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Biomedical subjects

D L Williams

Publications and source records attributed to D L Williams.

At least 19 recordsLinked to original sources
PubMed2006

Chronic ocular lesions in tawny owls (Strix aluco) injured by road traffic.

The chronic ocular lesions suffered by 50 tawny owls (Strix aluco) injured by road traffic were investigated. They included non-healing corneal erosions, cataracts and retinal scarring, and periretinal membrane formation. The intraocular pressure was significantly lower in the eyes with intraocular inflammatory pathology and higher in the eyes with irido- or cyclodialysis than in ophthalmically normal eyes. Cicatritial retinal lesions were not associated with high titres of antibodies to Toxoplasma species. The findings correlate with those observed in human beings with eye injuries due to high-speed blunt trauma.

Animals↗
PubMed2006

Ultrasonographic examination of ocular lesions in farmed halibut.

This paper describes the use of ultrasound to document ocular abnormalities occurring in farmed halibut. A cystic condition of the posterior segment of farmed halibut with a number of ocular sequelae has been reported previously. Further research to elucidate the aetiology and pathogenesis of this condition requires in vivo determination of ocular health over and above that provided by ophthalmoscopy alone. Ocular ultrasonography would appear to be an optimal technique for evaluating the presence of gas- or fluid-filled cysts in the posterior segment and retrobulbar space. The aim of this study was to evaluate this technique for investigation of the piscine eye and specifically to define the role of ultrasonography to detect gas bubble formation in the choroid of farmed halibut, a factor considered central to ocular pathology in many of these fish. In particular the study sought to assess the minimum size of halibut in which intraocular cystic lesions could be identified by ultrasonography and the minimum size of lesion identified by ocular ultrasonography. A second objective was to correlate ultrasonographic findings with lesions found at post mortem ocular examination. A number of halibut of varying sizes, with and without clinically apparent ocular lesions, were subjected to examination under anaesthesia. A proportion of these fish were subsequently sacrificed to allow post mortem ocular evaluation with the aim of correlating ultrasonographic findings with intraocular pathological defects.

Animals↗
PubMed2006

Overfeeding-induced weight gain suppresses plasma ghrelin levels in rats.

The elevation of plasma ghrelin associated with weight loss has been taken as evidence of a role for ghrelin in the adaptive response to body weight change. However, there has been no clear experimental evidence that circulating ghrelin is suppressed by weight gain. We investigate this issue using a model of involuntary (intra-gastric gavage) overfeeding-induced obesity. Rats were first maintained at normal body weight with 4 daily tube-feedings of liquid diet (2.11 kcal/ml), each delivered at a volume of 9 ml. Gavage volume was then increased to 13 ml/feeding for 2 weeks, during which rats gained 25% of their initial body weight. Fasting plasma ghrelin levels and the response to 9- and 13-ml intra-gastric load sizes were measured during the weight-stable and overfed conditions. We found that: 1) weight gain decreased circulating ghrelin levels; 2) this response could not be attributed to additional food in the gastrointestinal tract; 3) the ghrelin response to nutrient loads was diminished in the obese vs normal-weight conditions. Having discounted diet composition and differences in gastric contents at the time of blood sampling, the decrease in ghrelin levels with overfeeding can be unambiguously attributed to physiological correlates of weight gain.

Adipose Tissue↗
PubMed2006

Surgical removal of a canine orbital lipoma.

A 10-year-old, female, neutered Cairn terrier was presented with a progressively enlarging, cream-white fluctuant subconjunctival swelling in the right eye. A fine-needle aspirate performed under topical anaesthesia showed that the mass contained lipomatous tissue. Orbital ultrasonography showed the mass to have a distinct border and to extend into the posterior orbit. The mass was removed via a conjunctival incision. It had a distinct capsule anteriorly, while the border of the mass was less readily identified in the posterior orbit. Histopathological examination showed the mass to be a lipoma. The dog recovered uneventfully from surgery, and no recurrence has been noted after 12 months.

Anesthesia, Local↗
PubMed2006

The continuing challenges of leprosy.

Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases.

Animals↗
PubMed2005

Expression of nine-banded armadillo (Dasypus novemcinctus) interleukin-2 in E. coli.

The nine-banded armadillo (Dasypus novemcinctus) is the only immunologically intact animal that regularly develops lepromatous-type leprosy when inoculated with Mycobacterium leprae. However, the ability to exploit this model for understanding the pathogenesis of leprosy has been limited by a lack of suitable immunological reagents. Recently, efforts began to sequence the entire armadillo genome, and this sequence information will help make possible the development of a wide array of new immunological reagents suitable for use with armadillos. Using the available sequence data, a region of high homology to interleukin-2 of other mammals was identified. Primers were designed to amplify the coding region corresponding to the mature peptide and its exact sequence was confirmed. cDNA was made from ConA-stimulated armadillo PBMC. The amplified coding region was sub-cloned into a pET expression vector and transformed into Escherichia coli for over-expression. The subsequent product was characterized by SDS-PAGE and bioassays. Tritiated thymidine incorporation by CTLL-2 and armadillo lymphoblasts confirmed functionality of the recombinant product. The advent of the D. novemcinctus genome sequence and subsequent generation of immunological tools will assist in advancing the armadillo as a translational model for leprosy.

Amino Acid Sequence↗
PubMed2005

Aggravating factors in the development of ocular abnormalities in farmed Atlantic halibut (Hippoglossus hippoglossus).

Cystic lesions in the eyes of farmed halibut with a number of ocular sequelae have been reported previously with evidence that the condition can be associated with increased activity of choroidal carbonic anhydrase and elevated oxygen tension in the aqueous humour of affected fish. These changes may be compared to the 'bends' in human divers which are characterized by elevated circulating levels of nitrogen together with aggravating factors such as physical exercise. It is postulated that bubble formation and subsequent development of cysts in halibut require not only high aqueous humour oxygen tension but also the imposition of factors such as handling or intraspecific aggression which lead to bubble formation. A significantly higher incidence of lesions was noted in fish handled, weighed and measured every two weeks compared with a control group of unhandled fish, suggesting that physical activity associated with handled and possibly also intraspecific aggression is a factor in generation of ocular lesions in these fish.

Animals↗
PubMed2005

Efficacy of topical aciclovir for the treatment of feline herpetic keratitis: results of a prospective clinical trial and data from in vitro investigations.

This study aimed to evaluate the efficacy of topical ophthalmic aciclovir applied five times daily as a treatment for feline herpesvirus type 1 (FHV-1) keratitis in a group of cats in a first-opinion practice setting. Cats with ocular signs indicative of FHV-1 or Chlamydophila species infection, predominantly conjunctivitis and keratitis, were tested for FHV-1 antigen using an immunofluorescent technique on air-dried conjunctival swabs. They were first treated with topical chlortetracycline with efficacy against Chlamydophila species and then, in cases positive for FHV-1, with topical aciclovir. The time to recovery was determined and illustrated using a Kaplan-Meier plot. Three cats were infected with Chlamydophila species and showed a median time to recovery of 14 days (95 per cent confidence interval [CI] 10 to 18 days), while 30 cats infected with FHV-1 showed a median time to recovery of 12 days (95 per cent CI 10 to 14 days). The drug dose at which 50 per cent plaque reduction (ED50) occurred in a standard plaque reduction assay was determined in an in vitro study. This showed a mean (SD) ED50 of aciclovir of 25 (3.5) mg/ml compared with 0.4 (0.05) mg/ml for trifluorothymidine, a drug known to be efficacious against FHV-1. The study shows that even though aciclovir is generally considered to lack efficacy against ocular FHV-1 infection, when used frequently it can have a beneficial effect in FHV-1 conjunctivitis and keratitis.

Acyclovir↗
PubMed2004

Retinal dysplasia in wild otters (Lutra lutra).

Eyes from 88 otters found dead in south-west England between 1990 and 2000, were collected as part of a larger pathological study. Histopathological examination of 131 eyes revealed dysplastic changes such as rosetting and folding in the retinas of 26 of the otters. In the eyes of 42 of the otters there were postmortem and fixation-induced retinal detachment which complicated the differentiation of dysplastic from normal retina, but 11 eyes had folds which probably indicated a dysplastic pathology. The eyes of 18 of the otters had inflammatory or autolytic changes which precluded a definitive evaluation of their dysplastic status. Liver samples from 55 of the otters were analysed for a range of polychlorinated hydrocarbons and for vitamin A. The otters with dysplastic retinas had significantly lower concentrations of vitamin A and higher concentrations of dieldrin than the otters with normal retinas.

Animals↗
PubMed2004

Intraocular oxygen tensions in normal and diseased eyes of farmed halibut.

We have previously documented ocular abnormalities in farmed halibut and reported that the production of gas-filled posterior segment cysts appears to be central in the pathogenesis of many, if not all of the signs in these eyes. In a number of fish, gas bubbles may be seen in the anterior chamber of the eye, especially after trauma or strenuous exertion associated with handling. A knowledge of the composition of this gas is important in understanding fully the mechanism of gas and cyst production. Here we report investigations into the composition of gas in the globes of normal fish, fish in which intraocular cysts have been documented previously by ultrasonography and fish where post-mortem examination demonstrated both gas- and fluid-filled choroidal cysts. High levels of oxygen were demonstrated in samples of aqueous from all fish but fish with affected eyes had a statistically significantly higher partial pressure of oxygen than did fish with normal eyes.

Animals↗
PubMed2003

Brainstem melanocortin 3/4 receptor stimulation increases uncoupling protein gene expression in brown fat.

Central administration of melanocortin 3 and 4 receptor (MC3/4-R) agonists increases energy expenditure, with the hypothalamus commonly held as the primary site of action. It is also clear, however, that MC4-R are expressed in caudal brainstem structures of relevance to the control of energy expenditure. Three experiments investigated whether hindbrain MC-R contribute to the energy expenditure effects of central MC3/4-R agonist treatments; in each, we examined the effect of fourth intracerebroventricular (i.c.v.) administration of a MC3/4-R agonist, MTII (three injections, each separated by 12 h), on uncoupling protein 1 (UCP-1) gene expression in brown adipose tissue (BAT). First, we compared the effects of fourth and third i.c.v. administration of MTII and found that the hindbrain and forebrain treatments were equally effective at elevating UCP-1 mRNA expression in BAT compared with the respective vehicle-treated group results. A second experiment demonstrated that the fourth i.c.v. MTII-induced rise in UCP-1 expression was mediated by sympathetic outflow to BAT by showing that this response was abolished by surgical denervation of BAT. In the third experiment, we showed that chronic decerebrate rats, like their neurologically intact controls, elevated UCP-1 mRNA expression in response to fourth i.c.v. MTII administration. Taken together, the results indicate that: 1) there is an independent caudal brainstem MC3/4-R trigger for a sympathetically stimulated elevation in BAT UCP-1 gene expression, and 2) the MTII-induced rise in UCP-1 expression can be mediated by circuitry intrinsic to the caudal brainstem and spinal cord.

Adipose Tissue, Brown↗
PubMed2002

Use of punctal occlusion in the treatment of canine keratoconjunctivitis sicca.

Twenty eyes of 10 dogs with keratoconjunctivitis sicca (KCS) were treated by occlusion of the ventral nasolacrimal punctum with a silicone punctal plug in order to increase the volume of the remaining tear lake. Punctal size was measured using a commercially available punctal gauge and the appropriate sized plug was inserted under local anaesthesia. Seven dogs showed an increase in Schirmer tear test I (STT) value. STT values immediately prior to plug placement were 2.3 +/- 1.7 mm/minute. STT values with punctal occlusion were 6.1 +/- 4.1 mm/minute, giving a mean increase of 3.8 +/- 2.7 mm/minute (P<0.001). In 14 eyes of eight dogs, the increase in STT values was accompanied by a clinical improvement in the appearance of the ocular surface. In the three dogs with no increase in STT values, the use of punctal plugs reduced the frequency of artificial tear replacement therapy required to maintain a healthy ocular surface. These results show that use of punctal plugs in dogs with KCS may be appropriate where other lacrimomimetic medications have been unsuccessful.

Animals↗
PubMed2002

Clinical pathology accreditation: standards for the medical laboratory.

This article describes a new set of revised standards for the medical laboratory, which have been produced by Clinical Pathology Accreditation (UK) Ltd (CPA). The original standards have been in use since 1992 and it was recognised that extensive revision was required. A standards revision group was established by CPA and this group used several international standards as source references, so that the resulting new standards are compatible with the most recent international reference sources. The aim is to make the assessment of medical laboratories as objective as possible in the future. CPA plans to introduce these standards in the UK in 2003 following extensive consultation with professional bodies, piloting in selected laboratories, and training of assessors.

Accreditation↗
PubMed2001

Scavenger receptor class B, type I-mediated uptake of various lipids into cells. Influence of the nature of the donor particle interaction with the receptor.

Scavenger receptor (SR)-BI is the first molecularly defined receptor for high density lipoprotein (HDL) and it can mediate the selective uptake of cholesteryl ester into cells. To elucidate the molecular mechanisms by which SR-BI facilitates lipid uptake, we examined the connection between lipid donor particle binding and lipid uptake using kidney COS-7 cells transiently transfected with SR-BI. We systematically compared the uptake of [(3)H]cholesteryl oleoyl ether (CE) and [(14)C]sphingomyelin (SM) from apolipoprotein (apo) A-I-containing reconstituted HDL (rHDL) particles and apo-free lipid donor particles. Although both types of lipid donor could bind to SR-BI, only apo-containing lipid donors exhibited preferential delivery of CE over SM (i.e. nonstoichiometric lipid uptake). In contrast, apo-free lipid donor particles (phospholipid unilamellar vesicles, lipid emulsion particles) gave rise to stoichiometric lipid uptake due to interaction with SR-BI. This apparent whole particle uptake was not due to endocytosis, but rather fusion of the lipid components of the lipid donor with the cell plasma membrane; this process is perhaps mediated by a fusogenic motif in the extracellular domain of SR-BI. The interaction of apoA-I with SR-BI not only prevents fusion of the lipid donor with the plasma membrane but also allows the optimal selective lipid uptake. A comparison of rHDL particles containing apoA-I and apoE-3 showed that while both particles bound equally well to SR-BI, the apoA-I particle gave approximately 2-fold greater CE selective uptake. Catabolism of all major HDL lipids can occur via SR-BI with the relative selective uptake rate constants for CE, free cholesterol, triglycerides (triolein), and phosphatidylcholine being 1, 1.6, 0.7, and 0.2, respectively. It follows that a putative nonpolar channel created by SR-BI between the bound HDL particle and the cell plasma membrane is better able to accommodate the uptake of neutral lipids (e.g. cholesterol) relative to polar phospholipids.

Animals↗
PubMed2001

Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception.

The two mammalian neuropeptides NPFF and NPAF have been shown to have important roles in nociception, anxiety, learning and memory, and cardiovascular reflex. Two receptors (FF1 and FF2) have been molecularly identified for NPFF and NPAF. We have now characterized a novel gene designated NPVF that encodes two neuropeptides highly similar to NPFF. NPVF mRNA was detected specifically in a region between the dorsomedial and ventromedial hypothalamic nuclei. NPVF-derived peptides displayed higher affinity for FF1 than NPFF-derived peptides, but showed poor agonist activity for FF2. Following intracerebral ventricular administration, a NPVF-derived peptide blocked morphine-induced analgesia more potently than NPFF in both acute and inflammatory models of pain. In situ hybridization analysis revealed distinct expression patterns of FF1 and FF2 in the rat central nervous system. FF1 was broadly distributed, with the highest levels found in specific regions of the limbic system and the brainstem where NPVF-producing neurons were shown to project. FF2, in contrast, was mostly expressed in the spinal cord and some regions of the thalamus. These results indicate that the endogenous ligands for FF1 and FF2 are NPVF- and NPFF-derived peptides, respectively, and suggest that the NPVF/FF1 system may be an important part of endogenous anti-opioid mechanism.

Amino Acid Sequence↗
PubMed2001

Gemcitabine modulation of alkylator therapy: a phase I trial of escalating gemcitabine added to fixed doses of ifosfamide and doxorubicin.

BACKGROUND: The authors investigated the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) associated with the addition of a biomodulating dose of gemcitabine to an established regimen of ifosfamide and doxorubicin as part of a program to explore the potential of low-dose gemcitabine to modulate the activity of alkylating agents. METHODS: A Phase I trial was carried out in a population of patients with bladder or pelvic carcinoma for whom no standard therapy was available. Doses of ifosfamide and doxorubicin were held fixed at 2 g/m(2) for 4 days and 20 mg/m(2) for 3 days, respectively. Gemcitabine was given on Day 2 and Day 4 at doses of 90 mg/m(2), 150 mg/m(2), and 200 mg/m(2) per dose. RESULTS: A total of 18 patients received 53 courses of therapy. Myelosuppression was dose limiting. Nonhematologic toxicity also was significant, with 10 of 18 patients experiencing toxicity of Grade 3 or greater. For previously untreated patients with an intact performance status, the MTD for gemcitabine in this context was at least 150 mg/m(2) per dose. According to an intent-to-treat analysis, 11 of 18 patients demonstrated a clinically significant response to this regimen. CONCLUSIONS: The regimen of ifosfamide and doxorubicin with the addition of gemcitabine was significantly toxic but has promising activity. Based on the observed activity and the generally reversible nature of the toxicity, the authors have initiated a Phase II trial of this regimen in patients with untreated, metastatic urothelial carcinoma.

Adult↗