Structural features of growth factor receptors with oncogenic potential.
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Biomedical subjects
Publications and source records attributed to J McGrath.
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A novel potential cell surface receptor of the tyrosine kinase gene family has been identified and characterized by molecular cloning. Its primary sequence is very similar to that of the human epidermal growth factor receptor and the v-erbB oncogene product; the chromosomal location of the gene for this protein is coincident with the neu oncogene, which suggests that the two genes may be identical.
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Intracranial brain abscess was produced in three monkeys by embolization of a small pledget of polyvinyl alcohol (PVA) soaked in a broth of Staphylococcus aureus. Imaging of the chronic stable abscess was performed on the General Electric 8800 CT unit (Milwaukee, Wis.) and a 1.4 T superconducting small bore imaging system. Magnetic resonance imaging included saturation recovery, inversion recovery, and spin echo techniques. MR imaging was also performed after paramagnetic enhancement using gadolinium-DPTA (Gd-DTPA). Our results show that paramagnetic enhancement with T1-weighted imaging adds specificity and enables rapid assessment of abnormalities of the blood-brain barrier. T2-weighted imaging without paramagnetic enhancement was very sensitive in defining areas of abnormality in the brain but in our experiment lacked specificity. T2-weighted imaging with Gd-DTPA demonstrated no obvious change in the appearance of the lesion. The combination of T1-weighted Gd-DTPA and T2-weighted imaging appeared complementary in our experiment, and these images correlated well with the pathologic findings.
More than 90 percent of enucleated one-cell mouse embryos receiving pronuclei from other one-cell embryos successfully develop to the blastocyst stage in vitro. In this investigation, nuclei from successive preimplantation cleavage stages were introduced into enucleated one-cell embryos and the embryos were tested for development in vitro. Although two-cell nuclei supported development to the morula or blastocyst stage, four-cell, eight-cell, and inner cell mass cell nuclei did not. The inability of cell nuclei from these stages to support development reflects rapid loss of totipotency of the transferred nucleus and is not the result of simultaneous transfer of membrane or cytoplasm.
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The effect of short-term intake of LiCl in drinking fluid on NO2 toxicity was studied in mice as a function of mortality and of specific activities of mouse liver alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenases (L-ALDH). Pretreatment with LiCl for 10 days decreased mortality in mice exposed to 60 to 70 PPM NO2 for 6 hr compared to controls. Pretreatment with LiCl for 10 days under continued exposure to 5 PPM NO2 resulted in a decrease in liver weight compared to control. Lithium treated mice exposed to NO2 showed less gain in body weight than the controls treated with LiCl and exposed to air. The latter group showed an induction of mitochondrial but not cytoplasmic L-ALDH and the NO2 exposure did not alter endogenous L-ALDH from corresponding controls. This induction of mitochondrial ALDH was associated with an increase in both Vmax and the apparent Km. Exposure to NO2 for 10 consecutive days resulted in inhibition of cytoplasmic L-ALDH. The data suggest that Li+ antagonized NO2 toxicity. A possible mechanism for reduction of NO2 toxicity by LiCl may be due to Li+ action on stabilizing cell membranes and/or modifying intercellular pulmonary response to NO2 injury.
Transplantation of pronuclei between one-cell-stage embryos was used to construct diploid mouse embryos with two female pronuclei ( biparental gynogenones ) or two male pronuclei ( biparental androgenones ). The ability of these embryos to develop to term was compared with control nuclear-transplant embryos in which the male or the female pronucleus was replaced with an isoparental pronucleus from another embryo. The results show that diploid biparental gynogenetic and androgenetic embryos do not complete normal embryogenesis, whereas control nuclear transplant embryos do. We conclude that the maternal and paternal contributions to the embryonic genome in mammals are not equivalent and that a diploid genome derived from only one of the two parental sexes is incapable of supporting complete embryogenesis.
Gadolinium-DTPA, a paramagnetic contrast agent that distributes throughout the body in a manner similar to diatrizoate, was intravenously administered to a monkey with a hematogenously induced experimental intracranial abscess. Contrast enhanced computed tomography (CT) and gadolinium enhanced saturation-recovery nuclear magnetic resonance (NMR) were both performed immediately and repeated after a 30 min delay. The NMR images revealed marked ring enhancement at a time when CT showed a nodule. Both imaging modalities were analyzed with respect to the pathological specimen. Gadolinium-DTPA may be an effective agent for imaging alterations of the blood-brain barrier.
Nuclear transplantation in the mouse embryo was achieved by using a method that combines microsurgical removal of the zygote pronuclei with the introduction of a donor nucleus by a virus-mediated cell fusion technique. Survival of embryos was greater than 90 per cent in tests of this procedure. The embryos developed to term at a frequency not significantly different from that of nonmanipulated control embryos. Because nuclei and cytoplasm from genetically distinct inbred mouse strains can be efficiently interchanged, this procedure may be useful in characterizing possible cytoplasmic contributions to the embryonic and adult phenotype.
The ability of foreign nuclei to support development in nuclear transplantation manipulations has proven an effective means to assess the consequences of nuclear differentiation. In addition, nuclear transplantation might serve to define the persistence and role of maternally inherited cytoplasmic constituents during embryogenesis. We have extended the use of a technique that enables the efficient transfer of one-cell-stage pronuclei into the cytoplasm of enucleated mouse embryos, and have successfully transferred two-, four-, eight-cell-stage and inner cell mass (ICM) cell nuclei. We have also used this technique as a means to determining that the stage-specific embryonic antigen, SSEA-3, is a cytoplasmic contribution of the unfertilized ovum. The potential value of this technique in determining the developmental capacity of nuclei from various embryonic states, and in determining nuclear/cytoplasmic origins or early embryonic gene products, is discussed.
Secretory IgA, lactoferrin, albumin, and total protein were quantitated in colostrum and milk samples obtained from 215 Ethiopian nursing mothers over a period ranging from 1 day to 2 yr postparturition. IgG, IgM, C3, and C4 complement components were quantitated in 11 day 1 samples. The subjects were classified into three groups: lepromatous leprosy, borderline lepromatous leprosy, and a nonlepromatous group consisting of women with tuberculoid leprosy and healthy controls. Results obtained from the above groups were also compared with a group from Edinburgh. No major variation in levels of secretory IgA, lactoferrin, albumin, and total protein was found between the three groups of Ethiopian women. Results from the Edinburgh group were significantly higher, mainly in the level of total protein. When the individual proteins were expressed as a percentage of the total protein, there was no difference between the milk samples from the Ethiopian and Edinburgh mothers.
The responses of atria isolated from four groups of rats: (a) control (air/H2O) and test animals treated with (b) 5 PPM nitrogen dioxide NO2 for 72 hours, (NO2/H2O), (c) 10% ethanol (ET) in water for 13 days, (air/ET), or (d) combination of NO2 and ET (NO2/ET). Isolated atria were tested with norepinephrine and dose response curves determined. The chronotropic responses among groups were not different. However, there were significant differences when tested with pilocarpine and to lesser extent to increased calcium concentration in the bathing medium. Ethanol and/or NO2 attenuates parasympathetic activity possibly by altering receptor numbers or activity. The changes in calcium activity may result from altered calcium channel activity. This data indicates that acute exposure to NO2, ET and/or the interaction between these agents can alter cardiac activity.
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In vivo, embryos which are homozygous for the t6 mutation die during egg cylinder development (gestation days 5.5--6.5). In vitro, these mutant embryos can be distinguished from their wild-type littermates by their developmental arrest and by the failure of their trophoblast cells to transform to giant cells. We have investigated the nature of this lethality by constructing triploid embryos with varying combinations of the t6 mutant chromosome. The phenotypes of outgrowths from these triploid embryos were examined and compared with the phenotypes of outgrowths from +/+, +/t6, and t6/t6 embryos. The data show 1) that +/t6/t6 embryos are phenotypically wild-type, while t6/t6/t6 embryos are phenotypically mutant and 2) that t6/t6/t6 and t6/t6 embryos are developmentally arrested at the same stage of outgrowth.