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Biomedical subjects

K Kelliher

Publications and source records attributed to K Kelliher.

7 recordsLinked to original sources
PubMed1999

Transgenic shuttle vector assays for assessing oxidative B-cell mutagenesis in vivo.

The recent development of transgenic mutagenicity assays provides new opportunities for evaluating mutagenic processes in vivo. To asses mutant frequencies in tissue B cells, we decided to take advantage of two such assays that utilize the transgenic shuttle vectors, lambda LIZ and pUR288. Our main interest in this research is to test two basic premises of inflammation-induced plasmacytoma development in genetically susceptible BALB/c mice; i.e., the possibility that plasmacytoma precursor cells may become targets of phagocyte-mediated oxidative mutagenesis in situ and the prospect that plasmacytoma susceptibility/resistance genes may contribute to these phenotypes by enhancing/reducing oxidative mutagenesis in B cells. Based on our preliminary experience with the lambda LIZ and pUR288 transgenic in vivo mutagenicity tests, we propose to employ these assays as broadly applicable tools for assessing overall mutagenesis during normal and aberrant (malignant) B-cell development. Furthermore, transgenic shuttle vector assays appear to lend themselves as ideal methods to associate general B-cell mutagenesis with the peculiar, B cell-typical somatic hypermutation processes that target the V(D)J gene segment, the proto-oncogene bcl-6 and perhaps other, still unknown loci.

Animals↗
PubMed1998

Association of elevated mutagenesis in the spleen with genetic susceptibility to induced plasmacytoma development in mice.

Using the phage lambdaLIZ-based transgenic in vivo mutagenesis assay, mean mutant rates were determined in the spleen of mice exposed to sustained oxidative stress and were found to be increased approximately 3-fold in plasmacytoma-susceptible BALB/c and C.D2-Idh1-Pep3 mice, but not in plasmacytoma-resistant DBA/2N mice. This finding suggests a correlation between the genetic susceptibility to inflammation-induced peritoneal plasmacytomagenesis and the phenotype of increased mutagenesis in lymphoid tissues, raising the possibility that plasmacytoma resistance genes may inhibit tumor development by minimizing oxidative mutagenesis in B cells.

Animals↗
PubMed1996

Indications and results of combined anterior-posterior approaches for spine tumor surgery.

Spinal instrumentation currently allows gross-total resection and reconstruction in cases of malignancies at all levels of the spine. The authors analyzed the results in 110 patients who underwent surgery for primary and metastatic spinal tumors over a 5-year period (1989-1993) at a single institution. Major primary sites of tumor included breast (14 cases), chordoma (14 cases), lung (12 cases), kidney (11 cases), sarcoma (13 cases), plasmacytoma (10 cases), and others (36 cases). Prior to surgery, 55 patients (50%) had received prior treatment. Forty-eight patients (44%) were nonambulatory, and severe paraparesis was present in 20 patients. Fifty-three patients (48%) underwent combined anterior-posterior resection and instrumentation. 33 (30%) underwent anterior resection with instrumentation, 18 (16%) underwent anterior or posterior resection alone, and the remaining six patients (5%) underwent posterior resection and instrumentation. Major indications for anterior-posterior resection included three-column involvement, high-grade instability, involvement of contiguous vertebral bodies, and solitary metastases. Postoperatively, 90 patients improved neurologically. The overall median survival was 16 months, with 46% of patients surviving 2 years. Fifty-three patients (48%) suffered postoperative complications. Despite the high incidence of complications, the majority of patients reported improvement in their quality of life at follow-up review. Our findings suggest that half of all patients with spinal malignancies require combined anterior-posterior surgery for adequate tumor removal and stabilization.

Adult↗
PubMed1994

Growth factor expression in normal peritoneum of patients with gynecologic carcinoma.

Both epidermal growth factor receptor (EGFR) and HER-2/neu (neu) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma, but alterations in proto-oncogene expression of normal tissues of patients with gynecologic malignancies are unknown. Patients (118) undergoing laparotomy for gynecologic indications (78 ovarian cancer, 11 endometrial cancer, 19 benign gynecologic disease, 10 other cancers) had biopsies of normal peritoneum for quantitative assessment of neu and EGFR concentrations. Patients undergoing exploration for gynecologic malignancy were found to have significantly higher median neu expression in the peritoneal biopsies than patients with benign gynecologic disease (P = 0.002). Most patients in this study were found to have ovarian cancer, and median peritoneal neu expression was found to be significantly higher in patients with ovarian cancer versus benign ovarian masses (P = 0.0008) or any benign gynecologic disease (P = 0.004). No significant alteration of unbound EGFR was found in peritoneal biopsies of any of the groups of patients. No associations were found for a history of breast cancer, presence of ascites, or menopausal status with alteration of neu or EGFR expression in normal peritoneum. These findings of altered expression of neu in normal tissues of patients with ovarian cancer are suggestive of the presence of proto-oncogene alterations in loco-regional tissues of the peritoneum, such as might be seen if a paracrine influence existed between tumor and peritoneal cells. Alternatively, the alterations may represent subtle alterations of proto-oncogene expression of germ-line tissues.

Biomarkers, Tumor↗
PubMed1983

Mitochondrial genetics of mammalian cells: a mouse antimycin-resistant mutant with a probable alteration of cytochrome b.

Mouse LA9 antimycin-resistant mutants (ANT-R) were isolated and characterized. Genetic analyses established that this phenotype is encoded within the mtDNA: (1) the ANT-R phenotype showed frequent mitotic segregation and reassortment in hybrid clonal lines; (2) it was transmitted directly in cybrid crosses; and (3) it was cotransmitted in cybrid crosses with the mitochondrial CAP-R marker. Furthermore, the genetic studies suggested that the LA9 CAP-R ANT-R cells were heteroplasmic and contained at least two mtDNA genotypes, cap-r ant-s and cap-s ant-r. Cellular respiration of the ANT-R mutant was markedly more resistant to inhibition by antimycin than that of the parental ANT-S cells. The increased resistance of cellular respiration was entirely accounted for by an increase in the resistance of mitochondrial succinate-cytochrome c oxidoreductase to antimycin inhibition. There was no detectable change in the specific activity of the oxidoreductase in mitochondria of resistant ANT-R cells nor in the sensitivity of the complex to three other specific inhibitors of the complex: TTFA, myxothiazol, and HQNO. Taken together, these studies indicate that the ANT-R phenotype is most likely encoded within the mitochondrial cytochrome b gene and, more specifically, within an antimycin binding domain.

Animals↗
PubMedDate not supplied

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