Human leukocyte antigen (HLA)-G is an immune modulating molecule that is present on fetal extravillous trophoblasts at the fetal-maternal interface. Single nucleotide polymorphisms (SNPs) in the 3 prime untranslated region (3′UTR) of the HLA-G gene can affect the level of HLA-G expression, which may be altered in women with recurrent miscarriages (RM). This case-control study included 23 women with a medical history of three or more consecutive miscarriages who delivered a child after uncomplicated pregnancy, and 46 controls with uncomplicated pregnancy. Genomic DNA was isolated to sequence the 3′UTR of HLA-G. Tissue from term placentas was processed to quantify the HLA-G protein and mRNA levels. The women with a history of RM had a lower frequency of the HLA-G 3′UTR 14-bp del/del genotype as compared to controls (Odds ratio (OR) 0.28; p = 0.039), which has previously been related to higher soluble HLA-G levels. Yet, HLA-G protein (OR 6.67; p = 0.006) and mRNA (OR 6.33; p = 0.010) expression was increased in term placentas of women with a history of RM as compared to controls. In conclusion, during a successful pregnancy, HLA-G expression is elevated in term placentas from women with a history of RM as compared to controls, despite a genetic predisposition that is associated with decreased HLA-G levels. These findings suggest that HLA-G upregulation could be a compensatory mechanism in the occurrence of RM to achieve an ongoing pregnancy.
Patients with failure of vital functions are usually cared for in high technology labour-intensive specialized units, where the affected vital functions can be assisted or supplemented for variable periods of time during spontaneous or medically driven recovery. The main purpose of support therapy in intensive care units is to grant a sufficient physiological level of cellular metabolism in order to avoid cellular damage.One of the best indicators of cellular integrity in critically ill patients is the measurement of blood lactate levels. Although the actual blood lactate value depends not only on lactate production, but also on lactate metabolism and, thus, is not a straightforward indicator of overall cell function in the body, it has been shown to have prognostic value in critically ill patients [1]. Moreover, lactate levels may be useful in the short-term follow-up of the evolution of this kind of patient and thus, can be used to guide medical interventions.Blood lactate levels measurements are performed using a variety of methods, including enzymatic and biosensorbased techniques. Lactate can be measured either in whole blood or in plasma samples, and its value can be influenced by several factors including the sampling methodology (especially dilution of the sample), the measurement method itself, haemoglobin levels and protein levels in the sample. In the present study, we evaluated a new biosensor-based method (Ciba-Corning 865; Ciba-Corning Diagnostic Corporation, Medfield, MA, USA) and compared it with an older biosensor-based technique (YSI 2300; Yellow Springs Instrument Co., Yellow Springs, OH, USA) and with the classic enzymatic reference method (Sigma Diagnostics, St Louis, MO, USA). Materials and methodsLactate measurements were performed in arterial blood samples (n=71) obtained from 40 patients. Routine measurements of lactate were performed using the YSI 2300 analyser. Samples were not chosen randomly, but were selected in order to cover a wide range of lactate levels. Samples came from two types of patients: those admitted to the intensive care unit for severe conditions; and those attending the pneumology department for blood gas measurements during bicycle exercise testing. Assessment of the lactate biosensor methodology. B. Detry, W. Nullens, M.L. Cao, A. Frans, A. Robert, T. Clerbaux. ©ERS Journals Ltd 1998.ABSTRACT: The rapid determination of lactate level is useful for clinical emergencies, as in the case of shock conditions or during surgical operations, as well as in numerous cases of respiratory failure, in cardiac or paediatric pathology and during exercise tests. Moreover, it is of prognostic significance in critically ill patients. Photometric methods are slow and, even when performed in good conditions, will give results only 30 min after blood collection, during which time the clinical condition of the patient may change. In this study, we have assessed the lactate biosensor, a method that yields lactate measurements in less than 1 min with only 100 µL of biological fluid.In ord...
Soluble HLA‐G (sHLA‐G) levels in human seminal plasma (SP) can be diverse and may affect the establishment of maternal‐fetal tolerance and thereby the outcome of pregnancy. We investigated whether sHLA‐G levels in SP are associated with polymorphisms in the 3′‐untranslated region (UTR) and UTR haplotypes of the HLA‐G gene. Furthermore, we compared the HLA‐G genotype distribution and sHLA‐G levels between men, whose partner experienced unexplained recurrent miscarriage (RM), and controls. Soluble HLA‐G levels (n = 156) and HLA‐G genotyping (n = 176) were determined in SP samples. The concentration of sHLA‐G was significantly associated with several single‐nucleotide polymorphisms (SNPs): the 14 base pair (bp) insertion/deletion (indel), +3010, +3142, +3187, +3196, and + 3509. High levels of sHLA‐G were associated with UTR‐1 and low levels with UTR‐2, UTR‐4, and UTR‐7 (P < .0001). HLA‐G genotype distribution and sHLA‐G levels in SP were not significantly different between the RM group (n = 44) and controls (n = 31). In conclusion, seminal sHLA‐G levels are associated with both singular SNPs and 3UTR haplotypes. HLA‐G genotype and sHLA‐G levels in SP are not different between men whose partner experienced RM and controls, indicating that miscarriages are not solely the result of low sHLA‐G levels in SP. Instead, it is more likely that these miscarriages are the result of a multifactorial immunologic mechanism, whereby the HLA‐G 3′UTR 14 bp ins/ins genotype plays a role in a proportion of the cases. Future studies should look into the functions of sHLA‐G in SP and the consequences of low or high levels on the chance to conceive.
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