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Biomedical subjects

M J Healy

Publications and source records attributed to M J Healy.

At least 19 recordsLinked to original sources

Molecular analysis of the lethal(1)B214 region at the base of the X chromosome of Drosophila melanogaster.

Approximately 50 kb of genomic DNA was isolated from polytene chromosome bands 19F1 and 2 of Drosophila melanogaster. Bands 19F1 and 2 are in the immediate vicinity of the beta-heterochromatin at the base of the X chromosome and encompass the little fly-like and lethal(1)B214 complementation groups. The cloned DNA consists of an approximately 21 kb stretch of unique or low copy number sequence that is bounded by repetitive elements interspersed with further unique sequences. The presence of repeated sequences is characteristic of regions within and adjacent to beta-heterochromatin. At least part of a tRNA gene cluster is present within the 50 kb of cloned DNA. The cloned region also produces at least 18 discrete size classes of developmentally regulated poly(A)+ RNA species. A 2 kb EcoRI fragment (E10), which lies in the 21 kb stretch of unique sequence, generates seven of these transcripts (of sizes 3.5, 3.35, 2.1, 2.0, 1.5, 1.2 and 1.0 kb) in wild-type flies. However, a small deletion of approximately 75 bp in E10 in a lethal(1)B214 mutant allele is associated with alterations in the production or processing of all seven of these transcripts. These data identify E10 sequences as belonging to the lethal(1)B214 gene and suggest that the wild-type lethal(1)B214 gene encodes multiple transcripts. Furthermore, no transcripts of the same size and having the same developmental profile as those generated by the wild-type E10 fragment were identified by probes covering the remainder of the cloned region. This suggests that at least the larger transcripts hybridizing to E10 are partly transcribed from sequences located outside the cloned region, which indicates that the lethal(1)B214 gene extends for more than 20 kb and contains other transcriptionally active sequences within it.

Animals

Biochemical and physiological studies of soluble esterases from Drosophila melanogaster.

Twenty-two soluble esterases have been identified in D. melanogaster by combining the techniques of native polyacrylamide gel electrophoresis and isoelectric focusing. The sensitivity of each isozyme to three types of inhibitors (organophosphates, eserine sulfate, and sulfydryl reagents) identified 10 as carboxylesterases, 6 as cholinesterases, and 3 as acetylesterases. Three isozymes could not be classified and no arylesterases were identified. The carboxyl- and cholinesterases could each be further divided into two subclasses on the basis of inhibition by organophosphates and sulfhydryl reagents, respectively. Choline- and acetylesterases have characteristic substrate preferences but both subclasses of carboxylesterases are heterogeneous in substrate utilization. Subclass 2 carboxylesterases exhibit diverse temporal expression patterns, with subclass 1 carboxylesterases generally found in larvae and subclass 1 cholinesterases and acetylesterases more characteristic of pupae and adults. Tissues showing the greatest number of isozymes are larval body wall (eight) and digestive tract (six in larvae, six in adults). Carboxylesterases are distributed across a wide range of tissues, but subclass 1 cholinesterases are generally associated with neural or neurosecretory tissues and subclass 2 cholinesterases with digestive tissues.

Animals

The cyclic AMP phosphodiesterase encoded by the Drosophila dunce gene is concentrated in the mushroom body neuropil.

Drosophila dunce (dnc) flies are defective in learning and memory as a result of lesions in the gene that codes for a cAMP-specific phosphodiesterase (PDE). Antibodies to the dnc PDE showed that the most intensely stained regions in the adult brain were the mushroom body neuropil--areas previously implicated in learning and memory. In situ hybridization demonstrated that dnc RNA was enriched in the mushroom body perikarya. The mushroom bodies of third instar larval brains were also stained intensely by the antibody, suggesting that the dnc PDE plays an important role in these neurons throughout their development. The role of the dnc PDE in mushroom body physiology is discussed, and a circuit model describing a possible role of the mushroom bodies in mediating olfactory learning and memory is presented.

3',5'-Cyclic-AMP Phosphodiesterases

Mortality in elderly patients admitted for respite care.

OBJECTIVE: To determine whether admitting elderly patients to hospital to give temporary relief to their carers is associated with increased mortality. DESIGN: Prospective multicentre study comparing the mortality of patients admitted on a one off or rotational basis with that experienced while they were awaiting admission. SETTING: A wide range of urban and rural district general, geriatric or long stay, and general practitioner hospitals. PATIENTS: 474 Patients aged 70 or over who had 601 admissions. MAIN OUTCOME MEASURE: Death. RESULTS: 16 (3.4%) Of the 474 patients (2.7% of all 601 admissions) died while in hospital during an average stay of 15.7 days whereas 23 (4.9%) patients died while awaiting admission (average waiting time was 34.2 days). The 16 deaths in hospital and the 23 deaths during the longer waiting period correspond to death rates of 19.9 and 12.5 per 10,000 person days respectively. The difference between these of 7.4 is not statistically significant (95% confidence interval -3.6 to 18.3). The estimated relative risk of dying in hospital is 1.59 but the 95% confidence interval is wide (0.84 to 3.01). CONCLUSION: Although the death rates are slightly higher in those admitted to hospital for relief care than in those awaiting admission, the difference was not significant, and the death rate in both groups was reassuringly small.

Aged

Measuring importance.

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Data Interpretation, Statistical

Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age.

Regional cerebral blood flow (CBF), oxygen extraction ratio (OER), oxygen utilization (CMRO2) and blood volume (CBV) were measured in a group of 34 healthy volunteers (age range 22-82 yrs) using the 15O steady-state inhalation method and positron emission tomography. Between subjects CBF correlated positively with CMRO2, although the interindividual variability of the measured values was large. OER was not dependent on CMRO2, but highly negatively correlated with CBF. CBV correlated positively with CBF. When considering the values of all the regions of interest within a single subject, a strict coupling between CMRO2 and CBF, and between CBF and CBV was found, while OER was constant and independent of CBF and CMRO2. In 'pure' grey and white matter regions CMRO2, CBF and CBV decreased with age approximately 0.50% per year. In other regions the decline was less evident, most likely due to partial volume effects. OER did not change or showed a slight increase with age (maximum in the grey matter region 0.35%/yr). The results suggest diminished neuronal firing or decreased dendritic synaptic density with age.

Adult

Effects of an enteric anaerobic bacterial culture supernatant and deoxycholate on intestinal calcium absorption and disaccharidase activity.

Fifty two strains of anaerobic bacteria isolated from the upper gut of patients with small intestinal bacterial overgrowth were screened for phospholipase activity. Bacteroides melaninogenicus spp intermedius had the greatest activity. The effects of culture supernatants of this organism and deoxycholate on intestinal calcium absorption and disaccharidase activity were studied using a rat closed loop model. The supernatant decreased the in vitro uptake of calcium by 15% (p less than 0.001). Deoxycholate reduced calcium uptake by 16% (p less than 0.001). Combined culture supernatant and deoxycholate reduced calcium uptake by 39% (p less than 0.001) suggesting a potentiation of supernatant activity by deoxycholate. Culture supernatant and deoxycholate, both alone and combined, significantly reduced lactase, sucrase, and maltase activity. Electron microscopic evidence showed degeneration of microvilli, disruption of mitochondrial structure, and swelling of the endoplasmic reticulum after exposure of the intestinal loops to the supernatant or deoxycholate.

Animals

Transcriptional analyses of the uncoordinated region of Drosophila melanogaster.

RNA blotting experiments reveal that a genomic region encompassing the uncoordinated complementation group of Drosophila melanogaster produces two classes of transcripts. The first class contains five polyadenylated RNAs, of 4.35, 8.7, 9.0, 11.5, and 13.0 kb, and the second class contains a transcript of 7.3 kb that can be detected in both the total cellular and the poly(A)+ fractions. Transcripts of the first class are found predominantly in the early larval, pupal, and adult life stages, whereas the 7.3-kb species is present throughout the life cycle and is also found in the heads of adult flies. The two classes of RNAs derive from different combinations of exons. Analyses of RNAs derived from genotypes that are deficient for the uncoordinated complementation group and from seven uncoordinated mutant alleles support the suggestion that the uncoordinated gene (unc) has been isolated and encodes the multiple transcripts.

Alleles

The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party.

We have assessed the medium-term effect of a short course of high-dose, alternate-day prednisolone on adult nephrotic patients with membranous nephropathy, using a randomized, prospective, double-blind, controlled trial. Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years. One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial. One hundred and sixty further patients, excluded from the trial, but with membranous nephropathy were identified, followed and assessed retrospectively at the end of the trial. At 36 months there was no significant difference between control and treatment groups in plasma creatinine, creatinine clearance or 24-h excretion of protein. At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls. No significant benefit was therefore observed on renal function in the medium term.

Adult