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1.
The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. 总被引:16,自引:2,他引:14 下载免费PDF全文
D T Stein B E Stevenson M W Chester M Basit M B Daniels S D Turley J D McGarry 《The Journal of clinical investigation》1997,100(2):398-403
Lowering of the elevated plasma FFA concentration in 18- 24-h fasted rats with nicotinic acid (NA) caused complete ablation of subsequent glucose-stimulated insulin secretion (GSIS). Although the effect of NA was reversed when the fasting level of total FFA was maintained by coinfusion of soybean oil or lard oil (plus heparin), the more saturated animal fat proved to be far more potent in enhancing GSIS. We therefore examined the influence of individual fatty acids on insulin secretion in the perfused rat pancreas. When present in the perfusion fluid at 0.5 mM (in the context of 1% albumin), the fold stimulation of insulin release from the fasted pancreas in response to 12.5 mM glucose was as follows: octanoate (C8:0), 3.4; linoleate (C18:2 cis/cis), 5.3; oleate (C18:1 cis), 9.4; palmitate (C16:0), 16. 2; and stearate (C18:0), 21.0. The equivalent value for palmitoleate (C16:1 cis) was 3.1. A cis--> trans switch of the double bond in the C16:1 and C18:1 fatty acids had only a modest, if any, impact on their potency. A similar profile emerged with regard to basal insulin secretion (3 mM glucose). When a subset of these fatty acids was tested in pancreases from fed animals, the same rank order of effectiveness at both basal and stimulatory levels of glucose was seen. The findings reaffirm the essentiality of an elevated plasma FFA concentration for GSIS in the fasted rat. They also show, however, that the insulinotropic effect of individual fatty acids spans a remarkably broad range, increasing and decreasing dramatically with chain length and degree of unsaturation, respectively. Thus, for any given level of glucose, insulin secretion will be influenced greatly not only by the combined concentration of all circulating (unbound) FFA, but also by the makeup of this FFA pool. Both factors will likely be important considerations in understanding the complex interplay between the nature of dietary fat and whole body insulin, glucose, and lipid dynamics. 相似文献
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3.
Hydrosalpinges adversely affect markers of endometrial receptivity 总被引:22,自引:10,他引:22
Meyer WR; Castelbaum AJ; Somkuti S; Sagoskin AW; Doyle M; Harris JE; Lessey BA 《Human reproduction (Oxford, England)》1997,12(7):1393-1398
While in-vitro fertilization (IVF) was initially developed in women with
tubal factor infertility, recent clinical studies have suggested that the
presence of hydrosalpinges lowers implantation and pregnancy rates. We
postulated that these hydrosalpinges cause impaired endometrial
receptivity. A total of 103 women with hydrosalpinges were prospectively
evaluated, and compared with 55 infertile and 44 fertile controls. All
women had endometrial biopsies during the window of implantation, analysed
by conventional histological criteria, and also stained for three integrin
markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha
vbeta3). Women with hydrosalpinges (cases) expressed significantly less of
the alpha vbeta3 integrin compared with controls. There was no difference
in expression of alpha1beta1 or alpha4beta1 among groups. A significantly
greater number of cases had out of phase histology and missing alpha vbeta3
(type I defects) and absent integrin expression despite normal histological
maturation (type II) defects, compared with controls. Of 20 women with
impaired endometrial receptivity who were also biopsied after hydrosalpinx
surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven
percent of type I and 57% of type II defects were corrected
postoperatively. Using markers of endometrial receptivity, this study
demonstrates that inflammatory hydrosalpinges have an adverse effect on
endometrial receptivity, which in some cases may be overcome by surgical
treatment of the hydrosalpinx.
相似文献
4.
bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors 总被引:16,自引:0,他引:16
Proliferative expansion and apoptotic cell death play prominent roles in T
cell development. The molecular control of cell cycle progression and
apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit
apoptosis and slow cell cycle progression in cortical thymocytes and mature
T cells, particularly during the transition from the quiescent state into
the cell cycle. Here the impact of bcl-2 transgene expression on
CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival
of these progenitors at all of the four major differentiation stages, CD25-
CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and
CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover
only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice
expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene
we conclude that Bcl-2 inhibits proliferation only of T cell progenitors
that are activated via the pre- TCR, not those stimulated via c-Kit and the
IL-7 receptor.
相似文献
5.
Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism 总被引:3,自引:0,他引:3
Baron J; Winer KK; Yanovski JA; Cunningham AW; Laue L; Zimmerman D; Cutler GB Jr 《Human molecular genetics》1996,5(5):601-606
Parathyroid hormone secretion is negatively regulated by a 7- transmembrane
domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that
activating mutations in this receptor might cause autosomal dominant
hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified,
in two families with ADHP, heterozygous missense mutations in the
Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of
50 normal controls had either mutation. We also identified a de novo,
missense Ca(2+)-sensing receptor mutation in a child with severe sporadic
hypoparathyroidism. The amino acid substitution in one ADHP family affected
the N-terminal, extracellular domain of the receptor. The other mutations
involved the transmembrane region. Unlike patients with acquired
hypoparathyroidism, patients with these mutations had hypercalciuria even
at low serum calcium concentrations. Their greater hypercalciuria
presumably reflected activation of Ca(2+)-sensing receptors in kidney
cells, where the receptor negatively regulates calcium reabsorption. This
augmented hypercalciuria increases the risk of renal complications and thus
has implications for the choice of therapy.
相似文献
6.
Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule 下载免费PDF全文
Bianca LW Bendermacher Joep AW Teijink Edith M Willigendael Marie-Louise Bartelink Harry R Büller Ron JG Peters Jelis Boiten Machteld Langenberg Martin H Prins 《The British journal of general practice》2006,56(533):932-937
BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease. 相似文献
7.
Jana Hudcova Syed Talha Qasmi Robin Ruthazer Ahsan Waqas Syed Basit Haider Roman Schumann 《Transplantation proceedings》2021,53(1):119-123
PurposeWe examined the role of obesity and intraoperative red blood cell (RBC) and platelet transfusion in early allograft dysfunction (EAD) following liver transplantation (LT).MethodsThis is a retrospective analysis of 239 adult deceased-donor LT recipients over a 10-year period. EAD was defined by Olthoff’s criteria. Data collection included donor (D) and recipient (R) age, body mass index (BMI) ≥ 35 kg/m2, diabetes mellitus, allograft macrosteatosis, and intraoperative (RBC) and platelet administration. We employed logistic regression to evaluate associations of these factors with EAD. Results are presented as odds ratios (OR) and 95% confidence intervals (CI) with corresponding P values. A P ≤ .05 was considered statistically significant.ResultsEAD occurred in 85 recipients (36%). Macrosteatosis data were available for 199 donors. In the multivariate analyses, BMI-D ≥ 35 kg/m2 increased the odds of developing EAD by 156% in the entire cohort (OR 2.56, 95% CI 1.09-6.01) and by 187% in recipients with macrosteatosis data (n = 199, OR 2.87, 95% CI 1.15-7.15). Each unit of RBCs increased the odds for EAD by 8% (OR 1.08, 95% CI 1.02-1.14) and, for the subgroup of 238 recipients with macrosteatosis data, by 9% (OR 1.09, 95% CI 1.02-1.16).ConclusionWe found a significant independent association of donor obesity and intraoperative RBC transfusion with EAD but no such association for platelet administration, MELD score, age, recipient obesity, and diabetes. 相似文献
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9.
PT Clayton M Doig S Ghafari C Meaney C Taylor JV Leonard M Morris AW Johnson 《Archives of disease in childhood》1998,79(2):109-115
OBJECTIVE: To establish criteria for the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency in the UK population using a method in which carnitine species eluted from blood spots are butylated and analysed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). DESIGN: Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A985G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes. RESULTS: All patients with MCAD deficiency had an octanoylcarnitine concentration ([C8-Cn]) > 0.38 microM and no accumulation of carnitine species > C10 or < C6. Among the patients with MCAD deficiency, the [C8-Cn] was significantly lower in children > 10 weeks old and in children with carnitine depletion (free carnitine < 20 microM). Neonatal blood spots from patients with MCAD deficiency had a [C8-Cn] > 1.5 microM, whereas in heterozygotes and other normal neonates the [C8-Cn] was < 1.0 microM. In contrast, the blood spot [C8-Cn] in eight of 27 patients with MCAD deficiency > 10 weeks old fell within the same range as five of 15 MCAD heterozygotes (0.38-1.0 microM). However, the free carnitine concentrations were reduced (< 20 microM) in the patients with MCAD deficiency but normal in the heterozygotes. CONCLUSIONS: Criteria for the diagnosis of MCAD deficiency using ESI-MS/MS must take account of age and carnitine depletion. If screening is undertaken at 7-10 days, the number of false positive and negative results should be negligible. Because there have been no instances of death or neurological damage following diagnosis of MCAD deficiency in our patient group, a strong case can be made for neonatal screening for MCAD deficiency in the UK. 相似文献
10.
The appearance of the retinal blood vessels is an important diagnostic indicator of various clinical disorders of the eye and the body. Retinal blood vessels have been shown to provide evidence in terms of change in diameter, branching angles, or tortuosity, as a result of ophthalmic disease. This paper reports the development for an automated method for segmentation of blood vessels in retinal images. A unique combination of methods for retinal blood vessel skeleton detection and multidirectional morphological bit plane slicing is presented to extract the blood vessels from the color retinal images. The skeleton of main vessels is extracted by the application of directional differential operators and then evaluation of combination of derivative signs and average derivative values. Mathematical morphology has been materialized as a proficient technique for quantifying the retinal vasculature in ocular fundus images. A multidirectional top-hat operator with rotating structuring elements is used to emphasize the vessels in a particular direction, and information is extracted using bit plane slicing. An iterative region growing method is applied to integrate the main skeleton and the images resulting from bit plane slicing of vessel direction-dependent morphological filters. The approach is tested on two publicly available databases DRIVE and STARE. Average accuracy achieved by the proposed method is 0.9423 for both the databases with significant values of sensitivity and specificity also; the algorithm outperforms the second human observer in terms of precision of segmented vessel tree. 相似文献