Biomedical subjects
Publications and source records attributed to C Pratt.
A phoRc and a phoB mutation belong to the same complementation group suggesting that there is a single positive control gene for alkaline phosphatase synthesis.
Explore the source record for details and available documents.
Thirteen children with disseminated neuroblastoma that had become refractory to conventional chemotherapy were treated with the epipodophyllotoxin VM-26. Three patients developed partial responses (greater than 50% reductions in tumors and in the proportion of tumor cells in bone marrow). Acute nonhematologic toxicity after treatment was minimal. Hematologic toxicity was observed but could not be assessed accurately since most patients had abnormal hematopoiesis due to extensive tumor involvement of bone marrow. These results demonstrate that VM-26, as a single agent, can produce measurable tumor responses in children with neuroblastoma.
Twelve patients 11-20 years of age with recurrent osteosarcoma were immunized with either autologous or allogeneic tumor cells infected with influenza virus, strain B/Michigan or A/Port Chalmers. Six patients received only the vaccine, and the remaining six patients continued to receive methotrexate chemotherapy. The main objectives of this study were to determine if immunizations were toxic, if antibodies developed to the influenza virus antigen component of the vaccine, if this vaccine increased tumor-specific cellular and humoral immunity, and if the increase in immune response could be correlated with clinical course and prognosis. In all 12 cases, toxicity was negligible, and immunizations boosted antibody titers to both tumor cell and influenza virus antigens. However, in four of the six patients with advanced disease who received immunotherapy only, the vaccine did not stimulate mixed lymphocytes nor did it increase cell-mediated immunity. By contrast, five of six patients with minimal disease who continued methotrexate therapy developed cellular and humoral immunity in response to both allogeneic and autologous tumor cells. Although no clear-cut relationship between responses to the tumor cell vaccine and clinical course and prognosis could be demonstrated, three of the six patients with minimal disease have survived for 7-8 months after the first vaccination, without progression of disease. This study demonstrates that plasma membrane preparations derived from different lines of virus-infected osteosarcoma tumor cells will elicit an antibody response in patients with drug-resistant progressive osteogenic sarcoma.
Explore the source record for details and available documents.
A fine structure map of the phoR region of E. coli, mutations of which affect the rate of alkaline phosphatase synthesis, was constructed by Hfr X F- crosses. Mutations causing three different phenotypes (previously reported as phoRa, phoRb, phoRc (Garen and Echols 1962a,b) are clustered in three closely linked genetic loci. PhoR mutants of all three types, including the phoRb type not previously tested, are recessive to wild-type phoR+. In addition, phoRa and phoRc complement each other, while phoRa and phoRb do not. Our results support the hypothesis of Morris et al. (1974) that phoRc mutants represent a cistron (phoB) different from phoR.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A dominant constitutive mutation of the phoR locus controlling alkaline phosphatase synthesis in Escherichia coli is described. Its phenotype can be explained by the production of a poisonous subunit of the phoR gene product. The phoR gene product is inferred to consist of at least 3 or 4 subunits.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Children with developmental dyslexia are known to have problems with phonological awareness and, in particular, with phonological decoding. This study was aimed at determining the relationship between orthographic and phonological decoding strategies used by a group of children with developmental dyslexia and two groups of children who were average readers (matched on reading age and chronological age, respectively). The three groups of children, 12 in each, were presented with single words, either visually or orally. The children were asked to pronounce these words using either an orthographic (spelling) strategy following mental deletion of one letter, or a phonological (sounding) strategy following mental deletion of one sound. Analysis of variance (ANOVA) revealed that the reading age control group were more accurate when using phonological strategies than when using orthographic strategies, whereas the chronological age control group generally showed superior orthographic and phonological processing abilities compared with both the developmental dyslexia and reading age control groups. Compared with both chronological and reading age control groups, children in the developmental dyslexia group had more difficulty when using a phonological strategy, particularly when words were presented auditorily. However, compared with their performance on phonological tasks, the developmental dyslexia group performed at a level commensurate with their age when carrying out the orthographic tasks.
Beta-adrenergic blocking drugs are now commonly used in patients with ventricular arrhythmias. This review examines the possible mechanisms of their ventricular antiarrhythmic effect. Actions on the myocardial cell, as well as actions on the central and autonomic nervous system, are reviewed. Many clinical studies have attempted to show the efficacy of beta blockers in controlling ventricular arrhythmia and decreasing the incidence of sudden death after acute myocardial infarction. Although some of these clinical trials tended to show an impact on sudden death, the size of these trials or their design problems do not allow firm conclusions to be made. The Beta Blocker Heart Attack Trial (BHAT) is a placebo-controlled, double-blind, randomized trial of propranolol currently under way in the United States. Important additions to the previous trials include the addition of drug levels to ensure beta-blocking dosage, long-term electrocardiographic monitoring, and a study population of 4200 patients followed for an average of three years. These important design features will be of value in addressing some of the unanswered questions presented in this review.
The purpose of this study was to explore, using grounded theory, the process experienced by parents who are dealing with the first recurrence of cancer in their child. The sample of 33 guardians (27 mothers, 1 grandmother, and 5 fathers) was drawn from three pediatric oncology settings. Data were collected through interviews, observations, and medical record review. Thirteen parents were interviewed to validate first the evolving and, later, the complete study findings. Four interactive components emerged: regulating shock, situation monitoring, alternating realizations, and eyeing care-limiting decisions. The overall organizing construct induced from these components was labeled "coming to terms." This construct represents the parents' efforts to overcome shock and despair to make wise decisions about treatment while accepting that the outcome if beyond their control, and to help their child have the optimal chance for cure while preparing for the child's possible death.
PURPOSE: This study reviewed the Pediatric Oncology Group experience with phase II clinical trials in children (< 21 years of age) with refractory tumors. PATIENTS AND METHODS: Patients registered in Pediatric Oncology Group phase II studies were evaluated. Patients had to be < 21 years of age with recurrent and refractory measurable disease. Tumor types and response rates were determined. Death on therapy from either drug toxicity, progressive disease, infection, or hemorrhage was measured. Tumor-specific, disease-free survival curves were calculated by Kaplan-Meier analysis. RESULTS: Between 1984 and 1994, 2,465 patient entries were made on 45 phase II trials. Malignancies registered included acute lymphocytic leukemia (ALL) (16.7%), acute myeloid leukemia (AML) (12.0%), osteogenic sarcoma (7.8%), neuroblastoma (7.2%), astrocytoma (7.2%), medulloblastoma (7.1%), glioma (6.7%), ependymoma (6.1%), and others (29.2%). The overall response rate was 19.6% (CR + PR) for children entered on phase II trials. Tumor-specific response rates ranged from 62.1% (23/37) for children with Hodgkin's disease to no responses (0/23) in patients with hepatoblastoma. When comparing single versus multiagent trials, a significantly better initial response rate was seen in the latter studies. However, 5-year survival was comparable. Progression-free survival for all tumor histologies were 12.9% and 9.2% at 2 and 5 years, respectively. Death on study was seen in 11.6% of the patients; however, only three deaths were directly related to drug toxicity. There were no significant gender differences in regards to response, progressive disease, or death on study. CONCLUSION: Phase II studies conducted in children offer a considerable likelihood of therapeutic benefit without exposing these patients to untoward toxicity.
PURPOSE: A phase II study was designed to determine the efficacy of topotecan, an inhibitor of topoisomerase I, in the treatment of patients with progressive or recurrent pediatric extracranial solid tumors (STs). PATIENTS AND METHODS: Patients younger than 21 years at the time of initial diagnosis with refractory STs were treated with 2 mg/m2 topotecan given by 30-minute infusions for 5 days repeated every 3 weeks. Granulocyte colony stimulating factor (G-CSF) was added to the regimen only after occurrence of severe neutropenia or therapy delay due to sustained neutropenia. RESULTS: One hundred forty-one patients were treated with 539 courses of topotecan. Responses were seen in 34 patients (3 had complete responses [CRs], 2 had partial responses [PRs], and 24 had minor responses [MRs] or stable disease [SD]). The number of administered courses in patients with SD varied between 5 and 24, with a median of 10. The median time on the study for patients with SD was approximately 8.5 months. In patients without bone marrow involvement, the most frequent toxicity was myelosuppression: hemoglobin < 8 g/dl in 83 of 341 courses, absolute granulocyte count < 1,000/microl in 221 of 341 courses, and platelet count < 50,000/microl in 162 of 341 courses. Nausea and vomiting were infrequent; many patients were pretreated with ondansetron or granisetron. A recurrent rash developed in 16 patients and was usually well controlled with diphenhydramine and hydrocortisone. G-CSF was administered in 203 of 539 courses because of neutropenia. Therapy was delayed over 1 week in 33 instances. CONCLUSION: In previously treated patients, topotecan produced CRs and PRs in patients with neuroblastoma, Ewing's tumor, and retinoblastoma. In hepatoblastoma, rhabdomyosarcoma, and a few rare tumors, long-lasting MRs and SDs with excellent symptom control were seen. The toxicity of topotecan, predominantly myelosuppression, was tolerable.