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Biomedical subjects

A Davies

Publications and source records attributed to A Davies.

At least 145 records · Page 8Linked to original sources

A beta-subclass phosphatidylinositol-specific phospholipase C from squid (Loligo forbesi) photoreceptors exhibiting a truncated C-terminus.

A PCR-based strategy has been used to isolate a full length cDNA encoding a phosphatidylinositol-specific phospholipase C from a sized cDNA squid (Loligo forbesi) retinal library. The predicted protein sequence contains 875 amino acids, with calculated M(r) 98,181, and has marked similarity with PLC beta-isoforms, including conservation of the 'X' and 'Y' regions. It is unique in having a major C-terminal truncation. A major protein of apparent M(r) 120,000 estimated by SDS-PAGE has been isolated from squid photoreceptors and identified by partial protein sequence analysis to correspond to the protein sequence predicted from the cDNA clone. This protein has been shown to hydrolyse phosphatidylinositol 4,5-bisphosphate. It is not yet clear whether this represents the major light-activated PLC in squid vision.

Amino Acid Sequence↗

Effect of the C-terminal proline repeats on ordered packing of squid rhodopsin and its mobility in membranes.

Negative stain electron microscopy and saturation transfer electron spin resonance spectroscopy have been used to compare the lattice ordering and in-plane membrane mobility of full-length and C-terminally cleaved squid rhodopsin. The C-terminus of squid rhodopsin contains a negatively charged region followed by 9-10 repeats of a proline-rich sequence, not found in rhodopsins other than those of cephalopod invertebrates, but similar proline repeats are found in other, unrelated membrane proteins. We find that the proline repeats cluster the rhodopsins into small groups, interfering with two-dimensional crystallization and maintaining their mobility in the membrane.

Animals↗

Heart rate and oxygen uptake relationship: a comparison of loaded marching and running in women.

Heart rate (beats.min-1; fc) measured during marching with a load is often used to predict the oxygen cost (l.min-1; VO2) of the activity. The prediction comes from the fc/VO2 relationship determined from laboratory measures of fc and VO2 during treadmill running. Studies in men have suggested that this may not be appropriate although this has yet to be examined in women. This study, therefore, compared the fc/VO2 relationship between loaded marching and maximal running protocols in women. Sixteen female subjects [mean (SD), age 21.9 (2.3) years, height 6 (0.06) m, weight 62.6 (7.6) kg] had their fc (from three-lead chest electrodes) and VO2 measured first during standard treadmill run protocols, and again 1 week later during loaded marching protocols. The slopes and intercepts determined from linear regression of fc on VO2 for each individual for each protocol were compared as were the maximal fc(fcmax), VO2 and ratings of perceived exertion (RPE) from the last work period of each protocol in paired t-tests. The fc/VO2 slopes (P < 0.01) and intercepts (P < 0.05) differed significantly between loaded marching and running. fcmax for loaded marching were 90% of fcmax for running (P < 0.01) and VO2peak for loaded marching were 80% of those for running (P < 0.01). However, RPE at the final levels for the two protocols were not significantly different. The data suggest that in women the fc/VO2 relationships for loaded marching and for running are different. This difference is similar to that found in men when speed is held constant and the load and gradient are varied. The results suggest that it would be erroneous to use fc and VO2 measured during running protocols in the laboratory to estimate energy expenditure and work intensity during loaded marching in the field.

Adult↗

Impact of childbirth on a series of schizophrenic mothers: a comment on the possible influence of oestrogen on schizophrenia.

From a series of 180 admissions to a Mother-Baby Unit 45 patients with diagnoses of schizophrenia were identified. Demographic data together with clinical information were noted, and each file was rated using the OPCRIT programme. Two mutually exclusive groups were derived from OPCRIT, a 'narrow group' (n = 16), corresponding to subjects satisfying Feighner's criteria for schizophrenia, and a 'broad group' (n = 21), corresponding to those meeting ICD10 but not Feighner criteria. In addition to significant differences in age on admission, employment, home circumstances, ethnicity and age of onset of illness, there was a marked contrast between broad and narrow groups in course of illness post partum. 43% of the broad group experienced an acute illness episode after delivery compared with none of the narrow group, a contrast not attributable to differences in clinical state or treatment during pregnancy. These data suggests that childbirth may exert a differential effect on the course of illness in severe and more benign forms of schizophrenia, and that more severe schizophrenic illnesses may not be influenced by the changes associated with childbirth, such as the fall in oestrogen levels.

Age of Onset↗

The application of the human beta-globin gene locus control region and murine erythroleukemia cell system to the expression and pharmacological characterization of human endothelin receptor subtypes.

The cDNAs encoding both A and B subtypes of the human endothelin receptor have been inserted into mammalian cell expression vectors that utilize the human globin gene, locus control region. These constructs have been introduced into murine erythroleukemia cells and inducible high level expression of the receptors has been achieved (approximately 1.5-pM/mg membrane protein and approximately 13,500 binding sites/cell for both receptor subtypes). Cell lines expressing these receptors were obtained on a rapid time scale (3-4 weeks), facilitated by the need for the analysis of only small numbers of cell clones/receptor (approximately 6). Competitive binding assays with endothelin-1 gave IC50s of 130 +/- 30 pM for endothelin-A receptor and 160 +/- 30 pM for endothelin-B receptor. Similar studies with the different isoforms of endothelin, sarafatoxin-S6b and -S6c, BQ123 and BQ3020, all gave the expected selectivity profiles. The IC50s for all compounds were in close agreement with those reported for native receptors. Thus, this expression system, which has several advantages over other described expression systems, is capable of rapidly providing large quantities of receptor for detailed pharmacological analyses or drug screening. In addition, the expressed receptors display the expected pharmacological profiles in the absence of any complicating, competing interactions from other subtypes or binding sites.

Binding, Competitive↗

A novel ultrasonic aerosol generator.

An ultrasonic aerosol generator constructed from a domestic humidifier is described which has been used to produce liquid aerosols for physiological investigations. The instrument was constructed from a Pifco domestic humidifier modified to include an energy guide to direct the oscillations of the transducer through the coupling water, which would normally be aerosolized, onto a small membrane based sample chamber containing the liquid to be aerosolized. The size distribution of the aerosol produced was found to be between 2 and 6 mm, optimum for diffuse intrapulmonary deposition. Up to 4 ml/min of aqueous liquid was used; however the sample chamber could be made small enough to contain economic amounts of expensive material to administer by inhalation. The instrument has proved to be reliable over a period of three years.

Aerosols↗

Respiratory chlamydia: the management of an outbreak.

This investigation was undertaken in response to the occurrence of nine cases of respiratory chlamydial infection in 8 months within the district of Dudley. All nine cases of respiratory chlamydia were due to Chlamydia psittaci, not Chlamydia pneumoniae. Five cases had avian exposure, but no other aetiological factors were identified. Faecal specimens were obtained from only two of the implicated birds and were negative. Two local aviaries were identified as sources of implicated birds. The two aviaries were themselves linked. Bird faecal specimens were taken from the two implicated aviaries and were both positive for Chlamydia psittaci. Appropriate public health control measures were introduced in these aviaries. A press statement was released to identify and advise, by telephone, those who purchased birds from the aviaries.

Adult↗

Cholecystokinin attenuates incentive learning in rats.

The hypothesis that endogenous cholecystokinin (CCK) reduces the incentive value assigned to food was examined by training undeprived rats to lever press and chain pull, with one action earning food pellets and the other maltodextrin solution. All animals were then food deprived and reexposed to one outcome after an injection of CCK-8 and the other after an injection of vehicle (VEH). When maintained food deprived and given a choice between the lever and chain in an extinction test, the rats performed fewer of the action trained with the outcome that was reexposed under CCK whether tested under CCK or VEH. In a subsequent experiment, this preference was attenuated by coadministration of the 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2(di-n-propylamino)tetralin during reexposure, suggesting that CCK interacts with 5-HT to modify incentive value.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Crystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir.

The crystal structures of thymidine kinase from herpes simplex virus type-1 complexed with its natural substrate deoxythymidine (dT) and complexed with the guanosine analogue Ganciclovir have been solved. Both structures are in the C222(1) crystal form with two molecules per asymmetric unit related by a non-crystallographic two-fold axis. The present models have been refined to 2.8 A and 2.2 A, with crystallographic R factors of 24.1% and 23.3% for the dT and Ganciclovir complexes respectively, without the inclusion of any solvent molecules. The core of the molecule exhibits high structural homology with adenylate kinase and other nucleotide binding proteins. These structural similarities provide an insight into the mechanism of nucleoside phosphorylation by thymidine kinase.

Adenylate Kinase↗

EMG-responses to sudden onset free fall.

Recordings of axial and limb muscles in reaction to a free fall induced startle were performed in subjects while they were lying on a tilting couch with their eyes closed. Young normals (n = 24, aged 31.1 +/- 6.6 years) showed an activation sequence consisting of sternomastoid (N.XI: 57 ms), abdominal muscles (T10: 65 ms), quadriceps (L3: 75 ms) and deltoid (C5: 78 ms) and tibialis anterior (L4: 80 ms). The sequence of activation is not compatible with the current hypothesis of the startle being produced by a single volley spreading rostrally and caudally from the lower brainstem. Instead it is suggested that the startle is a patterned response organized by a putative reticular generator capable of spatio-temporal sequencing. Two avestibular patients had responses at mildly delayed latencies, showing that these can be elicited by non-vestibular inputs. Similar testing of 11 subjects aged 70-80 years showed a latency delay of ca. 26% in the EMG response but a similar activation sequence. The amount of delay in the elderly can only partially be attributed to age-dependent motor conduction slowing and suggests a prolongation of central processing time. In patients with advanced stages of akinetic-rigid syndromes abnormalities were seen in cases with an involvement of the brainstem reticular formation.

Accidental Falls↗

Identification of MIC 11 antigen as an epitope of the CD59 molecule.

The MIC 11 antigen is expressed on human cells and is characterized by reaction with a monoclonal antibody (mAb), 16.3A5. The gene controlling MIC 11 was recently mapped to the p13 region of chromosome 11 within 500 kb of the gene encoding CD59, a complement regulatory protein. The present report investigates the antigenic relationship between these cell-membrane determinants and sets out evidence that MIC 11 and CD59 are encoded by the same gene. Western blotting of human erythrocyte membrane proteins and purified membrane CD59 showed that 16.3A5 anti-MIC 11 antibody bound to a 19-24,000 MW band with the characteristic appearance of CD59 protein, and gave staining patterns identical to those obtained with the CD59 antibody, BRIC 229. The binding of 16.3A5 monoclonal IgG to purified urine-derived CD59 in enzyme-linked immunosorbent assay (ELISA) was inhibited by YTH 53.1 rat CD59 antibody, indicating that the MIC 11 epitope is the same as, or close to, that recognized by CD59 antibodies such as YTH 53.1, BRIC 229 and 2/24. Prior exposure of erythrocytes to 16.3A5 anti-MIC 11 also reduced the ability of the CD59 antibodies, BRIC 229 and YTH 53.1, to block the complement-inhibiting function of membrane CD59. Anti-MIC 11 antibody alone, however, had no inhibitory effect on CD59 function. This may be due to its relatively low binding affinity or to some slight difference in epitope specificity. Further studies using immunofluorescence showed that the MIC 11 epitope, like CD59, is absent from EBV-B cells lacking GPI-anchored proteins and from a B-cell line specifically deficient in CD59 protein. Overall, the results provide strong evidence that MIC 11 is a determinant on the CD59 molecule.

Animals↗

Diphtheria.

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Adult↗