Clip placement during axillary clearance: defining the radiotherapy target.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
C B Wilson
Publications and source records attributed to C B Wilson.
Reduction of radiotherapy-induced late complications in early breast cancer: the role of intensity-modulated radiation therapy and partial breast irradiation. Part I--normal tissue complications.
Radiotherapy after conservation surgery has been proven to decrease local relapse and death from breast cancer, and is now firmly established in the management of early breast carcinoma. Currently, the challenge is to minimise the morbidity caused by this treatment without losing its efficacy. This review will be divided into two parts, with Part I focusing on the radiation factors contributing to late normal tissue complications after radiotherapy for early breast cancer. Three major normal tissue side-effects will be discussed: cosmetic outcome, cardiac complications and pulmonary side-effects.
Atrophy↗
Reduction of radiotherapy-induced late complications in early breast cancer: the role of intensity-modulated radiation therapy and partial breast irradiation. Part II--Radiotherapy strategies to reduce radiation-induced late effects.
Radiotherapy after conservation surgery has been proven to decrease local relapse and death from breast cancer, and is now firmly established in the management of early breast carcinoma. Currently, the challenge is to optimise the therapeutic ratio by minimising treatment-related morbidity, while maintaining or improving local control and survival. The second part of this review examines the role of two approaches: intensity-modulated radiation therapy (IMRT) and partial breast irradiation, as means of improving the therapeutic ratio. Discussion of IMRT includes both inverse- and forward-planned methods: the breast usually requires minimal modulation to improve dose homogeneity, and therefore lends itself to simpler forward-planned IMRT techniques; whereas inverse-planned IMRT may be useful in selected cases. There are many dosimetry studies reporting the superiority of IMRT over conventional breast radiotherapy, but there is still a paucity of clinical data regarding patient benefit from these techniques. A critical literature review of clinical partial breast radiotherapy studies focuses on the influence of irradiated breast volume, dose and fractionation, and patient selection on normal tissue side-effects and local control. Clinical reports of partial breast irradiation show several encouraging, but some concerning results about local recurrence rates. Therefore, mature results from randomised trials comparing partial breast irradiation with whole-breast radiotherapy are required. Accurate localisation of the tumour bed and application of appropriate clinical target volumes and planning target volumes are discussed in detail, as these concepts are fundamental for partial breast irradiation.
Brachytherapy↗
Effects of grazing residues or feeding corn from a corn rootworm-protected hybrid (MON 863) compared with reference hybrids on animal performance and carcass characteristics.
One grazing and two feeding experiments were conducted to compare the feeding value of corn residue or corn grain from a genetically enhanced corn hybrid (corn rootworm-protected; event MON 863) with nontransgenic, commercially available, reference hybrids. In Exp. 1, two 13.7-ha fields, containing corn residues from either a genetically enhanced corn root-worm-protected hybrid (MON 863), or a near-isogenic, nontransgenic control hybrid (CON) were divided into four equal-sized paddocks. Sixty-four steer calves (262 +/- 15 kg) were stratified by BW and assigned randomly to paddock to achieve a stocking rate of 0.43 ha/steer for 60 d, with eight steers per paddock and 32 steers per hybrid. A protein supplement was fed at 0.45 kg/steer daily (DM basis) to ensure protein intake did not limit performance. Steer ADG did not differ (P = 0.30) between steers grazing the MON 863 (0.39 kg/d) and CON (0.34 kg/d) corn residues for 60 d. The four treatments for the feeding experiments (Exp. 2 and 3) included two separate reference hybrids, the near-isogenic control hybrid (CON), and the genetically enhanced hybrid (MON 863) resulting in two preplanned comparisons of CON vs. MON 863, and MON 863 vs. the average of the reference hybrids (REF). In Exp. 2, 200 crossbred yearling steers (365 +/- 19 kg) were fed in 20 pens, with five pens per corn hybrid. In Exp. 3, 196 crossbred yearling steers (457 +/- 33 kg) were fed in 28 pens, with seven pens per corn hybrid. In Exp. 2, DMI and G:F did not differ (P > 0.10) between MON 863 and CON; however, steers fed MON 863 had a greater (P = 0.04) ADG than steers fed CON. Gain efficiency was greater (P = 0.05) for MON 863 cattle than for REF cattle in Exp. 2, but other performance measurements (DMI and ADG) did not differ (P > 0.10) between MON 863 and REF. No differences (P > 0.10) were observed for performance (DMI, ADG, and G:F) between MON 863 and CON or MON 863 and REF in Exp. 3. In terms of carcass characteristics, no differences (P > 0.10) were observed between MON 863 and CON, as well as MON 863 and REF, for marbling score, LM area, or 12th rib fat thickness in both Exp. 2 and 3. Overall, performance was not negatively affected in the corn residue grazing or feedlot experiments, suggesting the corn rootworm-protected hybrid (event MON 863) is similar to conventional, nontransgenic corn grain and residues when utilized by beef cattle.
Animal Feed↗
A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial.
BACKGROUND: To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer. PATIENTS AND METHODS: Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were randomised to receive pre-operative infusional 5-FU 200 mg/m(2) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2) intravenous (i.v.) bolus on day 1 and cisplatin 60 mg/m(2) i.v. bolus on day 1, both repeating 3-weekly (infusional ECisF), or conventional bolus doxorubicin 60 mg/m(2) i.v. on day 1 and cyclophosphamide 600 mg/m(2) i.v. on day 1, both repeating 3-weekly (AC), both schedules for six courses. Patients subsequently had local therapy (surgery or radiotherapy or both) and tamoxifen 20 mg orally daily as appropriate. RESULTS: The 5 year results for AC and infusional ECisF, respectively, were as follows: overall response, 75% and 77%; complete clinical remission, 31% and 34%; pathological complete remission (pathCR), 16% for both; and pathCR with residual ductal carcinoma in situ (DCIS), 25% and 24%. Mastectomy rates were 37% and 34%, respectively. Five-year overall survival was 74% for AC and 82% for infusional ECisF (hazard ratio 0.76, 95% confidence interval 0.51-1.13; P = 0.18). Both treatments were well tolerated. Grade III/IV lethargy, vomiting, alopecia and plantar-palmar erythema were significantly greater for infusional ECisF; grade III/IV leucopenia was significantly greater for AC. CONCLUSIONS: Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer; with a median 5 year follow-up, the infusion-based schedule shows a non-significant trend towards improved survival.
Adult↗
Effect of organic matter addition to the pen surface and pen cleaning frequency on nitrogen mass balance in open feedlots.
Three finishing trials were conducted to determine the effects of dietary manipulation and management on N losses from open feedlots. In each experiment, 96 steers were assigned randomly to 12 nutrient balance pens. In Trial 1, calves were fed for 180 d during the winter/spring months; in Trial 2, yearlings were fed for 132 d in the summer. In Trials 1 and 2, N losses from pens were compared directly by adding OM to the pen surface or indirectly by feeding digestible ingredients designed to increase OM excretion. The dietary treatment (BRAN) included 30% corn bran (DM basis) replacing dry-rolled corn. Pens where OM was directly added received sawdust applications (SAWDUST) at a rate to match OM excretion from the BRAN diet. These two treatments were compared with a conventional, 75% dry-rolled corn diet (CON). Because CON and SAWDUST diets were identical, performance for both treatments was similar during Trials 1 and 2. The BRAN diet decreased (P < 0.10) gain efficiency during Trials 1 and 2 by 9.5% relative to CON. Fecal N excretion was greater (P < 0.01) for calves and yearlings when BRAN was fed compared with CON. Adding OM to the pen surface increased (P < 0.01) the amount of N in manure removed from pens and reduced (P < 0.10) N losses in Trial 1. Nitrogen losses were not significantly different among treatments in Trial 2. In Trial 3, calves were fed for 166 d during the winter/spring months. A 2 x 2 factorial design was used to evaluate pen cleaning frequency and diets similar to CON and BRAN. Pens were either cleaned monthly or once at the end of the feeding period. Daily DMI was greater (P = 0.01) and ADG was lower (P < 0.01) when cattle were fed BRAN compared with CON. Responses from all three trials indicate a negative effect of BRAN on gain efficiency. Dietary treatment and cleaning frequency interacted for N balance in the feedlot. Nitrogen losses decreased and manure N increased (P < 0.10) for cattle fed BRAN compared with CON when pens were cleaned monthly. Feeding BRAN did not affect total manure N, but resulted in higher N losses when pens were cleaned only once. For all trials, BRAN increased the amount of N remaining in composted manure. Adding OM to pen surfaces and/or cleaning pens more frequently may decrease N losses from open feedlot pens and from compost, although responses seem influenced by ambient temperature or season.
Animal Feed↗
Undegradable intake protein supplementation of compensating spring-born steers and summer-born steers during summer grazing.
Three trials were conducted to determine the effects of previous winter gain (Trials 1 and 3) and age of calf (Trials 1 and 2) on response to undegradable intake protein (UIP) supplementation during summer grazing. In Trial 1, 48 spring-born steers (243 kg) were used in a 4 x 2 factorial arrangement. Steers were wintered at four rates of gain: 0.65 (FAST), 0.24 (SLOW), 0.38 (S/F), and 0.38 (F/S) kg/d. The intermediate rates of gain (S/F and F/S) were created by switching steers from slow to fast or fast to slow midway through the wintering period. Following winter treatments, steers were assigned to one of two summer treatments: supplemented (S) or nonsupplemented (NS). In Trial 2, 32 summer-born steers were wintered at an ADG of 0.25 kg/d and allotted to the same summer treatments as Trial 1. The supplement was formulated to supply 200 g/d of UIP. Steers from both trials grazed upland Sandhills range from May to September 1998. In Trial 3, 49 spring-born steers (228 kg) were used in a 2 x 7 factorial arrangement of treatments. Steers were wintered at two rates of gain, 0.71 (FAST) and 0.24 kg/d (SLOW) and then assigned randomly to one of six levels of UIP supplementation or an energy control. Protein supplements were formulated to deliver 75, 112.5, 150, 187.5, 225, or 262.5 g/d of UIP. Sources of UIP for all trials were treated soybean meal and feather meal. In Trial 1, there were no (P > 0.05) winter by summer treatment interactions, and UIP supplementation increased (P = 0.0001) pasture gains over NS steers. In Trial 2, supplementation increased (P = 0.001) pasture ADG of summer-born steers by 0.15 kg/d compared with NS steers. In Trial 3, a winter gain by UIP supplementation interaction was observed (P = 0.09). Gain of FAST steers responded quadratically (P = 0.09) across UIP levels, with the maximum gain occurring at the 150 g/d UIP level. The SLOW steers responded linearly (P = 0.02) to increasing UIP levels; however, the response was negative. Levels of UIP above 150 g/d reduced steers gains; therefore, the data were reanalyzed excluding these levels. These new analyses showed that FAST steers responded linearly (P = 0.08; 0.2 kg/d) to increasing UIP, whereas the SLOW steers had no response to UIP. In Trials 1 and 3, SLOW steers experienced compensatory gain and had higher gains overall. We concluded that previous winter gain affected the response to UIP supplementation with the FAST winter gain group having a greater response.
Age Factors↗
Relationship between psychological well-being and lung health status in patients with bronchiectasis.
Patients with bronchiectasis often complain of abnormal tiredness, difficulty in concentrating or low spirits. This study was carried out to examine levels of anxiety and depression in bronchiectasis and their relationship with other measures of lung health. One hundred and eleven patients with bronchiectasis determined by high-resolution computed tomography (CT) scan were studied using a range of physiological and psychological outcome measures. Patients completed anxiety and depression, health status (quality of life), fatigue and dypnoea questionnaires. Lung function was measured and exercise capacity was assessed using a shuttle walk test. Anxiety and depression scores formed a continuum. Moderate-severe anxiety was more frequent than equivalent levels of depression (17 vs 9% of patients). Anxiety and depression scores were associated with perceived health status (r=0.33 and 0.55). Neither anxiety nor depression was associated with the extent of bronchiectasis on CT scan. Depression was correlated with breathlessness and exercise performance (r=0.33 and 0.40), but anxiety was not. The correlation between depression and exercise performance was not simply due to the influence of somatic items in the depression questionnaire. We conclude that anxiety and depression are quite common in bronchiectasis in that 34% of patients had elevated scores for anxiety depression or both. The non-somatic components of depression were linked to dyspnoea and exercise performance, but anxiety was only related to perceived health. Therefore, treatment aimed at reducing symptoms and improving exercise capacity will not reduce levels of anxiety which need alternative therapy.
Analysis of Variance↗
Effect of corn processing on starch digestion and bacterial crude protein flow in finishing cattle.
Six ruminally and duodenally cannulated yearling steers (523 kg) were used in a replicated 3 x 3 Latin square design experiment to study the effects of corn processing on nutrient digestion, bacterial CP production, and ruminal fermentation. Dietary treatments consisted of 90% concentrate diets that were based on dry-rolled (DRC), high-moisture (HMC), or steam-flaked (SFC) corn. Each diet contained 2.0% urea (DM basis) as the sole source of supplemental nitrogen. Each period lasted 17 d, with d 1 through 14 for diet adaptation and d 15 through 17 for fecal, duodenal, and ruminal sampling. Dry matter and OM intakes were similar for DRC and SFC but were approximately 15% higher (P < 0.05) for HMC. True ruminal OM digestibilities were 18 and 10% greater (P < 0.05) for HMC than for DRC or SFC, respectively. Ruminal starch digestibilities were similar between HMC and SFC and were approximately 19% greater (P < 0.05) than DRC. Postruminal OM digestibility was similar among treatments; however, postruminal starch digestibility was 15% greater (P < 0.05) for SFC than for DRC or HMC, which were similar. Total-tract DM and OM digestibilities were similar between HMC and SFC and were 4% greater (P < 0.05) than DRC. Likewise, total-tract starch digestibilities were similar between HMC and SFC and were 3% greater (P < 0.05) than DRC. Bacterial CP flow to the duodenum was 29% greater (P < 0.05) for HMC than for DRC or SFC, which were similar. Bacterial N efficiencies were similar among treatments. Based on bacterial CP flow from the rumen, we estimate that dietary DIP requirements are approximately 12% higher for HMC-based diets than for DRC or SFC-based diets, which were similar.
Animals↗
Role of cyclin kinase inhibitor p21 in systemic autoimmunity.
The cyclin kinase inhibitor protein p21 affects multiple processes relevant to the immune system, including cell cycle progression, replicative senescence, hemopoietic stem cell quiescence, and apoptosis. Therefore, malfunction of this protein may be a contributor to the pathogenesis of systemic autoimmunity. Here, we report that mixed background p21-deficient 129/Sv x C57BL/6 mice showed increased in vitro and in vivo T cell cycling and activation, moderate hypergammaglobulinemia and, at low penetrance, anti-chromatin autoantibodies. Homeostatic anti-self MHC/peptide ligand-induced proliferation of p21-deficient T cells was also enhanced. However, lymphoid organ enlargement was very mild, presumably due to increased apoptosis of the rapidly dividing cells. Moreover, the older p21-deficient mice had kidney pathology representing a similar, but slightly more advanced, state than that seen in the control mice. The timing and severity of the above serologic, cellular, and histologic manifestations in p21-deficient mice were unaffected by gender. Thus, p21 deficiency significantly enhances T cell activation and homeostatic proliferation, and can induce mild autoimmune manifestations at a low incidence without gender bias, but does not in itself generate the full spectrum of lupus-like disease.
Animals↗
DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals.
DNA methyltransferase I (Dnmt1), the maintenance enzyme for DNA cytosine methylation, is expressed at high levels in the CNS during embryogenesis and after birth. Because embryos deficient for Dnmt1 die at gastrulation, the role of Dnmt1 in the development and function of the nervous system could not be studied by using this mutation. We therefore used the cre/loxP system to produce conditional mutants that lack Dnmt1 in neuroblasts of embryonic day 12 embryos or in postmitotic neurons of the postnatal animal. Conditional deletion of the Dnmt1 gene resulted in rapid depletion of Dnmt1 proteins, indicating that the enzyme in postmitotic neurons turns over quickly. Dnmt1 deficiency in postmitotic neurons neither affected levels of global DNA methylation nor influenced cell survival during postnatal life. In contrast, Dnmt1 deficiency in mitotic CNS precursor cells resulted in DNA hypomethylation in daughter cells. Whereas mutant embryos carrying 95% hypomethylated cells in the brain died immediately after birth because of respiratory distress, mosaic animals with 30% hypomethylated CNS cells were viable into adulthood. However, these mutant cells were eliminated quickly from the brain within 3 weeks of postnatal life. Thus, hypomethylated CNS neurons were impaired functionally and were selected against at postnatal stages.
Animals↗
Phase III trial of accelerated hyperfractionation with or without difluromethylornithine (DFMO) versus standard fractionated radiotherapy with or without DFMO for newly diagnosed patients with glioblastoma multiforme.
PURPOSE: To report the results of a prospective Phase III trial for patients with newly diagnosed glioblastoma multiforme (GBM), treated with either accelerated hyperfractionated irradiation with or without difluromethylornithine (DFMO) or standard fractionated irradiation with or without DFMO. METHODS AND MATERIALS: Adult patients with newly diagnosed GBM were registered and randomized following surgery to one of 4 treatment arms: Arm A, accelerated hyperfractionation alone using 2 fractions a day of 1.6 Gy to a total dose of 70.4 Gy in 44 fractions; Arm B, accelerated hyperfractionation as above plus DFMO 1.8 gm/m2 by mouth every 8 h beginning one week before radiation until the last fraction was given; Arm C, single-fraction irradiation of 1.8 Gy/day to 59.4 Gy; Arm D, single-fraction irradiation as in Arm C plus DFMO given as in Arm B. Patients were followed for progression-free survival (PFS) and overall survival (OS), as well as for toxicity. Eligibility required histologically proven GBM, age > or =18, Karnofsky performance status (KPS) > or =60, and no prior chemotherapy or radiotherapy. Adjuvant chemotherapy was not used in this protocol. RESULTS: A total of 231 eligible patients were enrolled. There were 95 men and 136 women with a median age of 57 years, and median KPS of 90. Extent of resection was total in 23, subtotal in 152, and biopsy only in 56 patients. The 4 arms were balanced with respect to age, KPS, and extent of resection. Times to event measurements are from date of diagnosis. Median OS and PFS were 40 and 19 weeks for Arm A; 42 and 22 weeks for Arm B; 37 and 16 weeks for Arm C; and 44 and 19 weeks for Arm D (p = 0.48 for survival; p = 0.32 for PFS). Comparison of the 2 arms treated with DFMO to the 2 arms without DFMO revealed no difference in OS (37 weeks vs. 42 weeks, p = 0.12) or PFS and thus no benefit to the use of DFMO. Comparison of the 2 standard fractionation arms to the 2 accelerated hyperfractionation arms also resulted in no difference in OS (42 weeks vs. 41 weeks, p = 0.75) or PFS, showing no benefit to accelerated hyperfractionated irradiation. CONCLUSION: In this prospective Phase III study, no survival or PFS benefit was seen with accelerated hyperfractionated irradiation to 70.4 Gy, nor was any benefit seen with DFMO as a radiosensitizer. Standard fractionated irradiation to 59.4 Gy remains the treatment of choice for newly diagnosed patients with glioblastoma multiforme.
Adult↗
Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin.
Toll-like receptor (TLR) 2 and TLR4 play important roles in the early, innate immune response to microbial challenge. TLR2 is preferentially involved in the inflammatory response to lipoteichoic acid, lipopeptides, and glycans from a variety of microbes, whereas TLR4 is essential for a complete response to LPSs. We report here that TLR2 transduces the response to phenol-soluble modulin, a factor secreted by Staphylococcus epidermidis. The TLR2-mediated response to this modulin was enhanced by TLR6 but inhibited by TLR1, indicating a functional interaction between these receptors. We also demonstrate that a response to phenol-soluble modulin mediated by TLR2 and TLR6 was more refractory to inhibition by TLR1 than one mediated by TLR2 alone.
Animals↗
Carrier-mediated enhancement of cognate T cell help: the basis for enhanced immunogenicity of meningococcal outer membrane protein polysaccharide conjugate vaccine.
Haemophilus influenzae type b capsular polysaccharide (PRP) conjugate vaccines, which are thought to induce T cell-dependent antibody production, induce protective responses after a single dose in individuals under 15 months of age. However, multiple doses of these vaccines are required to induce protective antibody responses in infants, with the exception of PRP conjugated to meningococcal outer membrane proteins (OMPC), which does so after a single dose. The basis for this difference is not fully understood, although others have proposed that OMPC and porins, the major protein component of OMPC, act as adjuvants or mitogens. In this report OMPC is shown to enhance CD40 ligand-mediated, T cell-dependent antibody production in mice. This paralleled the induction by OMPC of CD86, CD80 and CD40 costimulatory molecules on human neonatal and murine B cells and of Th1 cytokines. Neither porins nor lipopolysaccharide fully reproduced the effects of OMPC. These studies indicate that OMPC acts both as carrier and adjuvant, and thereby enhances T cell-dependent antibody responses in human infants.
Adjuvants, Immunologic↗
Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis.
A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.
Bronchoalveolar Lavage Fluid↗
A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival.
The role of DNA methylation and of the maintenance DNA methyltransferase Dnmt1 in the epigenetic regulation of developmental stage- and cell lineage-specific gene expression in vivo is uncertain. This is addressed here through the generation of mice in which Dnmt1 was inactivated by Cre/loxP-mediated deletion at sequential stages of T cell development. Deletion of Dnmt1 in early double-negative thymocytes led to impaired survival of TCRalphabeta(+) cells and the generation of atypical CD8(+)TCRgammadelta(+) cells. Deletion of Dnmt1 in double-positive thymocytes impaired activation-induced proliferation but differentially enhanced cytokine mRNA expression by naive peripheral T cells. We conclude that Dnmt1 and DNA methylation are required for the proper expression of certain genes that define fate and determine function in T cells.
Animals↗
Vaccine safety--vaccine benefits: science and the public's perception.
The development of cowpox vaccination by Jenner led to the development of immunology as a scientific discipline. The subsequent eradication of smallpox and the remarkable effects of other vaccines are among the most important contributions of biomedical science to human health. Today, the need for new vaccines has never been greater. However, in developed countries, the public's fear of vaccine-preventable diseases has waned, and awareness of potential adverse effects has increased, which is threatening vaccine acceptance. To further the control of disease by vaccination, we must develop safe and effective new vaccines to combat infectious diseases, and address the public's concerns.
Humans↗
Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development.
Notch proteins influence cell-fate decisions in many developing systems. Several gain-of-function studies have suggested a critical role for Notch 1 signaling in CD4-CD8 lineage commitment, maturation and survival in the thymus. However, we show here that tissue-specific inactivation of the gene encoding Notch 1 in immature (CD25+CD44-)T cell precursors does not affect subsequent thymocyte development. Neither steady-state numbers nor the rate of production of CD4+ and CD8+ mature thymocytes is perturbed in the absence of Notch 1. In addition, Notch 1-deficient thymocytes are normally sensitive to spontaneous or glucocorticoid-induced apoptosis. In contrast to earlier reports, these data formally exclude an essential role for Notch 1 in CD4-CD8 lineage commitment, maturation or survival.
Animals↗