Tissue-specific expression in transgenic mice of a fused gene containing RSV terminal sequences.

Transgenic mice were generated with pRSV-CAT, a chimeric gene construct containing the long terminal repeat of Rous sarcoma virus (RSV) linked to the bacterial gene encoding chloramphenicol acetyltransferase (CAT). CAT expression, detected in adult animals of five independent strains, was preferentially directed to organs rich in tendon, bone, and muscle. This pattern reflects the disease specificity of the intact virus and suggests that the tissue tropism of RSV is determined at least in part by the presence of endogenous tissue-specific factors that can promote expression of genetic information linked to the long terminal repeat. In two of the mouse strains, insertion of the pRSV-CAT DNA resulted in developmental abnormalities. One of these strains was characterized by a dominant trait of embryonic lethality, the other by a recessive trait of fused toes in all four feet.

Removal of boron (B) from waste liquors.

This paper explores the use of electrocoagulation to remove boron from waste effluent in comparison with alum coagulation. In treating model test wastes, greater boron removals were achieved with electrocoagulation at low doses than conventional alum coagulation when reaction was undertaken for the same conditions (pH 8.5, and initial boron concentration was 500 mg/L). Al electrocoagulation can achieve good boron removal performance (68.3%) at a dose of 2.1 (as molar ratio of Al:B, and for current density of 62.1 A/m2), while alum coagulation can only achieve the maximum boron removal of 56% at a dose of 2.4. Also, Al electrocoagulation can remove 15-20% more boron than alum coagulation for the same dose compared in the treatment of both model test wastes and industry effluent. The estimation of running costs shows that to achieve 75% boron removal from industry waste effluent, i.e. removing 150 g of boron from 1 m3 of effluent, electrocoagulation was 6.2 times cheaper than alum coagulation. The economic advantage of electrocoagulation in the treatment of boron-containing waste effluent is thus significant.

Effects of celecoxib in human retinoblastoma cell lines and in a transgenic murine model of retinoblastoma.

BACKGROUND/AIM: Celecoxib, a cyclooxygenase-2 inhibitor and antiangiogenic agent, has demonstrated potent anticancer effects in preclinical studies and in human clinical trials. To evaluate the potential utility of this agent in the treatment of retinoblastoma, the authors investigated the effects of celecoxib in retinoblastoma cell lines and in a murine model of this disease. METHODS: Growth inhibitory effects of celecoxib were evaluated in Y79 and Weri-RB1 human retinoblastoma cell lines by WST-1 cell proliferation assay. For animal study, two groups of 24, 8 week old LHbeta-TAg transgenic mice were treated with celecoxib (250 mg/kg, orally once a day) or vehicle control, 5 days/week for 6 weeks. Mice were sacrificed on day 43. Enucleated eyes were serially sectioned and ocular tumour burden was quantified by histopathological analysis. RESULTS: Celecoxib did not inhibit proliferation of Y79 or Weri-RB1 cells, even at concentrations far exceeding clinically achievable levels. No significant difference in ocular tumour burden between celecoxib treated and control mice (p=0.73) was found. CONCLUSION: Celecoxib was ineffective at inhibiting proliferation of retinoblastoma cells in vitro and was ineffective at controlling retinoblastoma tumour growth in a murine model of this disease. On the basis of these findings, oral celecoxib therapy is unlikely to have clinical utility in the treatment of retinoblastoma.

External beam radiotherapy in retinoblastoma: tumor control and comparison of 2 techniques.

OBJECTIVE: To investigate eye conservation, local control, and complication rates among children with retinoblastoma treated with 2 different external beam radiotherapy (EBR) techniques. METHODS: Fifty-eight eyes in 42 patients received EBR as the primary treatment modality for retinoblastoma (median follow-up, 37 months). The EBR technique was relative lens-sparing (RLS) in 26 eyes and modified lateral beam (MLB) in 32 eyes. Both groups were comparable in Reese-Ellsworth retinoblastoma classification. If necessary, patients received focal salvage therapy. RESULTS: At 24 months, eye conservation rates were 88.5% and 89.1% among eyes treated with RLS and MLB, respectively (P = .40); tumor control rates without salvage therapy were 84.6% and 53.3% (P = .02), respectively. Among eyes with Reese-Ellsworth stage IV and V disease, eye conservation rates were 88%+/-8% and 83%+/-9% at 36 months in the RLS and MLB groups, respectively, and local tumor control rates were 81%+/-10% and 51%+/-12%. Percentages of eyes without cataract at 36 months were 83.1% and 63.0%, respectively (P = .40). Among patients observed for at least 18 months, midfacial hypoplasia developed in 38.5% and 29.4%, respectively (P = .70). CONCLUSIONS: The EBR technique was associated with high eye conservation and local control rates. Salvage therapy was performed significantly less frequently in the RLS group compared with the MLB group, and complication rates in both groups were similar.

Evaluation of efficacy and complications: primary pediatric orbital implants after enucleation.

BACKGROUND: Orbital implants are used routinely in pediatric patients at the time of enucleation. Complications, such as exposure, ptosis, and infection, may occur after implantation. Controversy continues regarding the rate of complications with newer implants in the pediatric population. OBJECTIVE: To examine the effects of orbital implants on children whose eyes have been enucleated. METHODS: Records of orbital implantation after enucleation performed by 5 surgeons on 120 pediatric patients (123 eyes) over a 10.5-year period were reviewed retrospectively. Demographic data, ocular diagnosis, prior ophthalmic surgery, implant characteristics, and postoperative complications were described using a standardized format for all patients, with a minimum of 6 months of follow-up (mean, 3 years). RESULTS: Complications were observed in 7 eyes (5.7%). Implant exposure (1 [0.8%]), implant extrusion (0 [0%), and implant migration (3 [2.4%) were rare. One hundred eighteen eyes (96%) had good cosmesis and 120 (98%) had good motility. CONCLUSIONS: Orbital implantation after enucleation is successful in the pediatric population. Complications are minimal. Hydroxyapatite implants were not associated with unacceptable complications in this pediatric population.

Evaluation of chemoprophylaxis in patients with unilateral retinoblastoma with high-risk features on histopathologic examination.

OBJECTIVES: To identify risk factors for metastatic disease on histopathologic specimens of enucleated eyes from patients with unilateral retinoblastoma, and to evaluate the value of chemoprophylaxis in preventing disease dissemination. METHODS: Medical records from patients with unilateral retinoblastoma who underwent primary enucleation were reviewed at the University of California, San Francisco (1977-1998) and Bascom Palmer Eye Institute, University of Miami, Miami, Fla (1991-1998). All routine histopathologic specimens were reexamined. The extent of tumor invasion into the optic nerve or ocular coats and the prescribed chemoprophylactic regimen were recorded. RESULTS: This retrospective study included 129 patients followed for a median of 54 months. Three patients had tumor invading the sclera. The optic nerve was involved to some extent in 82 patients, 11 of whom had tumor extension beyond the lamina cribrosa. The surgical margin of the optic nerve was involved in an additional 4 patients. The choroid was involved in 43 patients, and was considered massively affected in 12 patients. Anterior segment involvement was observed in 10 patients. Postenucleation chemoprophylaxis was administered to 4 of 4 patients who had tumor cells at the surgical margin of the optic nerve and to 7 of 11 patients with postlaminar disease, all of whom had at least 1 mm of postlaminar tumor extension. External beam radiotherapy was administered to 3/4 and 1/11 of these patients, respectively. Chemoprophylaxis was not administered to patients with choroidal or anterior chamber involvement unless the optic nerve was also involved beyond the lamina cribrosa. One patient with tumor extending to the surgical margin of the optic nerve died of metastatic disease. CONCLUSIONS: Chemoprophylaxis is necessary for patients with tumor extending to the surgical margin of the optic nerve and is likely to be beneficial in preventing metastases in patients with tumor extending beyond the lamina cribrosa. We did not offer chemoprophylaxis to patients with prelaminar optic nerve disease or isolated choroidal involvement, and these patients remained free of disseminated disease.

Instructional considerations for young children with autism: the rationale for visually cued instruction.

Instructional considerations for children with autism who continue to struggle with current treatment models are discussed. Specifically, the use of instructional strategies for children who may be characterized as visual learners are addressed. The discussion begins with a review of research that illuminates the learning style differences associated with autism. Next, the instructional strategies of both behavioral and incidental teaching methods are examined in light of the research. Finally, using a case study as the backdrop, the discussion concludes with a description of how visually cued instruction can be applied in various contexts.

Daily life therapy: a Japanese model for educating children with autism.

The controversial practice of Daily Life Therapy, as demonstrated at the Boston Higashi School in Massachusetts, is reviewed. Five fundamental principles of Daily Life Therapy are examined: instruction that is group-oriented; routine activities that are highly structured; instructional techniques that center on learning through imitation; a method for reducing children's levels of unproductive activity through rigorous physical exercise; and a curriculum that focuses on movement, music, and art. These central features of Daily Life Therapy are discussed in light of current theory, research, and educational practices in autism. Empirical questions raised by this unique treatment mode are outlined.

Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines.

AIMS: To investigate the cytotoxicity of beta-lapachone, a potent agent that may selectively target tumour cells, in retinoblastoma (RB) cell lines. METHODS: Growth inhibitory effects of beta-lapachone were evaluated in Y79, WERI-RB1, and RBM human retinoblastoma cell lines. Pro-apoptotic effects of beta-lapachone were evaluated in Y79 cells by detection of caspase 3/7 activity, by enzyme-linked immunosorbent assay for nucleosome fragments, and by cellular morphological analysis. RESULTS: Beta-lapachone induced significant dose-dependent growth inhibitory effects in all three retinoblastoma cell lines. The 50% growth inhibitory concentration (IC(50)) of this agent was 1.9 microM in Y79 cells, 1.3 microM in WERI-RB1 cells, and 0.9 microM in RBM cells. Beta-lapachone also induced proapoptotic effects in RB cells. Treatment of Y79 cells with 1.9 microM beta-lapachone (IC(50)) resulted in a peak, fourfold induction of caspase 3/7 activity at 72 h post-treatment; a peak, 5.6-fold increase in nucleosome fragments at 96 h post-treatment; and a peak, 1.7-fold increase in the frequency of apoptotic cells at 48 h post-treatment, relative to vehicle-treated controls. CONCLUSION: Beta-lapachone induced potent cytotoxic effects in RB cell lines at low micromolar concentrations, suggesting this agent could be useful in the clinical management of RB.

Environmental supports to enhance social-communication.

"Environmental support" is a general term used to define the systematic use of explicit visual and/or social cues to clarify meaning for children with autism. Environmental supports can serve as a compensatory means to structure and enhance language understanding, social engagement, and social-communicative interactions. The unique and atypical developmental patterns associated with autism provide the rationale for the use of two environmental supports: visually cued instruction and modified sociolinguistic input. Using empirical research, multiple examples of environmental supports to enhance social-communication are provided.