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Biomedical subjects

K Chandler

Publications and source records attributed to K Chandler.

At least 19 recordsLinked to original sources
PubMed2006

Brain and spinal cord haemorrhages associated with Angiostrongylus vasorum infection in four dogs.

Multifocal haemorrhages associated with Angiostrongylus vasorum infection were observed in the central nervous system of four dogs with neurological signs including depression, seizures, spinal pain and paresis. In magnetic resonance images the majority of the lesions were isointense or slightly hyperintense in T1-weighted images, hyperintense in T2-weighted images and hypointense in T2*-weighted (gradient echo) images, compatible with haemorrhages more than seven days old. Lesions were found in the brain of three of the dogs and in the spinal cord of two. The cerebrospinal fluid contained high concentrations of protein and evidence of erythrophagia. All the dogs had coagulopathy and pulmonary haemorrhage of varying severity. A vasorum larvae were detected in the faeces of each of the dogs. Neural A vasorum was confirmed at postmortem examination in two dogs.

Angiostrongylus↗
PubMed2005

Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.

BACKGROUND: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos. In contrast, a recurrent approximately 2 Mb microdeletion has been reported as responsible for approximately 50% of Japanese cases of Sotos. METHODS: We screened 471 cases for NSD1 mutations and deletions and identified 23 with 5q35 microdeletions. We investigated the deletion size, parent of origin, and mechanism of generation in these and a further 10 cases identified from published reports. We used "in silico" analyses to investigate whether repetitive elements that could generate microdeletions flank NSD1. RESULTS: Three repetitive elements flanking NSD1, designated REPcen, REPmid, and REPtel, were identified. Up to 18 cases may have the same sized deletion, but at least eight unique deletion sizes were identified, ranging from 0.4 to 5 Mb. In most instances, the microdeletion arose through interchromosomal rearrangements of the paternally inherited chromosome. CONCLUSIONS: Frequency, size, and mechanism of generation of 5q35 microdeletions differ between Japanese and non-Japanese cases of Sotos. Our microdeletions were identified from a large case series with a broad range of phenotypes, suggesting that sample selection variability is unlikely as a sole explanation for these differences and that variation in genomic architecture might be a contributory factor. Non-allelic homologous recombination between REPcen and REPtel may have generated up to 18 microdeletion cases in our series. However, at least 15 cannot be mediated by these repeats, including at least seven deletions of different sizes, implicating multiple mechanisms in the generation of 5q35 microdeletions.

Abnormalities, Multiple↗
PubMed2000

Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor.

Preeclampsia and fetal growth restriction are associated with placental hypoperfusion and villous hypoxia. The villous response to this environment includes diminished trophoblast differentiation and enhanced apoptosis. We tested the hypothesis that hypoxia induces apoptosis in cultured trophoblasts, and that epidermal growth factor (EGF), an enhancer of trophoblast differentiation, diminishes hypoxia-induced apoptosis. Trophoblasts isolated from placentas of term-uncomplicated human pregnancies were cultured up to 72 h in standard (PO(2) = 120 mm Hg) or hypoxic (PO(2) <15 mm Hg) conditions. Exposure to hypoxia for 24 h markedly enhanced trophoblast apoptosis as determined by DNA laddering, internucleosomal in situ DNA fragmentation, and histomorphology, as well as by the reversibility of the apoptotic process with a caspase inhibitor. Apoptosis was accompanied by increased expression of p53 and Bax and decreased expression of Bcl-2. Addition of EGF to cultured trophoblasts or exposure of more differentiated trophoblasts to hypoxia significantly lowered the level of apoptosis. We conclude that hypoxia enhances apoptosis in cultured trophoblasts by a mechanism that involves an increase in p53 and Bax expression. EGF and enhancement of cell differentiation protect against hypoxic-induced apoptosis.

Apoptosis↗
PubMed1999

Registrar experience in vaginal breech delivery. How much is occurring?

The debate surrounding the safety of vaginal breech delivery compared to Caesarean delivery may be close to resolution, with a large randomized trial underway. However, trends in the management of vaginal breech delivery over recent years have led to suggestions that training in the technique of such deliveries may be inadequate. We have attempted to quantify the level of training in vaginal breech delivery available to registrars. This was accomplished by surveying obstetric training schemes in comparable regions of England and South Australia. Our findings suggest that registrar exposure to this important obstetric skill may be insufficient to guarantee expertise.

Breech Presentation↗
PubMed1997

Partial trisomy 15q: report of a patient and literature review.

We report a girl with severe developmental delay, scoliosis and mild dysmorphism. She was found to have a partial duplication of the long arm of chromosome 15. Precise cytogenetic diagnosis was possible after additional in situ hybridisation. A Karyotype of 46,XX,dup (15) (pter-->q26.3::q24-->qter) was concluded. We compare her data with the literature. No specific phenotype was found.

Abnormalities, Multiple↗
PubMed1996

Computer assisted learning (CAL) of oral manifestations of HIV disease.

General dental practitioners (GDPs) in the UK may wish additional education on relevant aspects of human immunodeficiency virus (HIV) disease. The aim of the present study was to develop and assess a computer assisted learning package on the oral manifestations of HIV disease of relevance to GDPs. A package was developed using a commercially-available software development tool and assessed by a group of 75 GDPs interested in education and computers. Fifty-four (72%) of the GDPs completed a self-administered questionnaire of their opinions of the package. The majority reported the package to be easy to load and run, that it provided clear instructions and displays, and that it was a more effective educational tool than videotapes, audiotapes, professional journals and textbooks, and of similar benefit as post-graduate courses. The GDPs often commented favourably on the effectiveness of the clinical images and use of questions and answers, although some had criticisms of these and other aspects of the package. As a consequence of this investigation the package has been modified and distributed to GDPs in England and Wales.

Adult↗
PubMed1995

Detachment of transformed cells. Role of CD44 variants.

A parallel-plate flow chamber was used to quantify the detachment of normal cloned rat embryo fibroblasts (CREF) fibroblasts, ras-transformed CREF fibroblasts (CREF T24), and CREF T24 fibroblasts transfected with a Krev/RAP1A suppressor gene (HK B1) from a confluent monolayer of normal CREF fibroblasts to determine if the expression patterns of CD44 variants (mol wt 110 and 140 kDa) corresponded with detachment properties and metastatic potential. In the detachment assay, known shear stresses ranging from 20-24 dyn/cm2 were applied to the adherent cells and the number of cells detached from the monolayer after 180 s was determined. Results showed that cellular expression of CD44 variants correlated with the metastatic potential of the cells and with the cells' ability to detach from a monolayer of normal cells. Western blot analysis showed a low level of expression of the CD44 variants in the normal cell line, CREF, and the lowly metastatic cell line, HK B1. Detachment studies showed a low percentage of detachment of both of these cell lines from a normal cell monolayer. Tumor-derived (HK B1-T) and lung nodule-derived (HK B1-M) cell lines were established and both formed tumors and metastasis with reduced latency periods as compared to HK B1, but still showed a markedly delayed latency period compared to the highly metastatic cell line, CREF T24. Both of these cell lines showed a higher expression of the CD44 variants as compared to CREF and HK B1, and detached easier than CREF and HK B1. CREF T24 showed a much higher level of expression of the variants and had a higher percentage detachment than all other cell lines. To further test the role of the CD44 variants in the ability of the cells to detach from the normal monolayer, CREF cells were transfected with a DNA construct that constitutively expresses the CD44 variants and the detachment properties of three randomly selected clones were studied. Clones 2 and 3 showed a low level of expression of the CD44 variants after transfection and detached from the normal monolayer similar to CREF. Clone 1 showed a high level of expression of the CD44 variants and the detachment of these cells was significantly higher than CREF. From these results, it is concluded that in the five cell lines studied, expression of the CD44 variants play a significant role in the ability of the cells to detach from a monolayer of normal cells. It is hypothesized that this detachment may be an important component of a cell's ability to metastasize.

Animals↗
PubMed1994

The immune response of sheep infected with larvae of the sheep blowfly Lucilia cuprina monitored via efferent lymph.

Changes in lymphocyte traffic in efferent lymph from the prescapular lymph node of sheep were monitored during local primary and secondary infection with blowfly, Lucilia cuprina. During primary infections the response was characterised by an increase in the output of CD4+ T cells over CD8+ T cells for the first 48 h after wound initiation. By 72 h the output of CD8+ T cells exceeded that of CD4+ T cells. During secondary infections the increased output of CD8+ T cells was more pronounced and occurred earlier at approximately 48 h. The percentage of B lymphocytes as measured by sIg, CD45R and MHC class II expression increased at approximately 96-120 h after both primary and secondary infections, with the secondary response being greater than the primary. This increase in B cells corresponded with peak antibody titres recorded in the efferent lymph to a first instar antigen preparation as measured by ELISA. An increase in IFN-gamma and soluble IL-2 receptor was recorded after both primary and secondary infections, with the response after secondary infection being greater than that recorded after primary larval infections.

Animals↗
PubMed1993

Isolation of a human biliary glycoprotein inhibitor of cholesterol crystallization.

BACKGROUND: About 50% of populations in developed countries have bile supersaturated with cholesterol, which is a major risk factor for cholesterol gallstone formation. Despite the prevalence of supersaturated bile, only about 10% of these populations develop gallstones. The existence of a biliary protein that inhibits cholesterol crystallization was hypothesized to explain this discrepancy. This report outlines the purification and characterization of such a human biliary glycoprotein. METHODS: Chromatographic methods were used for separation and characterization. Additional steps included activity analysis by crystal growth assay, electrophoresis, and deglycosylation. RESULTS: The glycoprotein consists of a heterodimer, M(r) of 120 kilodalton, with subunits of M(r) of 63 kilodalton and 58 kilodalton. Each of the subunits is characterized by an isoelectric point of 6.6 and shows comparable inhibitory activity. Deglycosylation of the subunits show that they share a similar polypeptide backbone (M(r) of 35 kilodalton) based upon a highly similar amino acid profile. This suggests that differential subunit glycosylation alone may account for the apparent heterodimeric structure. CONCLUSIONS: No other human biliary glycoprotein has been found thus far that shows cholesterol crystal growth-inhibiting activity. Thus, it may be of importance in preventing gallstone formation in healthy populations.

Amino Acids↗
PubMed1991

Transcellular transport of organic anions in the isolated perfused rat liver: the differential effects of monensin and colchicine.

Nonbile salt cholephiles and bile salts are two classes of organic anions that are efficiently taken up and excreted by the liver. Recent evidence suggests that a microtubular system-dependent, colchicine-sensitive transcellular pathway may transport both classes of these ligands. The relationship of this pathway to flux rates, however, remains unclear. Some structural evidence suggests an important role for a Golgi-associated vesicular system. Monensin, like colchicine, is a perturbing agent that is believed to target primarily Golgi and related organelles. The effects of a minimal effective dose of both colchicine (0.06 mg to 0.12 mg/100 gm body wt) and monensin (0.6 mg/100 gm body wt) were examined in the isolated perfused rat liver in a single-pass mode. The nonbile salt cholephile, phenol red, was studied at two doses: 1 nmol and 5 mumol. Sodium taurocholate was studied at three doses: 2 nmol, 1 mumol and 5 mumol. Colchicine affected the transcellular transport for both classes of organic anions equally. Partially inhibitory effects on both anions occurred only at high ligand flux rates. In contrast, monensin greatly impaired the transport of nonbile salt cholephiles but had no influence on transcellular bile salt flux. We conclude that the monensin effect appears to define a distinct transcellular transport pathway for each of the two classes of organic anions.

Animals↗