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Biomedical subjects

N Jaffe

Publications and source records attributed to N Jaffe.

At least 253 records · Page 14Linked to original sources

Rhabdomyosarcoma of the head and neck: diagnosis and management.

Rhabdomyosarcoma represents the most common soft-tissue neoplasm of the head and neck found in children. The tumor is most commonly seen in Caucasian children under the age of 12, usually presenting as a painless mass. Distant metastases are frequently present, especially in regional lymph nodes, lung, and bone marrow. All patients suspected of having this disorder should have a thorough examination of the head and neck, as well as a complete radiographic evaluation of the primary region. Histologic disagnosis should be made as rapidly as possible. Once this has been accomplished, a thorough search for metastatic disease can be undertaken. Therapy must be individualized, and a team approach is advocated. The roles of surgery, radiation therapy, and chemotherapy are discussed. A staging system and a treatment-therapy plan are outlined.

Child↗

Single-stranded nucleic acid-binding protein, Pur alpha, interacts with RNA homologous to 18S ribosomal RNA and inhibits translation in vitro.

Pur alpha is a highly conserved, eukaryotic sequence-specific DNA- and RNA-binding protein involved in diverse cellular and viral functions including transcription, replication, and cell growth. Pur alpha exerts its activity in part by interacting with other viral and cellular proteins. One such protein is the human immunodeficiency virus (HIV) type I regulatory protein Tat. Earlier studies have demonstrated that this interaction is mediated by Pur alpha-associated RNA (PARNA) and that RNA immunopurified from mammalian expressed Pur alpha was capable of reconstituting the interaction between these two proteins. In the current study, we characterize four RNA species which were immunopurified with Pur alpha. Northern blot analysis with one of the PARNAs revealed a highly abundant signal of approximately 2.0 kilobases (kb) present in all cell lines tested. Sequence analysis of each of the four PARNA clones revealed a high homology to different regions of the human 18S ribosomal RNA sequence. Based on this homology, we investigated the influence of Pur alpha on translation. Luciferase assays were performed after coupled in vitro transcription/translation reactions with a vector containing a luciferase reporter construct and increasing concentrations of BSA, GST, and GST-Pur alpha. Inclusion of GST-Pur alpha in these reactions resulted in a dose-dependent inhibition of luciferase activity. Similar inhibition was observed with in vitro translation reactions performed with in vitro transcribed luciferase RNA and increasing concentrations of GST-Pur alpha. In control experiments, inclusion of increasing concentrations of GST-Pur alpha with luciferase protein resulted in no effect on luciferase activity. Taken together, these data demonstrate that Pur alpha inhibits translation reactions in vitro. Moreover, this Pur alpha-mediated inhibition of translation can be abrogated by HIV-1 Tat protein.

Animals↗

The potential for an improved prognosis with chemotherapy in osteogenic sarcoma.

Effective chemotherapeutic agents administered shortly after definitive primary treatment to patients with osteogenic sarcoma have altered the natural history of the disease. In contrast to past experience, pulmonary metastases fail to develop in the overwhelming majority of patients receiving treatment with chemotherapy. Patients with established pulmonary metastases have also been salvaged. The therapeutic strategy advocated for different categories of patients is outlined. Although chemotherapy involves additional hospitalization and inconvenience, this additional mode of treatment appears to be the only mechanism by which a substantial improvement in survival of osteogenic sarcoma can presently be achieved.

Bone Neoplasms↗

Acinetobacter calcoaceticus sepsis in children with malignancies.

The clinical and microbiologic characteristics of 29 episodes of sepsis caused by Acinetobacter calcoaceticus were reviewed in 25 children with underlying malignancies. Of the 29 episodes of sepsis with this organism 28 occurred from 1980 through 1984, compared with 1 episode from 1973 to 1979. Risk of infection was associated with the presence of intravascular cannulae, osteosarcoma and recent administration of antitumor chemotherapy. There was no association with neutropenia, malnutrition or focal infection. Of 28 organisms for which the biotypes were known, 14 (50%) were var. lwoffi and 14 (50%) were var. anitratus; 11 episodes (38%) were part of a polymicrobial bacteremia. All patients responded favorably to antimicrobial therapy.

Acinetobacter↗

Doxorubicin cardiotoxicity in children: reduced incidence of cardiac dysfunction associated with continuous-infusion schedules.

We retrospectively reviewed the medical records of 97 children (59 boys and 38 girls) with a median age of 13 +/- 4 years who had been treated with continuous infusion of doxorubicin at a dosage of 60 mg/m2 over 24 h (61 patients) or at a dosage of 75 mg/m2 over 72 h (36 patients). The drug was administered every 3 weeks. The cardiac status of patients was evaluated as a baseline and every 6 months during, and following therapy (median, 30.5 months). The evaluations included M-mode and two-dimensional echocardiography. Congestive heart failure developed in only one patient in this series, an 8-year-old girl who ultimately died of her cardiac complication. This incidence of doxorubicin-induced cardiotoxicity was compared with that seen in a control group of pediatric patients previously treated with doxorubicin at similar dosages but with a rapid infusion. The result compared favorably to the 13% incidence of cardiotoxicity (p = 0.03) and 7% mortality (p < 0.01) in the control group. No changes in the levels of tumor response were noted in children treated by continuous infusion when compared with historical controls. Continuous-infusion schedules of doxorubicin thus result in fewer incidences of cardiotoxicity in children and should be considered for wider application in pediatric cancer patients receiving doxorubicin.

Adolescent↗

Phase I. evaluation of cyclocytidine (NSC-145668).

Cyclocytidine is a repository form of cytosine arabinoside and has a prolonged plasma half-life (8 hours) compared to cytosine arabinoside (12 minutes). A phase I trail was undertaken to establish the maximum tolerated dose. Nineteen patients were entered into the study (ten children, nine adults) and the dose which achieved consistent myelosuppression was established in five escalation increments as 600 mg/m for 10 days. This dose is consistent with previously reported data on the basic pharmacology of cyclocytidine and with optimum dose data in aminal tumor systems. Limiting toxicity, however, was related to the induction of postural hypotension which is not dose related. Recommendation to proceed with phase II studies of cyclocytidine must await clarification of the mechanism and prevention of the postural hypotension.

Adult↗

An osteosarcoma cell line with hypodiploid chromosome number and complex structural anomalies.

Giemsa-banding analysis performed on a newly established metastatic osteosarcoma cell line (SP-388) that was passaged through the nude mouse revealed a hypodiploid stemline number of 39 chromosomes. This cell line showed both numerical and structural abnormalities, including the abnormally banded region in certain marker chromosomes. Chromosomes 3, 15, 17 and the X were the most frequently absent elements of this tumor. Segments of chromosomes 3, 15 and X could not be identified even in rearranged chromosomes (Ml to M15). We suggest that more cases of osteosarcoma should be studied so that specific primary and secondary chromosomal anomalies can be identified in human osteosarcoma.

Animals↗