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J Peacock

Publications and source records attributed to J Peacock.

18 recordsLinked to original sources
PubMed1992

Collateral resistance to photon and neutron irradiation is associated with acquired cis-platinum resistance in human ovarian tumour cells.

The melphalan resistant variant of the human ovarian OAW42 tumour cell line has previously been shown to be collaterally resistant to photon irradiation, but not to fast neutrons. In the present study, the "in vitro" photon and neutron radiosensitivity of human ovarian OAW42 tumour cells with acquired resistance to cis-platinum has been studied, to determine whether a similar pattern of cross-resistance exists between cis-platinum and these ionising radiations. Analysis of SF2 values suggests that resistance to cis-platinum conferred a 3-fold decrease in sensitivity to photons, primarily attributable to a 5-fold decrease in the magnitude of the initial slope (alpha). Depletion of GSH by BSO restored the magnitude of alpha to a value similar to that of the parental line. However, cis-platinum resistant OAW42/CP cells, in contrast to melphalan resistant cells, were 1.5-fold more resistant to "fast" neutrons (assessed at D0.1 survival level) than the parental OAW42 cell line. The mechanism for the collateral resistance between cis-platinum, and both photons and neutrons remains to be determined, but although GSH levels may be directly, or indirectly involved in the collateral resistance to photons, they would appear not to involved with the mechanisms responsible for collateral neutron resistance, in the cis-platinum resistant human ovarian cell lines used in this study.

Cell Survival↗
PubMed1992

BSO-induced reduction of glutathione levels increases the cellular radiosensitivity of drug-resistant human tumor cells.

Acquired resistance to cis-platinum and melphalan, in the human ovarian OAW42 tumor cell line, respectively, conferred a 3- and 1.5-fold decrease in photon sensitivity. Analysis of cell survival curves by the linear quadratic equation showed an accompanying 5- and 2-fold reduction in the magnitude of the initial slope (alpha). Treatment with the GSH depleting agent BSO restored the magnitude of alpha to a value similar to that of the parental line without evidence of dose modification in the high-dose region of the cell survival curve. This in conjunction with failure of alteration in GSH levels to affect parental OAW2 sensitivity and of the SER of BSO to reflect GSH levels suggest a possible GSH independent mechanism of action for BSO. If similar patterns occur in the clinic, the possibility exists of circumventing collateral resistance between chemotherapeutic agents and ionizing radiation, provided that tumor thiol levels can be preferentially depleted.

Buthionine Sulfoximine↗
PubMed1991

Ligand induced internalization of epidermal growth factor receptors by A431 cells decreases at high cell densities in culture.

Internalization of epidermal growth factor (EGF) receptors by human A431 epidermoid carcinoma cells was studied at various culture densities. The extent of EGF receptor internalization was measured by quantitation of internalized 125I-EGF during incubation at 37 degrees C for 30 min. When cell culture density was below 1 x 10(5) cells/cm2 receptor internalization was active; 30-40% excess moles of ligand over the moles of surface EGF receptors were internalized during this period. However, when culture density increased to above 1.5 x 10(5) cells/cm2 receptor internalization became less extensive, as only 30-50% of ligand bound to the cell surface underwent internalization during 30 min incubation. In parallel with this reduction in receptor internalization, the degradation rate of 35S-methionine labeled EGF receptors was reduced at a high culture density. In contrast with this regulation of receptor internalization, the affinity of EGF receptors for the ligand increased as culture density increased. The extent of EGF-dependent receptor phosphorylation was found to be constant at all culture densities tested. Thus, the observed low level of receptor internalization at high culture densities was not attributable to lower responsiveness of receptors to EGF. These data suggest the presence of an as yet unidentified cell density-dependent mechanism for regulating receptor internalization in cultured A431 cells.

Adenosine Triphosphate↗
PubMed1990

Endophthalmitis caused by exogenous nocardial infection in a patient with Sjögren's syndrome.

A 60-year-old woman receiving prednisolone therapy for Sjögren's syndrome presented with corneal perforation. Therapeutic penetrating keratoplasty was performed, but no causative organism was identified. Focal inflammatory infiltrates in both donor and host cornea and anterior uveitis developed postoperatively. Five months later the inflammation rapidly became much worse, with fulminating abscesses, and the eye was eviscerated because of severe endophthalmitis. Nocardia organisms were identified in the cornea, conjunctiva and vitreous by means of acridine orange and modified Ziehl-Neelsen stains. The infection produced both suppurative and granulomatous inflammation. Reexamination of the penetrating keratoplasty specimen with a modified Ziehl-Neelsen stain revealed a few Nocardia organisms, which suggested that infection had occurred at the time of corneal perforation.

Chloramphenicol↗
PubMed1988

Glucocorticoid receptor-mediated effects on rat fibrosarcoma growth.

Glucocorticoid receptors are present in most normal and malignant mammalian cells. To examine the hypothesis that the growth of methylcholanthrene-induced malignant sarcoma is glucocorticoid dependent, we evaluated the behavior of malignant fibrosarcoma (MCA) in adrenalectomized rats treated with either normal saline or deoxycorticosterone acetate and in intact rats treated with placebo or with the glucocorticoid receptor antagonist RU 486. Survival, tumor weight, and loss of body weight (an index of cachexia) were measured. In MCA-bearing rats, neither survival nor loss of body weight was affected by bilateral adrenalectomy or by treatment with RU 486. Tumor weight and time-integrated tumor volume, however, were significantly less in bilaterally adrenalectomized rats without deoxycorticosterone acetate replacement than in animals treated with deoxycorticosterone acetate. Similarly, tumor weight and time-integrated tumor volume were less in intact animals treated with RU 486 than in intact animals treated with placebo. The glucocorticoid receptors in the tumor cells had similar binding capacity (Ro) and equilibrium dissociation constant (Kd) as in control rat fibroblasts. These results suggest that the growth of MCA sarcoma cells is partially dependent upon glucocorticoids. This effect of glucocorticoids, however, was not of sufficient magnitude to improve survival and prevent cachexia. We conclude that glucocorticoids appear to influence MCA sarcoma growth in the rat, and that glucocorticoid receptor blockade, perhaps in combination with other antitumor agents, merits future study in the treatment of malignant tumors.

Adrenalectomy↗
PubMed1987

Early-stage developmental abnormalities induced by murine cytomegalovirus.

The onset of the effects of murine cytomegalovirus (MCMV) infection on an early stage of embryonic development (nine days) in a mouse model was studied with the aid of scanning electron microscopy. MCMV was injected into the endometrial lumina of pregnant mice at the time of implantation. The mice were later killed, and sites of embryonic implantation were examined. Compared with uninfected mice and mice inoculated with heat-inactivated virus, litter sizes were reduced, and the incidence of abnormal fetuses was significantly increased among MCMV-infected animals. Scanning electron microscopy also revealed maldeveloped cranial regions characterized by an unclosed neural tube and severely underdeveloped head. Ectodermal abnormalities, including poxlike formations and ballooning cells, were observed in several embryos. Thus, early cytomegalovirus infection may not only result in fetal loss, but may also interfere with the process of morphogenesis.

Animals↗
PubMed1987

Deletion of 5'-coding sequences of the cellular p53 gene in mouse erythroleukemia: a novel mechanism of oncogene regulation.

The p53 gene is rearranged in an erythroleukemic cell line (DP15-2) transformed by Friend retrovirus. Here, we characterize the mutation and identify a deletion of approximately equal to 3.0 kilobases that removes exon 2 coding sequences. The gene is expressed in DP15-2 cells and results in synthesis of a 44,000-dalton protein that is missing the N-terminal amino acid residues of p53. The truncated protein is unusually stable and accumulates to high levels intracellularly. Moreover, it appears to have undergone a change in conformation as revealed by epitope mapping studies. This study represents the first description of an altered p53 gene product arising by mutation during neoplastic progression and identifies a region in the p53 protein molecule that plays a role in determining p53 stability in vivo.

Animals↗
PubMed1986

Epidemiology of colonization by nontypable Haemophilus influenzae in children: a longitudinal study.

Eighty-six nasopharyngeal isolates of Haemophilus influenzae were prospectively obtained from three children who attended a day care center from infancy until early childhood (five to seven years). A majority of the strains were nontypable. We analyzed strains by comparing their biotypes and by performing electrophoresis of outer membrane proteins on polyacrylamide gels. Profiles of outer membrane proteins were very heterogeneous and could not be used as the basis for the development of a subtyping scheme. The children characteristically carried a nasopharyngeal strain defined by a unique outer membrane pattern for a period of months, lost it, and then acquired a new strain. We probed the outer membrane proteins of a child's strains by the western blot technique with serum obtained serially from the child. Isolates whose outer membrane proteins appeared identical on stained gels generally had similar antigenic bands on western blots but were occasionally immunologically distinct. Serum immunoglobulins of the IgG class that reacted with the outer membrane proteins did not appear to change greatly over time or to play a role in preventing or terminating colonization. We conclude that nasopharyngeal colonization in children by nontypable H. influenzae is a dynamic process and that factors that cause loss and acquisition of strains remain to be determined.

Antigens, Bacterial↗
PubMed1986

Diagnosis of cerebral toxoplasmosis using fluorescein-labeled antitoxoplasma monoclonal antibodies.

The direct immunofluorescence technique using monoclonal antitoxoplasma antibodies was used to detect Toxoplasma organisms in 13 brain touch preparations and six smears of cerebrospinal fluid. For comparison, Giemsa-stained smears and histologic sections of the same cases were also studied. Positive results were obtained from two cases of acquired immunodeficiency syndrome (AIDS) with all three methods. Toxoplasma cysts, pseudocysts, and tachyzoites were easily identified by the immunofluorescence technique, and no false-positive results were encountered in nine cases of AIDS with different kinds of encephalitides. It was difficult to identify tachyzoites in histologic sections and time-consuming to search for pseudocysts and cysts. The parasite was even more difficult to recognize in Giemsa-stained brain touch preparations due to the easy distortion of the organisms. In the present study, immunofluorescence technique was more sensitive than hematoxylin--eosin or Giemsa staining in terms of the number and range of forms demonstrated in tissue. Therefore, immunofluorescence technique using monoclonal antibodies appears to be the preferred method for a rapid diagnosis of cerebral toxoplasmosis as compared to Giemsa staining and histology.

Antibodies, Monoclonal↗
PubMed1986

Infectious endophthalmitis.

A clinical series of twenty-eight cases of suspected infectious endophthalmitis was reviewed. The combination of epidemiology and peroperative microscopy at the time of vitreous biopsy provided a useful indication of the pathogen involved. The visual prognosis was related to the virulence of the pathogen, and to the delay between recognition of symptoms or signs and treatment. It appears possible to predict high risk groups which warrant a high index of clinical suspicion and prompt diagnosis to enable early vitrectomy with injection of appropriate intraocular antibiotics.

Endophthalmitis↗
PubMed1985

Transformation associated p53 protein is encoded by a gene on human chromosome 17.

The human gene for the transformation-associated p53 phosphoprotein (P53) was assigned to the short arm of chromosome 17 using human-rodent somatic cell hybrids and Southern filter hybridization of cell hybrid DNA. The filters were hybridized to radiolabeled DNA from a genomic clone which contained P53 nucleotide sequences. Hybridization of the probe to a 2.5-kb human DNA fragment in HindIII-digested DNA was used to identify the human P53 gene.

Animals↗
PubMed1977

Synapse formation between two clonal cell lines.

Clonal neuroblastoma x glioma hybrid cells frequently formed synapses with clonal mouse striated muscle cells. Clonal myotubes were similar to cultured mouse embryo myotubes with respect to acetylcholine sensitivity and other membrane properties examined. However, acetylcholine sensitivity measurements indicate that acetylcholine receptors of clonal myotubes are distributed more uniformly over the cell surface than the receptors of cultured mouse embryo myotubes.

Acetylcholine↗
PubMed1976

Myosin synthesis increased by electrical stimulation of skeletal muscle cell cultures.

When cultures of skeletal muscle cells of the chick embryo are subjected to repetitive, electrical stimulation, the contractions increase the amount of protein produced by these cells. The increase is greater for contractile proteins such as myosin heavy chain than for total cellular protein. This demonstrates that in a culture system of skeletal muscle cells that have differentiated in the absence of innervation, one can elicit the protein synthetic response associated with skeletal muscle hypertrophy in vivo.

Animals↗