Extracellular matrix as a bioactive material for soft tissue reconstruction.
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Animals↗
Biomedical subjects
A J Hussey
Publications and source records attributed to A J Hussey.
Occult knee dislocation: the importance of secondary survey.
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Accidents, Traffic↗
The electrocardiography dot as a preoperative marker for nipple-areola complex reconstruction.
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Breast Neoplasms↗
Ruptured abdominal aortic aneurysm in a 12-month-old boy.
A rare case of abdominal aortic aneurysm in a 12-month-old boy is reported. The clinical presentation was one of acute catastrophic rupture. The morphologic and histologic findings suggested an idiopathic etiology.
Aortic Aneurysm, Abdominal↗
Inhibition of platelet thrombosis using an activated protein C-loaded stent: in vitro and in vivo results.
In high-risk and complicated coronary intervention, the risk of acute closure is unpredictable. Thrombus and platelet deposition at the intervention site may also have further effects on subsequent restenosis. In vivo infusion of activated protein C has previously been shown to achieve potent anticoagulation without any haemostatic side effects. We now evaluated the in vitro and in vivo efficacy of polymer-coated coronary stents loaded with purified rabbit Activated Protein C (APC). By measuring 125I-fibrinogen/fibrin deposition APC-loaded stent-wires were antithrombotic compared to albumin-loaded, inhibited-APC-loaded, plain polymer-coated and stainless steel stent-wires. In a balloon injury rabbit iliac artery model, APC-loaded stents did not occlude (0/14) compared to plain stents (9/15) and BSA-loaded stents (2/4). Relative 111In-labelled platelet deposition showed a similarly significant degree of inhibition. In conclusion, APC-loading could render stents significantly less thrombotic. Whether an effective antithrombogenic stent like this effectively reduces restenosis rates warrants further evaluation.
Adsorption↗
Human Mu-class glutathione S-transferases present in liver, skeletal muscle and testicular tissue.
The major human Mu-class glutathione S-transferases (GST) have been purified to allow comparisons of their catalytic, physicochemical and immunochemical properties. GST isoenzymes, purified from hepatic, testicular and skeletal muscle tissue were found to comprise three distinct subunits (M1, M2 and M3) which may combine to form both homodimeric and heterodimeric proteins. Two distinct subunits, M1a and M1b, which represent allelic charge variants have been isolated but no polymorphic forms encoded at the GST M2 and M3 loci have been observed. Three GST isoenzymes (M1a-1a, M1a-1b and M1b-1b) have been purified from a single liver specimen. In addition, GST M1a-2, M1b-2, M2-2 and M2-3 have been isolated from muscle, whilst the M3-3 homodimer has been purified from human testis. The homodimeric enzymes GST M1a-1a, M1b-1b, M2-2 and M3-3 have pI values of 6.1, 5.5, 5.3 and 5.0, whilst SDS-PAGE indicated that M1a, M1b, M2 and M3 have molecular masses of 26.7, 26.6, 26.0 and 26.3 kDa, respectively. The M1, M2 and M3 subunits isolated from either liver, skeletal muscle or testis, are catalytically distinct. Both M1-type subunits (M1a and M1b) possess a high activity for trans-4-phenyl-3-buten-2-one, whereas, the skeletal muscle subunit M2 has a high activity towards 1,2-dichloro-4-nitrobenzene. By contrast, the testicular GST subunit M3 has no detectable activity towards either of these substrates. However, all three Mu-class subunits are active towards the compounds 4-hydroxynonenal and 4-hydroxydecinal, possible endogenous substrates which are produced by lipid peroxidation. The human Mu-class subunits can be distinguished immunochemically; antisera raised against the testicular GST M3-3 showed no reactivity towards either the M1 or M2 subunits. The M3 subunit has a blocked N-terminus but automated amino-acid sequencing of a CNBr-derived peptide allowed 14 residues of the M3 subunit to be identified. These data indicated that testicular GST M3-3 is likely to correspond to the brain/testis Mu-class GST cDNA described by Campbell et al. (Campbell E., Takahashi Y., Abramovitz M., Peretz M., & Listowsky I. (1990) J. Biol. Chem. 265, 9188-9193).
Aged↗
Characterization of a human class-Theta glutathione S-transferase with activity towards 1-menaphthyl sulphate.
A purification scheme is described for a glutathione S-transferase (GST) from human liver that catalyses the conjugation of 1-menaphthyl sulphate (MS) with GSH; the method devised results in an approx. 500-fold increase in specific activity towards MS. The human enzyme which metabolizes MS is a homodimer comprising subunits of M(r) 25,100, and immunochemical experiments have shown it to be a member of the class-Theta GSTs. Automated Edman degradation of this enzyme has confirmed that it is a Theta-class GST bu the amino acid sequence obtained differs from that of GST theta described previously [Meyer, Coles, Pemble, Gilmore, Fraser & Ketterer (1991) Biochem. J. 274, 409-414]. We have therefore designated the enzyme that catalyses the conjugation of MS with GSH GST T2-2* (in the absence of complete amino acid sequence data, the T1 and T2 subunits are provisionally designated T1* and T2*); the evidence which indicates that GST theta (which should possibly now be called GST T1-1*) and GST T2-2* represent distinct isoenzymes is discussed.
Amino Acid Sequence↗
Variation in the expression of Mu-class glutathione S-transferase isoenzymes from human skeletal muscle. Evidence for the existence of heterodimers.
The cytosolic glutathione S-transferases (GST) from human skeletal muscle were purified by a combination of affinity chromatography and anion-exchange chromatography followed by either chromatofocusing or hydroxyapatite chromatography. Pi-class and Mu-class GST, but not Alpha-class GST, were isolated from muscle. In addition to a Pi-class GST subunit, which exists as a homodimer, this tissue also contains a total of three distinct neutral-type Mu-class GST subunits, which hybridize to form homodimers or heterodimers. The neutral-type subunits are referred to as N1-N3 and are defined by the decreasing isoelectric points of the homodimers; GST N1N1, N2N2 and N3N3 have estimated pI values of 6.1, 5.3 and less than 5.0 respectively. SDS/PAGE showed that N1, N2 and N3 have Mr values of 26,700, 26,000 and 26,300 respectively. The N1, N2 and N3 subunits are catalytically distinct, with N1 possessing a high activity for trans-4-phenylbut-3-en-2-one and N2 having high activity with 1,2-dichloro-4-nitrobenzene. In skeletal muscle the expression of the N1 subunit, but not of N2 and N3 subunits, was found to differ from specimen to specimen. The N1 subunit was absent from about 50% of samples examined, and the purification results from two different specimens are presented to illustrate this inter-individual variation. Skeletal muscle from one individual (M1), which did not express N1, contained only GST N2N2, N2N3 and pi, whereas the second sample examined (M2) contained GST N1N2, N2N2 and N2N3 as well as GST pi. N-Terminal amino acid sequence analysis supported the electrophoretic evidence that the N2 subunit in GST N1N2, N2N2 and N2N3 represents the same polypeptide. The peptides obtained from CNBr digests of N2 were subjected separately to automated amino acid sequencing, and the results indicate that N2 is distinct but closely related to the protein encoded by the human Mu-class cDNA clone GTH4 [DeJong, Chang, Whang-Peng, Knutsen & Tu (1988) Nucleic Acids Res. 16, 8541-8554]. GST N2N2 is probably identical with GST 4 [Board, Suzuki & Shaw (1988) Biochim. Biophys. Acta 953, 214-217], as over the 24 N-terminal residues of GST 4 there is complete identity between the two enzymes. Our data suggest that the GST 1 and GST 4 loci are part of the same multi-gene family.
Aged↗
Intravenous N-acetylcysteine, hepatotoxicity and plasma glutathione S-transferase in patients with paracetamol overdosage.
The concentration of glutathione S-transferase B1 (GST B1) subunits was measured in sequential plasma samples taken at frequent intervals for 48 h from ten patients with severe paracetamol poisoning who were treated with intravenous N-acetylcysteine. No significant increase in plasma GST B1 concentration was observed over the study period and with 4 h of starting treatment with N-acetylcysteine there were significant decreases in plasma GST B1 concentrations. None of the patients subsequently developed significant liver damage. At the dose used for the treatment of paracetamol poisoning, N-acetylcysteine has no hepatotoxic effects.
Acetaminophen↗
Plasma glutathione S-transferase and F protein are more sensitive than alanine aminotransferase as markers of paracetamol (acetaminophen)-induced liver damage.
Concentrations of glutathione S-transferase (GST; glutathione transferase; EC 2.5.1.18) B1 subunits, F protein, and the activity of alanine aminotransferase (ALT; EC 2.6.1.2) were measured in sequential plasma samples taken from nine patients with self-administered paracetamol (acetaminophen) poisoning. GST exceeded the reference interval in all patients at the time of admission, and F protein was increased in seven. In contrast, abnormal activities of ALT in plasma were found in only one of the nine on admission, a patient admitted 12 h after poisoning. Subsequent to admission nine, eight, and five patients, respectively, had abnormal concentrations of GST, F protein, and ALT. When expressed as multiples of the upper reference limit, the highest values for GST measured in each patient always far exceeded the greatest abnormalities in ALT; this was true for F protein in only five patients. Patients in whom the concentration of GST exceeded 10 micrograms/L on admission subsequently went on to develop moderate or severe liver damage, despite treatment with N-acetylcysteine. F protein and ALT measurements on admission were not as efficient as GST at predicting the clinical outcome of the patients. We conclude that GST and F protein offer clear advantages over ALT for detecting minor degrees of acute liver dysfunction, particularly when only centrilobular damage may be involved.
Acetaminophen↗
Measurements of glutathione S-transferase B1 in plasma after birth asphyxia: an early indication of hepatocellular damage.
Concentrations of glutathione S-transferase (glutathione transferase; EC 2.5.1.18) B1 and B2 subunits (B1 and B2) and activity of alanine aminotransferase (ALT; EC 2.6.1.2) were measured in sequential plasma samples taken from 14 infants with birth asphyxia. Within 6 h of asphyxia, abnormal concentrations of B1 were found in 11 infants, whereas only seven infants showed abnormal ALT activities at this time. In plasma sampled 24 h after birth, values for ALT were abnormal in 10, whereas values for B1 were abnormal in six. Abnormal concentrations of B2 were found in relatively few of these infants, apparently because this monomer is poorly expressed in liver samples obtained up to 41 weeks after conception. We conclude that measurement of B1 may provide a useful index of hepatic impairment in birth-asphyxiated infants.
Asphyxia Neonatorum↗
Glutathione S-transferase levels in autoimmune chronic active hepatitis: a more sensitive index of hepatocellular damage than aspartate transaminase.
Glutathione S-transferase (GST; EC 2.5.1.18), a sensitive marker of hepatocellular damage, was measured in patients on therapy for histologically proven, autoimmune chronic active hepatitis at various stages of the disease. GST levels were elevated in 65% of serum samples despite immuno-suppressive treatment compared with aspartate transaminase (AST) which was increased in only 23% of samples. In 55% of samples with normal AST concentrations, GST was elevated. No samples demonstrated abnormal transaminase with normal GST levels. It is concluded that continuing hepatocellular damage occurs in patients with autoimmune chronic active hepatitis on immuno-suppressive treatment.
Adolescent↗
Plasma glutathione S-transferase concentration as a measure of hepatocellular integrity following a single general anaesthetic with halothane, enflurane or isoflurane.
The plasma concentration of hepatic glutathione S-transferase (GST) was measured in matched groups of patients who received halothane, enflurane or isoflurane anaesthesia for elective minor surgery. The GST concentrations increased significantly at 3 h after anaesthesia in patients who received halothane or enflurane, but not in patients who were given isoflurane. A secondary increase in GST concentration, at 24 h, was seen in a small number of individuals who received halothane or enflurane. Abnormal GST concentrations were found in 50% of patients following halothane anaesthesia, 20% following enflurane and 11% after isoflurane. The small but significant increases in GST concentrations in patients receiving halothane or enflurane suggests an impairment of hepatocellular integrity following the administration of these anaesthetics. In contrast, isoflurane anaesthesia did not appear to be associated with this effect.
Adult↗
Post-transfusion non-A, non-B hepatitis: significance of raised ALT and anti-HBc in blood donors.
The FDA has recommended that all blood collected in the USA should be screened for antibody to hepatitis B core antigen (anti-HBc) and for raised alanine aminotransferase (ALT) as possible indicators of non-A, non-B hepatitis carriage. As part of an assessment of the medical and economic implications of such a screening programme, we have screened 1,742 regular blood donors for ALT and 2,086 (including the same 1,742) for anti-HBc. 42 (2.4%) of the 1,742 donors had ALT levels above 45 units/l. Clinical assessment of 33 of these revealed that 26 exceeded their ideal body weight by more than 10% and 15 by more than 20%. 11 admitted to an alcohol intake of over 40 g daily. In all, 82% of donors with raised ALT had a 'non-viral' clinical explanation for this abnormality. Anti-HBc was detected in 42 (2.0%) of the 2,086 donors screened. 27 (64%) also had anti-HBs, and 11 (26%) had anti-HBe. There was no overlap between donors with raised ALT and those with anti-HBc. Combined screening would lead to a loss of at least 4.4% of donations in the population studied. In view of the medical and economic implications of the introduction of these screening tests, and the poverty of data on the clinical significance of post-transfusion non-A, non-B hepatitis, we conclude that such a screening programme cannot be justified at present. Further studies are required, including a prospective controlled trial of the effects of screening.
Alanine Transaminase↗
The polymorphic expression of neutral glutathione S-transferase in human mononuclear leucocytes as measured by specific radioimmunoassay.
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Adolescent↗
Plasma glutathione S-transferase measurements in patients with alcoholic cirrhosis.
Hepatocellular damage has been assessed in 54 patients with biopsy proven alcoholic cirrhosis by measuring the activity of aspartate aminotransferase (AST) and the concentrations of glutathione S-transferase B1B1 (GST B1B1) and B2B2 (GST B2B2) in serum. The levels of AST, GST B1B1, or GST B2B2 were abnormal in 28, 28 and 17 patients respectively but abnormalities in AST and GST measurements appeared to identify different populations of patients.
Aspartate Aminotransferases↗
Hepatic glutathione S-transferase release after halothane anaesthesia: open randomised comparison with isoflurane.
Plasma concentrations of hepatic glutathione S-transferase (GST) are a more sensitive measure of acute hepatic damage than aminotransferase activity. Plasma GST concentrations have been measured by radioimmunoassay in an open randomised study after halothane or isoflurane anaesthesia. The concentration of GST was significantly increased after anaesthesia in patients who received halothane in 30% oxygen/70% nitrous oxide (n = 37) and in patients who received halothane in 100% oxygen (n = 17). The frequency of abnormal GST concentrations, defined as 4 micrograms/l or more, was 35% and 24%, respectively. GST concentrations usually reached a peak 3-6 h after the end of anaesthesia. In 17 patients who received isoflurane in 30% oxygen/70% nitrous oxide, there was no significant rise in GST concentration and no patient had a concentration above 4 micrograms/l. No patient in any of the groups had a significant increase in alanine aminotransferase. In clinically identical situations, anaesthesia with halothane but not isoflurane leads to demonstrable impairment of hepatocellular integrity.
Adult↗
Glutathione S-transferase subunits in the mouse and their catalytic activities towards reactive electrophiles.
The glutathione S-transferases (GST) are a major, multi-gene, group of detoxication proteins. A rapid, two-step purification, that employs S-hexylglutathione affinity chromatography and hydroxyapatite HPLC, is described for the GST isoenzymes in mouse liver. The major hepatic forms comprise Yf(Mr 24,500)-, Ya(Mr 26,000)- and Yb(Mr 27,000)-type subunits. The isoelectric points of the Yf, Ya and Yb dimers are 8.6, 9.2 and 7.8-8.2 respectively. Immunochemical experiments showed the purified mouse subunits cross-reacted with antisera raised against rat GST subunits that possessed equivalent molecular masses; the subunit sizes of the distinct subunit types are conserved between these two species. The catalytic activities of the purified mouse GST subunits are described. In common with other species the mouse GST are subject to tissue-specific expression. However, only mouse liver and not rat, guinea pig, hamster or human livers express the Yf polypeptide. The significance of this difference is unclear but, in the rat, the Yf subunit can serve as a marker for pre-neoplastic hepatocellular carcinogenesis.
Animals↗