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41.
The bias favoring deletion over inversion in DH-JH rearrangement has been
known for years, but the underlying mechanism has yet to be fully defined.
It has been suggested that the ratio of deletion/inversion is determined by
the combined effect of two factors: (i) the relative strengths of 5' and 3'
recombination signal sequences (RSS) of a DH segment, and (ii) the
efficiency with which the deletional product (one joint) forms relative to
the inversional product (two joints). In this study, we analyzed for the
first time the effect of factor 1 alone on the biased 3' RSS utilization in
DH-JH joining by using deletional plasmids in an extrachromosomal substrate
V(D)J recombination assay. It was found that the 3' RSS and associated
coding end (12 bp) mediate recombination more efficiently than the 5'
RSS/coding end DH-JH plasmids. These results demonstrate that the effect of
the RSS/coding end alone can account, at least partially, for the
predominant deletion in DH-JH recombination. The potential effect of the
relative strength of RSS and associated coding end on the ordered
rearrangement of DH-JH followed by VH to DH-JH was also assessed. When
recombination frequencies of D-->J (3' DH to J3) were compared with
frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found
that V-->D joining was, if anything, more efficient than D-->J
joining. Therefore, if all three segments were accessible, RSS/coding end
effects would not contribute to the ordered rearrangement of the IgH locus.
相似文献
42.
In vitro evidence for both the nucleus and cytoplasm as subcellular sites of pathogenesis in Huntington's disease 总被引:6,自引:1,他引:6
A unifying feature of the CAG expansion diseases is the formation of
intracellular aggregates composed of the mutant polyglutamine-expanded
protein. Despite the presence of aggregates in affected patients, the
precise relationship between aggregates and disease pathogenesis is
unresolved. Results from in vivo and in vitro studies of mutant huntingtin
have lead to the hypothesis that nuclear localization of aggregates is
critical for the pathology of Huntington's disease (HD). We tested this
hypothesis using a 293T cell culture model system that compared the
frequency and toxicity of cytoplasmic and nuclear huntingtin aggregates. We
first assessed the mode of nuclear transport of N-terminal fragments of
huntingtin, and show that the predicted endogenous NLS is not functional,
providing data in support of passive nuclear transport. This result
suggests that proteolysis is a necessary step for nuclear entry of
huntingtin. Additionally, insertion of nuclear import or export sequences
into huntingtin fragments containing 548 or 151 amino acids was used to
reverse the normal localization of these proteins. Changing the subcellular
localization of the fragments did not influence their total aggregate
frequency. There were also no significant differences in toxicity
associated with the presence of nuclear compared with cytoplasmic
aggregates. The findings of nuclear and cytoplasmic aggregates in affected
brains, together with these in vitro data, support the nucleus and cytosol
as subcellular sites for pathogenesis in HD.
相似文献
43.
44.
Cécile Couchoud Florian Bayer Muriel Rabilloud Carole Ayav Sahar Bayat Clemence Bechade Philippe Brunet Sebastien Gomis Emilie Savoye Olivier Moranne Thierry Lobbedez Rene Ecochard the REIN registry 《American journal of transplantation》2021,21(11):3608-3617
Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016–2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log-linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between-transplant center variability (0.23 ± 0.08) was 1.8 higher than between-dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18–64, 65–74, and 75–84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access. 相似文献
45.
46.
Differentiation of thrombi from slow flow in the pulmonary arteries, sometimes observed in the presence of pulmonary arterial hypertension, can be equivocal. Magnetic resonance (MR) imaging was performed in a patient with chronic pulmonary thromboembolism and pulmonary arterial hypertension using an electrocardiographically gated technique that allowed visualization of the pulmonary arteries at the end of diastole and multiple times during systole. These images were compared with those of a patient with primary pulmonary hypertension and those of healthy subjects. Thrombi were discrete structures, seen throughout the cardiac cycle on both the first and second spin-echo images, and decreased in signal intensity on the second image. Slow flow increased in signal intensity and changed in structure during the cardiac cycle and was seen best on the second image. MR may play an important role in excluding large central thrombi as the cause of pulmonary arterial hypertension. It is a noninvasive method for defining pulmonary arterial wall thickness and for direct visualization of chronic pulmonary thrombus. 相似文献
47.
Pulmonary manifestations of AIDS: review of 106 episodes 总被引:9,自引:0,他引:9
We reviewed the clinical records and chest radiographs of all patients admitted to our institution between 1982 and 1984 who had pulmonary disease and who were later proved to have acquired immunodeficiency syndrome (AIDS) (95 patients). Diffuse parenchymal lung disease was the most common finding. These infiltrates were usually interstitial and caused by Pneumocystis carinii pneumonia or P. carinii combined with cytomegalovirus infection. Focal, multilobar, interstitial infiltrates were also often seen and usually caused by P. carinii or P. carinii and cytomegalovirus infections. Rarely, well-defined, multiple, interstitial nodules less than 10 mm in diameter were the only or predominant characteristic and were seen only in association with Mycobacterium tuberculosis or Cryptococcus neoformans infections or Kaposi sarcoma. Hilar or mediastinal adenopathy occurred in 17 of the 21 patients with M. tuberculosis or C. neoformans infections. In contrast, only 4% of patients with P. carinii infections presented with these findings. We also found that hilar or mediastinal adenopathy was not significantly associated with peripheral adenopathy. Lung cavitation, pleural effusion, or a normal chest radiograph was uncommon. 相似文献
48.
The last few years have seen increasing concerns among anaesthetistsabout the risks of pharmacological prophylaxis for thromboembolicdisease. Increased bleeding during or after surgery is one concern,but of greater significance is the possibility of an increasedpredisposition to haematoma formation when regional block isused. Most of the recent consideration of this problem has beenin relation to vertebral canal haematoma formation after centralnerve block. Some thought must be given also to the possibilityof haematoma formation after peripheral techniques when thetarget nerve is deeply placed so that pressure cannot be usedto control bleeding after needle insertion. However, this reviewwill be focused on vertebral canal haematoma. 相似文献
49.
Sedigheh Farahani Leila Solgi Sahar Bayat Atieh Abedin Do Shohreh ZareKarizi Behnam Safarpour Lima Reza Mirfakhraie 《CNS Neuroscience & Therapeutics》2020,26(12):1315
AimsRAR‐related orphan receptor (RORA) involves in regulation of several biological processes including inflammation and circadian rhythm that probably are involved in migraine pathophysiology. In the current study, the association between RORA rs11639084 and rs4774388 variants and susceptibility to migraine were investigated in a sample of Iranian migraine patients for the first time.MethodsIn a case‐control study including 400 participants, 200 migraineurs and 200 healthy controls, genotyping of RORA rs4774388 and rs11639084 polymorphisms was performed using tetra‐primer amplification refractory mutation system–polymerase chain reaction (TP‐ARMS‐PCR).ResultsThe distribution of rs4774388 C/T and T/T genotypes differed significantly between the studied groups. Moreover, an association was observed between rs4774388 and migraine under the recessive mode of inheritance (P = 0.002; OR = 1.89.; CI = 1.25‐2.87). The distribution of rs11639084 alleles and genotypes was not significantly different between migraineurs and healthy controls.ConclusionCurrent results suggest RORA, as a molecular link, may explain inflammation and circadian rhythm dysfunction in migraine. Further studies in different ethnicities are required to confirm the function of RORA in migraine development. 相似文献
50.
It is highly recommended to conduct a prophylactic check for any dental problems on patients who suffer from leukaemia before chemotherapy begins. Bacteraemia caused by oral microflora may be very dangerous for patients with haematological malignancies. However, it should be noted that the prophylactic process itself might bring about life-threatening complications if there is only a short interval between dental treatment and the beginning of chemotherapy, or if the dental treatment is too aggressive. We present a case where this prophylactic procedure produced life-threatening complications for a patient with acute myeloid leukaemia. 相似文献