Search PubMed⌕ Search

Biomedical subjects

J Cowan

Publications and source records attributed to J Cowan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Negative cooperativity exhibited by the lytic amino-terminal domain of human perforin: implications for perforin-mediated cell lysis.

BACKGROUND: Cytolytic effector cells of the immune system recognize and lyse cells that carry non-self epitopes. One mechanism of cell lysis involves release of a 67-kDa pore-forming protein, perforin. The amino-terminal domain of perforin (>/= 19 residues) can account for most of the lysis activity, by a mechanism that is similar to that of holoperforin. Detailed mechanistic studies of this domain should yield useful insight into the factors underlying perforin activity in vivo. RESULTS: The mechanism of pore formation by the 22-residue amino-terminal domain of perforin was studied by kinetic and thermodynamic methods. Approximately 4 +/- 1 peptide monomers form an active pore by a mechanism that displays negative cooperativity. CONCLUSIONS: A negatively-regulated aggregation mechanism is likely to be common for pore-forming peptides. The positively-charged domain B of perforin (residues 7- 15) may mediate cooperativity through electrostatic interactions. Such a mechanism limits the number of protein molecules that are committed to any particular channel. This data supports smaller pores as the physiologically relevant aggregate, rather than the larger ring sizes identified by electron microscopy at higher, non-biological concentrations.

Humans↗
PubMed1996

Modern health care depends on technology, Part 2.

The first article in this series presented the principles and vocabulary of technology assessment and described the process used at St. Luke's, a tertiary care hospital in Bethlehem, Pennsylvania. This second article will describe the resources needed to support a technology assessment program. Technology planning, acquisition, and management will also be discussed. Historically, the health care marketplace has welcomed new technologies. In a future in which providers will be accountable for the outcomes of the care they provide, the ability to evaluate new and existing technologies will be essential for success.

Databases, Factual↗
PubMed1996

Attenuation of G2-phase cell cycle checkpoint control is associated with increased frequencies of unrejoined chromosome breaks in human tumor cells.

To test the hypothesis that attenuation in G2-phase checkpoint control leads to elevated frequencies of unrejoined chromosome breaks in mitosis, the relationship between G2-phase cell cycle checkpoint control and unrejoined chromosome break frequencies after radiation exposure was examined in cells of 10 human tumor cell lines: 8 squamous cell carcinoma cell lines and 2 lymphoblastoid cell lines. Most of the delay in progression through the cell cycle seen in the first cell cycle after radiation exposure in these cell lines was due to blocks in G2 phase, and there were large cell line-dependent variations in the length of the G2-phase block. There was a highly significant inverse correlation between the length of G2-phase delay after radiation exposure and the frequency of induced unrejoined chromosome breaks seen as chromosome terminal deletions in mitosis. This observation supports the hypothesis that the signal for G2-phase delay in mammalian cells is an unrejoined chromosome break and that attenuation of G2-phase checkpoint control allows cells with unrejoined breaks to progress into mitosis. Attenuation in G2-phase checkpoint control was not associated with alterations in the frequency of induced chromosome rearrangements, suggesting that most chromosome rearrangements develop prior to G2 phase, and there was no significant relationship between the length of G2-phase delay and inherent radiation sensitivity, suggesting that unrejoined chromosome breaks are not the primary toxic lesion induced by radiation in mammalian cells.

Chromosome Aberrations↗
PubMed1992

Chromosome 3p deletions in head and neck carcinomas: statistical ascertainment of allelic loss.

Loss of function of tumor suppressor genes is important in the origin and progression of common adult tumors. Loss of heterozygosity indicating allelic loss has been used to detect chromosomal regions that harbor these genes. Using over 20 restriction fragment length polymorphism markers spaced throughout the entire length of chromosome 3p, we have generated 3p allelotypes for 18-26 head and neck squamous cell carcinoma cell lines. We then estimated the average heterozygosity over 19 loci for a random sample drawn from natural populations to be 7.80 and that for the tumor lines to be 1.65, indicating a gross reduction of heterozygosity, presumably due to allelic loss. Further comparison of per locus heterozygosity in normal and tumor DNAs showed which loci contributed to the general loss of heterozygosity. We showed that the commonly deleted region of 3p probably lies telomeric to D3S3 (3p14) and centromeric to RAF1 (3p25). This large region includes several putative tumor suppressor genes involved in multiple common tumor types of lung, breast, kidney, ovary, and cervix. The data demonstrate that chromosome 3p allelic loss is a common event in head and neck cancers and suggest that chromosome 3p tumor suppressor genes contribute to the pathogenesis of these tumors.

Alleles↗
PubMed1991

Differential expression of N-myc in phenotypically distinct subclones of a human neuroblastoma cell line.

Neuroblastomas are malignant childhood neoplasms that arise from derivatives of the neural crest. We report the characterization of a new neuroblastoma cell line, designated NBL-W, derived from the primary tumor of a patient with stage IVS disease (S. L. Cohn, C. V. Herst, H. S. Maurer, and S. T. Rosen, J. Clin. Oncol., 5: 1441-1444, 1987) according to the criteria of Evans [A. E. Evans, G. J. D'Angio, and J. Randolf, Cancer (Phila.), 27: 374-378, 1971]. Neurite-bearing (N) and substrate-adherent (S) cell lines have been subcloned from the parent line. N and S cells can interconvert, and both cell types label with the neural crest cell surface marker antibody, HNK-1. Cells in the subcloned lines and in the parent line have been shown by Southern blot analysis to contain approximately 100 copies of the N-myc gene. Cytogenetic analysis shows a homogeneously staining region present on chromosome 19. Although these subclones are of identical genotype, the S cells express lower amounts of N-myc mRNA and protein as compared to the N cells. N cells express several neuronal proteins including the neurotransmitter-processing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase, the neuronal intermediate filament proteins peripherin and NF66/alpha-internexin, and the neural cell adhesion molecule. S cells generally lack neuronal markers but express the mesenchymal intermediate filament protein vimentin, and a small subset of the S cells express glial fibrillary acidic protein. Some S cells were labeled weakly with neural cell adhesion molecule antibody; others were negative. S cells did not express the glial marker S-100 or a melanocyte marker, tyrosinase. Thus, S cells express the neural crest marker HNK-1 but do not express a set of antigens characteristic of any known cell type derived from the neural crest. These results are consistent with the suggestion that differential N-myc expression may be involved in the interconversion of N and S cells but indicate that the S cell phenotype need not represent a highly differentiated neural crest derivative.

Cell Differentiation↗
PubMed1990

Hemiparetic multiple sclerosis.

Eight patients are described who presented with hemiparesis which involved the face in seven. Six of the eight subsequently developed clinically definite multiple sclerosis and in the remaining two patients multiple sclerosis was the likely diagnosis. Magnetic resonance imaging gave useful information about the site of the lesions responsible for the presenting syndrome and provided additional information in support of a diagnosis of multiple sclerosis.

Adult↗
PubMed1989

Phase II evaluation of bisantrene in acute leukemia. A Southwest Oncology Group Study.

Twenty-nine patients with heavily pretreated acute leukemia in relapse were treated with bisantrene (maximum dose 120 mg/m2/day x 5) in a phase II study. Twenty-seven of the 29 patients were evaluable for response, receiving a total of 53 courses of treatment. There were three complete remissions (11%) lasting 27, 107, and 115 days. One brief partial remission of 43 days was also seen for a total response rate of 15%. Toxicity was mainly limited to the expected myelotoxicity with minimal nonhematologic toxicity seen. Although the complete remission rate is low, an antileukemic effect was seen in the majority of the patients treated. Sixty-one percent of the patients had at least a 50% decrease in the circulating blast count and 32% had at least a 50% decrease in the number of bone marrow blasts. We conclude that bisantrene does have an antileukemic effect, but that the optimal starting dose is not yet established.

Acute Disease↗
PubMed1988

Acute respiratory illness among immunized and nonimmunized patients with high-risk factors during a split season of influenza A and B.

A prospective survey of acute respiratory illness (RI) was made among 329 vaccinated and unvaccinated ambulatory patients with high-risk factors for influenza. Surveillance for virus during the influenza season revealed the predominance of influenza A and B in sequential periods. During the influenza A period, febrile RI was greatest among patients with chronic pulmonary disease; among 66 patients, vaccination significantly reduced RI. Age greater than 65 y (199 patients) and heart (90 patients) and metabolic diseases (151 patients) did not increase the relative frequency of febrile RI, and vaccine administration caused no apparent reduction in frequency of RI. During the influenza B period, no differences in RI were observed between the groups, and the frequency of RI was unrelated to vaccination. Variability in virus and vaccine specificities may have been important. Except for one subset of specific virus and host conditions, no overall reduction in influenza-like or total RI was observed from vaccinating ambulatory, high-risk patients.

Acute Disease↗