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A Six

Publications and source records attributed to A Six.

At least 19 recordsLinked to original sources
PubMed1999

T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool.

Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differentiation to become T cells. Rearrangements of the variable (V), diversity (D), and joining (J) segments of the TCR genes result in deletion of the intervening chromosomal DNA and the formation of circular episomes as a byproduct. Detection of these extrachromosomal excision circles in T cells located in the peripheral lymphoid tissues has been viewed as evidence for the existence of extrathymic T cell generation. Because all of the T cells in chickens apparently are generated in the thymus, we have employed this avian model to determine the fate of the V(D)J deletion circles. In normal animals we identified TCR Vgamma-Jgamma and Vbeta-Dbeta deletion circles in the blood, spleen, and intestines, as well as in the thymus. Thymectomy resulted in the gradual loss of these DNA deletion circles in all of the peripheral lymphoid tissues. A quantitative PCR analysis of Vgamma1-Jgamma1 and Vbeta1-Dbeta deletion circles in splenic gamma delta and Vbeta1(+) alphabeta T cells indicated that their numbers progressively decline after thymectomy with a half-life of approximately 2 weeks. Although TCR deletion circles therefore cannot be regarded as reliable indicators of in situ V(D)J rearrangement, measuring their levels in peripheral T cell samples can provide a valuable index of newly generated T cells entering the T cell pool.

Animals↗
PubMed1997

Ontogeny of the immune system: gamma/delta and alpha/beta T cells migrate from thymus to the periphery in alternating waves.

The embryonic thymus is colonized by the influx of hemopoietic progenitors in waves. To characterize the T cell progeny of the initial colonization waves, we used intravenous adoptive transfer of bone marrow progenitors into congenic embryos. The experiments were performed in birds because intravenous cell infusions can be performed more efficiently in avian than in mammalian embryos. Progenitor cells, which entered the vascularized thymus via interlobular venules in the capsular region and capillaries located at the corticomedullary junction, homed to the outer cortex to begin thymocyte differentiation. The kinetics of differentiation and emigration of the T cell progeny were analyzed for the first three waves of progenitors. Each progenitor wave gave rise to gamma/delta T cells 3 d earlier than alpha/beta T cells. Although the flow of T cell migration from the thymus was uninterrupted, distinct colonization and differentiation kinetics defined three successive waves of gamma/delta and alpha/beta T cells that depart sequentially the thymus en route to the periphery. Each wave of precursors rearranged all three TCR Vgamma gene families, but displayed a variable repertoire. The data indicate a complex pattern of repertoire diversification by the progeny of founder thymocyte progenitors.

Adoptive Transfer↗
PubMed1997

[Conservative surgery and iridium 192 in stage pT2 bladder tumor. A 5-year follow up].

OBJECTIVE: Study of the 5-year oncological results of a series of 24 patients treated by conservative surgery and Iridium 192 for stage pT2 bladder transitional cell carcinoma. MATERIAL AND METHODS: Retrospective study of 24 patients (mean age: 60 years) treated between March 1979 and June 1988, for a solitary bladder tumour, with a diameter less than 5 cm, without lymphadenopathy or detectable metastases at the time of treatment. Treatment successively consisted of TUR of the lesion for histological diagnosis, preoperative pelvic irradiation of 10.5 Gy, lymph node dissection in 3 patients, insertion of brachytherapy tubes at the resection site (5 cases), associated with lumpectomy (9 cases) or partial cystectomy (10 cases). 18 patients underwent a brachytherapy with doses of 45 to 60 Gy, while 6 patients received a half-dose protocol: brachytherapy 30 Gy + postoperative external beam irradiation (20 to 30 Gy to the tumour site, 30 to 40 Gy to pelvic lymph node chains). RESULTS: At 5 years, 2 out of 6 deaths were attributable to bladder cancer. 4 other patients died without recurrence, 4 patients relapsed at the site of brachytherapy and/or away from this site, requiring salvage cystectomy in one patient, and repeated TUR +/- BCG therapy in the other three patients. Overall, 18 out of 24 patients were alive at 5 years, 17 had a functional bladder, and 14 were free of recurrence. CONCLUSION: Conservative surgery associated with Iridium 192 brachytherapy can be an oncologically reasonable alternative to total cystectomy for selected pT2 bladder tumours: unifocal tumours, less than 5 cm in diameter.

Adult↗
PubMed1996

Characterization of avian T-cell receptor gamma genes.

In birds and mammals T cells develop along two discrete pathways characterized by expression of either the alpha beta or the gamma delta T-cell antigen receptors (TCRs). To gain further insight into the evolutionary significance of the gamma delta T-cell lineage, the present studies sought to define the chicken TCR gamma locus. A splenic cDNA library was screened with two polymerase chain reaction products obtained from genomic DNA using primers for highly conserved regions of TCR and immunoglobulin genes. This strategy yielded cDNA clones with characteristics of mammalian TCR gamma chains, including canonical residues considered important for proper folding and stability. Northern blot analysis with the TCR gamma cDNA probe revealed 1.9-kb transcripts in the thymus, spleen, and a gamma delta T-cell line, but not in B or alpha beta T-cell lines. Three multimember V gamma subfamilies, three J gamma gene segments, and a single constant region C gamma gene were identified in the avian TCR gamma locus. Members of each of the three V gamma subfamilies were found to undergo rearrangement in parallel during the first wave of thymocyte development. TCR gamma repertoire diversification was initiated on embryonic day 10 by an apparently random pattern of V-J gamma recombination, nuclease activity, and P-and N-nucleotide additions to generate a diverse repertoire of avian TCR gamma genes early in ontogeny.

Amino Acid Sequence↗
PubMed1996

The expansion and selection of T cell receptor alpha beta intestinal intraepithelial T cell clones.

In conventional mice, the T cell receptor (TCR) alpha beta+ CD8 alpha alpha+ and CD8 alpha beta+ subsets of the intestinal intraepithelial lymphocytes (IEL) constitute two subpopulations. Each comprise a few hundred clones expressing apparently random receptor repertoires which are different in individual genetically identical mice (Regnault, A., Cumano, A., Vassalli, P., Guy-Grand, D. and Kourilsky, P., J. Ep. Med. 1994. 180: 1345). We analyzed the repertoire diversity of sorted CD8 alpha alpha and CD8 alpha beta TCR alpha beta+ IEL populations from the small intestine of individual germ-free mice that contain ten times less TCR alpha beta+ T cells than conventional mice. The TCR beta repertoire of the CD8 alpha alpha and the CD8 alpha beta IEL populations of germ-free adult mice shows the same degree of oligoclonality as that of conventional mice. These results show the intestinal microflora is not responsible for the repertoire oligoclonality of TCR alpha beta+ IEL. The presence of the microflora leads to an expansion of clones which arise independently of bacteria. To evaluate the degree of expansion of IEL clones in conventional mice, we went on to measure their clone sizes in vivo by quantitative PCR in the total and in adjacent sections of the small intestine of adult animals. We found that both the CD8 alpha alpha and the CD8 alpha beta TCR alpha beta IEL clones have a heterogeneous size pattern, with clones containing from 3 x 10(3) cells up to 1.2 x 10(6) cells, the clones being qualitatively and quantitatively different in individual mice. Cells from a given IEL clone are not evenly distributed throughout the length of the small intestine. The observation that the TCR alpha beta IEL populations comprise a few hundred clones of very heterogeneous size and distribution suggests that they arise from a limited number of precursors, which may be slowly but continuously renewed, and undergo extensive clonal expansion in the epithelium.

Animals↗
PubMed1996

Germline genomic structure of the B10.A mouse Tcra-V2 gene subfamily.

The number of mouse Tcra-V gene segments varies from one individual to another and is estimated to be about 100. Southern blot analysis revealed that most of the Tcra-V are organized in clusters composed of copies of Tcra-V belonging to different subfamilies. We analyzed in detail a Tcra-V subfamily and looked for new Tcra-V in order to improve the knowledge of the mouse Tcra locus organization. A series of genomic clones derived from the B10.A mouse strain enclosing these clusters was used to determined the structure of all the Tcra-V2. We were able to identify ten Tcra-V2. This study showed that the Tcra-V2 can be organized into three structural subgroups. The distribution of the genes along the Tcra locus, plus their structural organization, indicates that successive duplications occurred during the processes of expansion and contraction of the Tcra-V gene subfamilies. Several Tcra-V2 are also identical, indicating recent duplications. The most divergent Tcra-V2 differ by 7.4% nucleotides, leading to 5.2% differences in amino acid contents.

Amino Acid Sequence↗
PubMed1996

Combined surgery and brachytherapy in the treatment of some cancers of the bladder (partial cystectomy and interstitial iridium-192).

Eighty-five bladder cancers were treated at the Urology Clinic of Nancy and the Centre Alexis Vautrin from 1975 to 1992 with short course preoperative radiation therapy (3 x 3.5 Gy), conservative surgery and brachytherapy by iridium-192. The tumours were classified according to the 1979 UICC pTNM classification. There were 27 pT1, 31 pT2 and 22 pT3, two pT4 and three pTx. The pT1-pT2 cases received only one brachytherapy (50 Gy at least) after the short course preoperative irradiation. The pT3 cases received only 30 Gy of brachytherapy and an external irradiation boost (generally 40 Gy to the node areas and 30 Gy to the tumour, but the dose varied during the time course). Surgery was often preceded by an endoscopic resection consisting of a tumoral resection or a partial cystectomy according to the localisation. The plastic vector tubes were put into place at the time of partial cystectomy. Until 1983 the radioactive wires were loaded into the vector tubes on the day following surgery, thereafter it was done one week later. The 85 patients were classified into two groups: 63 patients who were untreated previously and 22 patients who had received one or more endoscopic resections for recurrences. The median follow-up was 84 months. The local controls at 5 years were 78% in the first group versus 56% in the second group (p = 0.005) with an overall survival of 73 and 65%, respectively. The local control did not vary according to the differentiation (grade 1/2 vs. grade 3). The local control for pT1, pT2, pT3 was 85, 64 and 70% with a specific survival of 85, 76 and 72%, and an overall survival of 78, 66 and 66%. Among early complications, delay in healing of the bladder wall with subsequent vesico-cutaneous fistula depends mainly on the loading time of radioactive wires after surgery and is rare if the loading is delayed by one week. The late complications depend mostly on dosimetric factors. We found 24 grade 1, three grade 2, four grade 3 and one grade 4. The following factors are significant: the surface treated (> 14 cm2), a distance between the sources of more than 2 cm and, especially, activity of the wires of more than 2 mCi/cm (this factor was found in the five complications of grade 3 and 4), the other factors were not significant in univariate analyses.

Brachytherapy↗
PubMed1993

T cell receptor V alpha gene segment with alternate splicing in the junctional region.

The locus encoding mouse TCR-alpha chain includes approximately 100 V alpha gene segments that can be organized in about 20 structural subfamilies. Southern blot analysis of a T cell line derived from the BALB/c strain, M5T, has indicated that both alpha loci were rearranged, as assessed by the deletion of the delta locus, and that the V alpha gene segment involved in one of the rearrangements did not belong to any of the V alpha subfamilies already described. Transcripts of TCR-alpha chains from the M5T line were cloned after cDNA synthesis and anchored-polymerase chain reaction, revealing a V alpha gene segment of an as yet unidentified subfamily, V alpha 5T. Molecular cloning of germ-line V alpha 5T gene segments has shown that this subfamily contained two members, one of them being a pseudogene. The two members were located to each extremity of the alpha locus associated with a member of the V alpha 13 and V alpha BWB subfamilies. Analysis of transcripts bearing the V alpha 5T gene segment in the M5T line as well as in thymocytes has revealed that J alpha are frequently absent. This is due to an alternate donor splice site generated at the V alpha 5T-J alpha junction that leads to a splicing from the end of V alpha 5T to C alpha instead of the J alpha to C alpha conventional splicing. The impact of J alpha spliced-out transcripts on the allelic exclusion process is discussed.

Alternative Splicing↗
PubMed1993

Identification of an endogenous mammary tumor virus involved in the clonal deletion of V beta 2 T cells.

Expression of V beta (beta-chain variable region) gene segments was investigated in the Mus m. domesticus DDO strain, which possesses a large genomic deletion encompassing 20 of the 29 V beta gene segments known in BALB/c. Stainings using V beta-specific monoclonal antibodies revealed that up to 60% of the peripheral T cells use 3 V beta gene segments. Variable frequencies of V beta 2 T cells were observed among DDO individuals. Segregation analyses of F2 crosses between V beta 2-deletor mice and mammary tumor virus (Mtv)-free mice led to the identification of a new endogenous Mtv, named Mtv-DDO, mediating V beta 2 T cell clonal deletion. Mtv-DDO structure is conserved with the exception of the carboxy-terminal region as compared to other Mtv. Comparison between Mtv sharing the same V beta specificity and isolated from laboratory or wild mice confirms that a stretch of 11 amino acids, defined as the V beta-specific region, is required for the V beta-specific interaction. Limited substitutions in this region account for the shift of the Mtv specificity towards different V beta.

Amino Acid Sequence↗
PubMed1991

Identification of a T cell receptor beta chain variable region, V beta 20, that is differentially expressed in various strains of mice.

A cDNA library of TCR beta chain transcripts from BALB/c thymocytes was constructed using anchored polymerase chain reaction (PCR). Screening of this library led to the identification of a V beta gene segment, V beta 20, structurally related to V beta 3 and V beta 17. Genomic analysis of mice displaying deletions in their V beta loci, together with mapping of cosmid clones, situated V beta 20 2.5 kb beside V beta 17. The expression of V beta 20 was estimated by PCR in mice of different H-2 and Mls types. Peripheral T cells from H-2k and H-2d mice did not express V beta 20, whereas in I-E-negative mice (C57Bl/6 and SJL), V beta 20 transcripts were detected. The lack of V beta 20 transcripts in (C57Bl/6 x CBA/J)F1, (C57Bl/6 x BALB/c)F1, and in congenic B6.H-2k mice suggests that the differential use of V beta 20 is due to an I-E-mediated clonal deletion process. The involvement of the Mls super antigens was excluded by analysis of all Mls type combinations. The nature of the V beta 20-deleting element(s) is discussed in the context of the I-E/superantigen systems controlling the expression of V beta 11 and V beta 17.

Amino Acid Sequence↗
PubMed1990

[The value of mobilization of the prostatic region via perineal approach in the treatment of ruptures and stenoses of the posterior urethra].

UNLABELLED: 11 cases of end to end anastomosis associated with the mobilization of the prostate is reported. The authors use only the perineal access. The operation is utilised in two circumstances: injuries or traumatic strictures to the membranous urethra. 4 ruptured prostato-membranous urethras with 4 good results. 7 stenosis with 5 good results. 2 recurrences which one of them had a good result with a simple urethrotomy. Complication: no incontinence. 2 cases of impotence are noted. One of them had recovered, the other is secondary of the pelvic fracture. Follow up: mean 3 years (6 months-5 years). CONCLUSION: our experience suggest that the mobilization of the prostate is an excellent aid to end to end anastomosis. This technique permits the only perineal access.

Adult↗
PubMed1990

[Value of arterioscopy in the prevention of renal artery stenosis after transplantation].

Renal artery stenosis is frequent after transplantation. The systematic pre-operative search for arterial injuries by angioscopy allows a reduction in their incidence. The authors report a series of 60 transplantations with pre-operative angioscopy, which revealed benign injuries and two major injuries which were successfully treated surgically. This prevention allows a reduction in the incidence of stenosis from 12 to 6.6% according to a previous series of 210 transplantations without angioscopy.

Endoscopy↗
PubMed1990

[Junctional syndrome responsible for prostatic urethral dilatation: a new pathological entity?].

The authors report two observations of monstrous ectasia of the prostatic urethra, in boys age 12, without any previous pathological history; discovered on at the time of major dysuria previous urinary troubles with chronic retention of 500 cl and 1.250 l respectively. In the absence of any organic obstacle, etiology relieves functional troubles. If functional explorations show a normal or hypertensive detrusor, then they discuss the possibility of vesico-sphincter dyssynergia or an obvious hypertension of the striated sphincter. From this moment onwards, purely intrinsic urethral functional trouble is plausible, all the more because the recovery was assured by treatments directed only at the urinary canal. In the first case, after surgical treatment owing to complex lesions (plastic reduction of the urethral ectasia preserving the posterior wall and respecting the striated sphincter) combined with diverticulectomies with urethral reimplantations), the patient recovered complete vesical waste removal at once, with normalisation of the flowmeter in six months. In the second case, a simpler treatment (sub-montanal urethrotomy of the principle) allowed a normalisation period of 10 months with complete vesical waste removal. The functional results are maintained after a period of nine and two years respectively. The integrity of the striated sphincter controlled post-operatively by the operatory gesture on the urinary canal and confronts the authors in the idea of intrinsic urethral pathology, although electronic microscopic examination may not have shown achalasia.

Child↗
PubMed1990

[Value of blood alcohol concentration in the assessment of legal responsibility].

We analysed the files of an Amts- and Landgericht from the years 1982/83. Among about 4000 cases we found 148 condemnations, in which sections 20/21 StGB were discussed. Each offence included 207 variables. 63 cases were left to be evaluated: 10 cases with section 20, 43 cases with section 21, 10 cases with refused section 21. Most of the delinquents lived alone, drank much alcohol very often, were socially unadaptable, previously convicted, unemployed and little qualified. Due to lack of findings of facts and diverging testimonies of psychic findings we found no significant correlation between level of blood alcohol concentration, psychic findings and degree of decreased condemnability.

Adolescent↗
PubMed1989

[Cystic prostatic utricle in adults. Apropos of 3 cases].

Three cases of cystic prostatic utricle, without any other urogenital abnormality, have been observed in patients of about thirty years old. Two of them were revealed by urinary and ejaculatory obstructive symptoms. The third, discovered by chance, contained calculi. In the three cases, treatment consisted of transurethral endoscopic resection of the anterior lining of the cyst which permitted ample drainage and ensured lasting healing.

Adult↗