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Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 91 records · Page 5Linked to original sources
PubMed2001

Killing of prion-damaged neurones by microglia.

The loss of neurones that occurs in the transmissible spongiform encephalopathies, or prion diseases, can be reproduced in vitro by incubating neuronal cultures with either peptides derived from the prion protein or with partially purified prion preparations. In the present studies, the extent of neuronal loss on exposure to these prions or prion peptides was increased by the addition of microglia, a process that was dependent upon the number of microglia added, the concentration of prions/peptides present and the degree of fibrillarity of the prion peptides. Microglia also killed scrapie-infected neuroblastoma cells expressing infectious PrP(SC). Microglia secreted low amounts of interleukin (IL)-6 when incubated with peptides alone but up to 10 times as much IL-6 when incubated with peptide-treated neurones, suggesting that microglia recognise peptide-induced changes in neurones.

Animals↗
PubMed2001

A guinea pig model of low-dose Mycobacterium bovis aerogenic infection.

In order to develop a model of Mycobacterium bovis infection with pathogenetical relevance, a modified version of the Henderson apparatus was used to deliver infectious aerosols directly to the snouts of guinea pigs. Aerosols generated from 10(6), 10(7), 10(8)CFU/ml M. bovis suspensions established disease in every animal, with estimated retained doses of 10, 100, 1000 CFU, respectively. For comparison, other guinea pigs were inoculated with 100 CFU M. bovis intramuscularly (i.m.). Pathology and bacterial colonisation of lungs and spleen varied according to the dose and route of inoculation. Animals inoculated i.m. gave a significant cutaneous tuberculin hypersensitivity reaction earlier after testing than those infected aerogenically. A serological response to M. bovis antigens was detected in all infected animals. Intensity of antigen recognition was dose-dependent and although the range of antigens recognised varied between animals, a 25 kDa antigen present in the cell fraction was serodominant. Thus, a reproducible guinea pig model has been defined that may be suitable for virulence, vaccination, and immunological studies.

Administration, Intranasal↗
PubMed2001

A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies characterized by chronic distal weakness with progressive muscular atrophy and sensory loss in the distal extremities. Inheritance can be autosomal dominant, X-linked or autosomal recessive (ARCMT). Recently, a locus responsible for a demyelinating form of ARCMT disease, named CMT4F, has been mapped on 19q13 in a large consanguineous Lebanese family. L- and S-periaxin are proteins of myelinating Schwann cells and homozygous periaxin-null mice display extensive demyelination of myelinated fibers in the peripheral nervous system, which suggests that the periaxin gene is a good candidate gene for an ARCMT disease. The human gene encoding the periaxins (PRX) was mapped to 19q13, in the CMT4F candidate interval. After characterizing the human PRX gene, we identified a nonsense R196X mutation in the Lebanese family which cosegregated with CMT. Histopathological and immunohistochemical analysis of a sural nerve biopsy of one patient revealed common features with the mouse mutant and the absence of L-periaxin from the myelin sheath. These data confirm the importance of the periaxin proteins to normal Schwann cell function and substantiate the utility of the periaxin-null mouse as a model of ARCMT disease.

Amino Acid Sequence↗
PubMed2001

Prevalence of HTLV-I-associated T-cell lymphoma.

In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials.

Black or African American↗
PubMed2001

Poststreptococcal acute disseminated encephalomyelitis with basal ganglia involvement and auto-reactive antibasal ganglia antibodies.

Antibasal ganglia antibodies (ABGA) are associated with Sydenham's chorea and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. We present 10 patients with acute disseminated encephalomyelitis (ADEM) associated with Group A beta hemolytic streptococcal infection. The clinical phenotype was novel, with 50% having a dystonic extrapyramidal movement disorder, and 70% a behavioral syndrome. None of the patients had rheumatic fever or Sydenham's chorea. Enzyme-linked immunosorbent assay, Western immunoblotting, and immunohistochemistry were used to detect ABGA. Neurological (n = 40) and streptococcal (n = 40) controls were used for comparison. Enzyme-linked immunosorbent assay results showed significantly elevated ABGA in the patients with poststreptococcal ADEM. Western immunoblotting demonstrated ABGA reactivity to three dominant protein bands of 60, 67, or 80 kDa; a finding not reproduced in controls. Fluorescent immunohistochemistry demonstrated specific binding to large striatal neurones, which was not seen in controls. Streptococcal serology was also significantly elevated in the poststreptococcal ADEM group compared with neurological controls. Magnetic resonance imaging studies showed hyperintense basal ganglia in 80% of patients with poststreptococcal ADEM, compared to 18% of patients with nonstreptococcal ADEM. These findings support a new subgroup of postinfectious autoimmune inflammatory disorders associated with Group A beta hemolytic streptococcus, abnormal basal ganglia imaging, and elevated ABGA.

Acute Disease↗
PubMed2001

Is it inherently prejudicial to try a juvenile as an adult?

Given only information that a youth who could have been tried as either an adult or as a juvenile was being tried as an adult for murder, 218 undergraduate mock jurors were able to form consistent impressions of the defendant. A very high percent of our mock jurors included a criminal or juvenile justice history as part of that impression. A very large majority of the mock jurors also said that knowledge of that criminal history would be relevant to their vote of guilty. Almost all mock jurors said they would be influenced toward voting guilty by knowledge of a previous criminal history. Few of the other components of the impression were so closely correlated with a judgment of relevance, or with a judgment that they would be influenced toward voting guilty by the knowledge of that component of the stereotype. The effect is relatively specific to knowledge of a previous criminal history. The study has limited ecological validity. Nonetheless, we raise questions about whether the fact that a youth is put on trial as an adult is inherently prejudicial, and violates the Sixth Amendment right to an impartial jury.

Adolescent↗
PubMed2001

The nature of siliceous mosaics forming the first shell of the brachiopod Discinisca.

The juvenile shell of the brachiopod Discinisca consists of a mosaic of micrometer-sized siliceous tablets embedded in a chitinous substrate. The first-formed tablets are secreted on glycocalyx by a newly differentiated collective of outer epithelial cells. They are mainly rhombic but may also be ellipsoidal, discoidal, or deformed and sporadically overlap one another. On the surrounding juvenile shell, secreted by an incipient outer mantle lobe, the tablets are nearly all perfect rhombic plates in rhombic arrays. Their constant size, arrangement, and centripetal crystallization suggest intracellular assembly. The tablets, which are normally bilamellar, consist of discrete aggregates of crystalline spherules of silica in rhombic arrays within an organic matrix of fibrous protein and, presumably, a soluble polysaccharide(s). Mosaic secretion ceases at about the time when juveniles settle on the sea bed, which more or less coincides with the secretion of a ring of lamellae around the mosaic, induced by rapid advances and retractions of the outer mantle lobe prior to deposition of the organophosphatic mature shell. Energy dispersion X-ray analyses of pelagic and newly settled juveniles show that phosphatic secretion, even in the site of the first-formed outer epithelial collective, does not begin until all siliceous secretion has ceased.

Animals↗
PubMed2001

Patello-femoral tracking in the weight-bearing knee: a study of asymptomatic volunteers utilising dynamic magnetic resonance imaging: a preliminary report.

Normal patello-femoral tracking is not well defined, and conventional radiological techniques do not allow imaging in the physiological, weight-bearing stance. A vertical-access open configuration magnetic resonance scanner allows imaging of patello-femoral tracking during weight-bearing and through a wide range of knee flexion. We imaged 40 asymptomatic knees in this way, producing axial scans which were analysed qualitatively and quantitatively using sulcus angle, congruence angle, lateral patello-femoral angle and patellar centralisation, to assess patellar tilt and displacement. Mild lateral tilting in hyperextension with the quadriceps relaxed was seen, but quantitative assessment of this was impeded by internal rotation of the femur in extension. One-half of the knees were slightly laterally displaced in hyper-extension, becoming central during the first 30 degrees of knee flexion. During passive flexion of the knee in a seated position, fewer knees were laterally tilted or displaced, and no consistent change was seen during flexion. These results indicate that mild lateral tilting and displacement can be normal phenomena in the weight-bearing knee in early flexion and should not necessarily be taken as evidence of abnormal tracking in symptomatic patients. Lateral to medial movement of the patella occurs during normal knee flexion. In addition, imaging in the weight-bearing knee can provide valuable information not gained by imaging during passive knee flexion.

Adult↗
PubMed2001

Visualization of the transport of primary and secondary bile acids across liver tissue in rats: in vivo study with fluorescent bile acids.

BACKGROUND/AIMS: Lysyl fluorescein conjugated bile acid analogues (LFCBAA) closely parallel their natural counterparts. To assess LFCBAA as a tool for the visualization of bile acid transport within liver tissue. METHODS: Wistar rats were administered physiological concentrations of the primary bile acid analogue cholyllysyl fluoroscein (CLF) and of the secondary bile acid analogue lithocholyllysyl fluorescein (LLF) and serial liver biopsies were taken at fixed intervals. Both compounds were also injected retrogradely into the biliary tree. Frozen sections were examined by fluorescence microscopy. RESULTS: Both CLF and LLF were rapidly taken up from sinusoidal blood but differed significantly in their hepatic handling. CLF was rapidly transported into bile, whereas LLF transport was slower and produced significantly more bile duct fluorescence. LLF clearance showed a lobular gradient with last remaining bile acid being confined largely to zone 3. Both compounds were avidly taken up by cholangiocytes after injection intravenously or retrogradely into the biliary tree. CONCLUSIONS: Visualization of LFCBAA by fluorescence microscopy may yield further information regarding hepatobiliary bile acid localization during studies of physiological and pathological mechanisms involved in transport of bile acids. The presence of both compounds within cholangiocytes strongly suggests that they may undergo a degree of chole-hepatic recirculation.

Animals↗
PubMed2001

Assessing Australian undergraduate clinical learning.

Determining the clinical preparedness of undergraduate nursing students is vital in developing graduates who are ready to assume the roles of registered nurses. This paper reports findings relating to clinical assessment in Australian undergraduate nursing programs. Using data collected in a national survey and selected case studies, current assessment practices are described. Although students were increasingly exposed to a narrower range of clinical experiences, claims to comprehensive preparation of nurses remain prominent. Issues in the congruity between assessment methods and purported outcomes of clinical learning programs are discussed.

Australia↗
PubMed2001

Eyes absent mediates cross-talk between retinal determination genes and the receptor tyrosine kinase signaling pathway.

Eyes absent (eya) encodes a member of a network of nuclear transcription factors that promotes eye development in both vertebrates and invertebrates. Despite extensive studies, the molecular mechanisms whereby cell-cell signaling pathways coordinate the function of this retinal determination gene network remain unknown. Here, we report that Drosophila Eya function is positively regulated by mitogen-activated protein kinase (MAPK)-mediated phosphorylation and that this regulation extends to developmental contexts independent of eye determination. In vivo genetic analyses, together with in vitro kinase assay results, demonstrate that Eya is a substrate for extracellular signal-regulated kinase, the MAPK acting downstream in the receptor tyrosine kinase (RTK) signaling pathway. Thus, phosphorylation of Eya appears to provide a direct regulatory link between the RTK/Ras/MAPK signaling cascade and the retinal determination gene network.

Animals↗
PubMed2001

NMR and pattern recognition studies on the time-related metabolic effects of alpha-naphthylisothiocyanate on liver, urine, and plasma in the rat: an integrative metabonomic approach.

We present here a novel integrative metabonomic approach to probe toxic effects of drugs in experimental animals using alpha-naphthylisothiocyanate (ANIT) as a model hepatotoxicant. Male Han-Wistar rats were dosed with ANIT (150 mg/kg, n = 25), and plasma and liver samples were collected for NMR and magic-angle spinning (MAS) NMR spectroscopy at 3, 7, 24, 31, and 168 h postdosing. Urine was collected continuously for 3 days prior to dosing and up to 168 h postdose. Histopathology and plasma clinical chemistry was also performed at all time points. Liver samples were analyzed either intact by 600 MHz 1H MAS NMR techniques or using high resolution (liquid state) 1H NMR of water-acetonitrile extracts. These data were related to sequential 1H NMR measurements in urine and plasma using pattern recognition methods. 1D 1H NMR spectra were data-reduced and analyzed using principal components analysis (PCA) to show the time-dependent biochemical variations induced by ANIT toxicity. From the eigenvector loadings of the PCA, those regions of the 1H NMR spectra and hence the combinations of endogenous metabolites marking the main phase of the toxic episode were identified. The ANIT-induced biochemical manifestations included a hepatic lipidosis associated with hyperlipidaemia; hyperglycaemia and glycosuria; increased urinary excretion of taurine and creatine; a shift in energy metabolism characterized by increased plasma ketone bodies with reduced urinary excretion of tricarboxylic acid cycle intermediates and raised hepatic bile acids leading to bile aciduria. The integration of metabolic data derived from several sources gives a holistic approach to the study of time-related toxic effects in the intact system and enables the characterization of key metabolic effects during the development and recovery from a toxic lesion.

1-Naphthylisothiocyanate↗
PubMed2001

Multiple impacts of the HIV/AIDS epidemic on the aged in rural Uganda.

This paper reports research conducted among the aged residents of a rural, Southwestern Ugandan village. It documents their knowledge of HIV/AIDS, their perceptions of their own risk of infection, and the multiple impacts of the current HIV/AIDS epidemic on their lives. Most older individuals have a sound understanding of the sexual transmission of HIV, and some consider themselves to be at risk of infection through having multiple sexual partners. They attempt to limit their children's exposure to HIV, but many of these children have left the village to live in urban areas of relatively high HIV prevalence. The loss of adult children deprives the aged of any support these children might have provided as their parents' capabilities declined with advancing age. Female-headed households were more affected in this way than were male-headed households. The AIDS epidemic has increased the number of burials taking place in the village, and their accumulated costs, both in time and money, and created new hardships for the aged, who also have to cope with grief that accompanies continuing deaths among their children and their contemporaries' children.

Journal Article↗
PubMed2001

A study of the reaction of oxygen with graphite: model chemistry.

A considerable amount of research has been directed towards the mechanism of oxidation of graphite as a model reaction system and because of its industrial importance. A number of recent studies have been concerned with ab initio molecular orbital calculations on graphite including model chemistry and the reactions with molecular oxygen. This study is concerned with oxidation steps involving the attachment of molecular oxygen to the graphene, the formation of carbon monoxide and, in particular, the subsequent oxidation reactions.

Journal Article↗
PubMed2001

Clinical use of Infliximab in Crohn's disease: the Edinburgh experience.

UNLABELLED: Infliximab is an established treatment for steroid-resistant and fistulating Crohn's disease. Although efficacy has been shown in clinical trials, financial implications often limit its use and limited data exist regarding clinical practice. AIMS: To audit the clinical effectiveness of Infliximab. METHODS: We prospectively audited 50 consecutive patients [28 females; median age, 34 years (17-70 years)]. Disease activity and response rates were assessed by the Harvey-Bradshaw index. Clinical and disease data were collected and blood was taken for inflammatory markers, complement and double-stranded DNA antibodies. Patients received Infliximab at 5 mg/kg and were followed for 12 weeks. RESULTS: Indications for Infliximab were refractory Crohn's disease in 39 patients, fistulating Crohn's disease in six, pyoderma gangrenosum in one, pouchitis in two and coeliac disease in two. Thirty-one (79%) of the refractory Crohn's disease patients and four (66%) of the fistulating patients responded at 4 weeks. Twenty-one (54%) of the refractory Crohn's disease patients had a continued response at 12 weeks. Perianal disease was more prevalent in non-responders (7/8 vs. 12/31, P < 0.02). CONCLUSIONS: Response rates to Infliximab in our group are comparable to those of clinical trials. Despite the expense, it remains a useful adjunct to treatment in this otherwise difficult group of patients. Patients with perianal disease responded less well in our cohort.

Adolescent↗