange in longitudinal T-tubules triggers release from apposing ryanodine receptors in KO, partially compensating for reduced SERCA by allowing for local Ca(2+) release near the myofilaments. T-tubule proliferation occurs without loss of the original ordered transverse orientation and thus constitutes the basis for compensation of the declining SR function without structural disarrangement. 相似文献
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TB Wyller LO Watne A Torbergsen K Engedal F Frihagen V Juliebø I Saltvedt E Skovlund J Ræder S Conroy 《BMC geriatrics》2012,12(1):36
ABSTRACT: BACKGROUND: Hip fracture mainly affect older people. It is associated with high morbidity and mortality, and in particular a high frequency of delirium. Incident delirium following hip fracture is associated with an increased risk of dementia in the following months, but it is still not firmly established whether this is an association or a causal relationship. Orthogeriatric units vary with respect to content and timing of the intervention. One main effect of orthogeriatric care may be the prevention of delirium, especially if preoperative and postoperative care are provided. Thus, the aim of Oslo Orthogeriatric Trial, is to assess whether combined preoperative and postoperative orthogeriatric care can reduce the incidence of delirium and improve cognition following hip fracture. Methods/design: Inclusion and randomisation will take place in the Emergency Department, as soon as possible after admission. All patients with proximal femur fractures are eligible, irrespective of age, pre-fracture function and accommodation, except if the fracture is caused by a high energy trauma or the patient is terminally ill. The intervention is pre-and post-operative orthogeriatric care delivered on a dedicated acute geriatric ward. The primary outcome measure is a composite endpoint combining the Clinical Dementia Rating Scale (CDR) and the 10 word memory task at four months after surgery. Secondary outcomes comprise incident delirium, length of stay, cognition, mobility, place of residence, activities of daily living and mortality, measured at 4 and 12 months after surgery. We have included 332 patients in the period 17th September 2009 to 5th January 2012. DISCUSSION: Our choice of outcome measures and our emphasis of orthogeriatric care in the preoperative as well as the postoperative phase will enable us to provide new knowledge on the impact of orthogeriatric care on cognition. Trials registration: ClinicalTrials.gov NCT01009268. 相似文献
9.
Nestaas E Stoylen A Sandvik L Brunvand L Fugelseth D 《Ultrasound in medicine & biology》2007,33(2):270-278
The optimal combination of region-of-interest (ROI) size and strain length (SL) allowing two-segment strain and strain rate analyses in term neonates was investigated. The impact of different ROI sizes and SLs on the strain and strain rate beat-to-beat variation (BBV) was assessed in 80 good-quality tissue velocity images. Both BBVs decreased with increased ROI length and with increased SL (p < 0.05). There were no significant differences in the BBVs for ROI width 2, 3 and 4 mm (p > 0.05). Among the combinations eligible for two segment analysis, the lowest BBVs were found using SL 10 mm, ROI length 1 mm and ROI width 3 mm. Using this combination, the mean difference between the single-cycle value and two-cycle compound value for peak systolic strain rate was 6.2%, peak systolic strain was 2.9% and end systolic strain was 3.2% of the two-cycle compound mean values. Hence, strain and strain rate measurement in tissue velocity images in neonates is feasible and reliable. 相似文献
10.
Our aim was to study autonomic function in patients with Irritable bowel syndrome (IBS) without constipation and psychiatric
comorbidity. Respiratory sinus arrhythmia (RSA) (representing cardiac vagal activity), skin conductance (representing sympathetic
activity) and heart rate were measured at baseline and as a response to emotional stress and rectal discomfort in 33 women
with IBS and 21 healthy women. Baseline heart rate was higher in the patients than in the healthy volunteers. Both groups
had decreased RSA and increased heart rate and skin conductance level when exposed to emotional stress, but the autonomic
responses did not differ significantly between the groups. At discomfort threshold the patients had increased heart rate response
and skin conductance amplitude when compared to the healthy volunteers. Correlations between autonomic responses and the depression
subscale of the Hospital Anxiety and Depression (HAD) score differed markedly between the diarrhea-predominant IBS patients
and the IBS patients with alternating stool habits. 相似文献