Enhanced expression of adenovirus-mediated sodium iodide symporter gene in MCF-7 breast cancer cells with retinoic acid treatment.

Increased expression of the sodium iodide symporter (NIS) is required for effective radioiodine treatment and reporter gene imaging of breast cancer. We investigated the effect of retinoic acid on adenovirus-mediated expression of the human NIS gene in the MCF-7 breast cancer cell line. METHODS: The MCF-7 cell line was infected with recombinant adenovirus carrying the human NIS gene (Rad-NIS). Levels of NIS messenger RNA (mRNA) and protein expression and radioiodine ((125)I) uptake were measured to evaluate adenovirus-mediated NIS gene expression in wild-type and Rad-NIS-infected MCF-7 cells after treatment with all-trans-retinoic acid (ATRA; 10(-8)-10(-6) mol/L). RESULTS: The transduction efficiency of adenovirus in MCF-7 cells at a multiplicity of infection (MOI) of 50 was >60%. After incubation with 10(-6) mol/L ATRA, the mRNA level in Rad-NIS-infected MCF-7 cells increased to 118.5 times that of wild-type MCF-7 cells, whereas the mRNA level in wild-type MCF-7 cells showed only a 2.1-fold increase. Western blot, immunocytochemical staining, and flow cytometry analyses showed that NIS protein expression in MCF-7 cells infected with Rad-NIS increased after ATRA treatment. With ATRA treatment, the amount of (125)I uptake increased in a dose-dependent manner (P < 0.001). The (125)I uptake in wild-type MCF-7 cells increased 3.1-, 5.5-, and 7.6-fold with treatment with 10(-8), 10(-7), and 10(-6) mol/L ATRA, respectively. Rad-NIS-infected cells showed a 4.0-fold increase in (125)I uptake. Treatment of Rad-NIS-infected cells with 10(-8), 10(-7), and 10(-6) mol/L ATRA increased (125)I uptake by 4.9-, 8.2-, and 27.6-fold, respectively, compared with wild-type MCF-7 cells. The level of NIS expression in Rad-NIS-infected MCF-7 cells treated with 10(-6) mol/L ATRA (245.0 +/- 13.7 pmol/10(6) cells) was much greater than the sum of the expression levels seen in ATRA-treated wild-type cells and Rad-NIS-infected wild-type cells. CONCLUSION: Retinoic acid increases adenovirus-mediated NIS expression in MCF-7 cells. Our results indicate that improved efficiency of NIS gene therapy or reporter imaging in breast cancer may be possible with retinoic acid treatment.     

Anterior translocaton of pulmonary artery without aortic transection in repair of tetralogy of Fallot with absent pulmonary valve.

We developed a technique of translocation of the pulmonary artery anterior to the ascending aorta without transection of the aorta in the repair of tetralogy of Fallot with absent pulmonary valve. Our technique includes detachment of the main pulmonary artery (MPA) from the pulmonary annulus, vertical division of the MPA, anterior translocation of the pulmonary artery with patch augmentation between the vertically divided MPA.     

Performance measurement of the microPET focus 120 scanner.

The microPET Focus 120 scanner is a third-generation animal PET scanner dedicated to rodent imaging. Here, we report the results of scanner performance testing. METHODS: A (68)Ge point source was used to measure energy resolution, which was determined for each crystal and averaged. Spatial resolution was measured using a (22)Na point source with a nominal size of 0.25 mm at the system center and various off-center positions. Absolute sensitivity without attenuation was determined by extrapolating the data measured using an (18)F line source and multiple layers of absorbers. Scatter fraction and counting rate performance were measured using 2 different cylindric phantoms simulating rat and mouse bodies. Sensitivity, scatter fraction, and noise equivalent counting rate (NECR) experiments were repeated under 4 different conditions (energy window, 250 approximately 750 keV or 350 approximately 650 keV; coincidence window, 6 or 10 ns). A performance phantom with hot-rod inserts of various sizes was scanned, and several animal studies were also performed. RESULTS: Energy resolution at a 511-keV photopeak was 18.3% on average. Radial, tangential, and axial resolution of images reconstructed with the Fourier rebinning (FORE) and filtered backprojection (FBP) algorithms were 1.18 (radial), 1.13 (tangential), and 1.45 mm full width at half maximum (FWHM) (axial) at center and 2.35 (radial), 1.66 (tangential), and 2.00 mm FWHM (axial) at a radial offset of 2 cm. Absolute sensitivities at transaxial and axial centers were 7.0% (250 approximately 750 keV, 10 ns), 6.7% (250 approximately 750 keV, 6 ns), 4.0% (350 approximately 650 keV, 10 ns), and 3.8% (350 approximately 650 keV, 6 ns). Scatter fractions were 15.9% (mouse phantom) and 35.0% (rat phantom) for 250 approximately 750 keV and 6 ns. Peak NECR was 869 kcps at 3,242 kBq/mL (mouse phantom) and 228 kcps at 290 kBq/mL (rat phantom) at 250 approximately 750 keV and 6 ns. Hot-rod inserts of 1.6-mm diameter were clearly identified, and animal studies illustrated the feasibility of this system for studies of whole rodents and mid-sized animal brains. CONCLUSION: The results of this independent field test showed the improved physical characteristics of the F120 scanner over the previous microPET series systems. This system will be useful for imaging studies on small rodents and brains of larger animals.     

Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.     

Teaching ethics to paediatrics residents: the centrality of the therapeutic alliance

Context Previous research on ethical issues encountered by medical professionals in training and practice have presented the thematic content of the cases they encounter rather than the activities in which clinicians engage and in which they most often encounter ethical issues. We conducted a direct observation study of paediatrics residents and their preceptors seeing patients in an out‐patient general paediatrics clinic. Our objectives were to describe the everyday ethics‐related issues paediatrics residents encounter as they interact with patients. Our ultimate goal is to use this knowledge to enhance current efforts to teach ethics to paediatrics residents. Methods The study team directly observed paediatrics residents discussing patients with their faculty preceptors (19 half‐day sessions, 76 hours) in an out‐patient general paediatrics clinic located in an urban academic medical centre. Each interaction between resident and preceptor about a single patient was considered a case for further analysis. Results A total of 247 cases were recorded. Forty‐one of the cases were coded as having ethics‐related content. A constant comparative method of qualitative data analysis revealed that residents were most likely to encounter ethical issues when engaged in the following activities: (i) maintaining a therapeutic alliance with the caregiver (e.g. the parent); (ii) prioritising patient or family needs; (iii) adjusting to the power embodied by the role of doctors, and (iv) distinguishing suboptimal care from abuse or neglect. In addition, our findings indicate that it is through their efforts to maintain the therapeutic alliance with the caregivers of their patients that residents engage in and integrate three processes: developing their medical knowledge; adhering to professional norms, and balancing the power inherent in the doctor’s role with their responsibility to serve the patient’s interests. Conclusions Medical faculty tasked with teaching ethics to paediatrics residents can utilise the results of this project to better target and enhance their ethics education efforts directed at residents in the out‐patient setting. Future research could further examine and test these findings in other clinical settings (e.g. adult general medicine).     

Retinopathy in hepatitis C patients due to combination therapy with pegylated interferon and ribavirin

Background  

To assess the nature, incidence, and risk factors of retinopathy associated with pegylated interferon and ribavirin combination therapy in chronic hepatitis C patients.     

Factors affecting penetration of zona-free hamster ova

The sperm penetration assay is an expensive, time-consuming test to assess male fertility in vitro. Although some investigators are enthusiastic in its application, others feel that it is not sensitive or specific enough to be used as part of the routine infertility evaluation. Indeed, this bioassay is not a faithful reproduction of in vivo conditions. However, if the SPA is abnormal, it is unlikely that sperm will fertilize a human ovum in vivo. Conversely, a normal SPA does not guarantee successful in vivo fertilization. No bioassay can be absolute in its predictive value, but false-negative results must be kept to a minimum for this bioassay to be of any clinical significance. Each laboratory performing the SPA should optimize the assay for sensitivity, reproducibility, and minimization of false-negative results and then establish normal and abnormal ranges of its own. If the limitations of the SPA are kept in mind, and if we employ it very selectively, it may still be useful.     

Congenital fistula from ectopic accessory parotid gland: diagnosis with CT sialography and CT fistulography.

We report a case of congenital fistula from ectopic accessory parotid gland to the cheek demonstrated by CT sialography and CT fistulography. The right parotid gland was abnormally located lateral to masseter muscle. The fistula was arising from an ectopic accessory parotid gland with ectopic duct positioned anterior to masseter muscle. CT sialography and CT fistulography were very helpful in the diagnosis and surgical planning.     

Change in chromatogram patterns after volatilization of some aroclors, and the associated quantitation problems

PCBs with the highest vapor pressures (fewest chlorines) in Aroclors 1016, 1242, 1254 and 1268 were enriched in the vapor phase relative to the original Aroclor during volatilization from a glass surface for up to 8 hr. PCBs with the lowest vapor pressures (most highly chlorinated) were enriched in the corresponding residue. Thus, visual matching of gas chromatograms with those of Aroclor standards may not be sufficient to identify a specific Aroclor since the past history of a sample is often unknown. The enrichment also was detected using isomeric classes, but not using total chlorine content. The perchlorination method and the Webb-McCall method using all chromatographic peaks agreed quantitatively; this was not always so for the NIOSH multiple peaks and the Webb-McCall methods.