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71.
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
72.
JM Hopkin 《Current opinion in immunology》1997,9(6):788-792
Atopy — a T helper 2 cell driven hypersensitivity to innocuous antigens (allergens) which causes most cases of asthma — is of complex genetic and environmental origins. There is compelling epidemiological evidence for a rise in atopic disease in ‘westernised’ communities. The changing pattern of microbial exposure in early childhood is suggested to be the principal candidate mechanism for this rise. 相似文献
73.
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75.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
76.
B lymphocytes secreting IgG linked to latent transforming growth factor- beta prevent primary cytolytic T lymphocyte responses 总被引:3,自引:0,他引:3
B lymphocytes secreting IgG linked to latent transforming growth factor
(TGF)-beta (IgG-TGF-beta) prevent cytolytic T lymphocyte (CTL) responses to
unrelated antigens in mixed lymphocyte cultures (MLC) so long as resting
resident macrophages and functional Fc receptors are present. This was
shown using IgG-secreting plaque-forming cells (PFC) to sheep erythrocytes
(SRBC) obtained from popliteal lymph nodes of mice injected repeatedly in
foot pads with SRBC. Remarkably, as few as approximately 300 PFC prevented
CTL responses of 5 x 10(5) normal syngeneic spleen cells in MLC.
Supranatants of short-term cultures of PFC also prevented CTL responses,
and suppression was prevented by eliminating or dissociating IgG and
TGF-beta present in supranatants or by antibody against active TGF-beta.
Furthermore, the latency- associated peptide of latent TGF-beta was
detected in approximately 10% of foci of IgG captured from single PFC,
indicating that at least some B lymphocytes secrete IgG-TGF-beta as a
complex. Resting resident macrophages (which do not produce latent
TGF-beta) and functional Fc receptors were required for suppression,
consistent with idea that IgG- TGF-beta is taken up through Fc receptors
for IgG and that active TGF- beta, cleaved from latent TGF-beta of the
complex, is delivered directly to potentially responding CTL. If CTL
responses in man are similarly regulated by B lymphocytes, then an ongoing
B cell response in patients with chronic viral infections or bearing
immunogenic cancers may prevent effective therapeutic vaccination.
相似文献
77.
78.
DL?MagerEmail author AD?Haffajee PM?Devlin CM?Norris MR?Posner JM?Goodson 《Journal of translational medicine》2005,3(1):27
Background
The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. 相似文献79.
The effectiveness of a treatment protocol for male lower urinary tract symptoms in general practice: a practical randomised controlled trial 下载免费PDF全文
Roelf JC Norg Kees van de Beek Piet JM Portegijs CP Onno van Schayck J Andr Knottnerus 《The British journal of general practice》2006,56(533):938-944
BACKGROUND: Randomised controlled trials have shown the efficacy of several treatment modalities for lower urinary tract symptoms (LUTS) in selected populations. The effectiveness in daily practice has hardly been investigated, especially in primary care and is dependent on choices between all possible treatment options and best investigated in a comprehensive study, including all treatment modalities (watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors, and surgery). AIM: Assessment of the effectiveness of a comprehensive treatment protocol for LUTS in primary care. DESIGN OF STUDY: Randomised controlled trial. SETTING: Fourteen general practices in the Netherlands. METHOD: Intervention: treatment protocol based on a formalised expert opinion. Control condition: usual care. Study population: 208 subjects with moderate to severe LUTS (IPSS > or =8, median = 13). OUTCOME MEASURES: symptom severity (IPSS [International Prostate Symptom Score]), bother score (Dan-PSS [Danish Prostate Symptom Score]), and maximum urinary flow (Q(max)); incidence of acute urinary retention and urinary tract infections. RESULTS: In the intervention group markedly more subjects used an alpha-blocker at end of follow-up than in the usual care group (24% versus 6%). No significant differences were found between intervention and control group in IPSS, Q(max) or Dan-PSS. CONCLUSION: alpha-blockers and watchful waiting are the most frequent treatment modalities for LUTS in primary care. Our study showed no evidence that a protocol using well-defined indications for all possible treatment modalities based on a formalised expert opinion procedure has added value. Based on our results, we cannot recommend a broadening of the indication for alpha-blockers, which, however, seems to be the current trend. 相似文献
80.