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Biomedical subjects

A M Turner

Publications and source records attributed to A M Turner.

At least 19 recordsLinked to original sources
PubMed2006

SLUG (SNAI2) overexpression in embryonic development.

The Snail-related zinc-finger transcription factor, SLUG (SNAI2), is critical for the normal development of neural crest-derived cells and loss-of-function SLUG mutations have been proven to cause piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. However, little is known about the consequences of SLUG overexpression in embryonic development. We report SLUG duplication in a child with a unique de novo 8q11.2-->q13.3 duplication associated with tetralogy of Fallot, submucous cleft palate, renal anomalies, hypotonia and developmental delay. To investigate the effects of Slug overexpression on development, we analyzed mice carrying a Slug transgene. These mice were morphologically normal at birth, inferring that Slug overexpression is not sufficient to cause overt morphogenetic defects. In the adult mice, there was a 20% incidence of sudden death, cardiomegaly and cardiac failure associated with incipient mesenchymal tumorigenesis. These findings, while not directly implicating Slug in congenital and acquired heart disease, raise the possibility that Slug overexpression may contribute to specific cardiac phenotypes and cancer development.

Abnormalities, Multiple↗
PubMed2005

Incontinentia pigmenti case series: clinical spectrum of incontinentia pigmenti in 53 female patients and their relatives.

A retrospective case series of 53 female patients with incontinentia pigmenti (IP) including 28 secondary cases (female relatives of probands) was reviewed and compared with other series in an attempt to estimate more accurately the true disease burden of patients with IP. We found that, while the frequency of the first three cutaneous stages of IP was comparable with previous studies, none of the secondary cases manifested any serious neurological complications but all displayed stage IV pale anhidrotic reticulate lines on their posterior calves. This important clinical feature of IP in secondary cases has previously been under-represented in studies that often involved only paediatric probands. Hence, mildly affected cases of IP are often undiagnosed and under-represented in case series to date, possibly leading to inappropriately high estimates of neurological and eye involvement. With the availability of genetic testing, it is now feasible to confirm the variability of the phenotype and the risk of complications in IP.

Adolescent↗
PubMed2005

Modified electrode placement must be recorded when performing 12-lead electrocardiograms.

BACKGROUND: Local observation has suggested that placing limb leads on the torso when recording the standard 12-lead resting electrocardiogram (ECG) has become commonplace. This non-standard modification has the important advantages of ease and speed of application, and in an emergency may be applied with minimal undressing. Limb movement artefact is also reduced. It is believed that ECGs obtained with torso electrodes are interchangeable with standard ECGs and any minor electrocardiographic variations do not affect diagnostic interpretation. STUDY DESIGN: The study compared 12-lead ECGs in 100 patients during routine electrocardiography, one being taken in the approved way and one taken with modified limb electrodes. RESULTS: It was found that the use of torso leads produced important amplitude and waveform changes associated with a more vertical and rightward shift of the QRS frontal axis, particularly in those with abnormal standard ECGs. Such changes generated important ECG abnormalities in 36% of patients with normal standard ECGs, suggesting "heart disease of electrocardiographic origin". In those with abnormal standard ECGs, moving the limb leads to the torso made eight possible myocardial infarcts appear and five inferior infarcts disappeared. Twelve others developed clinically important T wave or QRS frontal axis changes. CONCLUSIONS: It is vital that ECGs should be acquired in the standard way unless there are particular reasons for not doing so, and that any modification of electrode placement must be reported on the ECG itself. Marking the ECG "torso-positioned limb leads" or "non-standard" should alert the clinician to its limitations for clinical or investigative purposes, as any lead adaptation may modify the tracing and could result in misinterpretation.

Adult↗
PubMed2004

De novo interstitial duplication 4(q28.1q35) associated with choanal atresia.

We report a case of direct interstitial duplication of chromosome 4 from 4q28.1 to 4q35 associated with bilateral choanal atresia. The child also had dysmorphic features including a broad nasal bridge, telecanthus, downward slanting palpebral fissures, prominent ears, mild bilateral clinodactyly of the 5th fingers and bilateral hypoplasia of the 2nd-5th toenails. There was also a slightly dilated renal collecting system. At the age of 2.5 years, he had moderate global developmental delay, short, wide and tapering fingers, and short toes with hypoplastic toenails. To our knowledge, this is the second report of choanal atresia in a patient with trisomy 4q involving this region.

Adolescent↗
PubMed2001

Emergency drug availability for the cardiac arrest team: a national audit.

Cardiac arrest teams are called upon to deal with many different acute medical emergencies, including cardiac arrest. However, the drugs that are supplied for them to perform their role differs vastly from hospital to hospital. We have confirmed this in an audit of adult cardiac arrest teams from all the acute hospitals within Wales. The rational use of defibrillation and drugs during cardiopulmonary resuscitation has been standardised according to International guidelines, and there is no reason why resuscitation kits could not also be standardised. Further considerations of drug availability is needed for acute management of other collapsed patients without cardiac arrest, most commonly vaso-vagal syncope, anaphylaxis, hypoglycaemia, fits and respiratory arrest. Based upon recent recommendations from the project team of the Resuscitation Council (UK), augmented by other commonly needed drugs for first aid in the collapsed patient, we propose a reduced and simplified emergency drug list, employing a two box system covering immediate and most secondary requirements. A standardised format of drug kits for use by adult cardiac arrest teams could speed effective delivery of emergency care.

Cardiopulmonary Resuscitation↗
PubMed2000

Attachment of astroglial cells to microfabricated pillar arrays of different geometries.

We studied the attachment of astroglial cells on smooth silicon and arrays of silicon pillars and wells with various widths and separations. Standard semiconductor industry photolithographic techniques were used to fabricate pillar arrays and wells in single-crystal silicon. The resulting pillars varied in width from 0. 5 to 2.0 micrometer, had interpillar gaps of 1.0-5.0 micrometer, and were 1.0 micrometer in height. Arrays also contained 1.0-micromter-deep wells that were 0.5 micrometer in diameter and separated by 0.5-2.0 micrometer. Fluorescence, reflectance, and confocal light microscopies as well as scanning electron microscopy were used to quantify cell attachment, describe cell morphologies, and study the distribution of cytoskeletal proteins actin and vinculin on surfaces with pillars, wells, and smooth silicon. Seventy percent of LRM55 astroglial cells displayed a preference for pillars over smooth silicon, whereas only 40% preferred the wells to the smooth surfaces. Analysis of variance statistics performed on the data sets yielded values of p > approximately.5 for the comparison between pillar data sets and < approximately.0003 in the comparison between pillar and well data sets. Actin and vinculin distributions were highly polarized in cells found on pillar arrays. Scanning electron microscopy clearly demonstrated that cells made contact with the tops of the pillars and did not reach down into the spaces between pillars even when the interpillar gap was 5.0 microm. These experiments support the use of surface topography to direct the attachment, growth, and morphology of cells. These surfaces can be used to study fundamental cell properties such as cell attachment, proliferation, and gene expression. Such topography might also be used to modify implantable medical devices such as neural implants and lead to future developments in tissue engineering.

Actins↗
PubMed1996

FLT3 receptor expression on the surface of normal and malignant human hematopoietic cells.

FLT3 ligand is a hematopoietic growth factor that plays a key role in growth of primitive hematopoietic cells. FLT3 receptor mRNA is found in early hematopoietic progenitors and in human myeloid leukemia blasts. Much less is known about the surface expression of FLT3 receptor on human hematopoietic cells. Using human 125I-FLT3 ligand, we have identified and characterized surface FLT3 receptors on normal and malignant human hematopoietic cells and cell lines. Our results showed that surface display of FLT3 receptor was greatest in fresh myeloid leukemia blast cells and myeloid leukemia cell lines. Erythroleukemic and megakaryocytic leukemia cell lines (n = 5) bound little to no 125I-FLT3 ligand. Scatchard analysis of 125I-FLT3 ligand binding data shows that three myeloid leukemia cell lines, ML-1, AML-193, and HL-60, as well as normal human marrow mononuclear cells, exhibit high affinity FLT3 receptors. Crosslinking of 125I-FLT3 ligand to FLT3 receptors on the surface of ML-1 myeloid leukemia cells indicates that the FLT3 ligand. The rates of FLT3 ligand internalization and degradation were determined by binding 125I-FLT3 ligand to ML-1 cells and acid stripping to distinguish surface bound from internalized ligand. Internalized 125I-FLT3 ligand was detected within 5 minutes after binding to ML-1 cells. In addition, we evaluated the effect of FLT3 ligand on megakaryocytic colony growth and nuclear endoreduplication, alone or in the presence of thrombopoietin. FLT3 ligand did not promote colony forming unit megakaryocyte (CFU-Meg) colony growth or megakaryocyte nuclear maturation, nor did FLT3 ligand augment the effects of thrombopoietin on these measures of megakaryopoiesis. These data indicate that the FLT3 receptor shares several characteristics with the c-kit receptor including dimerization and rapid internalization. However, the more restricted cellular distribution of the FLT3 receptor may target the effects of FLT3 ligand to primitive hematopoietic cells and to myeloid and lymphoid progenitor cells, in contrast to the pleiotropic effects of the c-kit receptor ligand, stem cell factor.

Autoradiography↗
PubMed1995

Effects of stem cell factor on the growth and radiation survival of tumor cells.

Recombinant human stem cell factor (SCF) binds to the c-kit receptor on human bone marrow progenitor cells and enhances their survival following irradiation. Since the c-kit receptor has also been detected on malignant cells, experiments were performed to study the effect of SCF on the proliferation and radiation survival of a variety of both c-kit-positive and -negative human tumor cell lines using [3H]thymidine incorporation and colony formation assays. The addition of SCF to both c-kit-positive and -negative cell line cultures had no significant effect on the stimulation index (in [3H]thymidine assay). In contrast, colony formation by H69 (small cell lung cancer cell line), H128 (small cell lung cancer cell line), and HEL (erythroid leukemia cell line) cells was enhanced by SCF in a dose-dependent manner, but SCF did not promote the in vivo growth of H128 xenograft tumors in terms of graft rate, time from implantation to tumor detection, or tumor size. Furthermore, SCF did not significantly increase the surviving fraction of either c-kit-positive or -negative cell lines following radiation, and there were no statistically significant differences between D0 [defined by the slope of the terminal exponential region of the two-component (single-hit multitarget model) survival curve where slope = 1/D0], Dq (quasithreshold dose), n (extrapolation number), alpha, and beta values for any of the cell lines studied that were irradiated with and without SCF. Finally, nude mice with transplanted human LG425 cutaneous T-cell lymphoma (c-kit positive) were treated with 10 Gy with or without SCF (100 micrograms/kg i.p. 20 h before, 2 h before, and 4 h after irradiation). There were no significant differences in the median tumor quadrupling time between groups that received either no treatment or SCF alone, or between groups treated with 10 Gy and SCF or 10 Gy alone (P > 0.05). These results are encouraging and suggest that SCF does not stimulate tumor cell proliferation in vivo or enhance the survival of tumor cells following irradiation.

Animals↗
PubMed1995

Identification and characterization of a soluble c-kit receptor produced by human hematopoietic cell lines.

Stem cell factor (SCF) triggers cell growth by binding to cell surface c-kit receptors. Soluble forms of several cytokine receptors have been described and may play a role in the modulation of cytokine activity in vivo. For these reasons, we investigated whether human hematopoietic cells produce soluble c-kit receptors. The human leukemia cell lines OCIM1 and MO7e display approximately 80,000 and approximately 35,000 high-affinity cell surface c-kit receptors, respectively. Soluble c-kit receptors were detected by enzyme immunoassay in OCIM1 and MO7e culture supernatants. We determined the molecular weight and binding affinity of soluble c-kit receptor produced by OCIM1 cells, soluble c-kit receptor purified from human serum, and recombinant soluble c-kit receptor expressed in CHO cells. The three soluble c-kit receptors each have a molecular weight of 98 kD. Quantitative binding experiments with 125I-SCF indicate that the soluble c-kit receptors obtained from human serum or OCIM1 cells have binding affinities for SCF of approximately 200 to 300 pmol/L, in contrast to the recombinant form, which has a binding affinity of approximately 1.5 nmol/L. All three forms of the soluble c-kit receptor were able to compete with c-kit receptors on OCIM1 cells for 125I-SCF binding. Thus human hematopoietic cells can produce a soluble form of the c-kit receptor that retains high-affinity SCF binding activity. We speculate that the soluble c-kit receptor may bind SCF and function as a receptor antagonist in vivo.

Amino Acid Sequence↗
PubMed1994

Counselling risk figures for fragile X carrier females of varying band sizes for use in predicting the likelihood of retardation in their offspring.

We have derived risk figures for fra(X) syndrome carrier mothers based on their DNA status. Clinical and molecular information was analysed in 200 carrier mothers and their offspring. Individuals were classified as affected by a requirement for special education. Risk figures were calculated using the genotype of the intellectually normal offspring in order to reduce ascertainment bias. Analysis was made on women with differing mutation size to predict the proportion of affected offspring. Using this method the following risk figures were derived: 1. For carrier women with an increase (delta) of 0.06-0.14 Kb, the risk for having an affected son was 29% (1 in 3.5) and 25% for daughters (1 in 4). This predicts an overall 73% chance of a normal child. 2. For delta size 0.15-0.24 Kb, the risk of having an affected son was 46% (1 in 2.2) and 32% for daughters (1 in 3.1), predicting a 61% chance of a normal child. 3. For delta size > 0.24 Kb, normal transmitting male offspring were not seen, i.e., the risk for males was 50% (1 in 2) and for females 32% (1 in 3.1) which predicts a 59% chance of a normal child.

Adult↗
PubMed1994

Cardiovascular status in young patients with insulin-dependent diabetes mellitus.

BACKGROUND: Although the existence of diabetic cardiomyopathy in adults is firmly established, the presence of cardiac abnormalities in young diabetic patients is not universally accepted. We sought to determine the early stages of cardiac derangement and whether they are associated with renal dysfunction. METHODS AND RESULTS: Thirty-nine patients (29 boys; mean age, 17.6 +/- 3.4 years) with insulin-dependent diabetes mellitus underwent echocardiography and timed overnight urine collection. Echocardiographic evaluation consisted of left ventricular mass, performance (shortening fraction, velocity of circumferential fiber shortening, stroke volume, and cardiac index), preload (end-diastolic dimension and volume), after-load (end-systolic wall stress and systemic vascular resistance), and contractility (velocity of fiber shortening relative to wall stress). Creatinine clearance and albumin excretion were measured from the urine sample. Glycosylated hemoglobin levels were measured; height and weight were measured; and Quetelet index (weight/height2) was calculated. These data were compared with control data. Left ventricular mass (26 +/- 6 versus 22 +/- 6 g/ht2.7, P < .01), the indexes of performance, blood pressure, and contractility (0.14 +/- 0.14 versus 0.003 +/- 0.03 circumference/s, P < .0003) were significantly higher in the diabetic patients than in control subjects. To evaluate the correlates of left ventricular mass and contractility in the diabetic patients, univariate and multiple regression analyses were performed. Significant univariate correlations of mass included albumin excretion (r = .36, P < .02), glycosylated hemoglobin (r = .35, P < .04), and stroke volume (r = .34, P < .03). A multivariate model included Quetelet index, albumin excretion, and duration of diabetes. Significant univariate correlations of contractility included insulin dosage (r = -.36, P < .02), creatinine clearance (r = .40, P < .02), and Quetelet index (r = .34, P < .03). A multivariate model included insulin dosage and creatinine clearance. CONCLUSIONS: Early onset of diabetes mellitus is associated with increased left ventricular mass, performance, contractility, and blood pressure. These cardiovascular findings are correlated with increased creatinine clearance and microalbuminuria. These relations suggest that alterations in cardiovascular and renal function may occur in parallel in adolescents with insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1992

Nonhematopoietic tumor cell lines express stem cell factor and display c-kit receptors.

Human stem cell factor (SCF) acts in the presence of other growth factors to stimulate the growth of primitive hematopoietic progenitor cells. These effects are performed by activation of the SCF receptor, c-kit. Because of the potential use of SCF in patients undergoing chemotherapy and bone marrow transplantation, the effect of SCF on nonhematopoietic tumors requires investigation. To determine whether human tumor cell lines display c-kit receptors, we performed binding experiments with 125I-SCF on a breast carcinoma cell line (Du4475), a gastric carcinoma cell line (KATO III), a melanoma cell line (HTT144), as well as two small cell lung carcinoma cell lines (H69 and H128). The biologic effect of SCF on tumor cell lines was assessed by its ability to stimulate tritiated thymidine uptake and to enhance colony growth in methylcellulose. The breast carcinoma cell line, Du4475, as well as two small cell lung carcinoma cell lines, H69 and H128, exhibit high-affinity c-kit receptors with approximate binding affinities of 40, 100, and 90 pmol/L, respectively. The number of high-affinity receptors per cell ranged from 700 to 9,500. The gastric carcinoma cell line, as well as the melanoma cell line, showed trace binding of 125I-SCF. In the presence of SCF alone, or in combination with granulocyte-macrophage colony-stimulating factor or interleukin-3, there was less than a 17% increase in the colony growth of Du4475, H69, or H128 cell lines. Postulating that the lack of growth response could be secondary to endogenous SCF production by the tumor cell lines, we used an RNAse protection assay to determine whether the tumor cell lines contain SCF messenger RNA (mRNA). In addition, we tested tumor cell line supernatants for the presence of secreted SCF protein by enzyme immunoassay, and analyzed the tumor cell lines for membrane-bound SCF by indirect immunofluorescence. Our results show that the Du4475, H69, and H128 cell lines, as well as a melanoma cell line (HTT144), have multiple copies of SCF mRNA. Soluble SCF protein was detected in the cell supernatants in the Du4475 and H69 cell lines and SCF was found on the surface of all four cell lines. These data show that some human solid tumor cell lines display high-affinity c-kit receptors and produce SCF, which can be detected on the cell surface. These results suggest the possibility that autocrine production of SCF by c-kit receptor-bearing tumor cells may enhance cell growth in tumor cell lines.

Animals↗
PubMed1992

X-linked lymphoproliferative disease: prenatal detection of an unaffected histocompatible male.

Chorionic Villous Biopsy (CVS) for diagnosis of XLP was undertaken at 10 weeks gestation in an obligate carrier. The fetus was found to be male by cytogenetic analysis. XLP (Xq25-q26) is closely linked to the RFLP markers DXS10, DXS37 and DXS42, but only DXS10 (distal to XLP) was informative for prenatal diagnosis in this family. RFLP analysis using this marker gave a 7% risk that the fetus was affected, based on the known recombination frequency between DXS10 and XLP. Further investigation was then undertaken to obtain a rapid and more accurate diagnosis using the three highly polymorphic PCR based markers. These were the AC repeat markers DXS424 (XL5A) and DXS425 (XL90A3) and the tetramer repeat marker within HPRT. DX425 is approximately 10 cM proximal to DXS10 and HPRT but is not known with certainty to map proximal or distal to XLP. DXS424 is proximal to DXS10 and HPRT and was inferred to be proximal to XLP on the basis of map distance from HPRT estimated by linkage analysis of data from CEPH pedigrees. This was confirmed by a recombinant in the XLP family between DXS424 and DXS425, placing DXS424 proximal to XLP. Diagnosis by linkage using DXS424 and DXS425, at least one of which is proximal to XLP, and distal markers DXS10 and HPRT, increased the accuracy of diagnosis using flanking marker analysis to greater than 99% that the fetus was unaffected. HLA DR typing of the CVS showed that the fetus was DR identical to a male sibling with XLP. HLA compatibility was confirmed at delivery by full HLA typing and MLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1992

Report on the X-linked lymphoproliferative disease in an Australian family.

X-linked lymphoproliferative disease is characterized by immune deficiency, particularly to the Epstein-Barr virus and by a tendency to develop fatal infectious mononucleosis, acquired hypogammaglobulinaemia or malignant lymphoma. This disorder has been diagnosed in three boys, two brothers and a maternally related cousin, residing in Australia. The proband presented at 6 years of age with fulminating infectious mononucleosis. His 9 year old male cousin had developed an ileal Burkitt lymphoma one year earlier. Immunological and molecular genetic evidence is presented to support our view that his younger sibling is also affected with this condition. DNA linkage studies using probes to DXS10 and DXS37 provide confirmatory evidence for the diagnosis in the proband's brother and information on carrier status in female family members.

Agammaglobulinemia↗
PubMed1992

Profile of renal permselectivity by simultaneous enzyme-linked immunosorbent assay of albumin, transferrin, IgG, and alpha 1-microglobulin with a new microplate reader.

A competitive enzyme-linked immunosorbent assay (ELISA) is described for determining a renal permselectivity profile involving the urinary proteins albumin, transferrin, IgG, and alpha 1-microglobulin (alpha 1-m). The ELISA reader uses a computer-controlled array of multiplexed light-emitting diode (LED)-photodiode pairs for rapid measurements of absorbance on microplates. A 3,3'-dimethylnaphthidine reagent adapts the 3,5,3',5'-tetramethylbenzidine chromophore to monochromatic LED emission at 550 nm. We applied this ELISA to the determination of renal permselectivity in healthy children and young adults and in children with insulin-dependent diabetes mellitus. The geometric means (and SD) of protein excretion rates in a group of 85 normal subjects were as follows: albumin, 3.5 micrograms/min (1.83); transferrin, 173 ng/min (2.76); IgG, 1.11 micrograms/min (2.22), and alpha 1-m, 0.98 microgram/min (2.36).

Adolescent↗