White matter attenuation and megalencephaly.
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Adolescent↗
Biomedical subjects
T Cox
Publications and source records attributed to T Cox.
Nurses' evaluations of sources of information about HIV and AIDS.
Reviews of the literature indicate that nurses feel ill-informed about HIV/AIDS and that poor knowledge is associated with anxiety and negative attitudes towards infected patients and their care. Although some studies have sought to identify the sources of HIV/AIDS information available to nurses, few have attempted to understand how nurses evaluate such sources. In this study in 1992, 15 sources of HIV/AIDS information were identified during group discussions with nursing staff and nurse tutors. 277 nursing staff evaluated each of the sources in terms of perceived frequency (how often the source is used) and six items chosen to assess the usability and usefulness of each source (e.g. how informative the source is, how easy it is to understand). The results indicate that in-service training, basic training and professional colleagues are the sources evaluated most highly while posters and advertisements, television and radio and popular newspapers are the most frequently used sources of information. Trades unions' journals and pamphlets are the least frequently used sources of information and receive only modest evaluations. 20% of respondents report never having received any training regarding HIV and AIDS. Implications for the future provision of HIV/AIDS information and directions for further research are discussed.
Acquired Immunodeficiency Syndrome↗
Histologic, molecular, and radiologic characterization of resolving cerebral posttransplant lymphoproliferative disorder.
Lymphoproliferative disorders (LPDs) are commoner in pediatric versus adult immunosuppressed transplant recipients, and frequently involve the central nervous system. In these circumstances, the justification for biopsy is heavily influenced by the likely diagnostic yield. The present study centers on a 12-y-old renal transplant patient who developed multifocal cerebral LPD and had serial magnetic resonance (MR) examinations during the course of her illness from which she has completely recovered upon reduction of immunosuppression. She underwent stereotaxic biopsy, which was analyzed by both immunocytochemistry and polymerase chain reaction to examine the general question of how to release the maximum amount of information contained within, as well as to obtain a tissue diagnosis in this particular case. We show that a combination of these methods permits identification of the immunophenotype, lineage, clonality, viral involvement, and origin of abnormal cellular infiltrates. The biopsy also showed a novel histologic pattern of LPD, comprising numerous benign T cells obscuring a tiny clone of B cells. The MR examinations documented, for the first time, the differences in signal that accompany clinical resolution at both biopsied and nonbiopsied sites, showing that the latter may be associated with reduction, but not elimination, of MR signal abnormality. We conclude: 1) a combination of conventional and polymerase chain reaction analysis offers the greatest diagnostic yield from stereotaxic biopsies, even when the available tissue is minimal; 2) a focal polyclonal T cell infiltrate should prompt further investigation to exclude an underlying B cell lesion.
Adult↗
Amiloride analog stimulation of short-circuit current in larval frog skin epithelium.
The skin of the bullfrog Rana catesbeiana tadpole contains an apical non-selective cation channel that is activated by amiloride. This is in contrast to the adult skin, which has a highly Na+-selective channel that is blocked by amiloride. The purpose of the present study was to characterize further the nature of the tadpole channel using amiloride and its analogs benzamil, dimethyl amiloride (DMA), 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) and methyl isobutyl amiloride (MIBA). Tadpole skins were mounted in modified Ussing chambers with Ca2+-free KCl or NaCl Ringer on the apical side and standard NaCl Ringer (containing 2 mmol l-1 Ca2+) on the basolateral side. Drugs were added to the apical solution at concentrations between 0.1 and 1000 micromol l-1. Amiloride caused the short-circuit current (Isc) to increase rapidly from near zero to a peak of approximately 30-50 microA and then to decline back towards zero over several seconds. The peak response was largest at 100 micromol l-1. The rate of decline was noticeably faster at the higher concentrations. Benzamil and DMA had similar time courses to amiloride, but with smaller effects on Isc. The largest peak responses occurred at 5-50 micromol l-1. EIPA and MIBA gave small responses at 1-10 micromol l-1 and, at higher concentrations (50-500 micromol l-1), the responses consisted of rapid, small increases in Isc followed by rapid decreases. The largest peak response occurred at 10 micromol l-1 for both drugs. After apical membrane resistance had been reduced by nystatin, addition of analogs to the apical solution caused no change in Isc or transepithelial resistance. This suggests that the decline in Isc after amiloride analog treatment was not due to increases in the resistance of the basolateral membrane. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) blocked stimulation by all of the analogs. These data are consistent with amiloride analogs acting as both activators and inhibitors of short-circuit current in tadpole skin and extend the list of ligands that activate these channels.
Amiloride↗
The alpha-1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation.
Organ xenografts in discordant combinations such as pig-to-man undergo hyperacute rejection due to the presence of naturally occurring human anti-pig xenoantibodies. The galactose alpha(1,3)-galactose epitope on glycolipids and glycoproteins is the major porcine xenoantigen recognized by these xenoantibodies. This epitope is formed by alpha(1,3)-galactosyltransferase, which is present in all mammals except man, apes, and Old World monkeys. We have generated mice lacking this major xenoantigen by inactivating the alpha(1,3)-galactosyltransferase gene. These mice are viable and have normal organs but develop cataracts. Substantially less xenoantibody from human serum binds to cells and tissues of these mice compared with normal mice. Similarly, there is less activation of human complement on cells from mice lacking the galactose alpha(1,3)-galactose epitope. These mice confirm the importance of the galactose alpha(1,3)-galactose epitope in human xenoreactivity and the logic of continuing efforts to generate pigs that lack this epitope as a source of donor organs.
Animals↗
Mammalian AMP-activated protein kinase subfamily.
The mammalian 5'-AMP-activated protein kinase (AMPK) is related to a growing family of protein kinases in yeast and plants that are regulated by nutritional stress. We find the most prominent expressed form of the hepatic AMPK catalytic subunit (alpha 1) is distinct from the previously cloned kinase subunit (alpha 2). The alpha 1 (548 residues) and alpha 2 (552 residues) isoforms have 90% amino acid sequence identity within the catalytic core but only 61% identity elsewhere. The tissue distribution of the AMPK activity most closely parallels the low abundance 6-kilobase alpha 1 mRNA distribution and the alpha 1 immunoreactivity rather than alpha 2, with substantial amounts in kidney, liver, lung, heart, and brain. Both alpha 1 and alpha 2 isoforms are stimulated by AMP and contain noncatalytic beta and gamma subunits. The liver alpha 1 isoform accounts for approximately 94% of the enzyme activity measured using the SAMS peptide substrate. The tissue distribution of the alpha 2 immunoreactivity parallels the alpha 2 8.5-kilobase mRNA and is most prominent in skeletal muscle, heart, and liver. Isoforms of the beta and gamma subunits present in the human genome sequence reveal that the AMPK consists of a family of isoenzymes.
Amino Acid Sequence↗
Haemochromatosis: strike while the iron is hot.
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Biotechnology↗
Episodic memory dysfunction during sodium amytal testing of epileptic patients in relation to posterior cerebral artery perfusion.
The effect of filling of the posterior cerebral artery (PCA) on memory performance during the intracarotid sodium amytal test (IAP) was investigated in 57 patients with unilateral temporal epileptic seizure foci under consideration for surgical therapy. Memory functioning was tested following injection of the internal carotid artery contralateral and ipsilateral to the side of seizure focus. In both cases, patients with PCA filling observed using conventional angiography showed a greater memory deficit, although this effect was more robust with contralateral injections. In a subsample of patients with left hemisphere dominance for language, the effect of PCA filling on memory performance was only significant when the right hemisphere was injected. The implications of these findings are discussed in terms of the validity of the IAP test and the different factors that need to be taken into account when interpreting IAP memory performance.
Adult↗
Focal abnormalities detected by 18FDG PET in epileptic encephalopathies.
A prospective study of 32 children with epileptic encephalopathies 12 years or younger revealed a high incidence of focal cortical metabolic defects on 18-fluorodeoxyglucose positron emission tomography (PET) not suspected from clinical, EEG, or magnetic resonance imaging findings. PET scans were normal in all five children with typical de novo Lennox-Gastaut syndrome but showed cortical metabolic abnormalities in three out of four with atypical de novo Lennox-Gastaut syndrome, five out of six with Lennox-Gastaut syndrome following infantile spasms, six out of eight with severe myoclonic epilepsy in infancy, one out of two with epilepsy with myoclonic-astatic seizures, and four out of six with an unclassified epileptic encephalopathy. This suggests that some children with epileptic encephalopathies previously thought to have primary generalised seizures or seizures due to multifocal pathology may have unifocal cortical origin for their seizures. Such an origin may be amenable to surgery.
Child↗
Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2.
Interleukin-15 is a new cytokine that stimulates the proliferation of T cells and other cells of the immune system. Some of the biological properties of interleukin-15 overlap that of interleukin-2. Using murine models, the present studies have shown that interleukin-15, in vivo, is three to four times more potent than interleukin-2 in generating cytolytic effector splenocytes that lyse YAC target cells. It is approximately one-third as potent as interleukin-2 in inducing specific cytolytic cells that lyse allogeneic target cells. Interleukin-15 is approximately half as potent as interleukin-2 in suppressing pulmonary metastasis induced by MCA-205 tumor cells. The dose of interleukin-15 required to induce pulmonary vascular leak in mice is six times higher than that required for interleukin-2. These results support the view that interleukin-15 exhibits a therapeutic index that is superior to interleukin-2.
Animals↗
White matter signal hyperintensities in the brains of patients with late paraphrenia and the normal, community-living elderly.
We determined the prevalence and anatomical location of areas of white matter hyperintensity visualized by magnetic resonance imaging in the brains of 38 late paraphrenic patients with an onset of psychotic illness after the age of 60 and 31 healthy aged community volunteers. All degrees of white matter signal hyperintensity were very common in both groups, and there was no excess of such changes in the brain of patients. Periventricular white matter and subcortical grey matter hyperintensities were significantly associated with both measured diastolic and systolic blood pressure in patients and control subjects. Periventricular and deep white matter, together with subcortical grey matter hyperintensities, were significantly associated with increased age. The excess of such presumed brain-imaging abnormalities previously reported in patients with an onset of psychosis late in life may be a consequence of earlier authors' failure to include examination of appropriate community control populations and to carefully exclude patients with evidence of stroke.
Aged↗
Catalytic subunits of the porcine and rat 5'-AMP-activated protein kinase are members of the SNF1 protein kinase family.
The 5'-AMP-activated protein kinase (AMPK) regulates the fatty acid and sterol synthesizing pathways via phosphorylation of acetyl-CoA carboxylase and HMG-CoA reductase, respectively. Highly purified kinase from porcine liver contains three apparent subunits of molecular mass 63 kDa, 40 kDa and 38 kDa. Peptide sequencing of the 63 kDa protein (AMPK63cat) revealed that this polypeptide is the catalytic subunit of the kinase. Porcine peptide sequences were used to clone by RT-PCR partial length cDNAs for the catalytic domains of the porcine AMPK63cat, and its rat homolog, which were virtually identical in deduced amino acid sequence. Screening of a rat liver cDNA library with these partial length cDNAs and with degenerate oligonucleotides yielded several unique clones, some of which had a 142 bp deletion in the catalytic domain of the kinase. A consensus full-length sequence with a 1.7 kb open reading frame has been constructed from overlapping library and PCR-derived clones. A large mRNA for rat AMPK63cat (8.5 kb) is expressed in nearly all rat tissues, with highest levels detectable in heart and skeletal muscle. Using PCR, the presence of two mRNA species with or without the 142 bp deletion in the catalytic domain was noted in all rat tissues examined. Comparison of the deduced protein sequence of AMPK63cat reveals highly conserved homologies in both the catalytic and non-catalytic domains to several members of the SNF1 kinase family, including kinases from Arabidopsis, barley, rye, and S. cerevesiae, as well as to other mammalian kinases and to a C. elegans kinase. The high evolutionary conservation of both kinase structure and function (metabolite sensing) coupled with their pattern of tissue/organism expression suggest that the mammalian members of this kinase family likely play wider roles than the regulation of cellular lipid metabolism.
AMP-Activated Protein Kinases↗
A measure of knowledge and confidence in relation to HIV and AIDS: reliability and validity.
Knowledge of HIV and AIDS is widely seen as an important determinant of anxiety about such infection in health care workers. However, existing measures of this knowledge suffer from a number of methodological problems and few demonstrate adequate reliability and validity. This paper documents the development of a new measure detailing its reliability and validity. Knowledge, and also confidence in knowledge, were assessed across seven domains of relevant information (e.g. epidemiology, personal risk, symptomatology) in one non-expert group (non-medical undergraduate psychologist) and in three groups with greater expertise (nursing students and third year and final year medical students). The measure was shown to be reliable and to discriminate between the four groups in a manner consistent with the level of education received by each group and in terms of both the scale scores for the seven domains and the individual items. In general, final year medical students were shown to be more knowledgeable, and more confident in their knowledge, than the other groups. The non-medical undergraduates showed the lowest level of knowledge. In general, the groups appeared under-confident in their knowledge about HIV/AIDS. This was interpreted in terms of members of these groups exhibiting caution and the perceived fluctuating nature of the HIV knowledge base. Implications for the training of health care workers in relation to HIV/AIDS are discussed.
Adult↗
Idiopathic intracranial hypertension associated with tetracycline use in fraternal twins: case reports and review.
Fraternal twin sisters developed idiopathic intracranial hypertension (IIH) shortly after beginning tetracycline for treatment of acne. We reviewed from the literature 19 familial cases of IIH and 37 cases of IIH associated with tetracycline usage. Among the 37 combined adult and pediatric cases, 26 of 37 had resolution of signs or symptoms of IIH within hours to days of stopping the antibiotic, and rapid recurrence with reinitiation of drug occurred in 4 of 37. We suggest that these cases may be tetracycline-induced, may be related to an underlying genetic susceptibility, and support the notion of multifactorial etiologies for IIH.
Acne Vulgaris↗
MRI in cerebellar hypoplasia.
Cerebellar hypoplasia may present with a wide variety of neurological and systemic features, ranging from aplasia causing neonatal death to mild hypoplasia in an asymptomatic adult. MRI clearly documents the size of the cerebellum and any associated abnormalities. We describe 7 cases of cerebellar hypoplasia of varying aetiology--3 inherited, 2 associated with spinal dysraphism, 1 with Joubert's syndrome and 1 with pontine agenesis, probably as a result of basilar artery infarction in utero. T1- and T2-weighted images were obtained in each case and gadolinium-DTPA was administered in one. Associated features such as a Chiari malformation (2 cases), brain stem hypoplasia (2 cases), Dandy-Walker cyst and pachygyria (3 cases) and spinal dysraphism (2 cases) were clearly identified. Accurate documentation of these appearances assists in genetic counselling.
Cerebellum↗
Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens and c-Ha-ras transfection.
The objective of this work was to determine whether transformation of the human breast epithelial cell line MCF-10F by the chemical carcinogens 7, 12-dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP), or c-Ha-ras oncogene transfection, influence the expression of epidermal growth factor receptor (EGFR), estrogen (ER) or progesterone (PR) receptors, and the content of cathepsin-D (Cath.D). MCF-10F control cells did not express any of the phenotypes of neoplastic transformation, whereas carcinogen-treated cells and clones derived from the latter formed colonies in agar-methocel, and exhibited increased chemotaxis and chemoinvasion. Clone BP-1E was also tumorigenic in SCID mice. The BP1 cell line transfected with mutated c-Ha-ras oncogene, named BP1-Tras, became more aggressive after transfection and decreased the latency time to tumorigenesis. Radioligand binding and immunocytochemical reactions were utilized for determining the receptors and Cath.D content of control and carcinogen-treated cells and their derived clones. MCF-10F cells contained 37 fmol/mg of protein of EGFR, ER and PR were undetectable, and Cath.D content was 70 fmol/mg protein. EGFR content was significantly higher in D3-1 and BP1-E cell lines vs the control MCF-10F and the other DMBA and BP clones, correlating positively with the emergence of the transformation phenotype. Whereas EGFR levels were not significantly different in BP1-Tras cells when compared with BP1-E, the former were more tumorigenic in SCID mice, an observation suggesting an alternative pathway in these cells in the formation of tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
9,10-Dimethyl-1,2-benzanthracene↗
Burnout: a challenge to healthcare in the 90s.
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Burnout, Professional↗
Facile preparation of nuclease resistant 3' modified oligodeoxynucleotides.
An efficient chemical procedure for the immobilization of carboxylate containing conjugate groups onto controlled pore glass (CPG) is described. The derivatized supports were used in the automated synthesis of an oligodeoxynucleotide (20-mer ODN) containing a 3' phosphodiester linked hexanol, aminohexyl, acridine, or cholesterol group. The stability of the oligomer in a hepatoma cell culture was found to be prolonged two to three fold by the presence of any of the 3' tails. By contrast, an aminohexyl group appended to the 5' terminus of the ODN only marginally improved its nuclease resistance. These data support the notion that antisense ODNs are primarily degraded by 3' exonucleases. Introduction of simple 3' tails which incorporate a normal phosphodiester linkage can increase ODN stability by interfering with these enzymes.
Base Sequence↗