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J Allsop

Publications and source records attributed to J Allsop.

At least 19 recordsLinked to original sources
PubMed2006

Technical report: Magnetic resonance direct thrombus imaging at 3 T field strength in patients with lower limb deep vein thrombosis: a feasibility study.

AIM: To investigate the feasibility of imaging lower limb deep vein thrombosis using magnetic resonance imaging (MRI) at 3.0 T magnetic field strength with an optimized a T1 magnetization prepared rapid gradient echo technique (MP-RAGE) in patients with normal volunteers as controls. MATERIALS AND METHODS: Patients with deep vein thrombosis (n = 4), thrombophlebitis (n = 2) and healthy volunteers (n = 9) were studied. MRI of the distal thigh and upper calf was performed at 3.0 T with MP-RAGE using two pre-pulses to suppress blood and fat (flip angle 15 degrees, echo time 5 ms, and repetition time 10 ms). A qualitative analysis was performed for detection of thrombi and image quality. Contrast-to-noise ratios were determined in thrombosed and patent veins. RESULTS: Thrombi were clearly visible as high-signal intensity structures with good suppression of the anatomical background. A blinded reader accurately diagnosed 15 out of 16 cases. The contrast-to-noise ratio measurements showed a positive contrast of thrombus over background muscle 16.9 (SD 4.3, 95% CI: 12.5-21.3) and a negative contrast of the lumen to muscle in patent veins of normal volunteers -7.8 (SD 4.3, 95% CI: -11.1 to -4.5), with p = 0.0015. CONCLUSION: Thrombi generate high signal intensity at 3.0 T allowing for their direct visualization if flowing blood, stationary blood and fat are sufficiently suppressed. This preliminary data supports the development of these techniques for other vascular applications.

Adult↗
PubMed2006

Smaller cerebellar volumes in very preterm infants at term-equivalent age are associated with the presence of supratentorial lesions.

BACKGROUND AND PURPOSE: Traditionally cerebellar functions are thought to be related to control of tone, posture, gait, and coordination of skilled motor activity. However, there is an increasing body of evidence implicating the cerebellum in cognition, language, memory, and motor learning. Preterm infants are at increased risk of neurodevelopmental delay, cognitive dysfunction, and behavioral and emotional disturbances. The role of the cerebellum in these adverse outcomes is unclear. OBJECTIVE: The objective of this study was to determine whether absolute cerebellar volumes differ between term-equivalent preterm infants and term-born control infants and to assess whether cerebellar volume is influenced by any possible antenatal, perinatal, and postnatal factors. METHODS: The study compared the MR imaging cerebellar volume by using a manual quantification program of 113 preterm infants at term-equivalent age and 15 term-born control infants. RESULTS: The median cerebellar volume of preterm at term-equivalent age was 25.4 cm3 and that of term-born control infants was 26.9 cm3. On initial analysis, there was a significant median difference of 2.0 cm3 (95% CI, 1.2 cm3 to 2.7 cm3) (2-sided P < .0001). However multiple regression analysis of perinatal variables showed that only infants with supratentorial lesions (P = .003) were significantly associated with the reduction in cerebellar volumes. The median cerebellar volumes were the following: supratentorial lesions, 18.9 cm3; no supratentorial lesions, 26.1 cm3; and term infants, 26.9 cm3 (analysis of variance, P < .0001). Hence, there was no significant difference in cerebellar volumes of preterm infants at term-equivalent age in the absence of supratentorial lesions. The median vermal volumes were 0.7 cm3 and were significantly related to cerebellar volumes both in preterm infants with and without lesions and in term-control infants. CONCLUSION: Premature infants at term-equivalent age have similar total cerebellar and vermal volumes compared with term infants in the presence of normal brain imaging. Reduced cerebellar volume in preterm infants at term-equivalent age is seen in association with supratentorial pathology such as hemorrhagic parenchymal infarction, intraventricular hemorrhage with dilation, and periventricular leukomalacia.

Cerebellum↗
PubMed2005

A comparison of MR cholangiopancreatography at 1.5 and 3.0 Tesla.

Clinical MR systems operating at 3.0 Tesla have the potential to significantly improve spatial resolution due to the boost in intrinsic signal to noise ratio. However, body imaging at these field strengths presents a number of technical challenges. We performed a prospective pilot study in which 10 patients underwent an MR cholangiopancreatography (MRCP) examination consecutively on 1.5 and 3.0 Tesla systems (both Philips Intera). An axial half Fourier segmented turbo spin echo (HASTE) sequence and a coronal thick-slab 2D turbo-spin echo (TSE) sequence were compared on both systems. A reader measured the signal intensity (SI) ratios of common bile duct (CBD): liver, and CBD: fat on HASTE images and CBD: liver on the TSE images. A second reader performed a qualitative analysis of the intrahepatic and extrahepatic biliary anatomy. Quantitative data was compared using the paired t-test and qualitative data with the paired Wilcoxon signed rank test with p < 0.05. The quantitative analysis of the HASTE sequences showed a slightly higher signal intensity ratio (CBD:liver) at 3.0 Tesla compared with 1.5 Tesla (8.1 vs 5.6, p = 0.002). No significant difference was found between the SI ratios of (CBD:fat) on HASTE images or (CBD:liver) on TSE images. The qualitative analysis showed superior image quality of 3.0 Tesla over 1.5 Tesla images on both HASTE (31 vs 25, p = 0.032), and TSE sequences (34 vs 28, p = 0.043). This pilot study shows that MRCP is feasible at 3.0 Tesla with some improvement in image quality and signal characteristics. Further development may be achieved with sequence optimization and improved coil design.

Adult↗
PubMed2003

Muscle magnetic resonance imaging in patients with congenital muscular dystrophy and Ullrich phenotype.

The aim of this study was to evaluate muscle magnetic resonance imaging findings in patients with congenital muscular dystrophy and Ullrich phenotype. Fifteen children with congenital muscular dystrophy and Ullrich phenotype were included in the study. All patients had collagen VI studies in muscle and, when family structure was informative, linkage studies to the collagen 6 loci. Three of the 15 patients had reduced collagen in muscle. One of the three was from an informative family and linked to one of the collagen 6 loci. Another patient was linked to one of the collagen 6 loci but had normal expression of collagen in muscle. The remaining 11 all had normal collagen expression in muscle. Only two of these 11 were from informative families and linkage to collagen 6 loci was excluded in them. All patients had muscle magnetic resonance imaging of their leg muscles using transverse T1 sequences. With the exception of the two patients in whom linkage to the collagen 6 loci was excluded, the other 13 patients showed the same pattern of selective involvement on magnetic resonance imaging of thigh muscles. This consisted of relative sparing of sartorius, gracilis, adductor longus and rectus. This pattern was also found in the case linked COL6A1/A2 locus but with normal collagen. This finding, and the striking clinical and magnetic resonance imaging concordance between patients with normal and reduced collagen VI in muscle suggest that collagen VI could still be the culprit in several cases with normal collagen expression, or alternatively a primary defect in a protein that closely interacts with collagen VI. Mutation analysis of the collagen 6 genes in cases with normal collagen VI expression is needed to resolve this issue.

Adolescent↗
PubMed2002

Selective muscle involvement on magnetic resonance imaging in autosomal dominant Emery-Dreifuss muscular dystrophy.

OBJECTIVE: The aim of this study was to evaluate the spectrum of muscle involvement on MRI in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2) due to mutations in the lamin A/C gene and to compare it to the pattern found in other conditions with similar phenotype. PATIENTS AND METHODS: Nine patients with a diagnosis of EDMD2 had MRI scanning of their leg muscles. Seven other patients, four with the X-linked form of Emery-Dreifuss muscular dystrophy (EDMD) and three with an Emery-Dreifuss-like phenotype but no detectable mutations in either the emerin or the lamin A/C gene were also scanned as disease controls. RESULTS: All patients with EDMD2 showed a characteristic involvement of the posterior calf muscles. The medial head of the gastrocnemius was always predominantly involved while the lateral head was relatively spared. This pattern was more obvious in mildly affected patients in whom the other calf muscles were spared or only mildly involved but was also recognisable in the patients with more advanced disease. In contrast, none of the patients with the X-linked EDMD or with Emery-Dreifuss-like phenotype but no mutation in either genes showed this pattern of muscle involvement. CONCLUSIONS: Our results suggest that patients with EDMD2 have a specific pattern of muscle involvement and that muscle MRI can be used, in combination with other techniques, to distinguish various genetic forms of Emery-Dreifuss muscular dystrophy.

Adolescent↗
PubMed2001

Intrauterine T-cell activation and increased proinflammatory cytokine concentrations in preterm infants with cerebral lesions.

Brain injury is common in very preterm infants, and intrauterine infection is a frequent antecedent of preterm birth. We examined the relation of cerebral damage to intrauterine antigen exposure and inflammation in 50 infants who were born at 23-29 weeks' gestation. Higher concentrations of cytokines (tumour necrosis factor alpha [TNF-alpha], and interleukins [IL], 1beta, 6, and 10) and CD45RO(+) T lymphocytes in umbilical blood predicted cerebral lesions detected by magnetic resonance imaging very soon after delivery. Our results suggest that infants who mount an immune response in utero are at higher risk of cerebral lesions.

Brain Injuries↗
PubMed1994

Primary hyperoxaluria type 1: genotypic and phenotypic heterogeneity.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT). The disease is notable for its extensive heterogeneity at the clinical, biochemical, enzymic and molecular genetic levels. A study of 116 PH1 patients over the past 8 years has revealed four main enzymic phenotypes: (1) absence of both AGT catalytic activity and immunoreactive AGT protein (approximately 40% of patients); (2) absence of AGT catalytic activity but presence of immunoreactive protein (approximately 16% of patients); (3) presence of both AGT catalytic activity and immunoreactive protein (approximately 41% of patients), in most of which cases the AGT is mistargeted to the mitochondria instead of the peroxisomes; and (4) a variation of the mistargeting phenotype in which AGT is equally distributed between peroxisomes and mitochondria, but in which that in the peroxisomes is aggregated into matrical core-like structures (approximately 3% of patients). Various point mutations, all occurring at conserved positions in the coding regions of the AGT gene, have been identified in these patients. The five mutations discussed in the present study, which have been found in individuals manifesting all of the four major enzymic phenotypes, account for the expressed alleles in about half of all Caucasian PH1 patients. The most common mutation found so far leads to a Gly170-->Arg amino acid substitution. This mutation, in combination with a normally occurring Pro11-->Leu polymorphism, appears to be responsible for the unprecedented peroxisome-to-mitochondrion mistargeting phenotype.

Amino Acid Sequence↗
PubMed1994

Cytosolic compartmentalization of hepatic alanine:glyoxylate aminotransferase in patients with aberrant peroxisomal biogenesis and its effect on oxalate metabolism.

Two patients with atypical manifestations of aberrant peroxisomal biogenesis are described. Contrary to previous studies, which had shown that Zellweger syndrome patients usually have normal levels of urinary oxalate excretion, the patients in the present study had evidence of abnormal oxalate metabolism in the form of hyperoxaluria and, in one of the patients, calcium oxalate urolithiasis. Activity of the liver-specific peroxisomal enzyme alanine:-glyoxylate aminotransferase (AGT), which is a major determinant of the level of endogenous oxalate synthesis in humans, was normal in one patient and markedly supranormal in the other. Using the technique of post-embedding protein A-colloidal gold immunoelectron microscopy, AGT was found to be mainly cytosolic in the livers of both patients, with significant amounts also localized in the nuclei. In a small minority of the hepatocytes of one patient, who was homozygous for the more common (major) AGT allele, large numbers of unidentified fibrillar arrays were found in the cytosol, which labelled heavily for immunoreactive AGT. The background cytosolic AGT labelling was markedly reduced in such cells when compared to the majority of cells that did not contain fibrils. In the other patient, who was heterozygous for the major and minor AGT alleles, there appeared to be low levels of mitochondrial AGT labelling. In the light of these data, the possible metabolic function of cytosolic AGT in the livers of panperoxisomal disease patients is discussed.

Alanine Transaminase↗
PubMed1994

Molecular characterization and clinical use of a polymorphic tandem repeat in an intron of the human alanine:glyoxylate aminotransferase gene.

The autosomal recessive disease primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate amino-transferase (AGT). This paper concerns the identification, characterization and clinical use of an unusual discretely polymorphic tandem repeat sequence in the fourth intron of the human AGT gene (gene locus designation AGXT). In a random Caucasian population, three alleles could be clearly recognized that consisted of either 12 (type III), 17 (type II) or approximately 38 (type I) tandemly repeated copies of a highly conserved 29/32-bp sequence with frequencies of 33%, 7% and 60%, respectively. In a random Japanese population, the allelic frequencies were markedly different (i.e. 31%, 45% and 19%, respectively). In addition, a fourth allele was identified, consisting of approximately 32 repeats (type IV), with an allelic frequency of approximately 5% in Japanese. The repetitive sequence was similar to previously identified mammalian sequences with homology to the Epstein-Barr virus IR3 repetitive element involving a 12/15-bp region GCA(GGN)GGAGGAGGG within the repeat unit. This IR3-like sequence was interspersed with a 17-bp sequence with no similarity to any currently known repetitive element. The type I and type III alleles were judged to be equivalent to a previously identified TaqI polymorphism. Two polymorphisms previously shown to be associated with the peroxisome-to-mitochondrion mistargeting of AGT in PH1 (a C154-->T point substitution in exon 1 and a 74-bp duplication in intron 1) were found to segregate exclusively with the type I intron 4 polymorphism in Caucasians, but not in Japanese. The polymorphic nature of the intron 4 tandem repeats makes them of potential use in the prenatal diagnosis of PH1, especially when coupled with the exon 1 C154-->T substitution or intron 1 duplication polymorphisms. A PH1 family, in which a fetus had been predicted previously to be either normal or a carrier by AGT enzymic analysis of a fetal liver biopsy, but who had been shown to be only partially informative with respect to the C154-->T/intron 1 polymorphisms, was analysed retrospectively. The family was completely informative for the intron 4 tandem repeat polymorphism and the carrier status of the fetus was confirmed.

Alanine Transaminase↗
PubMed1994

Evolution of alanine:glyoxylate aminotransferase 1 peroxisomal and mitochondrial targeting. A survey of its subcellular distribution in the livers of various representatives of the classes Mammalia, Aves and Amphibia.

As part of a wider study on the molecular evolution of alanine:glyoxylate aminotransferase 1 (AGT1) intracellular compartmentalization, we have determined the subcellular distribution of immunoreactive AGT1, using postembedding protein A-gold immunoelectron microscopy, in the livers of various members of the classes Mammalia, Aves, and Amphibia. As far as organellar distribution is concerned, three categories could be distinguished. In members of the first category (type I), all, or nearly all, of the immunoreactive AGT1 was concentrated within the peroxisomes. In the second category (type II), AGT1 was found more evenly distributed in both peroxisomes and mitochondria. In the third category (type III), AGT1 was localized mainly within the mitochondria with much lower, but widely variable, amounts in the peroxisomes. Type I animals include the human, two great apes (gorilla, orangutan), two Old World monkeys (anubis baboon, Japanese macaque), a New World monkey (white-faced Saki monkey), a lago, morph (European rabbit), a bat (Seba's short-tailed fruit bat), two caviomorph rodents (guinea pig, orange-rumped agouti), and two Australian marsupials (koala, Bennett's wallaby). Type II animals include two New World monkeys (common marmoset, cotton-top tamarin), three prosimians (brown lemur, fat-tailed dwarf lemur, pygmy slow loris), five rodents (a hybrid crested porcupine, Colombian ground squirrel, laboratory rat, laboratory mouse, golden hamster), an American marsupial (grey short-tailed opossum), and a bird (raven). Type III animals include the large tree shrew, three insectivores (common Eurasian mole, European hedgehog, house shrew), four carnivores (domestic cat, ocelot, domestic dog, polecat ferret), and an amphibian (common frog). In addition to these categories, some animals (e.g. guinea pig, common frog) possessed significant amounts of cytosolic AGT1. Whereas the subcellular distribution of AGT1 in some orders (e.g. Insectivora and Carnivora) did not appear to vary markedly between the different members, in other orders (e.g. Primates, Rodentia and Marsupialia) it fluctuated widely between the different species. Phylogenetic analysis indicates that the subcellular distribution of AGT1 has changed radically on numerous occasions during the evolution of mammals. The new observations presented in this paper are compatible with our previous demonstration of a relationship between AGT1 subcellular distribution and either present or putative ancestral dietary habit, and our previous suggestion that the molecular evolution of the AGT gene has been markedly influenced by dietary selection pressure.

Alanine Transaminase↗
PubMed1993

Enzymological and mutational analysis of a complex primary hyperoxaluria type 1 phenotype involving alanine:glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting and intraperoxisomal aggregation.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Three unrelated PH1 patients, who possess a novel complex phenotype, are described. At the enzymological level, this phenotype is characterized by a complete, or nearly complete, absence of AGT catalytic activity and reduced AGT immunoreactivity. Unlike normal individuals in whom the AGT is confined to the peroxisomal matrix, the immunoreactive AGT in these three patients was distributed approximately equally between the peroxisomes and mitochondria. The peroxisomal AGT appeared to be aggregated into amorphous core-like structures in which no other peroxisomal enzymes could be identified. Mutational analysis of the AGT gene showed that two of the three patients were compound heterozygotes for two previously unrecognized point mutations which caused Gly41-->Arg and Phe152-->Iso amino acid substitutions. The third patient was shown to be a compound heterozygote for the Gly41-->Arg mutation and a previously recognized Gly170-->Arg mutation. All three patients were homozygous for the Pro11-->Leu polymorphism that had been found previously with a high allelic frequency in normal populations. It is suggested that the Phe152-->Iso and Gly170-->Arg substitutions, which are only eighteen residues apart and located in the same highly conserved internal region of 58 amino acids, might be involved in the inhibition of peroxisomal targeting and/or import of AGT and, in combination with the Pro11-->Leu polymorphism, be responsible for its aberrant mitochondrial compartmentalization. On the other hand, the Gly41-->Arg substitution, either in combination with the Pro11-->Leu polymorphism or by itself, is predicted to be responsible for the intraperoxisomal aggregation of the AGT protein.

Adult↗
PubMed1992

A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase catalytic activity in a subset of patients with primary hyperoxaluria type 1.

We have synthesized and sequenced alanine:glyoxylate aminotransferase (AGT; HGMW-approved symbol for the gene--AGXT) cDNA from the liver of a primary hyperoxaluria type 1 (PH1) patient who had normal levels of hepatic peroxisomal immunoreactive AGT protein, but no AGT catalytic activity. This revealed the presence of a single point mutation (G----A at cDNA nucleotide 367), which is predicted to cause a glycine-to-glutamate substitution at residue 82 of the AGT protein. This mutation is located in exon 2 of the AGT gene and leads to the loss of an AvaI restriction site. Exon 2-specific PCR followed by AvaI digestion showed that this patient was homozygous for this mutation. In addition, three other PH1 patients, one related to and two unrelated to, but with enzymological phenotype similar to that of the first patient, were also shown to be homozygous for the mutation. However, one other phenotypically similar PH1 patient was shown to lack this mutation. The mechanism by which the glycine-to-glutamate substitution at residue 82 causes loss of catalytic activity remains to be resolved. However, the protein sequence in this region is highly conserved between different mammals, and the substitution at residue 82 is predicted to cause significant local structural alterations.

Alanine↗
PubMed1992

Diagnosis of decreased cholinesterase activity by amniocentesis.

We report a case in which amniocentesis, performed in order to exclude a fetal chromosomal abnormality, led to a diagnosis of decreased cholinesterase activity. This is a rare but clinically useful application of the amniotic fluid cholinesterase assay.

Journal Article↗
PubMed1991

Mistargeting of peroxisomal L-alanine:glyoxylate aminotransferase to mitochondria in primary hyperoxaluria patients depends upon activation of a cryptic mitochondrial targeting sequence by a point mutation.

In approximately one-third of primary hyperoxaluria type 1 patients, disease is associated with a unique protein sorting defect in which hepatic L-alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44), which is normally peroxisomal, is mistargeted to mitochondria. In all such patients analyzed to date, the gene encoding the aberrantly targeted AGT carries three point mutations, each of which specifies an amino acid substitution. In this paper we show that one of these substitutions, a proline-to-leucine at residue 11, is necessary and sufficient for the generation of a mitochondrial targeting sequence in the AGT protein. AGT with this substitution appears to interact specifically with the mitochondrial protein import machinery, via a discrete N-terminal domain of the AGT protein. The N-terminal 19 amino acids of AGT with this substitution are sufficient to direct mouse cytosolic dihydrofolate reductase to mitochondria, and a synthetic peptide corresponding to this same 19-amino acid region reversibly inhibits mitochondrial protein import, not only of AGT but also of ornithine transcarbamoylase, a genuine cytoplasmically synthesized mitochondrial protein. We have extended these studies to analyze a region of normal human AGT cDNA directly upstream of the coding region. This sequence appears to correspond to an ancestral mitochondrial targeting sequence deleted from the human coding region by point mutation at the initiation codon. We show that reestablishment of this initiation codon produces an active mitochondrial targeting sequence that is different to that found in the hyperoxaluria patients. These results are discussed with reference to the AGT targeting defect in primary hyperoxaluria and also in relation to the highly unusual species specificity of subcellular distribution of AGT among mammals.

Alanine Transaminase↗