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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

At least 361 records · Page 20Linked to original sources
PubMed1988

Mutant but not normal p21 ras elevates inositol phospholipid breakdown in two different cell systems.

Expression of oncogenic mutant p21 ras either in stably transformed NIH3T3 fibroblasts or transiently in COS-1 cells elevates the basal rate of inositol phosphate production. Additional mutations in the effector region or the carboxy terminal region which abolish transforming capacity on NIH3T3 cells block the effect of oncogenic mutant p21 ras on basal rates. Overexpression of normal (Gly12) p21 ras has no such effect on this second messenger signalling system. These differences between overexpressed normal p21 ras and oncogenic mutant p21 ras strongly suggest that the increased basal rate of inositol phosphate production is a direct consequence of constitutively activated p21 ras activity.

Cell Line↗
PubMed1987

Activated N-ras controls the transformed phenotype of HT1080 human fibrosarcoma cells.

To investigate whether the activated N-ras oncogene of HT1080 human fibrosarcoma cells contributes to the expression of the transformed phenotype, we have isolated flat revertants. In two independent revertant lines, an increase in chromosomal ploidy occurred without a concomitant increase in the number of copies of the N-ras transforming allele. Immunoprecipitation confirms that the level of the mutant N-ras p21 gene product in the revertants is correspondingly lower than in HT1080. Analysis of sporadic tumors derived from the revertant cells reveals an increased dosage of the transforming allele. The revertants also retransform after transfection of cloned activated ras oncogenes. These results imply direct participation of an N-ras oncogene in maintaining the transformed phenotype of a human tumor cell line.

Alleles↗
PubMed1987

Reduced levels of drug-induced DNA cross-linking in nitrogen mustard-resistant Chinese hamster ovary cells expressing elevated glutathione S-transferase activity.

We have reported previously (C. N. Robson et al., Cancer Res., 46: 6290-6294, 1986) the isolation of a Chinese hamster ovary cell line, designated CHO-Chlr, that exhibits resistance to bifunctional nitrogen mustards while maintaining the normal parental level of sensitivity to several other alkylating agents. We have compared the rate of formation and repair of DNA cross-links induced by mechlorethamine in CHO-Chlr and parental CHO-K1 cells, both in intact cells and in isolated nuclei. Equimolar doses of mechlorethamine induce significantly fewer DNA interstrand cross-links in CHO-Chlr cells than in CHO-K1 cells, but levels of DNA-protein adducts are approximately equivalent in the two lines. There is a correlation between the relative resistance of CHO-Chlr cells to mechlorethamine (34-fold) and the amount of drug required to induce approximately equal numbers of DNA interstrand cross-links in the two cell lines. This strongly implicates DNA-DNA adducts in the cytotoxic action of mechlorethamine. DNA cross-linking studies on isolated nuclei reveal only minor differences between the two lines even with identical drug treatments. The rate of cross-link repair is comparable in the two cell lines. These results, taken together with our earlier observation that the rate of drug accumulation is identical in these two lines, suggest that enhanced cytoplasmic drug detoxification is the underlying resistance mechanism in CHO-Chlr cells. We have measured cellular glutathione S-transferase activity, using both the general substrate 1-chloro-2,4-dinitrobenzene, and substrates with some specificity for the different classes of transferase isoenzymes. Total enzyme activity (as measured with 1-chloro-2,4-dinitrobenzene) is elevated 3-fold in the resistant cells. A 2- and 5-fold increase, respectively, in activity against ethacrynic acid and cumene hydroperoxide is detectable in CHO-Chlr cells. This elevation in catalytic activity in the resistant cells is reflected in higher levels of both the Yf- and Ya-type transferase subunits.

Animals↗
PubMed1987

Interaction of the human insulin receptor with the ras oncogene product p21.

Autophosphorylation of the purified human insulin receptor tyrosyl kinase was found to be inhibited by the ras oncogene product p21 in a concentration- and GDP-dependent manner. GDP-beta-S but not Gpp(NH)p could substitute for GDP in eliciting the ras-dependent inhibition. The inhibition was seen with both normal or mutant (Lys-61) p21N-ras and normal or mutant (Val-12) p21Ha-ras. Inhibition occurred at 23 degrees C but not 4 degrees C and was unaffected by the presence or absence of insulin although insulin stimulated the autophosphorylation rate of the receptor beta-subunit some 2-fold. The insulin receptor did not phosphorylate native p21Ha-ras in the presence or absence of added guanine nucleotide. After denaturation of p21Ha-ras with urea it became a substrate, but then failed to inhibit receptor autophosphorylation even in the presence of added GDP.

GTP-Binding Proteins↗
PubMed1987

Who gets committed?

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Commitment of Persons with Psychiatric Disorders↗
PubMed1987

Unpredictable cold-immobilization stress effects on voluntary ethanol consumption in rats.

The effects of exposure to a schedule of unpredictable cold-immobilization stress on voluntary ethanol consumption were examined. Following testing for ethanol preference, rats were divided into high, medium and low ethanol consuming groups on the basis of daily ethanol intake (g/kg/day) and exposed to immobilization stress over an 18 day period. Voluntary ethanol consumption was monitored during the stress period and for an additional 36 days post-stress. Results indicated a differential effect of stress on ethanol intake in that low ethanol consuming rats increased their ethanol intake during the stress period and maintained this increase throughout the entire post-stress period as compared to non-stressed controls. High ethanol consuming groups demonstrated a small (marginally significant) decrease in ethanol intake during the stress period as compared to baseline levels. No change in ethanol intake was observed for the medium ethanol consuming groups. The results suggest that unpredictable immobilization stress has a differential effect on ethanol intake depending upon pre-stress levels of ethanol consumption.

Alcohol Drinking↗
PubMed1987

Hox-1.6: a mouse homeo-box-containing gene member of the Hox-1 complex.

Hox-1.6, a mouse homeo-box-containing gene member of the Hox-1 complex, is described. The Hox-1.6 homeo-box shows more divergence than the other members of the complex with the Drosophila Antennapedia-like homeo-box class. This previously undescribed gene was studied with respect to its transcription pattern and was found to be expressed during mouse fetal development in an intestine-specific manner in adults, and in tumours or cell types exhibiting early endodermal-like differentiation. The study of embryonic partial Hox-1.6 cDNA clones revealed structural features common to other Drosophila and vertebrate homeo-box-containing genes, but also indicated that Hox-1.6 transcripts might display splicing patterns more complex than those known for other vertebrate homeo-genes. One of these cDNA clones contains a rather short open reading frame which would encode a protein of approximately 14.5 kd. The use of this clone as a probe for S1 nuclease mapping confirmed that different Hox-1.6 transcripts were present both in embryonic total RNA and in embryonal carcinoma cell cytoplasmic RNA. These various transcripts are probably generated by an alternative splicing mechanism and may thus encode a set of related proteins.

Amino Acid Sequence↗
PubMed1987

Dynamic fatty acylation of p21N-ras.

To study the acylation of p21N-ras with palmitic acid we have used cells which express the human N-ras gene to high levels under control of the steroid-inducible MMTV--LTR promoter. Addition of [3H]palmitate to these cells resulted in detectable incorporation of label into p21N-ras within 5 min, which continued linearly for 30-60 min. Inhibition of protein synthesis for up to 24 h before addition of [3H]palmitate had no effect on acylation of p21N-ras, suggesting that this can occur as a late post-translational event. Acylated p21N-ras with a high SDS--PAGE mobility is found only in the membrane fraction, whereas approximately 50% of the [35S]methionine-labelled p21N-ras is cytoplasmic and has a lower mobility. Conversion of the acylated high mobility form to a deacylated form of slightly lower mobility can be achieved with neutral hydroxylamine, which is known to cleave thioesters. This treatment also results in partial removal of p21N-ras from the membranes. A remarkably high rate of turnover of the palmitate moiety can be demonstrated by pulse--chase studies (t1/2 approximately 20 min in serum-containing medium) which cannot be attributed to protein degradation. The data suggest an active acylation--deacylation cycle for p21N-ras, which may be involved in its proposed function as a signal transducing protein.

Acylation↗
PubMed1987

Partial transformation of mouse fibroblastic and epithelial cell lines with the v-myc oncogene.

To investigate the role of the myc gene in mammalian cell transformation, plasmid constructs containing the v-myc oncogene and a co-selectable G418 resistance marker were introduced into both mouse fibroblasts (NIH-3T3) and bladder epithelial cells (BBN3 and BBN7). After transfection or microinjection of DNA, no transformed foci could be detected on confluent monolayers but, when the cells were cultured under conditions in which individual cells were allowed to grow and form colonies, morphological transformation was observed. Unlike ras-transformed NIH-3T3 cells, v-myc-transformed cells were unable to grow in serum-free medium and therefore still required exogenous growth factors. v-myc-transformed NIH-3T3 cells were poor at forming foci when co-cultivated with untransformed cells; however, the efficiencies could be increased by addition of EGF to the medium. Both v-myc-transformed fibroblasts and epithelial cells acquired the ability to grow in soft agar, though at efficiencies lower than the corresponding ras transformants. Subcutaneous inoculation of v-myc-transformed NIH-3T3 cells into nude mice resulted in no tumours within 6 weeks. After protracted periods (2-3 months) a few tumours were detected, but at a frequency barely above that for spontaneous tumour formation. Epithelial cells transformed by v-myc were either non-tumorigenic or gave a very low incidence of tumours. We conclude that the v-myc oncogene induces morphological changes and anchorage independence in immortal mouse fibroblasts and epithelial cell lines but further events are required for the cells to become tumorigenic.

Animals↗
PubMed1987

Early weaning effects on voluntary ethanol consumption and stress responsivity in rats.

The present study examined the effect of early maternal deprivation (early weaning) on voluntary ethanol consumption and responses to cold-immobilization stress in adult rats. Rats were weaned at 16 and 21 days of age and housed individually with food and water ad lib until they reached 190 +/- 5 g at which time half of the animals from each group were exposed to increasing concentrations (3 to 9%) of ethanol in a free choice with water every alternate day. Following acquisition of ethanol drinking, animals were provided with water and ethanol (9%) daily for eight days. At the end of this period, animals were divided into stressed and non-stressed groups. Stressed animals were exposed to cold immobilization stress for 3 hr. Results showed that the early-weaned animals consumed significantly more ethanol as compared to normal-weaned animals. Stomach pathology data revealed little ulcer formation in water-only groups. However, normal-weaned/ethanol-exposed animals exhibited significantly more severe ulcers when compared to all other water- or ethanol-exposed groups. We suggest that early maternal deprivation may predispose animals to increased ethanol consumption as adults. Stress ulcer susceptibility in these animals was likely influenced by interactions among the effects of early weaning, ethanol intake and handling and needs further clarification.

Alcohol Drinking↗
PubMed1987

Biochemical and biological properties of the human N-ras p21 protein.

We characterized the normal (Gly-12) and two mutant (Asp-12 and Val-12) forms of human N-ras proteins produced by Escherichia coli. No significant differences were found between normal and mutant p21 proteins in their affinities for GTP or GDP. Examination of GTPase activities revealed significant differences between the mutant p21s: the Val-12 mutant retained 12% of wild-type GTPase activity, whereas the Asp-12 mutant retained 43%. Both mutant proteins, however, were equally potent in causing morphological transformation and increased cell motility after their microinjection into quiescent NIH 3T3 cells. This lack of correlation between transforming potency and GTPase activity or guanine nucleotide binding suggests that position 12 mutations affect other aspects of p21 function.

Animals↗
PubMed1987

Brief psychotherapy in the treatment of anorexia nervosa. Outcome at one year.

Thirty out-patients with severe anorexia nervosa were randomly allocated to either 12 sessions of dietary advice or 12 sessions of combined individual and family psychotherapy. At one-year follow-up both groups showed significant overall improvement, and the dietary advice group showed significant weight gain. A similar mean weight gain for the psychotherapy patients did not reach statistical significance, but this group made significant improvements in sexual and social adjustment.

Adolescent↗
PubMed1987

The effect of state regulations on the quality and sale of insurance policies to Medicare beneficiaries.

This paper examines the effects of state regulations on the quality of insurance policies sold to Medicare beneficiaries and on the amount of sales abuse reported in the sale of such policies. State regulations regarding such policies relate to policy content and format, minimum rates of return, sale of these policies related to disclosure requirements, consumer information activities, and penalties for agent and company abuse. This paper examines the impact of specific regulations on the ratio of the expected policy benefits per premium dollars and on the number and kind of abusive sales practices reported by purchasers and nonpurchasers in agent and mail sales. The study finds that loss ratio floors, minimum benefit standards, and the development of states of consumer information guides for prospective policyholders have a positive impact on the quality of the policies purchased. In addition, the study finds that the amount of abuse reported is less when insurance companies routinely issue press releases concerning agent or company misrepresentation and when consumer guides are developed and available from the state.

Aged↗
PubMed1987

The place of family therapy in the treatment of anorexia nervosa.

There has been widespread, uncritical support for family therapy as the treatment of choice for all anorexia nervosa patients since Minuchin's report in 1976, but recent research has not been able to validate Minuchin's theories about the functioning of anorexia nervosa families. In the only controlled trial to date, the efficacy of family therapy was found to be superior to that of individual therapy, but only in younger patients. Selection factors for family therapy in the treatment of anorexia nervosa are illustrated by a report on 23 consecutive referrals to an eating disorder clinic. Although knowledge of the patient's family was an essential part of the assessment for all patients, and nuclear family sessions were considered to be highly desirable for all patients, in only six instances was nuclear family therapy a major component of treatment. These patients were mainly younger, had a recent onset of illness and lived in an intact nuclear family with co-operative parents.

Adolescent↗