Biomedical subjects
Publications and source records attributed to C Holt.
Infrared spectra of type cultures of the six recognized species of the genus Listeria and of Listeria grayi subsp. murrayi were recorded. By use of a library of 59 spectra, comprising at least six replicates of each type, discrimination by canonical variate analysis of the spectral amplitudes allowed all of the spectra to be correctly classified.
A large number of anesthetics, tranquilizers, hypnotic sedatives, and anticonvulsants are used clinically. Although these agents are generally well tolerated, liver injury of differing patterns is well recognized with their use. Knowledge of the likelihood of hepatotoxicity and the characteristic clinical features with these compounds is important as fatal outcomes due to liver failure have been reported with several of these agents. This article describes the potential mechanisms and clinical features of drug hepatotoxicity associated with these compounds.
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STUDY OBJECTIVES: To assess a single (donor) sample by the use of five computer-assisted semen analysis (CASA) systems. SETTING: British Andrology Society advanced course on computer-assisted semen analysis techniques, September 1992. PARTICIPANTS: Clinical, technical and scientific personnel with mixed experience of CASA techniques, but all interested in semen assessment technology. RESULTS: 22 sets of data, comprising 6 commonly derived parameters, from the same sample were obtained using five CASA systems. The coefficients of variation for sperm concentration (29%) and proportion motile (24%) were comparable to those previously reported for manual assessments. For all parameters, "within system" variability was considerably greater than "between system," indicating that differences in sample handling and operator expertise were more significant sources of variation than the CASA systems themselves. CONCLUSIONS: Emphasis on operator training and standardization of sample handling techniques would enhance the reproducibility of CASA measurements more than improvements in the CASA systems themselves. There was evidence, however, that the CASA measurements were more consistent than equivalent manual measures, and also provide information about the quality of sperm motility which cannot be obtained by alternative techniques.
1. Milk and milk ultrafiltrate samples from four women (Homo sapiens) during the first 16 weeks of lactation were analysed for the main salt constituents, protein and lactose and the interrelationships of these constituents were determined. 2. A good positive correlation was observed between ultrafiltrate calcium and citrate concentrations, as previously observed for cow (Bos taurus) and goat (Capra hircus) milk but the expected negative correlation of lactose with ultrafiltrate salts was poor. 3. An invariant ion activity product for milk calcium phosphate was found for a dicalcium phosphate stoichiometry but the milk serum was less supersaturated with respect to calcium phosphate and citrate salts than ruminant milks. 4. The observed interrelationships are discussed in relation to the constraints on human milk composition arising from a fixed osmotic pressure, overall charge neutrality and saturation with respect to calcium phosphate.
A brief overview is given of the methods of determining and predicting secondary structure in proteins. The secondary structures of the milk serum proteins, lactoferrin, alpha-lactalbumin, lysozyme, and beta-lactoglobulin, as determined by x-ray crystallography, are compared with the results of a joint prediction method. This comparison evaluates critically the degree of success achieved and helps define what can reasonably be expected from a prediction in the absence of a known structure. The value of supplementary information from spectroscopic methods and the use of templates and sequence information from related proteins in improving the confidence of predictions are illustrated. One point that emerges is the general overprediction of helix content by the joint prediction method such that, for an all-beta protein such as beta-lactoglobulin, the method of Garnier, Osguthorpe, and Robson, applied with the correctly selected decision constants, provides a somewhat better approach. Secondary structure of the caseins can be predicted with less confidence than for globular proteins, and the results should be interpreted as evidence of a propensity to form transient secondary structures of the indicated type in view of the generally open and flexible conformation of caseins in solution.
The developing axons of retinal ganglion cells follow a stereotyped trajectory through the diencephalon to the optic tectum. In Xenopus, this trajectory closely parallels that of a preexisting fiber tract, the tract of the postoptic commissure (TPOC). This tract comprises part of the early CNS scaffold and has been proposed to play a critical role in guiding the later growing optic axons. We have tested this possibility using heterochronic and xenoplastic transplants of eye primordia to force optic axons to enter the brain before scaffold tracts have arisen in the forebrain. We show that optic axons can navigate appropriately in the absence of the TPOC or any other axons, indicating that axonal pathfinding cues are present in the axonless neuroepithelial sheet. We suggest that molecularly distinct heterogeneities within the neuroepithelium are used for pathfinding by early and late developing axons alike in normal development.
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The authors assessed psychological disorders in 50 chronic TMD patients. These disorders appear to be a major concomitant factor in chronic TMD, and may need to be treated for successful outcomes.
We have isolated and characterized cDNAs corresponding to the Xenopus En-2 gene. Comparison of amino acid sequences between the entire Xenopus En-2 and the Drosophila engrailed proteins confirms conservation of sequences inside as well as proximal to the homeobox and reveals a region of similarity towards the N terminus. Two transcripts encode the Xenopus En-2 protein. Both transcripts are regulated temporally in an identical fashion and are likely to be transcribed from two copies of the En-2 gene. We have also analyzed the distribution of the protein in the head tissue and in the dissected brain of tailbud stage embryos. In addition to the main band of expression at the midbrain-hindbrain boundary, we show that the protein is expressed in three novel areas: the mandibular arch, the optic tectum and the region of anterior pituitary.
This study reports the long term efficacy of a brief intensive (2 days) group cognitive behavioural programme for the treatment of agoraphobia with panic attacks. A total of 97 patients was included in the study. Seventy-four patients were in the treated group and 23 were on the waiting list control group. The Fear Questionnaire (FQ), Fear Survey Schedule (FSS), Maudsley Personality Inventory (MPI), the Hostility and Direction of Hostility Questionnaire (HDHQ) and a clinical assessment based on structured interview to assess current levels of functioning were used as dependent measures. The results show that patients in the treated group show significant improvement on FSS and FQ when compared with the patients in the control group. Clinical rating shows that 85% of the patients were either symptom free or their symptoms had been reduced and these effects of treatment were shown to be maintained at follow-up which was on average 1 year after the treatment.
The developing uncrossed retinocollicular projection in the Syrian hamster undergoes a characteristic set of changes during the first 2 postnatal weeks. The retinal fibres, which initially project across the whole superior colliculus, withdraw from the caudal part and their terminals become clustered into deep, discrete clumps rostrally. Coincident with these afferent changes, there is substantial retinal ganglion cell death. To examine whether neuronal activity plays a role in these changes, we made daily injections of the sodium channel blocker tetrodotoxin (TTX) into one or both eyes from postnatal day 2 or 4 up to day 12. Following TTX treatment, the uncrossed terminals retracted on schedule from the caudal and superficial parts of the superior colliculus and came to lie, as normal, in the deep layers rostrally. Within the rostral superior colliculus, however, the uncrossed terminals from TTX-injected eyes lost their characteristic patchy distribution and were arranged diffusely. When only one eye received TTX injections, this inhibiting effect on terminal segregation was seen only in the projections from the TTX-treated eye. The effect of TTX treatment on terminal segregation was much less severe than that of unilateral enucleation, after which uncrossed terminals persis throughout the entire superior colliculus. TTX injections appeared to have little effect on overall ganglion cell death since the total number of ganglion cells in the crossed projection from TTX-treated eyes was similar to that in normal eyes. However, the relative distribution of uncrossed cells in temporal and nasal retina was altered. In eyes that received TTX injections, the proportion of uncrossed cells in nasal retina was about 1.6 times that in normal animals and was close to the proportion seen in unilaterally enucleated animals. This increase in the treated eye occurred whether one or both eyes were injected with TTX. We conclude that neuronal activity plays a role in the segregation of uncrossed terminals into discrete clumps in rostral colliculus and in the preferential elimination of uncrossed cells from the nasal retina. The inactive uncrossed projections from TTX-treated eyes showed the greatest degree of disruption. The extent of the disruption was similar whether the crossed input from the other eye was active or inactive. This suggests that the activity-drive interactions between ganglion cells within one eye are more significant than those between the two eyes in shaping the final form of the uncrossed retinocollicular projection.
Immunization of C57BL/6 (B6) mice with FBL, a Friend murine leukemia virus (F-MuLV), induces both tumor-specific cytolytic CD8+ (CTL) and lymphokine-producing CD4+ Th that are effective in adoptive therapy of B6 mice bearing disseminated FBL leukemia. The current study evaluated the F-MuLV antigenic determinants expressed on FBL that are recognized by FBL-reactive CD8+ and CD4+ T cells. To identify the specificity of the FBL-reactive CD8+ CTL, Fisher rat embryo fibroblast (FRE) cells transfected with plasmids encoding F-MuLV gag or envelope (env) gene products plus the class I-restricting element Db were utilized. FBL-reactive CTL recognized FRE target cells transfected with the F-MuLV gag-encoded gene products, but failed to recognize targets expressing F-MuLV env. Attempts to generate env-specific CD8+ CTL by immunization with a recombinant vaccinia virus containing an inserted F-MuLV env gene were unsuccessful, despite the generation of a cytolytic response to vaccinia epitopes, implying that B6 mice fail to generate CD8+ CTL to env determinants. By contrast, CD4+ Th clones recognized FRE target cells transfected with env and not gag genes, and immunization with the recombinant vaccinia virus induced an env-specific CD4+ T cell response. These data show that in a Friend retrovirus-induced tumor model in which tumor rejection can be mediated by either CTL or Th, antigens derived from discrete retroviral proteins are predominantly responsible for activation of each T cell subset.
Extended x-ray absorption fine structure (EXAFS) spectra were recorded, above the K absorption edge of Ca, from 10 encrusted urinary (Foley) catheters obtained from 10 different patients. The presence of poorly crystalline apatite was demonstrated in all the deposits, even though this phase could not be detected in the x-ray powder diffraction patterns of most samples because of the obscuring effect of struvite, which was also present. Furthermore, the EXAFS spectra could be interpreted to yield quantitative information on the average short-range structure surrounding the Ca2+ ions in the poorly crystalline apatite.
In free solution, the caseins behave as non-compact and largely flexible molecules with a high proportion of residues accessible to solvent. Historically, they have been described as random coil-type proteins with only a nutritional function. Nevertheless, secondary structure prediction algorithms indicate that many parts of the (unphosphorylated, unglycosylated) polypeptide chains can form regular structures. In particular, a recurrent motif of the Ca2+-sensitive caseins in man, rat, mouse, guinea pig and ruminant species is an alpha-helix--loop--alpha-helix conformation in which the loop region typically contains a cluster of sites of phosphorylation. The biological function of the caseins is considered and it is suggested that the potential or actual conformations of the group of Ca2+-sensitive caseins are suited to the function of modulating the precipitation of calcium phosphate from solution. Either they can act as sites for nucleation or they can bind rapidly to calcium phosphate nuclei as they form spontaneously from supersaturated solution.
Casein and lactose concentrations in milks of various species vary by at least 1-2 orders of magnitude, yet no single species secretes both components at either the high or the low end of the ranges. This pattern of variation could result from evolutionary adaptations in a single secretory mechanism.
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Skim-milk samples from rat, rabbit, pig, sheep, goat, horse and man were analysed for lactose, casein and the total and ultrafilterable concentrations of the main salts. Results are compared with data for the cow. The ultrafiltrate concentrations of Ca and Mg were positively correlated with that of citrate and the colloidal concentrations of Ca, Mg and citrate were positively correlated with that of Pi, suggesting that common, general, principles determine the partition of salts in milks. Casein concentration in the skim-milks was inversely related to that of lactose in accordance with a recent theoretical treatment of the principal mechanism of milk secretion. It is postulated that much of the interspecific diversity in milk composition can be explained by adaptations in a single secretory mechanism.