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Biomedical subjects

C Tucker

Publications and source records attributed to C Tucker.

At least 19 recordsLinked to original sources

Cyathostome fecal egg count trends in horses treated with moxidectin, ivermectin or fenbendazole.

Commercial preparations of fenbendazole (Safe-Guard, Intervet), ivermectin (Eqvalan, Merial) or moxidectin (Quest, Fort Dodge) were administered once to horses scheduled for routine parasiticide treatment. In total, 93 horses from six cooperating farms were used in the study. Computer generated, random allocation of horses to treatment group was conducted at each farm. Fecal egg counts were determined for all horses on trial days 0, 56, 84 and 112, with corresponding calendar dates that were unique to each farm. Only strongyle egg counts from animals which were positive at day 0 were used for analysis of variance and comparisons. Counts for the three treatment groups were similar at day 0, moxidectin<ivermectin<fenbendazole for days 56 and 84, and moxidectin<ivermectin=fenbendazole on day 112 (P<0.05). Reductions of geometric mean egg counts from day 0 levels were 99.1, 97.6 and 94.9% for moxidectin, 16.4, -27.0 and -32.0% for fenbendazole and 85.9, 24.2 and -8.1% for ivermectin on trial days 56, 84 and 112, respectively. Adverse reactions to treatment were not observed for any of the parasiticides.

Animals↗

Interactions within the coiled-coil domain of RetGC-1 guanylyl cyclase are optimized for regulation rather than for high affinity.

RetGC-1, a member of the membrane guanylyl cyclase family of proteins, is regulated in photoreceptor cells by a Ca(2+)-binding protein known as GCAP-1. Proper regulation of RetGC-1 is essential in photoreceptor cells for normal light adaptation and recovery to the dark state. In this study we show that cGMP synthesis by RetGC-1 requires dimerization, because critical functions in the catalytic site must be provided by each of the two polypeptide chains of the dimer. We also show that an intact alpha-helical coiled-coil structure is required to provide dimerization strength for the catalytic domain of RetGC-1. However, the dimerization strength of this domain must be precisely optimized for proper regulation by GCAP-1. We found that Arg(838) within the dimerization domain establishes the Ca(2+) sensitivity of RetGC-1 by determining the strength of the coiled-coil interaction. Arg(838) substitutions dominantly enhance cGMP synthesis even at the highest Ca(2+) concentrations that occur in normal dark-adapted photoreceptor cells. Molecular dynamics simulations suggest that Arg(838) substitutions disrupt a small network of salt bridges to allow an abnormal extension of coiled-coil structure. Substitutions at Arg(838) were first identified by linkage to the retinal degenerative disease, autosomal dominant cone rod dystrophy (adCORD). Consistent with the characteristics of this disease, the Arg(838)-substituted RetGC-1 mutants exhibit a dominant biochemical phenotype. We propose that accelerated cGMP synthesis in humans with adCORD is the primary cause of cone-rod degeneration.

Calcium↗

Demographic and medical predictors of medication compliance among ethnically different pediatric renal transplant patients.

Medication adherence in African-American and European-American pediatric renal transplant recipients was evaluated by four separate measures. Demographic and medical factors were analyzed. Based on pill count/refill history, European-American females were more compliant than their male counterparts. Based on self-ratings of compliance, African-American recipients were more compliant if they had vs. had not had dialysis experience prior to their transplant. These recipients also had higher self-ratings of compliance if their donors were cadaveric rather than living related.

Adolescent↗

Assessment of DNA vaccine potential for juvenile Japanese flounder Paralichthys olivaceus, through the introduction of reporter genes by particle bombardment and histopathology.

Genetic immunisation potential, following DNA bombardment for juvenile Japanese flounder, Paralichthys olivaceus was examined. GFP plasmids bombarded at two pressures, 150 and 300psi were sampled at 1, 7, 14 and 28 days, greater immunofluorescence was observed at the higher bombardment pressure. Histopathology, at 3 h post bombardment showed considerable damage to fish epithelial and dermal tissues when bombarded at pressures greater than 200 psi, with many DNA-coated gold particles present. At 150psi there was little pathology and no DNA-coated particles. Histopathology, up to 28 days again showed little pathology at 150 psi with few DNA-coated particles, whereas at 300 psi there was significant pathology observed with many DNA-coated particles seen in conjunction with the cytoplasm of inflammatory cells. By day 28 epithelial coverage was observed with tissue damage restricted to the dermal layer. Chloramphenicol acetyltransferase (CAT) assay showed long term and stable expression of the CAT protein from day 1 to day 60. The transcription activity of two promoters; pCMV-CAT and pSV2-CAT showed greater activity in the former. It was concluded that DNA vaccination potential for juvenile flounder is a viable option.

Animals↗

Dose confirmation of moxidectin pour-on against natural nematode infections in lactating dairy cows.

The nematocidal effectiveness of moxidectin, administered topically at the rate of 500 mcg/kg BW, was determined for lactating dairy cows. Naturally infected animals were given either topical vehicle or moxidectin (Cydectin Pour-On Fort Dodge Animal Health) at the rate of 1 ml/10 kg BW (10 animals per treatment group), and sacrificed 14-18 days post-treatment for nematode enumeration. 100% efficacies were recorded for Ostertagia lyrata males, Cooperia punctata males and Oesophagostomum radiatum L4, with treatment group differences in geometric means significant (P < 0.05) for all. Populations of Trichostrongylus L4 and adult O. radiatum were also reduced by 100%, but low prevalence rates in the control animals precluded meaningful statistical inference. Nematode populations for which efficacies ranged from 96.7 to 99.6% (based on geometric means) and for which treatment group differences were significant (P < 0.05) included Ostertagia spp. adult females, inhibited L4 and developing L4, O. ostertagi adult males, Trichostrongylus axei adults and Cooperia spp. adult females. For all nematodes combined, moxidectin was 98.9% efficacious. In addition to exhibiting excellent nematocidal effectiveness, topical moxidectin was demonstrated to be safe, with animal health and milk production unaffected during the study.

Abomasum↗

Designing response scales for cross-cultural use in health care: data from the development of the UK WHOQOL.

Designing response scales for use in cross-cultural situations presents several semantic and conceptual challenges. Here we report response scales designed in the UK, using a method developed collaboratively by the WHOQOL Group to tackle some of these issues. The response scales were generated for use with items established for a British version of a new cross-cultural quality of life measure for health and health care--the UK WHOQOL. A quota sample of 20 sick and well people assigned 60 descriptions to separate 100 mm lines (15 for each of 4 types of response scale) where the polar anchor points had been internationally agreed as meaningful in 10 countries. Means and standard deviations (SD) were calculated for each label appropriate to that response scale. The closest mean and smallest SD earmarked labels for each type of scale at the 25%, 50% and 75% interval. This research provides a set of contemporary, 5-point interval response scales that have the potential to be used in any number of British health and health-care questionnaires where subjective measures are needed.

Adult↗

Living with schizophrenia: caring for a person with a severe mental illness.

Data from a survey of a total population of patients with schizophrenia or schizoaffective disorder were used to examine the relationship between patient behaviours and the experience of caregiving. Carers were more distressed by depressed behaviours in the patient than any other type of behaviour, including behaviour associated with florid psychotic episodes. The number of patient needs met by the caregiver was also associated with a negative appraisal of caregiving. A comparison of patients who were living with an informal carer and those who were living alone or in hostel accommodation showed that the former group were less likely than the latter to have been either and inpatient or a day patient during the previous year.

Adult↗

Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to viral reverse transcription.

Infection of monocytes with human immunodeficiency virus type 1(Ba-L) (HIV-1(Ba-L)) is significantly inhibited by treatment with the serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI). SLPI does not appear to act on virus directly, but rather the inhibitory activity is most likely due to interaction with the host cell. The current study was initiated to investigate how SLPI interacts with monocytes to inhibit infection. SLPI was found to bind to monocytes with high affinity to a single class of receptor sites (approximately 7,000 receptors per monocyte, K(D) = 3.6 nmol/L). The putative SLPI receptor was identified as a surface protein with a molecular weight of 55 +/- 5 kD. A well-characterized function of SLPI is inhibition of neutrophil elastase and cathepsin G. However, two SLPI mutants (or muteins) that contain single amino acid substitutions and exhibit greatly reduced protease inhibitory activity still bound to monocytes and retained anti-HIV-1 activity. SLPI consists of two domains, of which the C-terminal domain contains the protease inhibiting region. However, when tested independently, neither domain had potent anti-HIV-1 activity. SLPI binding neither prevented virus binding to monocytes nor attenuated the infectivity of any virus progeny that escaped inhibition by SLPI. A polymerase chain reaction (PCR)-based assay for newly generated viral DNA demonstrated that SLPI blocks at or before viral DNA synthesis. Therefore, it most likely inhibits a step of viral infection that occurs after virus binding but before reverse transcription. Taken together, the unique antiviral activity of SLPI, which may be independent of its previously characterized antiprotease activity, appears to reside in disruption of the viral infection process soon after virus binding.

Binding Sites↗

Probing the kinesin-microtubule interaction.

Kinesin is a mechanoenzyme that couples adenosine triphosphate hydrolysis to the generation of force and movement along microtubules. To gain insight into the interactions of kinesin and microtubules, cross-linking, mapping, and proteolysis experiments were executed. The motor domain of kinesin was consistently cross-linked to both alpha- and beta-tubulin subunits. Initial mapping of the cross-linked kinesin suggested that amino acids within the N- and C-terminal cyanogen bromide fragments of the motor domain formed cross-links to both alpha- and beta-tubulin subunits. Mapping of the cross-linked tubulin suggested that cross-linking to kinesin motors occurred within the negatively charged, C-terminal cyanogen bromide fragments of alpha- and beta-tubulin subunits. Treatment of microtubules with subtilisin, a protease that cleaves C-terminal fragments from alpha- and beta-tubulin, reduced their ability to be cross-linked to kinesin motors supporting the idea that C-terminal sequences of alpha- and beta-tubulin may interact with kinesin motors. Finally, of three synthetic peptides, a peptide consisting of the last 12 C-terminal amino acids of beta-tubulin competitively interfered with the microtubule-stimulated adenosine triphosphatase activity of the kinesin motor, further suggesting that C-terminal sequences of beta-tubulin may be involved in kinesin binding.

Animals↗

Endectocidal efficacies of doramectin in naturally parasitized pigs.

The studies reported here were conducted to investigate the effectiveness of doramectin, given intramuscularly at the rate of 300 micrograms kg-1 of bodyweight, in the treatment of naturally acquired porcine nematodosis and acariasis. Twenty pigs demonstrated to be naturally infected with pulmonary and gastrointestinal nematodes were used in one control study, and 22 pigs demonstrated to be naturally parasitized with Sarcoptes scabiei var. suis were used in a second study. In both studies, animals were evenly divided between doramectin plus vehicle and vehicle-treated groups by restricted randomization. In the anthelmintic study, all pigs were necropsied for parasite collection on post-treatment Days 14 and 15. The acaricidal evaluation study was 28 days in duration after treatment, with mite population quantifications on the day of treatment and on post-treatment Days 7, 14, 21 and 28. Doramectin proved 100% effective in the removal of Metastrongylus salmi, M. elongatus, M. pudendotectus, Strongyloides ransomi, Ascaris suum and Oesophagostomum dentatum. Levels of Hyostrongylus rubidus, Ascarops strongylina and Macracanthorhynchus hirudinaceus, as observed at necropsy in the doramectin-treated pigs, were reduced by 99.2%, 99.5% and 62.1%, respectively, as compared with levels seen in the control pigs. In regard to Sarcoptes scabiei var. suis, no live mites were recovered from doramectin-treated pigs during the 7-28 day post-treatment period. In conclusion, doramectin proved highly effective in the treatment of naturally acquired porcine nematodosis and Sarcoptes scabiei var. suis infestation. In addition, all treatments were safe and well tolerated, with no adverse reactions noted in any trial animals.

Animals↗

Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-I.

Despite the presence of HIV-1 in the oral cavity, transmission of the virus through saliva has not been proven. Consistent with these observations, we recently identified an endogenous 12 kD protein, secretory leukocyte protease inhibitor (SLPI), in saliva which blocks HIV-1 infection in vitro. Whereas other salivary proteins tested were inactive, purified native or recombinant SLPI inhibited HIV-1 infection of human monocytes at 100 ng ml-1. Levels of SLPI quantitated by ELISA in saliva from control and HIV-1 infected individuals exceeded this level, consistent with in vivo antiviral activity. As in saliva, levels of SLPI mRNA determined by Northern hybridization, and protein as assessed by immunohistochemistry in the salivary glands of control and infected populations were comparable. In contrast to adults, oral transmission occurs in infants, possibly due to their lack of fully developed salivary glands. To determine whether the inadequate antiviral protection might be compensated for by maternal sources, we evaluated breast milk samples obtained 6 months postpartum. Levels of SLPI were significantly lower than in saliva and not sufficient to provide antiviral protection in contrast to colostrum samples in which SLPI levels were equivalent to those in saliva and able to inhibit HIV-1 infection when tested in vitro. These data suggest that breast milk may provide transient antiviral activity in the newborn, but that this maternal source of SLPI is of insufficient duration to maintain protection against mucosal transmission of the virus over time. The high functional levels of SLPI in saliva and the low levels in mature breast milk correlate with negligible rates of HIV-1 transmission by saliva and higher rates by breast feeding.

Adult↗

The quality and management of written information presented to women undergoing hysterectomy.

A study of a random sample of hospitals in England that provide information leaflets for women undergoing hysterectomy indicates a large variation in quality. In general, the findings reveal that written information for patients is given a relatively low priority. Production and dissemination of information for hysterectomy patients is somewhat ad hoc. It is not clear that any evaluation of the leaflets has been conducted to prove the efficacy of the available literature. While the majority of leaflets include information deemed essential by past hysterectomy patients, the presentation of the recovery process often implies no control for the patient, and conceives normality with a narrow perspective about what healthy behaviour means for women. The provision of a specific timetable for resumption of housework duties in 65% of the leaflets is a case in point. On the basis of the results of the survey, recommendations are made concerning the improvement of the standard of patient information leaflets.

England↗

Developmental analysis of the cytomegalovirus enhancer in transgenic animals.

The major immediate-early promoter (MIEP) of human, cytomegalovirus (HCMV) constitutes a primary genetic switch for viral activation. In this study, regulation of the enhancer-containing segment (nucleotides -670 to +54) of the HCMV MIEP attached to the 1acZ reporter gene was examined in the developing embryos of transgenic mice to identify temporal and tissue-specific expression. We find that the transgene reporter is first detected as a dorsal stripe of expression in the neural folds of embryos at day 8.5 postcoitum (p.c.). A broad expression pattern is exhibited in embryos at day 9.5 p.c. This pattern becomes more restricted by day 10.5 p.c. as organogenesis progresses. By day 14.5 p.c., prominent expression is observed in a subpopulation of central nervous system cells and spinal ganglia, endothelial cells, muscle, skin, thyroid, parathyroid, kidney, lung, liver, and gut cells, and the pancreas and submandibular and pituitary glands. This distribution pattern is discussed in relation to human congenital HCMV infection. These results suggest that the transcriptional activity of the HCMV MIEP may determine in part, the ability of the virus to specifically target developing fetal tissues in utero.

Animals↗