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Biomedical subjects

D Carney

Publications and source records attributed to D Carney.

At least 37 records · Page 2Linked to original sources
PubMed1994

Infusional cyclophosphamide, doxorubicin and etoposide in HIV-related non-Hodgkin's lymphoma: a follow-up report of a highly active regimen.

Based on our prior data suggesting a therapeutic advantage for infusional administration of cyclophosphamide (C), doxorubicin (D), and etoposide (E) in patients with relapsed and resistant non-Hodgkin's lymphoma (NHL), we administered C (750 mg/m2), D (50 mg/m2), and E (240 mg/m2) via continuous intravenous infusion over 96 hours as first line therapy for 21 patients with intermediate- or high-grade non-Hodgkin's lymphoma associated with human immunodeficiency virus (HIV) infection. Treatment was repeated every 28 or more days. The median CD4 count of the study group was 87/ul, and the median serum lactate dehydrogenase was 383 IU/L. Extranodal disease, lymphomatous marrow involvement, and lymphomatous meningitis were present at diagnosis in 90%, 33%, and 10% of patients, respectively. Complete response (CR) occurred in 13 patients (62%, 95% confidence intervals 41%, 81%) and partial response occurred in five patients (24%). The estimated median survival of the study group was 18.0 months. Hematologic toxicity required dose reduction for 47% of cycles and for 79% of patients who received at least two cycles. The mean dose intensity for C, D, and E were 73%, 70%, and 73% of the intended dose intensity, respectively. Opportunistic infection included oral/esophageal candidiasis (N = 7), herpes labialis (N = 3), pulmonary Mycobacterium avium-intracellulare (N = 1), candidemia (N = 1), pneumonitis (N = 1), and disseminated aspergillosis than resulted in a single treatment-related death (5%). Treatment resulted in a significant decrease in the CD4+ lymphocytes, as well as total lymphocytes, T lymphocytes, and CD8+ lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Treatment of advanced non-small cell lung cancer with very high-dose cisplatin combined with etoposide and mitomycin C.

BACKGROUND: Treatment options for advanced non-small-cell lung cancer are inadequate. There remains a critical need for more effective systemic therapies. METHODS: Forty-one patients with advanced non-small-cell lung cancer were treated on a 28-day cycle with a very high-dose, cisplatin-based three-drug regimen. A treatment cycle consisted of an intravenous (IV) injection of cisplatin 100 mg/m2 on days 1 and 8; etoposide 60 mg/m2 IV over 30 minutes on days 1, 2, 8, and 9 (cycles 1 and 3 only); and mitomycin C 8 mg/m2 IV bolus on day 1 (cycles 2 and 4 only) (PEM regimen). RESULTS: The median dose intensity of cisplatin delivered was 49 mg/m2/wk, or 98% of the planned dose. One patient achieved a complete response and 16 patients a partial response or regression, yielding an overall objective response rate of 41%. The median duration of response was 21 weeks. Median survival of all patients was 38 weeks. Neurologic toxicity was dose limiting. The frequency of peripheral neuropathy and ototoxicity was directly related to cumulative cisplatin dose. In five patients, a progressive peripheral neuropathy developed after discontinuation of cisplatin. Hematologic toxicity also was significant. CONCLUSIONS: This very high-dose, cisplatin-based chemotherapy regimen has appreciable activity in advanced non-small-cell lung cancer. In comparison with previous reports on the use of very high-dose cisplatin alone, however, this combination appears at best to be only marginally more active, to confer no additional survival advantage, and to be considerably more toxic.

Adult↗
PubMed1993

Resection of an intracardiac metastasis from malignant teratoma of the testis.

Nonseminomatous germ cell testicular neoplasm is a disease cured primarily by platinum-based combination chemotherapy. Operation is reserved for those patients who continue to harbor residual masses after chemotherapy. Locoregional lymph nodes and lungs are common sites for residual deposits. Intracardiac metastases are very rare. We report a case of successful resection of bilateral lung and single intracardiac secondary deposits from a malignant teratoma, treated by orchidectomy 6 years previously.

Adult↗
PubMed1989

Anthropometric measurements of adolescent and professional classical ballet dancers.

This study examined anthropometric measures of 83 female adolescent students attending the Boston Ballet summer program and 15 professional dancers from the Boston Ballet Company. Thirty-one were in the least advanced level (group A), 38 were in the moderately advanced level (group B) and 14 were in the most advanced level (group C). The adolescent dancers devoted between 17 and 23 hours per week in dance training, while professional dancers spent 39.2 hours per week in class and rehearsals. Compared to normative data, the dancers tended to be tall and slim. The skinfold, diameter, and circumference measurements were found to be very similar among groups A, B and C, and between group C and the company members. The somatograms demonstrated that the ballet dancers had relatively smaller upper arms and larger calves and ankles compared with the reference female. The data from this study suggest that the body type characteristics associated with professional classical ballet dancers are already apparent in the pre-professional adolescent dancers.

Adolescent↗
PubMed1988

18th Sir Hans Krebs lecture. Knowledge-based protein modelling and design.

A systematic technique for protein modelling that is applicable to the design of drugs, peptide vaccines and novel proteins is described. Our approach is knowledge-based, depending on the structures of homologous or analogous proteins and more generally on a relational data base of protein three-dimensional structures. The procedure simultaneously aligns the known tertiary structures, selects fragments from the structurally conserved regions on the basis of sequence homology, aligns these with the 'average structure' or 'framework', builds on the loops selected from homologous proteins or a wider database, substitutes sidechains and energy minimises the resultant model. Applications to modelling an homologous structure, tissue plasminogen activator on the basis of another serine proteinase, and to modelling an analogous protein, HIV viral proteinase on the basis of aspartic proteinases, are described. The converse problem of ab initio design is also addressed: this involves the selection of an amino acid sequence to give a particular tertiary structure, in this case a symmetrical domain of two Greek-key motifs.

Base Sequence↗
PubMed1986

Heterogeneity of cell surface antigen expression of human small cell lung cancer detected by monoclonal antibodies.

Using immunohistochemistry, radiobinding, and indirect immunofluorescence assays, seven distinct cell surface antigens, detected by monoclonal antibodies, were analyzed for the degree of homogeneity or heterogeneity of antigen expression on a panel of human small cell lung cancers. The panel included 7 tumors taken directly from patients, 21 established cell lines (9 of which were derived from different metastatic sites of 3 patients), and 33 clonal derivatives of 3 lines. With all assays, considerable heterogeneity of antigen expression between tumors from different patients was observed. In both fresh tumors and in cell lines, as well as in cell lines established from different metastatic sites in an individual patient, we observed intratumor heterogeneity finding antigen positive and negative cells and variation in antigenic density, by immunohistochemistry and indirect immunofluorescence assays. Antigenic expression was not cell cycle dependent. In addition, when cell lines or patient samples expressing antigen positive and antigen negative tumor cells were cloned, heterogeneity of antigenic expression was still present in the clonal lines. This suggests that either the expression of the antigen was not heritable and/or the ability to regenerate antigenic heterogeneity is an intrinsic property of the tumor cells. The heterogeneity of antigen expression on lung cancer cells has significant implications for the use of these and other monoclonal antibodies in the study and therapy of lung cancer.

Antibodies, Monoclonal↗
PubMed1985

The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line.

The human genes for prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NPII) and prepro-oxytocin-neurophysin I (prepro-OT-NPI) were cloned from a human genomic library and the nucleotide sequence of both genes was determined. The two genes are similar in their intron-exon structure, linked together with 12 kilobases intervening, and transcribed from opposite DNA strands. A human small cell lung cancer cell line, H378, produces significant quantities of pre-pro-AVP-NPII mRNA using a transcription unit predicted from the genomic DNA sequence. Despite the proximity of the actively transcribed prepro-AVP-NPII gene, transcription of prepro-OT-NPI is not detected in this cell line.

Amino Acid Sequence↗
PubMed1985

Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer.

We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A,B,C and beta 2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of HLA-A,B,C and beta 2-microglobulin (beta 2m) antigen expression was demonstrated with both radiobinding assays and indirect immunofluorescence assays. Immunoprecipitation of metabolically labeled cells with antibodies to class I antigens showed most SCLC lines to have synthesized almost no beta 2m and HLA-A,B,C proteins. Northern blot analysis, using human HLA-A,B, and beta 2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and beta 2m mRNA, but both gene products could be induced with interferon treatment of SCLC lines. We conclude that human SCLC, in contrast to other lung cancer types, is characterized by greatly reduced transcription of HLA-A,B,C and beta 2m genes, which suggests the existence of a mechanism for evading the host immune response to the tumor and of an E1a-like product in this type of tumor cell.

Antigens, Surface↗