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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

At least 343 records · Page 19Linked to original sources

A study to compare the healing of a Plasma-TFE synthetic artery in the dog.

The physiochemical and healing characteristics of the Plasma-TFE synthetic artery (Atrium Medical Corp., Amherst, NH) were studied and compared to a similarly constructed polyethylene terephthalate graft without Plasma-TFE treatment. Plasma-TFE treatment is a method of coating a graft's surface with tetrafluoroethylene and was found to alter significantly the surface chemistry and energy of the graft. However, results of this study suggested that Plasma-TFE treatment had no effect on tissue penetration and neointima formation after implantation into the abdominal aorta of the dog for 8 weeks.

Animals↗

Scrape-loading of Swiss 3T3 cells with ras protein rapidly activates protein kinase C in the absence of phosphoinositide hydrolysis.

Scrape-loading has been used to analyse the biochemical function of purified p21ras protein. We have shown that scrape-loading oncogenic p21ras into quiescent Swiss 3T3 cells causes morphological transformation of 90% of the cell population within 15 h. Since large numbers of cells can be loaded with p21ras, early induced biochemical changes can be analysed. In this way we have shown that oncogenic p21ras causes rapid activation of protein kinase C five minutes after introduction of protein, but that ras protein fails to stimulate measurable inositol phosphate formation. It appears, therefore, that the stimulation of protein kinase C activity is due to a ras induced increase in diacylglycerol from a source other than inositol phospholipids. Efficient stimulation of DNA synthesis by oncogenic p21ras only occurs in the presence of insulin. This stimulation of DNA synthesis by ras is absolutely dependent on functional protein kinase C activity.

Cycloheximide↗

Warts.

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Humans↗

Kinetic analysis of the hydrolysis of GTP by p21N-ras. The basal GTPase mechanism.

The rate constants have been determined for elementary steps in the basal GTPase mechanism of normal p21N-ras (Gly-12) and an oncogenic mutant (Asp-12): namely GTP binding, hydrolysis, phosphate release, and GDP release. By extrapolation from data at lower temperatures, the GTP association rate constant at 37 degrees C is 1.4 x 10(8) M-1 s-1 for the normal protein and 4.8 x 10(8) M-1 s-1 for the mutant. Other rate constants were measured directly at 37 degrees C, and three processes have similar slow values. GTP dissociation is at 1.0 x 10(-4) s-1 (normal) and 5.0 x 10(-4) s-1 (mutant). The hydrolysis step is at 3.4 x 10(-4) s-1 (normal) and 1.5 x 10(-4) s-1 (mutant). GDP dissociates at 4.2 x 10(-4) s-1 (normal) and 2.0 x 10(-4) s-1 (mutant). GDP association rate constants are similar to those for GTP, 0.5 x 10(8) M-1 s-1 for normal and 0.7 x 10(8) M-1 s-1 for mutant. Both hydrolysis and GDP release therefore contribute to rate limitation of the basal GTPase activity. There are distinct differences (up to 5-fold) between rate constants for the normal and mutant proteins at a number of steps. The values are consistent with the reduced GTPase activity for this mutant and suggest little difference between normal and mutant proteins in the relative steady-state concentrations of GTP and GDP complexes that may represent active and inactive states. The results are discussed in terms of the likely role of p21ras in transmembrane signalling.

Escherichia coli↗

All three human ras genes are expressed in a wide range of tissues.

We examined the expression of the ras gene family (Ha-ras, Ki-ras, N-ras) in human fetal tissues (14 week) and in several human tumor cell lines. Dot blot hybridization showed that the three ras genes were expressed in all of the samples analysed, with a range of expression between 10 and 180 molecules/cell. There was no correlation between levels of expression of ras genes and the type of ras gene activated in different tumor types.

Embryo, Mammalian↗

The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product.

About 30% of human tumours contain a mutation in one of the three ras genes leading to the production of p21ras oncoproteins that are thought to make a major contribution to the transformed phenotype of the tumour. The biochemical mode of action of the ras proteins is unknown but as they bind GTP and GDP and have an intrinsic GTPase activity, they may function like regulatory G proteins and control cell proliferation by regulating signal transduction pathways at the plasma membrane. It is assumed that an external signal is detected by a membrane molecule (or detector) that stimulates the conversion of p21.GDP to p21.GTP which then interacts with a target molecule (or effector) to generate an internal signal. Recently a cytoplasmic protein, GAP, has been identified that interacts with the ras proteins, dramatically increasing the GTPase activity of normal p21 but not of the oncoproteins. We report here that GAP appears to interact with p21ras at a site previously identified as the 'effector' site, strongly implicating GAP as the biological target for regulation by p21.

Animals↗

Effects of 4-acetylpyridine on stress ulcer formation in mice.

4-Acetylpyridine, earlier reported by us to be an anticonvulsant, offers long-lasting protection after a single administration against hypothermic restraint stress-induced gastric ulceration in mice. Electroshock convulsions, marginally but not significantly protective against such ulcers themselves, when coupled with 4-acetylpyridine administration fully prevented gastric ulcers from occurring in this murine model of experimentally induced stress.

Animals↗

The factor structure of the eating disorders inventory.

The Eating Disorders Inventory (EDI) is a promising new measure of the cognitive and behavioral characteristics of anorexia nervosa and bulimia, although the replicability of its eight subscales has not been evaluated. Therefore, a factor analysis of the EDI was carried out that used the FACTOREP procedure. The results, using non-patient responses, did not confirm the original eight subscales, but did show three clear and replicable factors to exist. It was suggested that these may be of clinical value as preliminary screening measures or as indices of response to treatment, although further validation would be required to establish their utility.

Adult↗

Actin polymerization and pseudopod extension during amoeboid chemotaxis.

Amoebae of the cellular slime mold Dictyostelium discoideum are an excellent model system for the study of amoeboid chemotaxis. These cells can be studied as a homogeneous population whose response to chemotactic stimulation is sufficiently synchronous to permit the correlation of the changes in cell shape and biochemical events during chemotaxis. Having demonstrated this synchrony of response, we show that actin polymerization occurs in two stages during stimulation with chemoattractants. The assembly of F-actin that peaks between 40 and 60 sec after the onset of stimulation is temporally correlated with the growth of new pseudopods. F-actin, which is assembled by 60 sec after stimulation begins, is localized in the new pseudopods that are extended at this time. Both stages of actin polymerization during chemotactic stimulation involve polymerization at the barbed ends of actin filaments based on the cytochalasin sensitivity of this response. We present a hypothesis in which actin polymerization is one of the major driving forces for pseudopod extension during chemotaxis. The predictions of this model, that localized regulation of actin nucleation activity and actin filament cross-linking must occur, are discussed in the context of current models for signal transduction and of recent information regarding the types of actin-binding proteins that are present in the cell cortex.

Actins↗

Ras (proto)oncogene induces N-linked carbohydrate modification: temporal relationship with induction of invasive potential.

The effect of expression of the ras oncogene on protein glycosylation was studied. VSV G-protein and class I histocompatibility antigens were analysed to monitor ras-mediated changes in glycosylation. Transient expression of the c-Ha-ras oncogene, introduced into NIH 3T3 cells by the DEAE-dextran method, altered protein glycosylation within 25 h of transfection. The same result was obtained after dexamethasone-induced expression of p21-ras in stable NIH 3T3 transfectants containing either an activated Ha-ras oncogene or a normal N-ras proto-oncogene under control of the glucocorticoid-inducible MMTV promoter. The alteration of cell surface carbohydrates, induced by the ras (proto)oncogene and the subsequent acquisition of invasive potential, occurred prior to morphological transformation.

Animals↗

Bleomycin and X-ray-hypersensitive Chinese hamster ovary cell mutants: genetic analysis and cross-resistance to neocarzinostatin.

We have previously reported the isolation of 3 mutants of Chinese hamster ovary cells which exhibit hypersensitivity to bleomycin. 2 mutants were isolated on the basis of bleomycin-sensitivity [designated BLM-1 and BLM-2, Robson et al., Cancer Res., 45 (1985) 5304-5309] and 1 as adriamycin-sensitive [ADR-1, Robson et al., Cancer Res., 47 (1987) 1560-1565]. Because bleomycin generates DNA-strand breaks via a free-radical mechanism, we have studied the survival response of these mutants to a range of drugs which also generate free radicals and consequently DNA-strand breaks. The mutants are all hypersensitive to phleomycin, which differs from bleomycin in being unable to intercalate due to a modified bithiazole moiety. However, BLM-2 cells alone are hypersensitive to pepleomycin, a semi-synthetic bleomycin analogue. In contrast, BLM-1 cells are more sensitive than BLM-2 to streptonigrin (which operates via a hydroquinone intermediate). ADR-1 cells show wild-type resistance to streptonigrin. The results obtained with neocarzinostatin, an antibiotic requiring thiol activation, are unusual in that both BLM-1 and BLM-2 are approximately 3-fold more resistant than parental cells. However, the steady-state intracellular level of the major non-protein thiol, glutathione, is not altered in BLM-1 or BLM-2 cells. ADR-1 cells show essentially wild-type resistance to neocarzinostatin. Analysis of cell hybrids shows that BLM-1 and BLM-2 cells are phenotypically recessive in combination with parental CHO-K1 cells and represent different genetic complementation groups not only from one another, but also from the bleomycin-sensitive mutant xrs-6, isolated on the basis of X-ray sensitivity by Jeggo and Kemp [Mutation Res., 112 (1983) 313-319]. These results indicate that at least 3 gene products are involved in cellular protection against bleomycin toxicity in mammalian cells.

Animals↗

Inhibition of some spontaneous tumors by 4-hexylresorcinol in F344/N rats and B6C3F1 mice.

4-Hexylresorcinol (4-HR) is used as an anthelmintic and antiseptic in human and veterinary medicine. Toxicology and carcinogenesis studies were conducted by administering 4-HR in corn oil by gavage at 0, 62.5, or 125 mg/kg to F344 rats and B6C3F1 mice of each sex for 2 years. The nonneoplastic lesions associated with 4-HR exposure were nephropathy and osteosclerosis in dosed male and female mice. The only evidence of neoplasia associated with 4-HR was marginally increased incidences of adrenal gland pheochromocytomas and harderian gland tumors in male mice. Decreases were observed in the incidences of mononuclear cell leukemia in dosed male and female rats, hepatocellular adenomas or carcinomas in dosed male mice, and circulatory system tumors in high-dose male and female mice. These negative tumor trends in rats and mice, along with an indication of reduced overall incidences of benign and malignant tumors in treated groups compared to controls, suggest that 4-HR may deserve further study as a possible antineoplastic agent.

Animals↗

N-ras-like sequences on chromosomes 9, 6 and 22 with a polymorphism at the chromosome 9 locus.

Two clones, pCN1 and pCN2, which together form full-length cDNA for N-ras, were used to search for restriction fragment length polymorphisms. pCN2, which entirely consists of 3' non-translated sequences, revealed more bands on DNA transfer hybridizations than could be accounted for using the known restriction map of N-ras. None of the extra cross hybridizing sequences is located on chromosome 1. One of these sequences showed a high-frequency two-allele polymorphism with the restriction enzyme TaqI and maps to the short arm of chromosome 9. Of the remaining two sequences, one maps to chromosome 22 and the other maps to the short arm of chromosome 6. pCN1A, which contains the 5' untranslated regions and all the coding exons of N-ras only hybridized to the chromosome 1 site. No polymorphisms have been found for pCN1 with TaqI, MspI, BclI, BglI, EcoRI, BstXI, XbaI, BamHI, BglII or HindIII.

Chromosomes, Human↗

The development of a multi-disciplinary approach to the assessment and management of child sexual abuse in an inner city Health District.

With increasing numbers of child sexual abuse referrals in 1985, professionals in an inner city health district recognised the limitations of existing child abuse guidelines for the sensitive investigation of such cases. A multi-disciplinary working party was set up under the auspices of the District Child Abuse Review Committee to develop more flexible guidelines, particularly for suspected cases. New guidelines were implemented which involved early consultation with a specialist multi-disciplinary team to allow a specific co-ordinated approach for the investigation and management of each case. The guidelines, the cases and the difficulties encountered by the different professionals involved are described.

Child↗