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Biomedical subjects

R Woodward

Publications and source records attributed to R Woodward.

At least 37 records · Page 2Linked to original sources
PubMed1994

Molecular characterisation of a novel, repetitive protein of the paraflagellar rod in Trypanosoma brucei.

A partial cDNA clone, termed 5.20, was isolated from a lambda-gt11 phage expression library using a complex antiserum to the T. brucei cytoskeleton. Antisera against the fusion protein product of this 5.20 cDNA recognized a closely-spaced polypeptide doublet of high molecular weight (ca. 180-200 kDa) on immunoblots of T. brucei cytoskeletal preparations. Immunogold labelling suggested the 5.20 protein is intracellular and localized along the entire length of the paraflagellar rod. This pattern is similar to that generated with a monoclonal antibody, ROD1, which recognizes a high molecular weight protein doublet indistinguishable from that detected by 5.20-specific antisera. ROD1 recognizes mammalian spectrin, but the use of specific anti-spectrin antibodies for immunoblotting did not support ideas that 5.20 encodes spectrin or that spectrin can be specifically detected in T. brucei by such methods. Moreover, the sequence of the 5.20 cDNA insert bears little similarity, either in its nucleotide or predicted amino acid sequence to other known proteins and appears to be a unique cytoskeletal protein characterized especially by sequential amino acid sequence repetitiveness. The location of this novel protein suggests it may be responsible for providing either paraflagellar rod-membrane links or for organizing the more abundant paraflagellar rod structural proteins.

Amino Acid Sequence↗
PubMed1994

Structural studies on D2 dopamine receptors: mutation of a histidine residue specifically affects the binding of a subgroup of substituted benzamide drugs.

A histidine residue (His394) that is likely to be located in the ligand-binding region of the D2 dopamine receptor has been mutated to a leucine (Leu394), and the properties of the mutant receptor have been determined. For a range of antagonists the mutation has only a minor effect on the affinity of the receptor for the antagonist. The mutation does, however, elicit a structurally specific effect on the affinity with which certain members of the substituted benzamide class of antagonist bind to the receptor. Some of these drugs, e.g., sulpiride, sultopride, and tiapride, bind with reduced affinity to the mutated receptor, whereas others, e.g., clebopride and metoclopramide, bind with increased affinity. However, the Na+/H+ sensitivity of the binding of sulpiride to the receptor is not reduced by the mutation. These findings have been interpreted in terms of the productive or unfavourable interaction of the His394 residue with these compounds.

Amino Acid Sequence↗
PubMed1994

Longitudinal bone mineral density changes in early rheumatoid arthritis.

A prospective longitudinal study of patients with early RA was performed to examine the influence of disease duration, disease activity and physical activity on bone loss. Sixty-seven patients with non-steroid treated RA of less than 5 yr duration, including 16 patients with disease duration less than 6 months, had BMD measurements of the femoral neck and the lumbar spine over a 12-month period using dual energy X-ray absorptiometry. The BMD changes were compared with values from 72 control patients and were also correlated with serial measurements of disease activity (measured by the Stoke Index) and disability [measured by the Health Assessment Questionnaire (HAQ) score], at 3-monthly intervals over the 12-month period. No significant differences in BMD changes were found between RA patients and controls overall. Patients with disease duration of less than 6 months had significantly greater loss of BMD at the femoral neck (-3.9%, S.E.M. 1.5) than the remainder of the cohort (-0.2%, S.E.M. 0.7) (P = 0.02) and controls (-0.8%, S.E.M. 0.6). Lumbar spine BMD changes correlated with the initial Stoke Index (Rs-0.373, P = 0.01) but not mean Stoke Indices. There was no correlation of BMD changes with age or HAQ scores. These findings suggest that significant bone loss occurs within the first few months of disease in patients with RA.

Adult↗
PubMed1994

Bone mineral density in nonsteroid treated early rheumatoid arthritis.

OBJECTIVES: To determine whether significant reduction in bone mass is detectable in early disease in patients with rheumatoid arthritis (RA) and to examine the possible influences of disease activity and physical disability on bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN). METHODS: LS and FN BMD values were measured and Z scores determined in a cross-sectional study of 104 patients with RA of less than five years duration. BMD values were also compared between a subgroup of 64 patients and a normal control group matched for age, sex, menopausal status and body mass. BMD values and Z scores were correlated with disease activity, measured by the Stoke Index, disability, measured by HAQ score, and disease duration. RESULTS: Premenopausal female patients with RA had significantly reduced mean FN Z scores (-0.62, 95% CI -0.30 to -0.94) which correlated with HAQ scores (Rs 0.358, p = 0.05) and age (Rs 0.397, p = 0.03). There were no significant changes of BMD in males or postmenopausal females. Disease duration and disease activity did not correlate with BMD changes. CONCLUSION: BMD is reduced in premenopausal female patients with early RA possibly related to the attainment of peak bone mass. No significant reduction of BMD was found in males or postmenopausal females with early disease. Physical disability but not disease activity appears to play a role in the reduction of FN bone mass.

Adult↗
PubMed1992

Development of high-affinity 5-HT3 receptor antagonists. 2. Two novel tricyclic benzamides.

Two new classes of potent 5-HT3 agents have been developed and examined as inhibitors of cytotoxic drug induced emesis in the ferret and dog. The absolute configuration of the most active molecules 10 and 18 have been determined by X-ray crystallography. These two compounds are more potent than known 5-HT3 receptor antagonists both in vivo and in vitro in blocking 5-HT3 receptor activation and preventing chemotherapeutic induced emesis. Compared with 5-HT3 antagonists, such as GR 38032F, zacopride, BRL 43694, and ICS 205-930, compound 10 was more potent in (1) inhibiting binding to 5-HT3 receptor binding sites in rat cortex (Ki = 0.17 nM), (2) blocking the von Bezold-Jarisch effect in the rat (lowest effective dose, 1 microgram/kg iv), and (3) inhibiting 5-HT-induced contraction of guinea pig ileum (lowest effective concentration, 10(-9) M). This novel agent was as effective given po as when given iv in reducing cisplatin-induced emetic episodes in the ferret (ED50 = 4 micrograms/kg iv or po). A 1 mg/kg po dose of 10 virtually abolished cisplatin-induced emesis for 10 h in the ferret. However, it was inactive against apomorphine or copper sulfate-induced vomiting. These data, coupled with receptor binding studies of ligands for D2-dopamine, a1, a2, 5-HT1, 5-HT2, and muscarinic receptors demonstrate that 10 is a highly selective 5-HT3 receptor antagonist with remarkable potency in vivo.

Amides↗
PubMed1992

Isolation of cDNA clones encoding proteins of complex structures: analysis of the Trypanosoma brucei cytoskeleton.

We have adapted a group of well-known procedures in order to devise a simple method that allows the isolation of specific cDNAs encoding proteins located in different regions of the Trypanosoma brucei cytoskeleton. cDNA clones were isolated by screening a lambda gt11 expression library with a polyspecific, polyclonal antiserum against a complex immunogen, in this case the complete cytoskeleton. The fusion proteins produced by the clones were then used as an affinity immunoadsorbant to select monospecific polyclonals. The monospecific antisera isolated were used as probes to identify and localize different cytoskeleton proteins by Western blotting and immunofluorescence. This method proved particularly useful for the molecular identification of minor components in a complex structure. It should prove applicable to the molecular analysis of other organelles or protein complexes.

Animals↗
PubMed1991

Effects of nicotine gum on repeated administration of the Stroop test.

Using a double-blind procedure, 24 non-smoking subjects chewed either 2 mg nicorette gum or a placebo for 20 min, before completing a Stroop test on three occasions. Colour-word reading and simple colour naming times were consistent across repeats, and were unaffected by nicotine. However, the time taken to name the colour of incongruous colour word stimuli declined across trials. This increase in speed across repeats was significantly greater in those subjects who had received nicotine. These data are consistent with previous reports of a decreased Stroop effect following nicotine administration, but are not compatible with a simple model which assumes that nicotine alters the way in which information is filtered by selective attentional mechanisms. The present results can be explained by postulating that nicotine influences either the rate at which colour naming become more automatic, or changes the way in which resources are allocated to non-automatic processes.

Adolescent↗
PubMed1991

Single-injection peribulbar local anaesthesia--a study of fifty consecutive cases.

Peribulbar anaesthesia is becoming an increasingly popular alternative to retrobulbar anaesthesia for local anaesthesia in intraocular surgery. The results of 50 consecutive single-injection peribulbar anaesthetics performed by the same surgeon are reported. A description of the procedure is included. The technique produced adequate conditions for surgery in all cases. Only 4% (two cases) were considered to have inadequate akinesia five minutes after the injection and required additional injections. None of the complications described with retrobulbar and other forms of peribulbar anaesthesia were observed. The procedure is relatively easy to master. It can be performed by surgeons or anaesthetists and can be used in the in-patient or day surgery setting. The study shows it to be a safe and reliable alternative to previously described methods of local anaesthesia.

Anesthesia, Local↗
PubMed1991

Effect of pre-exercise protein ingestion upon VO2, R and perceived exertion during treadmill running.

The study investigated the effect of pre-exercise protein ingestion upon the oxygen consumption (VO2), respiratory exchange ratio (R) and perceived exertion (PE) of athletes during treadmill running at intensities of approximately 60, 80, 90 and 100% of their VO2max. Seventeen female athletes aged between 17 and 22 years participated in the study. Subjects completed six assessment sessions, each being preceded by one of the following dietary regimens: a protein solution ingested 3h before assessment (P3), a protein solution ingested 1 h before assessment (P1) and the ingestion of water 1-3 h before assessment (B). The subjects' VO2, R and PE were measured at all exercise intensities using standardized procedures. The results showed that P1 produced significantly higher values for VO2 (P less than 0.05) at all exercise intensities and was associated with an increased PE (P less than 0.01). The findings could have implications for athletes when considering the composition of their pre-exercise meal, especially if performing in activities which require the participants to exercise close to or at their VO2max.

Adolescent↗
PubMed1990

Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei.

We have used immunofluorescent detection of 5-bromo-2-deoxyuridine-substituted DNA in order to determine the timing of initiation and the duration of nuclear and kinetoplast S-phases within the procyclic stage of the Trypanosoma brucei cell cycle. Both nuclear and kinetoplast S-phases were shown to be periodic, occupying 0.18 and 0.12 of the unit cell cycle, respectively. In addition, initiation of both of these S-phases were in approximate synchrony, differing by only 0.03 of the unit cell cycle. We have also used a monoclonal antibody that recognises the basal bodies of T. brucei in order to visualise cells possessing a new pro-basal body and hence determine the time of pro-basal body formation within the cell cycle. Pro-basal body formation occurred within a few minutes of the initiation of nuclear S-phase, at 0.41 of the unit cell cycle. This provides detection of the earliest known cell cycle event in T. brucei at the level of the light microscope. Cell cycle events including initiation of nuclear and kinetoplast DNA replication and pro-basal body formation may be strictly coordinated in T. brucei in order to maintain the precise single-mitochondrion (kinetoplast), singleflagellum status of the interphase cell.

Animals↗
PubMed1989

Chronic carbamazepine inhibits the development of local anesthetic seizures kindled by cocaine and lidocaine.

The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine- and cocaine-induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure-related mortality in the cocaine-injected rats. Acute CBZ over a range of doses (15-50 mg/kg) had no effect on completed lidocaine-kindled or acute cocaine-induced seizures. Repeated i.p. injection of CBZ (15 mg/kg) also was without effect on the development of lidocaine- or cocaine-kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic-kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated.

Anesthetics↗
PubMed1989

Context-dependent cocaine sensitization: differential effect of haloperidol on development versus expression.

Repeated, intermittent administration of psychomotor stimulants has been shown to produce increasing effects (behavioral sensitization) in many species of animals. In a novel two-day sensitization paradigm, rats that received a single high dose of cocaine (40 mg/kg) compared with saline on day 1 showed an increased locomotor response to a challenge dose (10 mg/kg) on day 2. This effect is conditioned or context-dependent; i.e., it is only observed if the rats received cocaine in an environment similar to the test environment. If the cocaine-induced hyperactivity on day 1 is prevented with pharmacological agents such as haloperidol and diazepam, sensitization on day 2 does not occur. Furthermore, although moderate (0.2 mg/kg) and high doses (0.5 mg/kg) of haloperidol (day 1) prevented the development of sensitization to cocaine, they were ineffective when given prior to the day 2 challenge dose in preventing the expression of sensitization. Thus, this type of cocaine sensitization appears to involve conditioning, show stimulus generalization, and offer a possible model for clinical neuroleptic nonresponsiveness once stimulant-induced pathological behavior has been induced.

Animals↗