Biomedical subjects

J E Champion

Publications and source records attributed to J E Champion.

12 recordsLinked to original sources

PubMed1990

Adjuvant chemotherapy for osteosarcoma of the extremity. Long-term results of two consecutive prospective protocol studies.

Seventy-six patients with classic high-grade osteosarcoma of an extremity received adjuvant chemotherapy by two protocols, initiated in 1972 and 1977, respectively, after appropriate amputations. Chemotherapy consisted of high-dose methotrexate, doxorubicin, and cyclophosphamide. Dose intensity of high-dose methotrexate and doxorubicin was greater for the patients treated with the protocol initiated in 1977. The proportion of long-term disease-free survivors on the two protocols are 46% and 56%. A better outcome (P = 0.042) was seen for the latter group, which received more intensive chemotherapy. Overall, metastases developed in 35 patients; in 19 who were receiving chemotherapy and in 16 after chemotherapy. The outcome for these two protocols, compared with two control groups that were given no chemotherapy or ineffective chemotherapy (biweekly vincristine and cyclophosphamide), confirms the results of controlled studies that showed an advantage of adjuvant chemotherapy after amputation for osteosarcoma.

Adolescent↗

PubMed1990

Developmental expression of the putative transcription factor Egr-1 suggests that Egr-1 and c-fos are coregulated in some tissues.

We have investigated developmental expression of the gene Egr-1, which encodes a protein containing three zinc fingers. Egr-1 like c-fos is a serum inducible, early response gene, which is co-induced with c-fos in a variety of quite different situations. A single 3.7-kb RNA was detected throughout fetal mouse development, which increased in absolute levels in total fetal RNA from 9.5 to 12.5 days post coitum (p.c.). In situ hybridization to 14.5- and 17.5-day p.c. fetal tissues demonstrated Egr-1 accumulation at several specific sites. These included mesenchymal components of the developing tooth germs and salivary and nasal glands; an ectodermally derived component of the whisker pad and developing muscle, cartilage, and bone. Expression of Egr-1 in cartilage and bone showed a strikingly similar expression to previously published reports of c-fos in these tissues. High levels of Egr-1 RNA was observed at the perichondrial interface of opposing cartilaginous elements and in interstitial cells that lie in between. Bone expression was observed in membranous bone of the head, alveolar bone around the tooth germs, and at periosteal and endochondral ossification sites in the limb bones. Our data support the idea that Egr-1 and c-fos may be coregulated in vivo and together may regulate normal development of the skeleton.

Animals↗

PubMed1987

Endoperoxidation, hyperprostaglandinemia, and hyperlipidemia in a case of erythrophagocytic lymphohistiocytosis. Reversal with VP-16 and indomethacin.

Clinicopathologic and histopathologic evidence of both endoperoxidation with hyperprostaglandinemia and hyperlipidemia in a 5-week-old infant with a hemophagocytic syndrome is reported. Institution of histiocytolytic (VP-16) and cyclo-oxygenase inhibitor (indomethacin) therapies returned the prostaglandin levels and lipid profile to a nearly normal state coincidental with clinical recovery. It appears that by reducing the cell mass of histiocytes and controlling the over-production of prostaglandins, some types of hemophagocytic syndrome can be reversed.

Dinoprost↗

PubMed1987

cDNA cloning, sequencing and chromosome mapping of a non-erythroid spectrin, human alpha-fodrin.

Several overlapping cDNA clones encompassing 2760 nucleotides of the alpha-subunit of a human non-erythroid spectrin (termed fodrin) were isolated from a human lung fibroblast cDNA library. DNA and RNA blot analyses indicated that a single copy alpha-fodrin gene encodes a 9-kb transcript. The cDNA clones were sequenced, and all were found to contain long open reading frames. The overlapping regions were identical except for a 60-nucleotide inframe insertion at position 1133 in the composite sequence. This result suggests that at least two distinct transcripts exist in fibroblast cells. The chromosomal location of human alpha-fodrin was assigned to 1p34-1p36.1 by hybridization to somatic cell hybrids, and it is thus distinct from that of human alpha-spectrin which has been mapped to 1q22-1q25. Alignment of the composite 919 amino acids of the predicted protein sequence of human alpha-fodrin with that of human alpha-spectrin indicated that alpha-fodrin has a similar 106-amino-acid repeating structure, which is homologous with alpha-spectrin repeats 7-15. Repeats 10 and 11 are anomalous in sequence and structure from other repeats. A comparison of nucleic acid and amino acid homologies between alpha-spectrin and the alpha-fodrin of several vertebrates indicated that human non-erythroid alpha-fodrin and the common alpha-subunit of erythroid and non-erythroid cells of non-mammalian vertebrates are closely related (90%-96% amino acid homology), whereas alpha-fodrin is only distantly related to the erythroid-specific alpha-spectrin subunit of mammals (55%-59% amino acid homology). These data suggest that mammalian erythroid alpha-spectrin evolved by duplication and rapid divergence from an ancestral alpha-fodrin-like gene.

Amino Acid Sequence↗

PubMed1987

A molecular analysis of mouse development from 8 to 10 days post coitum detects changes only in embryonic globin expression.

The pattern of protein synthesis in 8-, 9- and 10-day post coitum (p.c.) mouse embryos was examined by 2-D gel electrophoresis of [35S]methionine-labelled proteins. Of the 600-800 polypeptides detected only one, a 14 X 10(3) Mr (14K) protein, was found to accumulate over this period. To isolate cDNA clones that potentially encode this protein, 32P-labelled cDNA was synthesized from 9 and 10 days p.c. embryo poly(A) +RNA, and used for the differential screening of an 8.5-day p.c. mouse embryo cDNA library cloned in lambda gt10. Six clones that hybridized strongly to the 10-day probe were purified and their inserts subcloned into plasmid vectors. Cross hybridization and restriction mapping of these inserts indicate that they fall into four distinct groups. Each of these hybridize with transcripts of approximately 600 nucleotides, which accumulate in the embryo from 9 to 10 days p.c. Expression was barely detectable in adult tissues and restricted to liver and spleen. Expression of one of these clones, 10.1, was examined by in situ hybridization of 35S-labelled RNA probes to 8.5-12.5 day p.c. embryo sections. Strong hybridization was observed in yolk sac blood islands, fetal liver and embryonic erythrocytes, suggesting that 10.1A encodes an erythrocyte-specific protein. DNA sequence analysis indicates that the four classes of cDNA were derived from transcripts of the alpha 1, zeta, beta h1 and epsilon globin genes. Labelling of 10-day p.c. erythrocyte proteins with [35S]methionine, followed by 2-D gel electrophoresis, clearly demonstrates that the most abundant polypeptide migrates to the same position as the 14K protein which accumulates from 8 to 10 days p.c. Thus the only abundant transcripts and corresponding proteins that change over a period of profound morphogenetic change correspond to globins of the newly established blood system.

Amino Acid Sequence↗

PubMed1987

Phase I study of iproplatin in pediatric patients: a Pediatric Oncology Group Study.

Iproplatin was evaluated in a phase I study in children to determine the maximum tolerated dosage. The dose-limiting toxic effect was found to be myelosuppression, which in part was related to the amount of prior therapy with irradiation and other anticancer agents. The dosage recommended for phase II trials in children is 324 mg/m2 iv over 2 hours every 3-4 weeks.

Adolescent↗

PubMed1985

Treatment of unresectable or metastatic osteosarcoma with cisplatin or cisplatin-doxorubicin.

Responses and toxicity after treatment with cisplatin and cisplatin-doxorubicin were compared in two groups of patients with unresectable or metastatic osteosarcoma. Complete or partial responses developed in 3 of 18 individuals treated with cisplatin, and in 5 of 19 after the two-drug combination. Hematologic and gastrointestinal complications were more frequent and severe in patients who received both agents. The combined use of cisplatin and doxorubicin is justified for patients with unresectable or metastatic osteosarcoma at diagnosis because of the potential therapeutic benefits for these individuals.

Adolescent↗

PubMed1984

The effect of prior cisplatin therapy on the pharmacokinetics of high-dose methotrexate.

The pharmacokinetics of high-dose methotrexate (MTX, 5-15 g/m2) were evaluated in 11 children and adolescents who had previously received two to eight doses of cisplatin (90 mg/m2) in the treatment of malignant solid tumors. The half-life for disappearance of MTX from serum during the first 24 hours after infusion was determined from serum samples obtained at the end of a six-hour infusion and six, 12, and 24 hours after infusion. These values were compared to a mean half-life of 2.83 (+/- 0.34) hours following 489 courses administered to 71 patients who had not received cisplatin. Stepwise multiple linear regression analysis of patient variables revealed cumulative cisplatin dosage and time from last cisplatin dose as the best predictors of MTX half-life (r2 = 65.4%, p less than 0.001). The best predictors of 24-hour serum concentration were cumulative cisplatin dosage and MTX dosage (r2 = 54.2%, p less than 0.001) in the multiple linear regression model. Patients with delayed MTX clearance received additional leucovorin and experienced no severe toxicity. Patients receiving up to 270 mg/m2 of cisplatin appear to have minimal increases in MTX half-life, while the likelihood of delayed clearance increases in patients who have received 360 mg/m2 or more of cisplatin. All patients who have previously received cisplatin should be treated cautiously with high-dose MTX and prospective pharmacokinetic monitoring should be routinely performed.

Adolescent↗

PubMed1984

Distribution and properties of type I and type II binding proteins in the cyclic adenosine 3':5'-monophosphate-dependent protein kinase system in Wilms' tumor.

We compared the relative amounts and properties of cyclic adenosine 3':5'-monophosphate (cAMP)-binding proteins in surgical specimens of Wilms' tumor and normal kidney. Cytosolic fractions of both tissues contained type I and type II isozymes of cAMP-dependent protein kinase (adenosine triphosphate: protein phosphotransferase, EC 2.7.1.37). Among tumor samples, the mean ratio of type I to type II cAMP-binding activity was 2.76 +/- 0.52 (S.D.) contrasted with 1.36 +/- 0.23 for normal kidney (p less than 0.001). The total soluble cAMP-binding activities in normal and malignant tissues differed only slightly. Photoaffinity labeling of cytosol from either tissue, using cyclic adenosine 3':5'-[8-azido-32P]monophosphate, disclosed three cAMP-binding proteins (Mr 47,000, 51,000, and 55,000) that were identified as regulatory subunits of the holoenzyme. Three lower-molecular-weight proteins with unknown function were considered to be proteolytic products of the larger proteins. The Mr 47,000 protein, a monomeric regulatory subunit of type I kinase, was clearly the dominant protein in tumor specimens, but it was much less abundant in normal kidney. The temperature sensitivities of the cAMP-binding proteins and their dissociation constants for cyclic adenosine 3':5'-[8-azido-32P]monophosphate incorporation did not differ appreciably between tumor and normal tissues. Wilms' tumor appears to have a full complement of regulatory subunits of cAMP-dependent protein kinase that are capable of normal cellular function.

Carcinoma, Hepatocellular↗

PubMed1983

Limb salvage procedures for children with osteosarcoma: an alternative to amputation.

Amputation remains the standard surgical management for patients with osteosarcoma. However, in carefully selected patients, eradication of the primary tumor can be achieved by En-Bloc resection of the affected bone preserving both anatomical and functional status. Our criteria for limb salvage procedures are that patients must: (1) be age 12 years or older, (2) have no angiographic or clinical evidence of neurovascular involvement, (3) have low-grade osteosarcoma and/or good response to preoperative chemotherapy, and (4) be compliant. Between November 1980 and October 1982, 32 patients with osteosarcoma of an extremity were seen. Eight patients ranging in age from 13 to 21 years underwent limb salvage procedures. Five of these had Tikhoff-Linberg procedures for upper extremity lesions, two had En-Bloc resections for distal femur lesions, and one patient had a segmental arthrodesis for a distal tibial lesion. Of these eight patients, two had low-grade parosteal osteosarcoma. Follow-up ranged from 10 to 28 months (median 16 months). The two patients with parosteal osteosarcoma received no further therapy, while the other six patients received multiple agent chemotherapy. One patient died at 18 months with bilateral pulmonary disease. None have had local recurrences. Two of the eight patients had minor skin necrosis, requiring revision subsequently. Three patients have had transient nerve palsy. All have had good functional results. With careful selection of patients by rigid criteria, limb salvage procedures can be a viable alternative to amputation.

Adolescent↗

PubMed1983

Cisplatin-induced changes in bleomycin elimination.

Bleomycin disposition was studied in two children who received at least six courses of vinblastine, bleomycin, and cisplatin. Total plasma clearance of bleomycin decreased from 39 to 18 ml/min/m2, while the terminal-phase half-life increased from 4.4 to 6.0 hrs since the cumulative cisplatin dose was greater than 300 mg/m2. In one patient, renal clearance of bleomycin decreased from 30 to 8.2 ml/min/m2. Changes in serum creatinine or BUN were not predictive of changes in bleomycin elimination.

Adolescent↗

PubMed1979

Acute lymphoblastic leukemia--hand mirror variant. An analysis of a large group of patients.

One hundred and thirty-four initial bone marrows and 102 peripheral blood smears were evaluated for hand mirror cells (HMC) on pediatric patients with acute lymphoblastic leukemia (ALL). Twenty (15%) of the 134 patients were found to have greater than 5% HMC in their bone marrows. Only rarely were a few HMC noted in the peripheral blood. Survival did not appear to be related to the number of HMC in the bone marrow. Also, the median survival was not significantly greater in those HMC patients with greater than 40% HMC in their bone marrows when compared to the non-HMC group. From the available data in this study, it would appear that the number of HMC does not affect prognosis in the bone marrows of children with ALL. However, the prognostic significance of the HMC has not been clearly established in adults.

Adolescent↗