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Biomedical subjects

M Hirst

Publications and source records attributed to M Hirst.

At least 37 records · Page 2Linked to original sources

The role and self-perceived training needs of nurses employed in general practice: observations from a national census of practice nurses in England and Wales.

This paper outlines the results of a national census of practice nurses in England and Wales. It not only shows that the numbers of practice nurses have increased dramatically in recent years but also demonstrates how their role has evolved. Many practice nurses are now involved in health promotion, and home visiting, as well as advice and counselling. The findings also indicate that many practice nurses express a need for training. Continuing education for practice nurses is important in ensuring practice nurses are fully qualified and trained for the tasks they undertake. In addition, it also enables them to develop their role and work alongside other community health professionals.

Adult↗

Recombination between genetically modified and unmodified Autographa californica nuclear polyhedrosis virus in Trichoplusia ni larvae.

Trichoplusia ni larvae have been injected with a mixture of wild-type Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) and a mutant derivative, AcRP8.UW1.lacZ, which lacks the polyhedrin gene, and has the p10 gene replaced by the Escherichia coli beta-galactosidase gene. Following plaque assay of the haemolymph and subsequent staining for beta-galactosidase activity and scoring for polyhedra, recombinant plaques were identified and the recombination frequency estimated as 6.6%.

Animals↗

Construction of an improved baculovirus insecticide containing an insect-specific toxin gene.

Baculoviruses provide alternatives to chemicals for controlling insect pests and can be applied by spraying. Baculoviruses have a limited host range, but work relatively slowly. They are dissolved in the midgut of insect larvae to release infectious virions which enter gut epithelial cells and begin to replicate. Replication in other organs causes extensive tissue damage and eventually death. This process can take 4-5 days, but in the field may last for more than a week, allowing the larvae to feed for longer and thereby damaging the host plant. Baculovirus expression vectors expressing foreign genes, such as those for insect-specific toxins, hormones or enzymes, might alleviate this problem. We have now constructed a recombinant baculovirus derived from Autographa californica nuclear polyhedrosis virus containing an insect-specific neurotoxin from the venom of the North African (Algerian) scorpion, Androctonus australis Hector. The neurotoxin acts by causing specific modifications to the Na+ conductance of neurons, producing a presynaptic excitatory effect leading to paralysis and death; it has no effect in mice. Expression of the neurotoxin by the virus causes a reduction in the time required to kill the host insect.

Amino Acid Sequence↗

Dissolution and reconstitution of families with a disabled young person.

Cross-sectional data on a large, nationally representative sample of disabled young people were obtained by personal interview. A comparative survey of young people in the general population, matched for age and location, was also conducted. The findings suggest that families with a disabled young person are just as likely as families in the general population to have both natural parents present. Where their natural parents were living apart, disabled young people were no more likely to be living in one-parent families than young people generally. There was no firm evidence that the presence, type and degree of disability in young people increased the risk of family dissolution or reduced the possibilities for reconstitution.

Adolescent↗

Text telecommunication for people who are deaf: assessing the use of a text-relay service.

This study investigated the pattern and frequency of telephone use by people with a profound or severe hearing impairment. The main purpose was to assess the benefits of text telecommunication for making calls by typing rather than speaking and listening. Data on 169 adults were obtained by personal interview. The sample was stratified between subscribers to an experimental text-relay service and non-subscribers: a minority of respondents in both groups used a text telephone for direct telecommunication. Access to the relay service increased independent use of the telephone significantly above that of other respondents, whether for social contact, conducting personal business, or in paid work. The text-relay service was less than satisfactory for urgent calls and apparently did not encourage reciprocal contact. Nearly all respondents, subscribers and non-subscribers alike, relied on other people making or receiving calls on their behalf via an ordinary telephone. Direct text telecommunication was as important as the text-relay service for social contact, especially with friends. The costs of telephone text equipment were substantially more than those normally incurred by hearing people. The implications for improving deaf people's access to the telephone are discussed.

Deafness↗

Hormone-free mouse glucocorticoid receptors overexpressed in Chinese hamster ovary cells are localized to the nucleus and are associated with both hsp70 and hsp90.

In this work, we examine the cellular localization and protein interactions of mouse glucocorticoid receptors that have been overexpressed in Chinese hamster ovary (CHO) cells (Hirst, M. A., Northrop, J. P., Danielsen, M., and Ringold, G. M. (1990) Mol. Endocrinol. 4, 162-170). We demonstrate that wild-type unliganded mouse glucocorticoid receptor, which is expressed in CHO cells to a level approximately 10 times that of L cells, is localized entirely to the nucleus by indirect immunofluorescence with the BuGR antireceptor monoclonal antibody. Overexpressed receptors that have either no hormone binding activity or no DNA binding activity because of point mutations also localize to the nucleus, providing genetic proof that the nuclear localization cannot reflect a steroid-mediated shift of the receptor from the cytoplasm to the nucleus and that DNA binding activity is not required for nuclear localization. Like unliganded progesterone receptors, which also associate in a loosely bound "docking" complex with the nucleus, the mouse glucocorticoid receptor overexpressed in CHO cells is associated with both hsp90 and hsp70. This is in contrast to the untransformed mouse glucocorticoid receptor in L cell cytosol, which is associated with hsp90 but not hsp70. The difference in hsp70 association between cell types could reflect overexpression of the receptor in CHO cells. However, like receptors in CHO cells selected for very high levels of overexpression, receptors in CHO cells selected for an intermediate level of receptor expression that is comparable to that of L cells are also bound to hsp70. This observation argues against an explanation of hsp70 association based purely on receptor overexpression, and we speculate that association of the unliganded glucocorticoid receptor with hsp70 might be a consequence of its nuclear localization in the CHO cells. Although there are differences between the mouse receptor in CHO cells and L cells, the nuclear localization signal of the untransformed mouse receptor reacts equivalently with the AP64 antibody against NL1 in cytosols prepared from both cell types.

Animals↗

Suppression of ethanol-induced cardiac hypertrophy by beta-adrenoceptor blockade.

The effects of D,L-propranolol and its resolved epimers on cardiac size in rats given ethanol, or a control diet containing maltose-dextrin, every 8 h by gavage, for 48 h were assessed. Co-treatment with ethanol plus saline for 48 h resulted in increases of approximately 10% in wet and dry heart weights, and in their proportional measures (g/kg body wt). Cardiac protein content was increased similarly. Administration of D,L-propranolol (10, 20 mg/kg), or L-propranolol (5, 10, 20 mg/kg), suppressed the increases in response to ethanol, D-Propranolol (10, 20 mg/kg) was ineffective in attenuating ethanol-induced increases in heart weights and protein content. Values of total cardiac DNA and fractional water content were unaffected by any of the treatments. Adrenaline and noradrenaline levels in urine were elevated during 48 h of intoxication in all rats given ethanol. The results suggest that severe, subacute intoxication with ethanol induces cardiac hypertrophy. Further, the data implies that the hypertrophy is mediated through activation of cardiac beta-adrenoceptors.

Adrenergic beta-Antagonists↗

Construction of genetically engineered baculovirus insecticides containing the Bacillus thuringiensis subsp. kurstaki HD-73 delta endotoxin.

The delta-endotoxin gene from Bacillus thuringiensis subsp. kurstaki HD-73 was inserted into Autographa californica nuclear polyhedrosis virus (AcMNPV) using two transfer vector systems. In the first, the delta-endotoxin gene was placed under the control of the polyhedrin gene promoter in lieu of the polyhedrin coding sequences, thus deriving a polyhedrin-negative virus. In the second, it was inserted under the control of a copy of the AcMNPV p10 promoter positioned upstream of the polyhedrin gene to produce a polyhedrin-positive virus. Analysis of infected cell extracts showed that the delta-endotoxin was expressed in insect cells as 130K, 62K and 44K proteins, with peak syntheses at 18 h post-infection. Each of these products reacted with antisera specific for the complete protoxin and the cleaved, active form. When extracts from the cells infected with the polyhedrin-negative virus were fed to Trichoplusia ni larvae, feeding by the insects was inhibited and deaths occurred that were inconsistent with virus infection. This effect was also observed after the inoculum had been treated with detergents to inactivate virus particles prior to feeding to the larvae. These data indicate that the expression of the B. thuringiensis delta-endotoxin gene by a baculovirus in insect cells produces material with insecticidal activity. The biological activities of the two recombinant viruses were assessed in conventional bioassay tests by feeding virus particles or occlusion bodies to the insects. The polyhedrin-negative virus preparation appeared to be contaminated with endotoxin which inhibited feeding of the insects and prevented determination of the LD50 value. The polyhedrin-positive virus had an LD50 value about twofold higher than that of unmodified AcMNPV. The significance of these data for the genetic engineering of virus insecticides is discussed.

Animals↗

Metoprolol suppresses the development of ethanol-induced cardiac hypertrophy in the rat.

Subacute, severe intoxication with ethanol stimulates the peripheral sympathetic nervous system in the rat and enhances the excretion of adrenaline and noradrenaline. In association with this effect there is a rapid development of cardiac hypertrophy, with proportional heart weight increasing by 12% within 48 h. At this time adrenal medullary adrenaline content was depressed by more than 35%, whereas nonadrenaline content of the adrenal and heart were not affected. Metoprolol (20 mg/kg, t.i.d.) was without effect when used alone and had little if any impact on the ethanol-induced changes. Metoprolol (100 mg/kg, t.i.d.) reduced adrenal catecholamine content, but not cardiac noradrenaline content, and diminished cardiac weight in control animals. The combination of ethanol with the high dose of methoprolol enhanced the loss of medullary catecholamine and reduced cardiac noradrenaline content, whereas cardiac weight was the same as in control animals. A correlation between sympathetic activation and increasing cardiac mass and its antagonism by metoprolol implies a beta-adrenoceptor mediated link in the cardiac hypertrophy induced by ethanol.

Adrenal Glands↗

Patterns of impairment and disability related to social handicap in young people with cerebral palsy and spina bifida.

This paper explores the inter-relationships between impairment and disability in a sample of 119 teenagers in relation to their psychological adjustment and quality of social life. Poor psychological adjustment and extreme social isolation are associated not so much with individual functional limitations as with particular configurations of impairments and disabilities. It seems that social handicap is not a direct consequence of any impairment or disability but arises generally from severe functional loss and is shaped by dependency on others, restricted choices, physical barriers and adverse reactions of others.

Activities of Daily Living↗

Lack of cardiac alpha 1-adrenoceptor involvement in ethanol-induced cardiac hypertrophy.

The development of cardiac hypertrophy was examined in rats given ethanol in a nutritionally adequate, liquid diet mixture, by intubation, in severely intoxicating doses at 8-h intervals for up to 96 h, alone or in combination with prazosin. Other groups of rats received isocalorically paired quantities of maltose-dextrin. Adrenal glands of rats receiving ethanol were larger than those from control animals. Prazosin did not affect this measure. In contrast, concurrent treatment with prazosin enhanced the loss of medullary catecholamines and noradrenaline from hearts of rats given ethanol, while it had no such effects in controls. Reflecting these changes, excreted quantities of catecholamines were markedly increased in rats given ethanol and prazosin. Hearts of animals given the combined treatment of ethanol and prazosin showed cardiomegaly at 24 h, when there was an increase of about 20% in proportional heart weight, an increase that persisted through the remaining 3 days of the study. At 48 h, hearts of animals given prazosin and ethanol were heavier than those given ethanol alone. A significant correlation between catecholamine excretion and the development of cardiac hypertrophy was identified. The results of the study show that prazosin can enhance effects of ethanol on the peripheral sympathetic nervous system. Moreover, the results suggest that postsynaptic alpha 1-adrenoceptor stimulation in the heart is not an important contributor to ethanol-induced cardiomegaly.

Adrenal Glands↗

Esthesiometric evaluations of corneal anesthesia and prolonged analgesia in rabbits.

Esthesiometry was used to evaluate prolonged corneal analgesia, induced by repeated intramuscular injections in New Zealand White rabbits of 2.3 to 4.9 kg body weight of two analgesics: meperidine (10 mg/kg) or buprenorphine (200 micrograms/kg) following short term anesthesia induced by ketamine (35 mg/kg) and xylazine (5 mg/kg). The surface pressure was calculated, using data supplied by the manufacturer, for the fiber length just sufficient to elicit the corneal reflex. Thus the corneal reflex was used as a proxy for pain. For the 12 injections of meperidine, at 2 hr intervals, the surface pressure peaked one hour after each injection of meperidine, and subsequently declined at the next hour when the injection was repeated resulting in a saw-tooth pattern of responsiveness. For the 5 injections of buprenorphine, at 5 hr intervals, the surface pressure to elicit the corneal reflex rose after a second injection to overlap the pressures generated by meperidine. The consistent analgesia continued until after 24 hours. Accordingly long-term analgesia may be conveniently measured using a quantitative technique, esthesiometry. Comparison of the two regimens suggests buprenorphine is preferred over meperidine in experiments that require sustained analgesic coverage for periods of 24 hours.

Analgesia↗

Detection of enkephalin-like immunoreactive material in human saliva.

1. A specific radioimmunoassay (RIA) was used to detect the presence of enkephalin-like activity in mixed saliva from healthy male and female human subjects, whose ages ranged from 20 to 30 and from 55 to 65 years. 2. Enkephalin-like immunoreactivity was measured in saliva from all subjects. Within the limits posed by the immunoassay no significant differences in levels were evident among the various groups. 3. The results of this study provide the first demonstration of opioid-like substances in saliva. 4. As the collection of saliva involves non-invasive techniques, this source may prove useful for monitoring enkephalin levels during various clinical procedures or experimental treatments.

Adult↗

Salt-induced activation of 1,25-dihydroxyvitamin D3 receptors to a DNA binding form.

In this report we examine the DNA-cellulose binding and sedimentation properties of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) receptors from rat intestine and cultured human mammary cancer cells (MCF-7) extracted in nonactivating (low salt) buffers. Receptors prepared in hypotonic buffer had low DNA binding (13%) compared to receptors extracted with 0.3 M KCl (50%). Treatment of low salt receptor preparations with KCl significantly increased (approximately 3-fold) DNA-binding (activation), demonstrating that receptors can be "activated" in vitro. Activated receptors eluted from DNA-cellulose at 0.18 M KCl. Sedimentation analysis followed by DNA-cellulose binding indicated that activated receptors are approximately 3.2 S and unactivated receptors 5.5 S in size. These results suggest that dissociation of an aggregated moiety may lead to receptor activation. Treatment of unactivated receptor with RNase did not alter DNA binding or sedimentation properties of the aggregated receptor. Treatment of unactivated receptor complexes with heat did not increase DNA binding, and molybdate did not block subsequent salt activation. In summary these results suggest that 1,25(OH)2D3 receptors undergo a salt-induced activation step similar to that described for other steroid receptor systems. However, 1,25(OH)2D3 receptors differ from other steroid receptors in not exhibiting heat activation nor having salt activation blocked by molybdate.

Animals↗

Opioid involvement in the control of feeding in an insect, the American cockroach.

Administration of the kappa opiate agonist, U-50,488H (0.10-10 mg/kg), produced over three hours a significant dose-dependent increase in the ingestive responses of free feeding American cockroaches, Periplaneta americana. These effects could be decreased by the opiate antagonist, naloxone (1.0 mg/kg), with naloxone by itself blocking the augmented feeding responses of food-deprived cockroaches. The mu opiate agonist, morphine (1.0-20 mg/kg) caused a significant dose-dependent and naloxone-reversible increase in the locomotory activity of cockroaches. These results suggest that opioid systems may be involved in the control of the feeding in cockroaches in a manner analogous to that proposed for vertebrates.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Ethanol-induced cardiac hypertrophy: effects of peripheral sympathectomy.

The development of cardiac hypertrophy was examined in rats that had undergone sympathectomy with 6-hydroxydopamine. After 4 days, the rats were given severely intoxicating doses of ethanol or isocalorically paired quantities of maltose-dextrin by intubation at 8-h intervals up to 48 h. The ethanol and sugar intubations were applied in a nutritionally adequate, liquid diet mix. The extent of the peripheral sympathectomy was evident from the absence of detectable quantities of noradrenaline in hearts of animals injected with the neurotoxin and in the reduced levels of excreted noradrenaline. The adrenal medullary catecholamine contents of sympathectomized rats were unchanged in the absence of ethanol; there were reduced quantities of adrenaline in the medullae of rats given ethanol. The adrenal glands of rats given ethanol were larger than those from control animals. Urine samples from sympathectomized and control rats, given ethanol, displayed equivalent increases in excreted adrenaline and noradrenaline. Increases in relative cardiac weight were evident in hearts from sympathectomized animals after 4 days of sympathectomy, and this change reached significance in the hearts from 6-hydroxydopamine-treated rats after a further 2 days on the control diet. Hearts from animals exposed to ethanol showed a marked, rapid development of cardiomegaly; after 24 h there was an increased mass of some 17%, which was sustained over the remaining 24-h period. The proportion of cardiac protein did not differ in the large hearts from ethanol-treated animals and those from their controls, hence myocardial oedema could not account for the increase in weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗