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1.  Unlocking mechanisms in interleukin-1β-induced changes in hippocampal neurogenesis—a role for GSK-3β and TLX 
Translational Psychiatry  2012;2(11):e194-.
Glycogen synthase kinase-3β (GSK-3β) and the orphan nuclear receptor tailless homolog (TLX) are key regulators of hippocampal neurogenesis, which has been reported to be dysregulated in both neurodegenerative and psychiatric disorders. Inflammation is also implicated in the neuropathology of these disorders because of increased levels of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the brain. At elevated levels, IL-1β signaling through the IL-1 receptor type 1 has been shown to be detrimental to hippocampal neurogenesis. TLX is required to maintain neural stem/progenitor cells (NSPCs) in an undifferentiated state and is involved in NSPC fate determination, while GSK-3β negatively regulates Wnt signaling, a vital pathway promoting neurogenesis. This study shows that GSK-3β inhibition using a small-molecule inhibitor and the mood stabilizer lithium restores the IL-1β-induced decrease in NSPC proliferation and neuronal differentiation of embryonic rat hippocampal NSPCs to control levels. The IL-1β-induced effect on NSPCs is paralleled by a decrease in TLX expression that can be prevented by GSK-3β inhibition. The present results suggest that GSK-3β ameliorates the anti-proliferative and pro-gliogenic effects of IL-1β, and that TLX is vulnerable to inflammatory insult. Strategies to reduce GSK-3β activity or to increase TLX expression may facilitate the restoration of hippocampal neurogenesis in neuroinflammatory conditions where neurogenesis is impaired.
doi:10.1038/tp.2012.117
PMCID: PMC3565766  PMID: 23168994
GSK-3β; hippocampus; IL-1β; lithium; neurogenesis; TLX
2.  Diet, Breakfast, and Academic Performance in Children 
Annals of nutrition & metabolism  2002;46(0 1):24-30.
Objective
To determine whether nutrient intake and academic and psychosocial functioning improve after the start of a universal-free school breakfast program (USBP).
Methods
Information was gathered from 97 inner city students prior to the start of a USBP and again after the program had been in place for 6 months. Students who had total energy intakes of <50% of the recommended daily allowance (RDA) and/or 2 or more micronutrients of <50% of RDA were considered to be at nutritional risk.
Results
Prior to the USBP, 33% of all study children were classified as being at nutritional risk. Children who were at nutritional risk had significantly poorer attendance, punctuality, and grades at school, more behavior problems, and were less likely to eat breakfast at school than children who were not at nutritional risk. Six months after the start of the free school breakfast programs, students who decreased their nutritional risk showed significantly greater: improvements in attendance and school breakfast participation, decreases in hunger, and improvements in math grades and behavior than children who did not decrease their nutritional risk.
Conclusion
Participation in a school breakfast program enhanced daily nutrient intake and improvements in nutrient intake were associated with significant improvements in student academic performance and psychosocial functioning and decreases in hunger.
PMCID: PMC3275817  PMID: 12428078
School breakfast; Low-income children; Psychosocial functioning; Nutrition; Dietary intake
3.  Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase γ (POLG1) 
BMJ Case Reports  2009;2009:bcr12.2008.1303.
We report the case of a 2-year-old boy with seizures who developed hepatic failure shortly after commencing sodium valproate. Unexpectedly, liver function returned to normal on stopping the drug. Sequencing of the mitochondrial polymerase γ gene (POLG1) revealed four heterozygous substitutions, two of which have been identified in cases of Alpers–Huttenlocher disease.
doi:10.1136/bcr.12.2008.1303
PMCID: PMC3028092  PMID: 21686371
4.  Role of MC1R variants in uveal melanoma 
British Journal of Cancer  2003;89(10):1961-1965.
doi:10.1038/sj.bjc.6601358
PMCID: PMC2394456  PMID: 14612910
MC1R; uveal melanoma
5.  Parentage, reproductive skew and queen turnover in a multiple-queen ant analysed with microsatellites. 
We investigated the fine genetic structure of colonies of the ant, Leptothorax acervorum, to examine how queens share parentage (skew) in a social insect with multiple queens (polygyny). Overall, 494 individuals from eight polygynous field colonies were typed at up to seven microsatellite loci each. The first main finding was that surprisingly many sexual progeny (60% of young queens and 49% of young males) were not the offspring of the extant queens within their colonies. This implies that a high turnover (brief reproductive lifespan) of queens within colonies could be an important feature of polygyny. The second main result was that in most colonies relatedness among sexual progeny fell significantly below that expected among full siblings, proving that these progeny were produced by more than one singly-mated queen, but that skew in two colonies where the data permitted its calculation was moderate to high. However, relative to a German population, the study population is characterized by low queen-queen relatedness and low skew in female production, which is in line with the predictions of skew theory.
PMCID: PMC1688249  PMID: 9061974
6.  Marshall-Smith syndrome: the expanding phenotype. 
Journal of Medical Genetics  1997;34(10):842-845.
We report a child of 3 years 9 months with the Marshall-Smith syndrome (MSS), characterised by the typical facial features, developmental delay, and advanced bone age. After the diagnosis was made at 5 months of age, careful observation for respiratory complications and failure to thrive was initiated. By 3 1/2 years of age, although our patient had no life threatening respiratory complications, investigation showed significant upper airway obstruction, which has been successfully treated. Aggressive treatment for failure to thrive has also allowed her to maintain a weight on the 50th centile. The purpose of this report is to suggest that early diagnosis and aggressive management may improve the ultimate prognosis with respect to the respiratory and feeding difficulties seen in this rare syndrome.
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PMCID: PMC1051092  PMID: 9350818
7.  Antibody coated bacteria in urine of patients with recent spinal injury. 
Journal of Clinical Pathology  1990;43(11):953-956.
Twenty patients with an acute spinal injury were prospectively studied to assess the clinical importance of antibody coated bacteria (ACB) in the urine and the association among the different bacterial species with a positive antibody coated bacteria test. Clinical urinary tract infection was associated with a positive ACB test on 45% of occasions. Three hundred and ninety nine urine samples containing 541 bacterial isolates were assessed for the presence of ACB; 13% were found to be positive and 87% negative for ACB; 67% of urines contained a single bacterial isolate. Pseudomonas aeruginosa was most commonly associated with clinical urinary tract infection, found in 25% of episodes, followed by Proteus mirabilis (17.5%), Klebsiella sp (12.5%), and Proteus morganii (10%). Providencia stuartii, however, was most commonly associated with a positive ACB test (found in 17%). Other bacteria associated with a positive ACB test included Klebsiella sp (14%), Acinetobacter sp (12.5%), Pseudomonas aeruginosa (12%), Citrobacter sp (11.5%). A positive ACB test is not to be expected from a patient with spinal injury who has a catheter in place, and the test may provide a useful guide to identify those patients with an invasive infection. It is doubtful that a decision to treat or not treat bacteriuria could rest on the identification of the bacterial species alone.
PMCID: PMC502911  PMID: 2262569
9.  Anal abnormalities in childhood myotonic dystrophy--a possible source of confusion in child sexual abuse. 
Archives of Disease in Childhood  1992;67(4):527-528.
Myopathic involvement of the perianal musculature is one of the less well recognised features of myotonic dystrophy in children and may present with physical signs suggestive of sexual abuse. Details of six children with myotonic dystrophy are presented to emphasise the importance of considering an underlying myopathic condition in the differential diagnosis of anal laxity.
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PMCID: PMC1793345  PMID: 1580686
10.  Adrenoleucodystrophy. 
Archives of Disease in Childhood  1991;66(7):830-832.
PMCID: PMC1793237  PMID: 1863093
11.  Oncogene N-ras mediates selective inhibition of c-fos induction by nerve growth factor and basic fibroblast growth factor in a PC12 cell line. 
Molecular and Cellular Biology  1990;10(4):1556-1563.
A cell line was generated from U7 cells (a subline of PC12 rat pheochromocytoma cells) that contains a stably integrated transforming mouse N-ras (Lys-61) gene under the control of the long terminal repeat from mouse mammary tumor virus. Such cells, designated UR61, undergo neuronal differentiation upon exposure to nanomolar concentrations of dexamethasone, as a consequence of expression of the activated N-ras gene (I. Guerrero, A. Pellicer, and D.E. Burstein, Biochem, Biophys. Res. Commun. 150:1185-1192, 1988). Exposure of UR61 cells to either nerve growth factor (NGF) or basic fibroblast growth factor (bFGF) results in a marked induction of c-fos RNA, with kinetics paralleling those of NGF- or bFGF-induced expression of c-fos RNA in PC12 cells. Dexamethasone-induced expression of activated N-ras p21 results in blocking of c-fos RNA induction by NGF or bFGF in a time-dependent manner. Activated N-ras p21-mediated inhibition of c-fos RNA induction in UR61 cells is selective for NGF and bFGF and is not due to selective degradation of c-fos RNA. Normal and transforming N-ras can trans activate the chloramphenicol acetyltransferase gene linked to mouse c-fos regulatory sequences when transient expression assays are performed. Our observations suggest that N-ras p21 selectively interacts with pathways involved in induction of c-fos expression which initiate at the receptors for NGF and bFGF.
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PMCID: PMC362260  PMID: 2108319
12.  Optic nerve hypoplasia: associations and management. 
Archives of Disease in Childhood  1990;65(1):103-106.
Since its first description optic nerve hypoplasia has been identified with increasing frequency, and a range of associated problems have been described. The major neurological and endocrine associations are well established, but those factors that predispose to the development of optic nerve hypoplasia remain unclear. To understand the aetiology of these problems better, and to formulate a management regime, we studied a consecutive series of 40 patients who were divided into three groups. Group 1 (n = 24) had severe bilateral optic nerve hypoplasia; group 2 (n = 10) had mild, bilateral optic nerve hypoplasia; and group 3 (n = 6) had unilateral optic nerve hypoplasia. Previously described aetiological factors (for example, low maternal age or maternal alcohol or drug ingestion) were not present in any of the groups; this removes the need to screen a specific population. It is important that careful neurological and developmental assessments are carried out in children with optic nerve hypoplasia to identify potential disease. The role of imaging is discussed.
PMCID: PMC1792399  PMID: 2301970
13.  Tuberculous meningitis due to Mycobacterium bovis: a report of two cases. 
Postgraduate Medical Journal  1986;62(729):653-655.
Two Caucasian patients with bovine tuberculous meningitis are described. Classical Mycobacterium bovis was isolated from the cerebrospinal fluid on both occasions. Despite the elimination of cattle tuberculosis in this country, reactivated primary disease due to the bovine tubercle bacillus may still occur.
PMCID: PMC2418736  PMID: 3529067
14.  Monoclonal antibodies show Listeria monocytogenes in necropsy tissue samples. 
Journal of Clinical Pathology  1988;41(9):983-988.
Stable mouse monoclonal hybridoma cell lines secreting antibodies against Listeria monocytogenes were produced. Antibodies from two of these cell lines (designated CL2 and CL17) have been partially characterised. The specificities of these antibodies were assessed using indirect immunofluorescence antibody tests and L monocytogenes (166 strains) grown in vitro, other species of Listeria (21 strains), and bacteria from 14 other genera (87 strains). The antibodies were found to be specific for Listeria, and when used in combination, reacted with almost all strains of L monocytogenes. A simple and rapid direct immunofluorescence technique was developed, and the presence of L monocytogenes was shown in necropsy tissue from three patients where listeriosis had been confirmed by isolation of the bacterium. Bacteria were also confirmed using one of these antibodies in necropsy tissue from one further patient in whom listeriosis was suspected, but not confirmed by the cultivation of L monocytogenes.
PMCID: PMC1141657  PMID: 3142937
16.  Variant forms of ataxia telangiectasia. 
Journal of Medical Genetics  1987;24(11):669-677.
Two ataxia telangiectasia patients with unusual clinical and cellular features are described. Cultured fibroblasts and PHA stimulated lymphocytes from these two patients showed a smaller increase of radiosensitivity than cells from other A-T patients, as measured by colony forming ability or induced chromosome damage respectively, after exposure to ionising radiation. The response of DNA synthesis to irradiation of these cells was, however, the same as for other A-T patients. Cells from a third patient with some clinical features of A-T but with a very protracted course also showed low levels of radiation induced chromosome damage, but colony forming ability and the response of DNA synthesis after irradiation were no different from cells of normal subjects. There was, however, an increased level of translocations and unstable chromosomal rearrangements in this patient's lymphocytes.
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PMCID: PMC1050344  PMID: 3430541
17.  Levels of short (1-15 ms) electrical shocks from a 50 Hz supply inducing ventricular fibrillation in hyperbaric helium and oxygen. 
An investigation was undertaken to determine the ventricular fibrillation (VF) threshold of anaesthetised dogs subjected to external application of electric shocks between a foreleg and a hindleg. The shocks were 2-15 ms sections of 50 Hz sine waveform starting at peak current and were applied at a known time in the heart cycle. The object of the experiment was to determine if there was an increase in cardiac susceptibility to electrically induced VF at 31 atmospheres absolute (atm abs) in a helium and oxygen environment. The duration and position of that part of the cardiac cycle most vulnerable to induction of VF by electrocution was found (seven animals) using 4 ms shocks and then the minimum fibrillating current for shocks of 2-15 ms (min FC2-15) delivered at the most vulnerable point of the cycle (five animals). Body resistance was calculated from the data so gathered. Fibrillation thresholds were not changed by compression and there were no significant changes in the vulnerable period of the cardiac cycle. Min FC2 was significantly higher than for other durations under both control (3.21 A, SD 1.08) and test conditions (3.26 A, SD 0.39), p = 0.001. There was no difference in body resistance at 31 atm abs (395.5, SD 12.9) from control values at 1 atm abs (396.7, SD 10.9). From these data it was concluded that the heart is no more susceptible to the induction of VF at 31 atm abs in a helium oxygen environment and additional safety factors are unnecessary from this point of view.
PMCID: PMC1007914  PMID: 3689707
18.  Who needs a brain scan? 
Archives of Disease in Childhood  1987;62(11):1094-1096.
PMCID: PMC1778553  PMID: 3688912
19.  Biochemistry of protein-isocyanate interactions: a comparison of the effects of aryl vs. alkyl isocyanates. 
In addition to their use in the polyurethane and pesticide industries, isocyanates have proven to be useful probes for the exploration of protein structure. This paper focuses on three aspects of isocyanates: their broad reactivity, their reversible interaction with cholinesterases, and the relative hydrolysis rates of alkyl and aryl isocyanates. The broad reactivity of isocyanates as well as the demonstrated affinity labeling of serine and sulfhydryl esterases are discussed. Extension of the affinity labeling studies to include the analysis of the inhibition of cholinesterases by methyl isocyanate shows that methyl isocyanate is not an effective inhibitor of any of the cholinesterases. The inhibition of cholinesterases by alkyl isocyanates shows a pattern of decreased specificity with decreased alkyl chain length. The inhibition of cholinesterases by isocyanates is shown to be reversible, with a maximum rate of reversal seen at physiological pH. This reversal is characteristic of the reaction of an isocyanate with a sulfhydryl group. Finally, the affinity labeling of proteins must compete successfully with the hydrolysis of isocyanates in aqueous solution. The hydrolysis of alkyl isocyanates is shown to be significantly slower than that of the aryl isocyanates.
PMCID: PMC1474642  PMID: 3622443
22.  Serial concentrations of C-reactive protein as an indicator of urinary tract infection in patients with spinal injury. 
Journal of Clinical Pathology  1986;39(8):851-855.
C-reactive protein (CRP) was measured serially in 16 patients with an acute spinal injury. Twelve episodes of acute urinary tract infection (UTI) occurred during the study period. These were all associated with an increased concentration of CRP greater than 50 mg/l, which returned to normal after successful treatment. Thirteen episodes of asymptomatic bacteriuria associated with increased concentrations of CRP greater than 20 mg/l occurred, indicating tissue damage. More commonly, significant bacteriuria was associated with normal concentrations of CRP, and presumably, simple colonisation of the urinary tract, which, we suggest, does not require treatment with antibiotics. Serial measurement of CRP in patients with spinal injury may help distinguish between urinary tract colonisation and infection and be useful in monitoring the response to the treatment of clinical UTI.
PMCID: PMC500107  PMID: 3745475
24.  Ischaemic spinal cord injury after cardiac surgery. 
Archives of Disease in Childhood  1985;60(6):517-520.
The case records of eight children with an acute spinal cord lesion after cardiac surgery were reviewed. All had been operated on for congenital heart disease over the past 10 years. The prognosis for neurological recovery was poor and scoliosis and bladder dysfunction were common complications. Ischaemic cord injury is usually associated with coarctation of the aorta but may occur when surgery is performed for other cardiovascular defects.
PMCID: PMC1777365  PMID: 4015168
25.  Specificity of gene expression in adipocytes. 
Molecular and Cellular Biology  1985;5(2):419-421.
During the differentiation of preadipose 3T3 cells into adipose cells, the mRNAs for three proteins increase strikingly in abundance. To determine the degree of cell-type specificity in the expression of these mRNAs, we estimated their abundances in several nonadipose tissues of the mouse. None of these mRNAs was strictly confined to adipocytes, but the ensemble of three mRNAs was rather specific to adipocytes. Insofar as is revealed by these three markers, the distinctive phenotype of adipocytes is the result of the enhanced expression of a number of genes, none of which is completely silent in all other cell types.
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PMCID: PMC366727  PMID: 3974575

Results 1-25 (102)