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Biomedical subjects

M Hynes

Publications and source records attributed to M Hynes.

At least 37 records · Page 2Linked to original sources
PubMed1996

The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.

The protein Sonic hedgehog (Shh) controls patterning and growth during vertebrate development. Here we demonstrate that it binds Patched (vPtc), which has been identified as a tumour-suppressor protein in basal cell carcinoma, with high affinity. We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened (vSmo), and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly. These findings, combined with available genetic evidence from Drosophila, support the hypothesis that Ptc is a receptor for Shh, and that vSmo could be a signalling component that is linked to Ptc.

Amino Acid Sequence↗
PubMed1995

Control of neuronal diversity by the floor plate: contact-mediated induction of midbrain dopaminergic neurons.

The notochord and floor plate contribute to patterning the ventral neural tube in part by expressing a diffusible factor that induces motoneurons. To determine the mechanisms that direct the development of other classes of ventral neurons, we studied the development of dopaminergic neurons that reside near motoneurons in the ventral midbrain. We provide evidence that dopaminergic neurons develop in the vicinity of the floor plate and that they can be specified by the floor plate in vitro and in vivo. Unlike motoneurons, efficient induction of dopaminergic neurons requires contact with floor plate cells. These results suggest that neuronal diversification along the dorsal-ventral axis may be achieved partly through the concerted action of diffusible and contact-dependent signals from a single organizing center, the floor plate.

Animals↗
PubMed1995

Induction of midbrain dopaminergic neurons by Sonic hedgehog.

Midbrain dopaminergic neurons, whose loss in adults results in Parkinson's disease, can be specified during embryonic development by a contact-dependent signal from floor plate cells. Here we show that the amino-terminal product of Sonic hedgehog autoproteolysis (SHH-N), an inductive signal expressed by floor plate cells, can induce dopaminergic neurons in vitro. We show further that manipulations to increase the activity of cyclic AMP-dependent protein kinase A, which is known to antagonize hedgehog signaling, can block dopaminergic neuron induction by floor plate cells. Our results and those of other studies indicate that SHH-N can function in a dose-dependent manner to induce different cell types within the neural tube. Our results also provide the basis for a potential cell transplantation therapy for Parkinson's disease.

Animals↗
PubMed1992

Public health nursing in Ireland: the general practitioners' view.

Present health policy in Ireland is directed towards a shift in emphasis from the provision of services on a hospital inpatient basis to a community or outpatient basis. This study set out to elicit views of general practitioners (GPs) in relation to the home visiting activities of the nursing services in the community. Of the thirty-five (76%) GPs whose questionnaires were included in the analysis, 88% were satisfied with the quality of nursing services provided by the public health nurse (PHN) but were dissatisfied with access to service (37%), out of hours service (48%) and communication with PHNs (25%). Eight GPs had contact with public health nurses on a weekly basis, 11 had contact monthly and 14 had contact three monthly or less frequently. For chronic conditions requiring dressings, over 70% of GPs refer to the PHN and when given a choice, 25% of GPs would refer these conditions to a registered general nurse (RGN). Care by an RGN or nurses' aide for conditions such as monitoring of vital signs, continence care and administration of enemas, was found acceptable by 50% of GPs. The findings indicate that there is need for review of the structure of the nursing services in the community.

Attitude of Health Personnel↗
PubMed1991

Acquired immunodeficiency syndrome prevention. Knowledge, attitudes, and practices of primary care physicians.

We conducted a telephone survey of a probability sample of 473 internists, family practitioners, general practitioners, and obstetrician-gynecologists in New York City (NY) in 1988 to assess their knowledge, attitudes, and practices with respect to the prevention of the acquired immunodeficiency syndrome (AIDS). Although 71% of the physicians had cared for a patient with AIDS and 90% had been involved in ordering the human immunodeficiency virus antibody test, only about a third of them took appropriate sexual histories of new patients and only about a quarter (28%) counseled new patients about reducing the risk of contracting AIDS. Multivariate analysis revealed that physician knowledge about AIDS prevention was associated with younger age, more positive attitude toward homosexual males and intravenous drug users, confidence that counseling would result in behavioral change among patients, and specialty other than obstetrics-gynecology. Results indicate a need for increased training and education of primary care physicians about AIDS prevention.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Patients 21 days or more in an acute hospital bed: appropriateness of care.

Patients occupying beds for 21 days or more in acute hospitals were studied. Using predetermined objective criteria, the appropriateness of the previous day's hospitalisation was assessed. Barriers to appropriate care and the level of care required were identified in those deemed inappropriate. Of the 421 patients identified, 194 were considered to be inappropriately placed in an acute hospital bed. Patients deemed inappropriate were more likely to be older (p less than 0.05), female (p less than 0.05), have lost a spouse (p less than 0.05), have been admitted through the Accident and Emergency Department (p less than 0.05), and have longer lengths of stay (p less than 0.001) than those considered appropriate. The most frequently identified barrier to appropriate care (N = 143) was that the patient was awaiting another level of care. The level of inappropriate use of acute beds in Dublin is unacceptably high. Additional longstay accommodation especially for geriatric patients is needed. Alternatives to acute hospital care for patients requiring rehabilitation or nursing care should be explored.

Acute Disease↗
PubMed1991

Behavioural risk factors among young adults in small areas with high mortality versus those in low-mortality areas.

A community-based cross-sectional survey of behavioural risk factors for premature mortality was carried out on a group of 354 adults aged 25-44 from previously identified high-mortality 'black-spots' in Dublin who were compared with 333 others from low-mortality areas. In the black-spot areas, 50.9% of respondents were current smokers versus 28.5% in low-mortality areas and 14.6% took 'sufficient' exercise versus 31.4% in low-mortality areas. People living in black spots were also less likely to make 'healthy' dietary choices than those in low-mortality areas. There is a higher prevalence of behavioural risk factors for premature mortality among young adults living in electoral wards/district electoral divisions (DEDs) with high standardized mortality ratios (SMRs) from all causes than among those in areas with low SMRs. A health promotion programme aimed at increasing exercise levels, reducing smoking and encouraging healthy eating should be aimed at young adults in DEDs with high SMRs.

Adult↗
PubMed1990

Complementation of the Aspergillus nidulans arg B1 mutation by ornithine transcarbamylase cDNA from rat liver.

An Aspergillus nidulans strain which is deficient in ornithine transcarbamylase due to the arg B1 mutation was transformed with a plasmid containing the ornithine transcarbamylase cDNA from rat liver under the control of the amd S promoter. Stable transformants were obtained by selection on arginine free medium indicating complementation of the arg B mutation. Proof of expression of the rat enzyme in transformants was obtained by immunoprecipitation of all ornithine transcarbamylase activity from cell extracts with antibodies specific for the rat enzyme. The presence of catalytically active rat ornithine transcarbamylase in the transformants indicated that it is capable of being imported into mitochondria in A. nidulans, proteolytically processed and assembled into its homotrimeric form. In vitro uptake experiments using isolated A. nidulans mitochondria demonstrate that processing of the precursor of rat ornithine transcarbamylase occurs in two temporally separated steps as it does in rat liver mitochondria suggesting evolutionary conservation of the processing machinery. Up to 560 ng of active rat enzyme was produced per gm wet weight mycelia. Use of beta-D-alanine, an inducer of amd S, as sole N-source resulted in increased levels of active rat ornithine transcarbamylase relative to uninduced cultures.

Animals↗
PubMed1989

Regulation of the hepatic transferrin receptor in hereditary hemochromatosis.

The liver is the main site of iron accumulation and pathologic sequelae in hereditary hemochromatosis. Whether this is a result solely of inappropriately increased absorption of iron by the gastrointestinal tract or a more generalized regulatory failure of iron balance is unknown. Using immunohistochemical techniques, we have examined the effects of therapeutic changes in liver iron stores on the expression of the hepatic transferrin receptor in hereditary hemochromatosis. Ten patients with untreated hereditary hemochromatosis had no detectable staining for transferrin receptor in their liver biopsies. All had increased hepatic ferritin (mean = 19.9 micrograms per mg protein, range = 1 to 31.7 micrograms per mg protein) and hepatic iron levels (mean = 36.2 micrograms per mg protein, range = 3.6 to 69.9 micrograms per mg protein). In contrast, hepatocyte transferrin receptor was detected in seven patients in whom hepatic iron stores were markedly depleted by venesection (hepatic ferritin mean = 0.32 microgram per mg protein, range = 0.16 to 0.53 microgram per mg protein; hepatic iron mean = 0.98 microgram per mg protein, range = 0.3 to 2.1 micrograms per mg protein). Sequential data from one patient confirmed the reexpression of receptor in response to therapeutic iron depletion, whereas data from another patient studied during treatment illustrated a reciprocal relationship between liver tissue distribution of iron and expression of transferrin receptor. The finding that appropriate physiologic regulation of the hepatic transferrin receptor operates in hereditary hemochromatosis does not support the concept of a generalized defect in receptor-mediated uptake of transferrin-bound iron.

Antibodies, Monoclonal↗
PubMed1989

Optimizing the immunohistochemical signal from the transferrin receptor in liver tissue.

Cellular expression of the transferrin receptor is determined by the proliferative state and iron requirements of the cell. Previous immunohistochemical studies using a number of anti-(transferrin receptor) monoclonal antibodies confirmed the biochemical evidence that hepatocytes express the receptor, although the distribution shown was patchy with only a small number of cells showing positive staining. In the present study, a number of techniques have been compared to optimize detection of the immunohistochemical signal from the transferrin receptor in human liver tissue. Using an alkaline phosphatase detection system, widespread expression of this receptor with both cytoplasmic and membrane staining was found in all parenchymal and non-parenchymal cells.

Alkaline Phosphatase↗
PubMed1989

Community notification of child sexual abuse.

There has been a heightened awareness of sexual abuse of children in Ireland in the past four years. One-hundred and forty seven cases of alleged sexual abuse notified to the Director of Community Care in 1986-1987 were reviewed retrospectively from the medical and social work notes. In 81 (55%) cases, sexual abuse was either confirmed or strongly suspected and these were analysed further. Victims were twice as likely to come from an urban as from a rural background. Girls were more likely to be abused at all ages, and this was particularly marked in the teenage years. Abusers were either intra-familial or known to the family in most cases. A surprising number were under 16 years of age. The study highlights the time commitment needed to manage this problem in the community and the need to develop services directed towards the young perpetrator. It also raises concern at the sizable percentage of children who, following investigation, are found not to have been abused.

Adolescent↗
PubMed1988

Meta-analysis of the effects of educational and psychosocial interventions on management of diabetes mellitus.

A meta-analysis of the literature of controlled studies of educational and psychosocial interventions in the treatment of diabetes mellitus yielded 93 studies of 7451 patients testing the effects of eight intervention types: (1) didactic education, (2) enhanced education, (3) diet instruction, (4) exercise instruction, (5) self-monitoring instruction, (6) social learning/behavior modification, (7) counseling, and (8) relaxation training. An overall mean effect size (ES) of +0.51 +/- 0.11 was found moderate but significant (P less than 0.05) improvements for all intervention subjects. Physical outcome and knowledge gain were most affected, followed by psychological status and compliance. Diet instruction and social learning interventions showed the strongest (ES = +0.68 +/- 0.58 and ES = +0.57 +/- 0.42, respectively) and relaxation training the weakest (ES = +0.30 +/- 0.74) effects. Associations between study and sample characteristics and mean ES values were explored with type of setting and methodological weaknesses such as single group design and non-random assignment achieving statistical significance. Neither intervention type, number of visits, sex, age, nor type of diabetes were significantly correlated with mean ES values. Implications of these findings for clinical treatment and future research are discussed.

Diabetes Mellitus↗
PubMed1988

Demographics in demographic-economic models: a note on the basic activity-commodity framework.

The authors present a critique of an early basic formulation for the development of demographic-economic models by M. Madden and P. W. J. Batey in 1980. They assert that more attention needs to be paid to the demographic components of these models and that "distinctions between household types must be treated more adequately, and mechanisms for changes in household type must be articulated and refined." A reply by M. Madden (pp. 1,537-42) is included, as well as a response by the authors (pp. 1,543-5).

Demography↗
PubMed1985

Some studies on the metabolism of labelled molybdenum compounds in cattle.

An initial experiment showed that [99Mo]di- and trithiomolybdates could be detected in bovine plasma after the introduction of [99Mo]molybdate into the rumen. It was felt that this justified the use of [99Mo]trithiomolybdate for the subsequent studies made of plasma thiomolybdate metabolism in vivo in cattle. Rapid intravenous injection of [99Mo]trithiomolybdate into cattle showed that doses of 50 mg Mo were subject to extensive hydrolysis over the first few minutes postinjection, but at lower dose rates this was reduced so that tracer doses (less than 1.5 mg Mo) were relatively stable. The plasma metabolism was unaffected by copper status within the limits of the experiments (that is, liver copper levels down to 9 mg/kg d.m.) The disappearance of [99Mo] and [35S]trithiomolybdate (1 mg Mo) from plasma was delayed for up to 10 hr by the immediate preinjection of copper, although no chemical modification of the thiomolybdate appeared to occur.

Animals↗
PubMed1985

Direct action of mazindol on guinea-pig ventromedial hypothalamic neurons: intracellular studies in slice preparation.

Neuronal responses in the ventromedial hypothalamic nucleus (VMH) to mazindol (MZD) were examined by intracellular recordings in hypothalamic slices in vitro. Bath application of MZD caused depolarization of the membrane by 8.0 +/- 3.4 mV (mean +/- S.D.) associated with an increase in the input membrane resistance (23.0 +/- 5.8%) among 20% of the cells examined. Current-voltage plots, obtained simultaneously, showed the reversal potential between -80 and -90 mV. These results indicate that MZD depolarizes VMH neurons by reducing the K+ conductance, through a mechanism similar to that of glucose, and the anorectic action of MZD can be explained by its direct effects on the VMH.

Animals↗
PubMed1984

Some studies on the metabolism and the effects of 99Mo- and 35S-labelled thiomolybdates after intravenous infusion in sheep.

Sheep were infused intravenously with 99Mo- and 35S-labelled tri- and tetrathiomolybdates (1-2 mg Mo). Most of the plasma radioactivity was trichloroacetic acid (TCA)-insoluble after infusion, but the stability of this fraction was reduced by pre-infusion or subsequent infusion with unlabelled thiomolybdates. Most of the 99Mo and 35S was shown to be associated with albumin. It was concluded that compounds bound to albumin were relatively stable, but displaced or unbound thiomolybdates were rapidly hydrolysed to molybdate and sulphate. There was no evidence of an irreversible interaction of either 35S or 99Mo with copper in plasma, despite the appearance of a TCA-insoluble Cu fraction. Increased dietary Cu did not increase the retention of 35S in plasma or affect the exchangeability of 36S-labelled thiomolybdates bound to albumin.

Animals↗
PubMed1983

Cholinergic role in monkey dorsolateral prefrontal cortex during bar-press feeding behavior.

Cholinergic involvement in the neuronal activity of the dorsolateral (DL) prefrontal cortex in the monkey was investigated during bar-press feeding behavior. Iontophoretic application of ACh increased the firing rate of more than half of the cells through muscarinic receptors. Activity of ACh-sensitive cells did not correlate with any particular event during the feeding task. Continuous application of ACh markedly enhanced increases in response to events during the feeding task, and application of an ACh antagonist diminished response levels. This indicates that ACh release may occur during the feeding task and affect cortical cells to improve the signal-to-noise ratio of the excitatory input. Decreased responses to events during the feeding task diminished during ACh application. Driven discharges in the cells were evoked by stimulation of the basal nucleus of Meynert (BNM) where ACh containing cells are localized. This response was specifically blocked by iontophoretic application of atropine. In conclusion, cholinergic inputs arising from the BNM are distributed profusely among the cortical cells and modulate their excitability during bar-press feeding behavior.

Acetylcholine↗