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Biomedical subjects

R Ward

Publications and source records attributed to R Ward.

At least 217 records · Page 12Linked to original sources
PubMed1992

A reconsideration of the primary visual system of the turtle Emys orbicularis.

The retinocerebral projections of Emys orbicularis were investigated by means of [3H]-proline or HRP, administered by intraocular injection. Two newly-hatched, two juvenile and seven adult specimens were examined. The results reveal contralateral retinal projections to fifteen sites: two in the hypothalamus (the nuclei suprachiasmaticus and periventricularis), five in the thalamus (the nuclei ovalis, geniculatus lateralis ventralis, geniculatus laleralis dorsalis, dorsolateralis anterior and ventrolateralis), five in the pretectal region (the nuclei geniculatus pretectalis, opticus pretectalis ventrolateralis, lentiformis mesencephali, posterodorsalis and griseus tectalis), two in the optic tectum (the stratum opticum and the stratum fibrosum et griseum superficiale), and one in the tegmentum (the nucleus opticus tegmenti). Ipsilateral projections to nine of these sites at thalamic, pretectal, tectal and tegmental levels, while weak, could be clearly demonstrated. These results differ considerably from those obtained in a previous investigation using a Nauta-paraffin technique; it is suggested that the differences are due to limitations of the latter technique. A review of the existing literature on the Chelonian primary visual system reveals considerable terminological diversity, and a standard nomenclature for the primary visual centres of turtles is proposed.

Afferent Pathways↗
PubMed1992

Physiological mechanisms for metalloproteinase activation.

The activation of procollagenase and prostromelysin by mechanisms that might be functional in vivo has been investigated. Studies with cell monolayers plated onto collagen films have indicated key roles for plasmin and TIMP in these processes. Prostromelysin activation could be rapidly effected by fibroblast monolayers in the presence of plasminogen, with identical kinetics to plasminogen-streptokinase generated plasmin. Procollagenase activation by plasmin was shown to be poor, although an M(r) shift of 11,000 occurred. Activation was enhanced ten-fold by the presence of active stromelysin even at a very low molar ratio. A tumour cell line secreting procollagenase but not stromelysin was found to be dependent upon the addition of both stromelysin and plasminogen to effect degradation of collagen films. Biochemical studies of metalloproteinase activation were carried out using other purified proteinases synthesized by connective tissue cells including endopeptidase 24.11, endopeptidase-2, cathepsin B and cathepsin L. None was a particularly effective activator relative to plasmin, but cathepsin B was shown to activate stromelysin. By use of both cell model systems and biochemical studies of purified enzymes we have found that the role of plasmin as the major metalloproteinase activator in normal connective tissue cells remains unchallenged.

Amino Acid Sequence↗
PubMed1992

Nurse staffing levels and skill mix in accident and emergency departments.

This paper examines the history of nurse staffing and skill mix in accident and emergency (A&E) departments, and reports results from a study which examines numbers of staff and relates this to numbers of patients and organisation of work in A&E departments throughout one region. The types of procedures undertaken by nurses and the qualifications they held are also analysed. Conclusions about present variations in staffing in A&E departments are drawn, with recommendations for further study.

Emergencies↗
PubMed1992

[Behavioral asymmetry in BALB/cCF mice with corpus callosum abnormalities].

The possible homology between anomalies of the corpus callosum in mice and in humans remains questionable. The small number of existing behavioural studies in mice have not shown effects, at the behavioural level, of the absence or reduction in size of the corpus callosum. We therefore examined the development, during the first 3 weeks of postnatal life, of a number of simple reflex and integrative responses in the members of a sample of 101 BALB/cCF mice; at autopsy carried out at 50 days of age, 29 mice showed anomalies of the corpus callosum (total absence or an area less than 0.75 mm2). Asymmetry of the development of these responses was measured either as the proportion of animals showing asymmetrical appearance of responses on the left and right sides, and as the delay between appearances on the left and right sides in "asymmetrical" mice. Both measures decreased over the first 15 postnatal days, at the same rate in normal and abnormal mice; in each case the decrease is better described by a second-order, quadratic, function than by a simple linear function. We therefore conclude that the integrity of the corpus callosum is not necessary for the normal maturation of sensorimotor behaviour in mice, and suggest that this conclusion may possibly be explained by the relatively recent appearance of mice in the mammalian radiation.

Agenesis of Corpus Callosum↗
PubMed1991

Lack of stereoselectivity in the pharmacokinetics and metabolism of the radiosensitizer Ro 03-8799 in man.

During a clinical toxicity study it was possible to obtain urine samples from six patients receiving either the R-(-)- or S-(+)-stereoenantiomeric forms of the developmental 2-nitroimidazole radiosensitizer Ro 03-8799 (pimonidazole). Paired plasma samples were also obtained from four patients. The pharmacokinetic data were compared with those for the racemic mixture in the same individuals. The results revealed no major differences in the plasma pharmacokinetics, urinary clearance or N-oxidation of the individual enantiomers as compared with the racemic mixture. A similar lack of stereoselectivity with respect to the acute dose-limiting CNS toxicity syndrome suggests that this may not involve a specific CNS receptor interaction.

Adenocarcinoma↗
PubMed1991

The combination of multiple doses of etanidazole and pimonidazole in 48 patients: a toxicity and pharmacokinetic study.

The two radiosensitizers etanidazole and pimonidazole, currently in clinical phase 3 trials, have different toxicities. The former produces a peripheral neuropathy after cumulative doses and the latter presents an accurate but transient central nervous system syndrome after each dose. A strategy for improving on the maximum radiosensitization achievable using either drug alone, has been investigated in the study reported in this paper. Escalating doses of the two drugs were given together to determine toxicity up to a maximum of 15 doses of 2.0 g/m2 etanidazole and 0.75 g/m2 pimonidazole/dose. 25 neuropathies were seen in the total of 48 patients (48%). This included 6 grade 2 neuropathies (12.5%) or 15% of those receiving 9 or more infusions. There were no significant correlations between the incidence of neuropathy and various dose and AUC parameters for the 31 patients receiving 10 or more infusions. However, in the selected group of 26 patients planned to receive multiple doses of etanidazole at 2 g/m2/dose with pimonidazole at 0.75 g/m2, significant correlations were seen with the cumulative dose, with single and cumulative AUCs for pimonidazole and also for the cumulative dose and the cumulative AUC for etanidazole, but not its single AUC. In the light of these observations and the recent reports of higher peripheral neuropathy rates than previously reported in studies in the USA, it is concluded that it is not possible at this time to determine whether there is toxicity interaction between the two drugs. There remains the possibility that, on the basis of the combined drug dosage achieved, an increased therapeutic efficacy can be reached with either drug alone.

Adult↗
PubMed1991

Divergence and collateral axon branching in subsystems of visual cortical projections from the cat lateral posterior nucleus.

The projections from the lateral (LPl), intermediate (LPi) and medial (LPm) subdivisions of the cat lateral posterior nucleus (n. LP) to visual areas 17, the posteomedial (PMLS) and posterolateral (PLLS) lateral suprasylvian and anterior ectosylvian (AEV) were studied using the retrograde labeling technique following concomitant injections of fluorescent dyes (Fast blue, Nuclear yellow, Evans blue and Rhodamine beta-isothiocyanate) into the different cortical loci. The results showed a medial-lateral topographical reversal of the visual n. LP-cortical connections: The ventral portion of LPl projects to area 17 whereas more dorsolateral regions of LPl and lateral LPi provide input to PMLS. Cells in medial LPi project mainly to the PLLS cortex and AEV receives afferents from the LPm. Areas of overlap were identified within the ventral LPl which projects to both area 17 and PMLS and within the LPi/LPm border region at the origin of connections to both PLLS and AEV. Furthermore, some single neurons within the areas of overlap were found to be double-labeled indicating divergent projections to their respective cortical targets via collateral axon branching. The data show that divergence and axonal branching are common features of the different n.LP-visual cortical subsystems and support the notion of the existence of families of thalamo-cortical systems which are distinct in their connection patterns and underlying functional properties.

Animals↗
PubMed1991

Medical Information Management System (MIMS) CareWindows.

The demonstration of MIMS/CareWindows will include: (1) a review of the application environment and development history, (2) a demonstration of a very large, comprehensive clinical information system with a cost effective graphic user server and communications interface.

Computer Communication Networks↗
PubMed1991

Scintigraphic evaluation of postoperative complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is gaining popularity as an alternative to standard open cholecystectomy. At our institution, approximately 400 laparoscopic cholecystectomies have been performed since May 1989. The frequency of major postoperative complications has been approximately 1.5% (6 out of 400 cases). The most common complications have been biliary tree injury, bile leak, and retained stone. We present three patients who developed postoperative complications that were properly diagnosed on 99mTc-DISIDA cholescintigraphy. Our report indicates that 99mTc-DISIDA scintigraphy facilitates the rapid and precise diagnosis of bile leaks in patients with abdominal pain and/or hyperbilirubinemia following laparoscopic cholecystectomy.

Adult↗
PubMed1990

Three-dimensional structure of frozen-hydrated paracrystals of myosin rod.

Myosin rod, the tail fragment of myosin, aggregates into various structures at physiological ionic strength. One form, the type II paracrystal, a thin, ribbon-like species, has recently been studied using conventional electron microscopy and was shown to possess two-dimensional order and, further, is likely to be useful in the investigation of the arrangement of myosin molecules in the backbone of the vertebrate muscle thick filament (Ward & Bennett, 1989). We have now examined this aggregate in the frozen-hydrated state by cryo-electron microscopy. Image analysis indicated that the projected structure has the same p12, plane group symmetry as seen after negative staining. A three-dimensional map, calculated from projections, indicated that the structure comprises a bilayer arrangement of strands of grouped rod molecules, with the strands parallel in each layer. The layers themselves are related by screw symmetry. Strands in adjacent layers have opposing polarity with their long axes at an angle of 32 degree to each other. Protein density measurements, carried out on unstained specimens using electron energy-loss spectroscopy, showed that the 44 X 13 X 13 nm unit cell is composed of 40% protein. The density measurements indicated that 9-12 rod molecules pass through each strand. Modelling rod molecules with 43 nm parallel overlaps in a body-centered tetragonal lattice produced a strand that compared favorably with the reconstructed strand. The size and content of these strands suggests that they are analogous to subfilaments observed in the vertebrate myosin thick filament.

Animals↗
PubMed1990

Abnormal clinical pharmacokinetics of the developmental radiosensitizers pimonidazole (Ro 03-8799) and etanidazole (SR 2508).

The hypoxic cell radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole) are under evaluation as single agents (Phase III) and in combination (Phase I). Ro 03-8799 produces an acute, transient central nervous system syndrome, whereas SR 2508 causes cumulative, peripheral neurotoxicity; both effects are dose-limiting. Pharmacokinetic studies have shown the importance of area under the plasma drug concentration versus time curve (AUC) in predicting the risk of peripheral neuropathy. Most patients have very similar pharmacokinetic parameters. This study reports 2/25 patients receiving 0.75 g/m2 Ro 03-8799 plus 2.0 g/m2 SR 2508 who showed significant discrepancies in drug handling. One patient exhibited a markedly elevated AUC and prolonged t1/2 beta for SR 2508 and this was associated with an unusually rapid onset of peripheral neuropathy. A second patient showed normal handling of SR 2508 but prolonged values for both t1/2 alpha and t1/2 beta for Ro 03-8799 and unusually low levels of its N-oxide metabolite. In addition a low peak Ro 03-8799 concentration combined with a very high volume of distribution was found in this patient, leading to a normal AUC value and toxicity profile. Both patients exhibited a relatively low creatinine clearance. The mechanisms which may underlie these findings are discussed, and the importance of pharmacokinetic monitoring in the use of these agents is emphasized.

Aged↗
PubMed1990

A quantitative study of cerebrovascular variation in inbred mice.

The arteries of the base of the mouse brain were examined after perfusion with India ink. A qualitative difference exists between inbred mice of three strains (C57BL/6J, 129/J and BALB/cCF) on the one hand, and genetically defined heterogeneous mice on the other; the latter consistently show anomalies similar to those previously described in genetically undefined rodents, whereas inbred mice do not. A quantitative morphometric analysis of the Circle of Willis of inbred mice was undertaken. The results of this analysis are consistent with the notion that the differences in shape between the circles of Willis of different strains of inbred mice are due to additive genetic variation between these strains.

Animals↗
PubMed1990

An experimental study of the retinal projections of the European eel (Anguilla anguilla), carried out at the catadromic migratory silver stage.

A radioautographic study of the European eel (Anguilla anguilla) was carried out in ten female specimens at the catadromic migratory silver stage. Terminal arborizations of contralaterally projecting visual fibres were identified in ten hypothalamic structures (area optica preoptica ventralis and the nuclei suprachiasmaticus, opticus hypothalamicus ventromedialis, preopticus magnocellularis lateralis, posterioris lateralis, posterioris dorsalis periventricularis posterioris dorsalis lateralis, posterioris dorsalis medialis, posterioris ventralis lateralis, and posterioris ventralis periventricularis), ten thalamo-pretectal structures (Areas C1 and C2, area optica tractus opticus ventrolateralis and the nuclei dorsolateralis thalami, ventrolateralis thalami pars ventralis, opticus ventralis thalami, geniculatus lateralis, opticus pretectalis partes dorsalis et ventralis, and opticus commissurae posterioris), and in the tectal strata opticum partes externa et interna, fibrosum et griseum superficiale, griseum centrale and album centrale. An accessory optic system was identified, and a contralateral retinal projection to the anterior region of the anterior semicircular torus (n. opticus dorsolateralis mesencephali) was identified. Ipsilateral projections to hypothalamic and thalamopretectal structures were also observed. Apart from the retinal projection to the preoptic area, which is exceptionally important in the silver eel, the general plan of organization of the primary visual centres of this form is comparable to that described in other species of teleost. However, the architecture of some primary visual centres shows characteristics similar to those described in more primitive Actinopterygians.

Anguilla↗
PubMed1990

Regeneration of the retinotectal system in a flatfish, Scophthalmus maximus L.

Regenerating retinotectal fibres were visualized by radioautography in turbots (Scophthalmus maximus L.) maintained at 10 degrees-14 degrees C either after crushing one optic nerve or after crushing one nerve and removing the contralateral eye. Regeneration was found to be more extensive 2 days after crushing the right optic nerve than after crushing the left and was further enhanced by contralateral enucleation. The difference between experimental groups was markedly less pronounced by 113 days postoperatively and by 293 days the specimens resembled normal material. Between 113 and 222 days, a transient projection to the ipsilateral tectum was found, which disappeared by 293 days whether or not the contralateral eye had been removed. The differences between the present results and previous findings in symmetrical Cyprinid fish are discussed.

Animals↗
PubMed1989

Defective T-cell activation by Mycoplasma arthritidis mitogen is restored by interferon-gamma.

A mitogen derived from supernatants of Mycoplasma arthritidis (MAS) has been shown to induce both T-cell activation and the production of interferon-gamma (IFN-gamma). MAS-induced response required the presence of accessory cells and is under the genetic control associated with the major histocompatibility complex (MHC). We found that recombinant IFN-gamma restored the proliferative response to MAS mitogen in unreactive mice strains, including H-2b and H-2s haplotypes. We postulated that these T-cells fail to respond since they lack part of the I-E molecules on their accessory cells. Our data suggest that interferon-gamma may be able not only to increase the levels of Ia antigens but also to promote the appearance of MHC products that are not usually present on the cell surface. Since Ia antigens have a central role on T-cell activation, we examined the effect of the level of IFN-gamma on MAS-induced T-cell activation. We analyzed the acquisition of responsiveness to IL-2 and IL-2 activity in cells pretreated with IFN-gamma and found that both the steps of T-cell activation were restored to the MAS mitogen in the unreactive mice strains by IFN-gamma.

Animals↗
PubMed1989

Characterization of gelatinase from pig polymorphonuclear leucocytes. A metalloproteinase resembling tumour type IV collagenase.

The metalloproteinase 'gelatinase' stored in the granules of pig polymorphonuclear leucocytes has been purified in the latent form. The enzyme is secreted as an Mr 97,000 proenzyme that can be activated in the presence of 4-aminophenylmercuric acetate (APMA) by self-cleavage to generate lower-Mr species, of which an Mr 88,000 form was the most active. Trypsin-initiated activation generated different Mr gelatinases of much lower specific activity. Activation was slowed but not prevented by the presence of the tissue inhibitor of metalloproteinases, TIMP. The activated gelatinase formed a stable complex (Mr 144,000) with TIMP, in a Zn2+- and Ca2+-dependent manner, and complex formation was inhibited by the presence of the substrate gelatin. Similar to the human granulocyte gelatinase, the organomercurial-activated pig enzyme degraded gelatin and TCA and TCB fragments of type I collagen, as well as elastin and types IV and V collagen. The degradation of type IV collagen was shown, both by polyacrylamide-gel electrophoresis and by electron microscopic analysis, to generate 3/4 and 1/4 fragments as described for mouse tumour type IV collagenase. Furthermore, an antiserum raised to mouse type IV collagenase recognized the pig granulocyte gelatinase. An antiserum to the pig polymorphonuclear leucocyte gelatinase recognized other high-Mr gelatinases, including those from human granulocytes, pig monocytes and rabbit connective tissue cells, but not the Mr 72,000 enzyme from connective tissue cells. These data suggest that there are two distinct major forms of gelatinolytic activity that also cause specific cleavage of type IV collagen. These enzymes are associated with a wide variety of normal connective tissue and haemopoietic cells, as well as many tumour cells.

Animals↗
PubMed1989

A preliminary description of the regeneration of optic nerve fibers in a reptile, Vipera aspis.

Crushing or freezing the optic nerve of the viper leads initially to the anterograde degeneration of the optic nerve fibers and to an extensive retrograde demyelination process associated with the degeneration of some retinal ganglion cells. By the 45th postoperative day, regenerating unmyelinated axons can be identified in the damaged region of the optic nerve. These fibers reach the chiasm and the marginal optic tract by the third postoperative month. The radioautographic tracing method shows that some nuclei of the primary visual system begin to be reinnervated by about the 5th postoperative month; this reinnervation was not, however, completely restored in those specimens with the longest postoperative survival of 220 days.

Animals↗