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Biomedical subjects

G E Moore

Publications and source records attributed to G E Moore.

At least 127 records · Page 7Linked to original sources

Absence of retinoblastoma protein expression in primary non-small cell lung carcinomas.

Retinoblastoma (RB) protein expression was examined in paraffin and frozen tissue sections of 36 primary non-small cell lung carcinomas (NSCLC) using immunohistochemistry with confirmation by direct Western blotting. A normal RB protein staining pattern was present in 24 and absent in 10 NSCLC. Two additional RB positive primary tumors have major foci in which all tumor cells showed no RB protein staining. Significantly more high-stage (stages III and IV) NSCLC had altered RB protein expression than those with low-stage (stages I and II) tumors (P less than 0.05). The results suggest that absence of the RB expression may be associated with the initiation and/or progression of many NSCLC. This is the first report of successful RB staining in paraffin sections.

Blotting, Northern↗

Trophoblast from anembryonic pregnancy has both a maternal and a paternal contribution to its genome.

In a series of 14 anembryonic pregnancies, deoxyribonucleic acid from trophoblast was examined with locus-specific minisatellite probes. It was found in each case that trophoblast from anembryonic pregnancy has both a maternal and a paternal contribution to its genome. This means that although anembryonic pregnancy shares characteristics with complete hydatidiform mole and androgenetic development in the mouse in that there is no embryo, it does not arise by the same genetic process. Of three anembryonic pregnancies that were successfully karyotyped, two had normal female 46,XX chromosome constitutions and one had an abnormal 47,XX + 16 complement. The sex of the trophoblast in each anembryonic pregnancy was determined with a deoxyribonucleic acid probe with Y-specific bands. A male-to-female ratio of 6:8 was found, which is not significantly different from normal.

Chromosome Mapping↗

Genetic conservation of cyclo-oxygenase.

Homology between sheep and mouse cyclo-oxygenase cDNA and a range of other species was investigated using "zoo blots". Both the sheep and mouse cDNAs showed a high degree of homology to other species. Human cyclooxygenase appears to have greater homology to sheep and other ruminants than to mouse. Both sheep and mouse cDNAs detected identically sized transcripts in human placental total RNA.

Animals↗

Bladder and liver tumorigenesis induced by 2-acetylaminofluorene in different F1 mouse hybrids: variation within genotypes and effects of using more than one genotype on risk assessment.

Several F1 mouse hybrids were used in a chronic bioassay to determine whether such an experimental design would provide greater statistical power than using only the B6C3F1 hybrid. For this purpose, the dose response of formation of hepatocellular and bladder tumors after 30 mo of feeding 2-acetylaminofluorene (2-AAF) in the diet was assessed in 4 F1 mouse hybrids, including the B6C3F1 hybrid. No strain background-related differences in frequency of bladder neoplasms between any F1 hybrids were detected. Bladder tumors occurred only at the highest 2-AAF dose in female mice. In males the lowest dose was already sufficient to induce bladder neoplasms with incidences of 25-48% adjusted for different nontumor mortality patterns across doses. No marked strain-related differences in hepatocellular tumor rates were apparent in either sex. Higher frequencies of hepatocellular neoplasms were observed among the untreated control males of the B6C3, AY, and CVA F1 hybrids than among the comparable females. Among treated mice, the lowest 2-AAF dose increased liver tumor incidence, more so among the females than among the males. The different background genomes resulted in somewhat different risk assessments for liver tumor formation in males due to differences in the time-to-tumor curves. Except for the much higher background liver tumor rate in the CVY mice, the adjusted liver tumor incidences were similar across the four hybrids. Hence, the levels of statistical significance obtained for dose-response trends and comparisons of treated and control groups were similar using 48 animals per dose groups with B6C3 mice, or combinations of 24 animals per dose from 2 genotypes, or 12 animals per dose from the 4 hybrid genotypes. Estimates of carcinogenic potency for bladder tumors were similar, within a factor of two, across the four hybrids. However, estimates of liver tumor potency across genotypes varied by a factor of two and six for females and males, respectively. Thus, the mean of cancer potency estimates across these genotypes would be more representative for mice than results from any single genotype. As in chronic carcinogenesis studies with other test agents, neoplasms developed in only a certain proportion, rather than in all, of the genetically identical animals exposed to a given dose of the toxicant for the same length of time under the same controlled environmental conditions. This phenotypic variability in toxic responses may reflect differential regulation of gene expression among the genetically identical test animals.

2-Acetylaminofluorene↗

X chromosome genes involved in the regulation of facial clefting and spina bifida.

Congenital malformations such as cleft palate and spina bifida may be multifactorial in etiology. They occur as a result of both environmental agents and defective genes. Consequently it is both practically and intellectually difficult to study their effects experimentally. The advent of molecular biology technology has enabled many genes on the human chromosome to be mapped and some to be cloned. Using these techniques and families that display common congenital malformations inherited in a purely genetic manner, the genetic defects can be separated from the environmental components. This report documents our studies of several families that have cleft palate or spina bifida as X-linked disorders. Their phenotype is similar to the more common multifactorial cases but segregates as a single gene in an X-linked fashion. Localization of these genes using different X chromosome DNA probes and linkage analysis is the first step towards our understanding of the genetic contribution to the etiology of congenital malformations.

Anencephaly↗

Interleukin-2-activated lymphocytes from brain tumor patients. A comparison of two preparations generated in vitro.

Two preparations of human recombinant interleukin-2 (rIL-2)-activated lymphocytes from patients harboring malignant brain tumors were characterized as autologous-stimulated lymphocytes (ASL) and lymphokine-activated killer (LAK) cells. ASL were generated from Ficoll-Paque-isolated, nonadherent, defibrinated peripheral blood lymphocytes (PBL) that were stimulated overnight with phytohemagglutinin (PHA) and cultured with rIL-2 (100 U/ml) for 10 days. LAK cells were produced by culturing all PBL in rIL-2 (500 U/ml) for 4 days. In 4-hour chromium release assays, LAK cells showed greater cytotoxicity than ASL against natural killer (NK)-sensitive and NK-resistant tumor cell lines; by 18 hours, the effectiveness of ASL equaled that of LAK cells. By electron microscopic study, PBL, LAK cells, and ASL showed differences. The helper/inducer to suppressor/cytotoxic ratio (T4+/T8+) of PBL, LAK cells, and ASL was 1.1:1, 1.0:1, and 0.4:1, respectively. ASL, when compared with PBL or LAK cells, have a significantly higher percentage of MO1+/DR+ and T8+/9.3+ subpopulations. ASL and LAK cells, used for the therapy of gliomas, are distinct.

Antibodies, Monoclonal↗

Operative splenic salvage in adults: a decade perspective.

The immunologic value of the spleen is now unchallenged; recognition of this fact has changed the management of splenic trauma radically over the past decade. This review describes our clinical experience in adults during this metamorphosis. In the 10-year period ending December 1987, 314 adults had splenic injury identified at emergent laparotomy. Mean patient age was 30.1 years and 81% were men. Injury mechanism was blunt in 227 (72%), stab wound in 49, and gunshot wound in 38. In 1978 splenorrhaphy was accomplished in nine (29%) of 31 patients; during 1982-1987 the rate of operative splenic salvage has been 63% (107/170). Splenorrhaphy was achieved with hemostatic agents in 40%, debridement and suturing in 40%, formal splenic resection in 13%, and mesh bag in 7%. Grade I splenic injuries were amendable to hemostatic agents alone, and suturing or mesh enclosure was necessary in 43% of Grade II and in all Grade III injuries. Grade IV disruption required anatomic splenic resection for hemorrhage control in 88% of the cases. During this period 63 patients underwent splenectomy; 48 (76%) had Grade V injuries that were technically unapproachable. The remaining splenectomies were performed expeditiously in multisystem injured patients harboring other critical injuries. This decade perspective documents the feasibility of operative splenic salvage in nearly two thirds of acutely injured adults. Conversely, more than one third require prompt splenectomy due to massive splenic disruption or the presence of concomitant life-threatening injuries.

Adolescent↗

A unique pattern of proto-oncogene abnormalities in ovarian adenocarcinomas.

Twelve cases of ovarian adenocarcinoma were studied for alterations in proto-oncogenes, and a unique pattern of altered ras proto-oncogenes was observed. Amplification of ras-Ki was found in three of seven ovarian tumors and amplification of ras-Ha in one of 12. In contrast, ras-Ha amplification was not found in any of the 334 other tumors and ras-Ki amplification was only seen in breast cancer at a frequency of 3%. Other proto-oncogenes altered in ovarian adenocarcinomas included c-myc and c-erbb-2. Proto-oncogene abnormalities were more frequent in aggressive tumors of high histologic grade.

Adenocarcinoma↗

AIDS and common sense.

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Acquired Immunodeficiency Syndrome↗

The molecular heterogeneity of nonspecific cross-reacting antigen synthesized by tumor cells and granulocytes.

The molecular heterogeneity of nonspecific cross-reacting antigen (NCA) was examined. Metabolically-labeled glycoproteins were precipitated from cell lysates of human tumor cell lines and of normal peripheral granulocytes with antibodies specific for NCA, and analyzed by SDS-PAGE. NCA components synthesized by three tumor cell lines, QGP-1 (pancreas), HLC-1 (lung) and CAOV-2 (ovary) showed slightly different migration patterns on SDS-PAGE, but the molecular weights of their unglycosylated peptides synthesized in the presence of tunicamycin were all found to be 35K. On the other hand, two molecular species of NCA were identified in normal granulocytes: an 80K mature form derived from a 69K precursor peptide and a 58K mature form from a 41K precursor peptide. Upon SDS-PAGE, the migration pattern of the unglycosylated NCA peptides from tumor cells was affected by the presence of 2-mercaptoethanol, while that of the peptides of granulocytes was not. All the NCAs identified in this study possessed antigenic determinants common to carcinoembryonic antigen as well as those unique to NCA. These results suggest that the molecular heterogeneity of NCA observed thus far resulted from diverse glycosylation of the three fundamental molecular forms of unglycosylated peptides: one with a molecular weight of 35K produced by tumor cells and two with molecular weights of 69K and 41K produced by granulocytes.

Antigens↗