NK cell lines of different maturational status can be obtained from mouse foetal liver.
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Animals↗
Biomedical subjects
A Georgiou
Publications and source records attributed to A Georgiou.
Placebo mania. High quality placebos should be used.
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Controlled Clinical Trials as Topic↗
The low-affinity nerve growth factor receptor p75NGFR mediates death of PC12 cells after nerve growth factor withdrawal.
We have investigated the role of the low-affinity nerve growth factor (NGF) receptor p75NGFR in determining the death of neuronally differentiated PC12 cells after withdrawal of NGF. A range of high and low p75NGFR-expressing cells were obtained by a combination of fluorescence activated cell sorting (FACS) and stable transfection with a p75NGFR expression vector. Cells were readily differentiated to a neuronal phenotype irrespective of the level of p75NGFR expression. However, the rate and extent of neuronal death following NGF deprivation were extremely sensitive to the level of p75NGFR expression. The highest expressing cells died most rapidly. Cells selected for very low levels of p75NGFR expression exhibited resistance to NGF withdrawal, and remained as viable, differentiated neurons, with minimal cell death, for at least 5 days in the absence of NGF. Antisense oligonucleotides against p75NGFR were shown to down-regulate p75NGFR in PC12 cells and, further, to significantly enhance survival in the absence of NGF. These results consolidate and generalize our previous findings that p75NGFR induces cell death in postnatal sensory neurons in the absence of NGF. The ability to induce cell death in the absence of NGF appears to be a more general role of p75NGFR in differentiated neurons, and an important new paradigm for the mechanism of NGF-dependent survival.
Animals↗
Description of a symptomless cystic fibrosis L346P/M348K compound heterozygous Cypriot individual.
During the past few years we have been testing the hypothesis that Cyprus may have been spared many severe cystic fibrosis (CF) cases but not cystic fibrosis transmembrane conductance regulator (CFTR) mutations. We have been analysing by molecular methods patients with atypical mild phenotypes where CF enters the differential diagnosis. With this approach we identified a mutation, L346P, which in association with the severe mutation delta F508 or 1677delTA, confers a mild and atypical presentation. Recently, we identified another entirely symptomless 48-year-old individual, with genotype L346P/M348K. The fact that M348K was initially identified in a severely affected Italian patient strengthens the hypothesis that L346P, a putative mild mutation, is dominant over severe ones. One other explanation is that M348K is not a causative defect but a rare polymorphism. These findings have important implications for genetic counselling, especially when the counselling is sought by concerned couples for prenatal diagnostic purposes.
Child, Preschool↗
Th1 and Th2 cytokine induction in pulmonary T cells during infection with respiratory syncytial virus.
Helper T (Th) cells can be classified functionally into two main types. Broadly, Th1 cells play a major role in eliminating viral pathogens, while Th2 cells mediate anti-parasite immunity and allergic responses. These functions are thought to depend on characteristic and distinct patterns of cytokine production. Infection with human respiratory syncytial virus, an important common cold virus, causes transient lymphocytic bronchiolitis in mice. Activated T cells are partly responsible for this disease, but also eliminate the virus. To show whether polarized cytokine production occurs in individual cells during viral bronchiolitis, we sampled murine bronchoalveolar lavage and mediastinal lymph node cells before and after infection. RT-PCR of cellular mRNA and flow cytometric analysis of intracellular cytokine production showed a rapid IFN-gamma response at both sites, which persisted for more than 3 weeks in the lung. Most IFN-gamma-producing cells were CD8+. Some early CD4+ IFN-gamma-producing cells also made IL-10. Only low levels of IL-2, IL-4 and IL-5 mRNA or protein expression were detected at any time at either site. No cytokines were detected in B cell populations at either site. These novel techniques show the true complexity of cytokine production patterns on a cell-by-cell basis, allowing T cells to be reclassified according to function.
Animals↗
Analysis of the functional potential of mouse CD4+ T cells using a high-efficiency cloning system.
In order to examine the functional potential of individual mouse CD4+ T cells selected, as far as possible, in a random manner, a high-efficiency cloning system driven by Con A was utilized. Under optimal conditions, cloning efficiencies of CD4+ cells of about 50% were regularly attained. Although the relative proportion of different TH subsets varied depending on the cloning conditions, the high cloning efficiency, coupled with the analysis of over 100 clones, allowed important conclusions to be drawn regarding the general construction of the mouse CD4+ T cell repertoire. (1) At least 50% of all mouse splenic CD4+ T cells have the potential to produce IL4, supporting the view that TH subsets arise by an instructional or regulatory mechanism, rather than by selection. (2) TH0 clones produce amounts of IL2 and IL4 similar to those produced by TH1 and TH2 clones, respectively, but secrete much lower quantities of IFN than TH1 clones. (3) A large proportion of TH2 clones secrete measurable amounts of IFN. (4) Lymphokine secretion patterns among CD4+ T cells are clearly not determined at random, since IL2 production is always accompanied by IFN production. (5) At least 50% of all mouse splenic CD4+ T cells have cytolytic capacity as shown by killing in a 20-hr assay, but only a proportion can also kill in 4-hr assays. Killing in 4-hr assays was strongly correlated with the ability to secrete IL2, regardless of whether IL4 was also secreted.
Animals↗
Technical factors affecting morbidity in definitive irradiation for localized carcinoma of the prostate.
PURPOSE: The impact of some technical factors on morbidity was analyzed in 738 patients with histologically confirmed carcinoma of the prostate treated with definitive irradiation. METHODS AND MATERIALS: The records of all patients were reviewed, and morbidity of irradiation was evaluated according to severity. All patients were followed up for a minimum of 3 years (median observation, 6.5 years). RESULTS: The most frequent Grade 2 (moderate) intestinal complication was proctitis, which was observed in 5% of the patients, followed by enteritis (1%) and anal-rectal fibrosis or stricture (about 1%). Incidence of Grade 3 (severe) proctitis was less than 1% and small bowel obstruction, 0.2%. One patient developed radiation-induced ileitis complicated with peritonitis, which was fatal. The most frequent Grade 2 urinary complication was urethral stricture (5%) and cystitis with significant symptoms or hematuria (2%). A vesicosigmoid and a rectovesical fistula (.4%) were noted, which required colostomy. One patient with hemorrhagic cystitis (.2%) required an ileal bladder, and two cases of ureteral stricture (.3%) required surgical correction. Most cases of Grade 2-3 intestinal or urinary morbidity appeared within 2-5 years after therapy (8% moderate and 3% severe cumulative intestinal morbidity at 10 years, and 9% and 3%, urinary). The actuarial incidence of rectosigmoid Grade 2 and 3 morbidity was 10% for patients treated to the pelvic lymph nodes and the prostate and 3% for those treated to the prostate only (p = 0.04). The difference in urinary morbidity in these two groups of patients was not statistically significant. There was also no significant correlation of morbidity with boost portal size for prostate irradiation. Patients treated with a stationary portal technique that delivered higher doses to the urinary bladder had a significantly greater incidence of urinary morbidity (18% cumulative) compared with patients treated with rotational techniques (5%) (p < 0.1). However, patients treated with pelvic fields and rotational techniques had a higher intestinal and rectosigmoid morbidity (11%) than patients treated to the prostate only (< or = 5%) (p = 0.05). No statistically significant difference in intestinal or urinary morbidity was related to doses of irradiation (60-70 Gy). CONCLUSION: Volume treated and, to a lesser extent, dose of irradiation at tolerance levels are important factors influencing significant morbidity in patients with carcinoma of the prostate treated with definitive irradiation. With recent advances in three-dimensional (3-D) treatment planning and conformal radiation therapy techniques, it is imperative to precisely determine optimal volumes and doses of irradiation required to achieve the highest local-pelvic tumor control while minimizing morbidity to enhance the role of irradiation in the management of localized carcinoma of the prostate.
Adenocarcinoma↗
The majority of immature fetal thymocytes can be induced to proliferate to IL-2 and differentiate into cells indistinguishable from mature natural killer cells.
Although immature thymocytes from day 14 embryonic mice (FTC) express IL-2R, they have generally been considered to be unresponsive to IL-2. We show here that they can in fact undergo substantial and prolonged growth in vitro provided that high doses of IL-2 are present. The ability of FTC to grow in IL-2 could be enhanced slightly by PMA and also by IL-4, but dramatically by the combination of IL-4 + PMA with IL-2. Pretreatment of FTC with IL-4 + PMA for as little as 24 h primed FTC for rapid and prolonged responsiveness to IL-2, permitting the establishment of long term lines. Kinetic and clonal analysis revealed that most individual FTC could grow under these conditions. Although proliferating cells expressed functional IL-2R of only very low affinity, and IL-2R alpha chains were undetectable by immunofluorescence, blocking experiments showed unambiguously that both IL-2R alpha and IL-2R beta were involved in signal transmission. FTC lines and clones developed in this manner lacked lineage-specific markers of mature T cells, B cells, and myeloid cells, but expressed the NK cell markers NK1.1 and asialo-GM1. They displayed potent cytolytic activity against NK-sensitive targets, and, when stimulated with PMA+ionomycin, secreted IL-3 and IFN-gamma, but not IL-2 or IL-4. After intrathymic injection they showed no evidence of growth or differentiation. These results demonstrate that most, if not all, immature thymocytes have the capacity to differentiate into cells which appear to be indistinguishable from mature NK cells. They suggest that T cells and NK cells derive from a common precursor which in the thymic environment differentiates into T cells and in the extrathymic environment into NK cells.
Animals↗
Anatomic variation of gynecologic brachytherapy prescription points.
PURPOSE: The purpose of this report is to evaluate the geometric movement (relative to the bony pelvis) of fixed brachytherapy reference points during the time interval of the first and second gynecologic intracavitary implant. METHODS AND MATERIALS: The radiation therapy records of 40 consecutive patients with all stages of carcinoma of the cervix treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, from January 1991 through December 1991 were reviewed. All patients received external beam irradiation and two intracavitary implants with Fletcher-Suit tandem and ovoids. Prescription points, per ICRU #38, were used: point A, B, and P, bladder, and rectum. Comparison of the location of points for the first and second implants (2 weeks time interval) was performed using the bony pelvis as reference anatomy and calculating the 3-dimensional spherical coordinates from a common origin for both implants. RESULTS: Analysis of the movement of the second implant relative to the first revealed that the x, y, and z coordinates for the various points shifted from 0 to 6 mm in a single plain. Vector analysis showed that the magnitude and direction of the average shift was on the order of 1.0 to 1.5 cm with displacement posteriorly and inferiorly. The effect of this movement on dose rates to the various points can result in dose rate differences up to 35%. A regression analysis was performed to identify factors affecting this movement. The time interval from the first to the second implant was the factor which correlated best with the movement. CONCLUSION: There is movement of the absolute position of ICRU #38 reference points between the first and second intracavitary implants. This movement results in significant differences in absolute dose rates to these reference points in the two implants. The clinical significance of this movement relative to dose to the tumor is unknown.
Adult↗
Technical and tumor-related factors affecting outcome of definitive irradiation for localized carcinoma of the prostate.
PURPOSE: The influence of some tumor-related and technical factors on therapeutic outcome is analyzed in 738 patients with histologically confirmed carcinoma of the prostate treated with definitive irradiation. METHODS AND MATERIALS: This is a retrospective study of the records of the Radiation Oncology Center. The information was coded on computer-compatible forms and analyzed with multiple cross-reference checks to ensure data reliability. Detailed analysis of portal films and dose distribution isodose curves was carried out in 310 patients on whom this information was readily available. All patients were followed-up for a minimum of 3 years (median observation, 6.5 years). RESULTS: Disease-free survival rates in Stages A2 (T1b) and B (T2) were 76% at 5 years and 62% at 10 years; in Stage C (T3) it was 57% at 5 years and 38% at 10 years. Overall, prostate recurrence rates were: 8% for Stage A2, 17% for Stage B, 28% for Stage C, and 46% for Stage D1 (T4). The 10-year actuarial local failure rate by stage was 20% in Stage A2 (T1b), 24% in Stage B (T2), 40% in Stage C (T3), and 70% in Stage D1 (T4) tumors. When the inferior margin of the portals was at or caudal to the ischial tuberosity, the actuarial 5-year pelvic failure rate was 0% for Stage A2 (T1b), 18% for Stage B (T2), and 20% for Stage C (T3), in contrast to 60% for Stage A2 (T1b), 27% for Stage B (T2), and 38% for Stage C (T3) when the inferior margin was cephalad to the ischial tuberosity (p = 0.05 in Stage C). Local tumor control was comparable in Stages A2 (T1b) and B (T2) when either small fields limited to the prostate and periprostatic tissues were used or, in addition, the pelvic lymph nodes were irradiated (85% and 80%, respectively). In Stage C (T3) there was significantly better pelvic tumor control (80% of 274 patients) when all of the pelvic (including common iliac) lymph nodes were treated compared with 65% in a group of 137 patients on whom the lymph nodes were irradiated with smaller fields (14 x 14 cm) (p = 0.01). In Stage C (T3), 30 patients treated with doses less than 6000 cGy had a 50% overall pelvic failure rate compared with 35% in 20 patients receiving 6500 cGy and 24% in 362 patients treated with 7000 cGy (p = 0.01). Pelvic tumor control or failure was closely associated with development of distant metastasis. In patients with pelvic tumor control, the distant metastasis rate was 18% for stages A2 (T1b) and B (T2) and 30% for stage C (T3), in contrast to 30% (p = 0.02) and 65% (p < 0.01), respectively, when prostate/pelvic failure was detected. CONCLUSION: Volume treated and dose of irradiation are important factors influencing local/pelvic recurrence rate in carcinoma of the prostate, particularly in stage C tumors. With recent advances in three-dimensional treatment planning and conformal radiation therapy techniques, it is imperative to determine optimal volumes and doses of irradiation to be delivered to these patients while minimizing morbidity to enhance the role of irradiation in the management of localized carcinoma of the prostate.
Adenocarcinoma↗
Radiation induced lumbosacral plexopathy in gynecologic tumors: clinical findings and dosimetric analysis.
PURPOSE: Radiation-induced lumbosacral plexopathy is a rare complication of pelvic irradiation. METHODS AND MATERIALS: We report four cases among 2,410 patients treated to the pelvis for carcinoma of the cervix and carcinoma of the endometrium. All patients received both external beam and intracavitary radiation. The total calculated dose to the lumbosacral plexus was on the order of 7300 cGy. RESULTS: All 4 cases presented developed lumbosacral plexopathy. CONCLUSIONS: Although a few permanent lumbosacral lesions have been reported for patients treated with conventionally fractionated external beam, this syndrome is more often seen in patients treated with intracavitary irradiation for cervical or endometrial carcinoma.
Adult↗
[Prevention of fungal infections with ketoconazole in cancer patients receiving cytostatic therapy].
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Adolescent↗
Monitoring change in diabetes care using diabetes registers--experience from divisions of general practice.
BACKGROUND: The quality of care for patients with type 2 diabetes has been the subject of a number of government initiatives over the past decade. General practice has an especially important role in diabetes care. METHODS: The National Integrated Diabetes Program was introduced in 2001. Changes in the frequency of assessment and the physiological markers of diabetic control were assessed in a cohort of 2731 patients with type 2 diabetes from 16 general practice diabetes registers during 2000-2002. RESULTS: Frequency of assessment was better in patients living in low socioeconomic postcodes but did not change significantly over the 3 years. There were improvements in intermediate outcomes (HbA1c, systolic and diastolic blood pressure, lipid levels) over the period. DISCUSSION: These data provide a benchmark for improvement in the quality of diabetes care in general practice.
Adult↗