Defective glycosyltransferases are not good for your health.
Explore the source record for details and available documents.
Anemia, Dyserythropoietic, Congenital↗
Biomedical subjects
J Tan
Publications and source records attributed to J Tan.
Glutathione transferase T1 and M1 genotype polymorphism in the normal population of Shanghai.
Glutathione transferases are known to be important enzymes in the metabolism of xenobiotics. In humans genetic polymorphisms have been reported for the hGSTM1 and hGSTT1 genes leading to individual differences in susceptibility towards toxic effects, such as cancer. This study describes the distribution of the two polymorphisms of hGSTT1 and hGSTM1 in the normal Chinese population of Shanghai. Out of 219 healthy individuals having been genotyped for GSTT1 and GSTM1, 108 (49%) were identified to be homozygously deficient for the GSTT1 gene and 107 (49%) for the GSTM1 gene.
Adult↗
Randomized, double-blind, placebo-controlled trial of oral enalapril in patients with neurally mediated syncope.
BACKGROUND: The purpose of this study was to study the effect of enalapril on neurally mediated syncope (NMS). Several agents (except for angiotensin-converting enzyme [ACE] inhibitors) have been used to treat patients with NMS. It is unknown whether ACE inhibitors have beneficial effects on NMS. METHODS AND RESULTS: Thirty subjects who had reproducible NMS induced with head-up tilt table test (HUT) were randomly assigned and divided in double-blind fashion into placebo and enalapril (an ACE inhibitor) groups. Hemodynamics and plasma catecholamine concentrations were studied. Before administration of enalapril, syncope induced by HUT was associated with vigorous hypotension and bradycardia. Plasma catecholamine concentrations were significantly elevated during NMS compared with the supine position before tilt. Oral enalapril rather than placebo produced a marked reduction in diastolic blood pressure during supine positioning before tilt. Administration of enalapril prevented HUT-induced NMS and increase of plasma catecholamine concentrations in all patients examined. Conversely, placebo had no effect in the majority of patients with NMS (12 of 15 subjects). Follow-up data showed that NMS disappeared in 14 (93%) of 15 patients treated with enalapril. CONCLUSIONS: This study demonstrates that ACE inhibitors may efficiently prevent NMS, presumably through inhibition of sympathetic system activation and peripheral hypotensive effect.
Administration, Oral↗
Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma with ultrastructural evidence of microvilli with rootlets.
Villin (V) is a glycoprotein of microvilli associated with rootlet formation. Most colonic adenocarcinomas have a V positive (+), cytokeratin (CK) 20 (+), CK7-negative (-) immunophenotype; most lung adenocarcinomas have a CK20(-), CK7(+) immunophenotype. The reports of villin immunoreactivity in lung adenocarcinoma range from 6% to 68% in studies using various fixations and varied anti-villin antibodies. Some lung adenocarcinomas have microvilli with rootlets leading to possible diagnostic confusion with metastatic colonic adenocarcinoma to lung. Nine primary lung adenocarcinomas with rootlets on ultrastructure (including four bronchioloalveolar carcinomas [BAC]), four metastatic lung adenocarcinomas with rootlets, nine metastatic colon adenocarcinomas to lung, and 10 randomly selected lung adenocarcinomas without rootlets (including five BAC), were immunostained with monoclonal antibodies to villin (1D2C3), CK7 (OV-TL12/30), and CK20 (Ks20.8) using a streptavidin peroxidase technique with heat-induced epitope retrieval. All primary lung adenocarcinomas with rootlets were CK7(+) CK20(-), and six of nine (67%) were V(+). Cytoplasmic villin positivity occurred in a diffuse--five of nine (56%), focal--two of nine (22%), or brush border pattern--two of nine (22%). Two of four metastatic lung adenocarcinomas with rootlets were V(+). One metastatic lung adenocarcinoma had a CK7(+), CK20(+), V(-) phenotype. All metastatic colonic adenocarcinomas were V(+), CK20(+), CK7(-), and 1 of 10 (10%) lung adenocarcinomas without rootlets was V(+), and all 10 were CK20(-), and CK7(+). In summary, villin positivity is more common in lung adenocarcinoma with rootlets (67%) than those without rootlets (10%). AU primary lung adenocarcinomas were CK7(+), CK20(-). The combination of villin, CK 7, and CK 20 is helpful in differentiating metastatic colon adenocarcinoma from lung adenocarcinoma with rootlets.
Adenocarcinoma↗
Experimental studies on traumatic facial nerve injury.
PURPOSE: The purpose of this study was to investigate the outcome of different injuries to the facial nerve. MATERIALS AND METHODS: Six patterns of injuries (exposure, compression, crushing, stretching, division and post-division anastomosis) were produced in the buccal branches of the facial nerve in 60 rabbits. Electroneuronography (ENoG) and histology at definite time were used to evaluate the results. RESULTS AND CONCLUSIONS: Exposure and compression injuries produced a neuropraxic injury and rapid recovery. Crushing and stretching injuries resulted in axonotmesis and whilst complete recovery can take place it may be very slow. Division and post-division anastomosis fall into neurotmesis injury and do not completely recover within six months; the former recovers slower and later than the latter.
Animals↗
Transcriptional regulation of the human UDP-GlcNAc:alpha-6-D-mannoside beta-1-2-N-acetylglucosaminyltransferase II gene (MGAT2) which controls complex N-glycan synthesis.
UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase II (GnT II; EC 2.4.1.143) is essential for the normal assembly of complex Asn-linked glycans. Northern analysis showed a major transcript at 2.0 kb and a minor band at approximately 2.9 kb in five different human cell lines. The gene (MGAT2) has three AATAAA polyadenylation sites at 68, 688 and 846 bp downstream of the translation stop codon. 3'-RACE (rapid amplification of cDNA ends) using RNA from the human cell line LS-180 indicated that all three sites were utilized for transcription termination. 5'-RACE and RNase protection analyses showed multiple transcription initiation sites at -440 to -489 bp relative to the ATG translation start codon (+1). The data show that the entire GnT II gene is on a single exon. The gene has a CCAAT box at -587 bp but lacks a TATA box and the 5'-untranslated region is GC-rich and contains consensus sequences suggestive of multiple binding sites for Sp1; these properties are typical for housekeeping genes. A series of chimeric constructs containing different lengths of the 5'-untranslated region fused to the chloramphenicol acetyltransferase (CAT) reporter gene were tested in transient transfection experiments using HeLa cells. The CAT activity of the construct containing the longest insert (-1076 bp relative to the ATG start codon) showed a approximately 38-fold increase as compared to that of the control. Removal of the region between -636 and -553 bp caused a dramatic decrease in CAT activity indicating this to be the main promoter region of the gene.
Base Sequence↗
Impaired release of tissue plasminogen activator from the endothelium in Graves' disease - indicator of endothelial dysfunction and reduced fibrinolytic capacity.
BACKGROUND: Patients with hyperthyroidism have increased plasma levels of von Willebrand factor (vWF). Changes in tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1), another two endothelium-derived proteins and modulators of blood fibrinolytic activity, have not been reported in hyperthyroidism. METHODS: The release of t-PA by vascular endothelial cells after venous occlusion, basal blood concentrations of t-PA, PAI-1 and vWF were studied in 33 patients with hyperthyroidism, with most of them followed up 30 days after iodine radiotherapy. RESULTS: Compared with control subjects, both the basal t-PA levels in plasma and the increase in t-PA levels with venous occlusion were significantly decreased in patients (P < 0.001), whereas plasma PAI-1 and vWF levels were increased greatly (P < 0.001). At follow-up, patients with normal plasma free thyroxine (T4) and total tri-iodothyronine (T3) showed similar plasma levels of t-PA, PAI-1, vWF and release of t-PA from endothelial cells as the control subjects (P > 0.05). In those with persistent elevated T4 or T3 levels, however, the basal plasma t-PA level and the released t-PA from endothelial cells during venous occlusion were significantly lower than in the control subjects (P < 0.001 and P < 0.005), and blood concentrations of PAI-1 and vWF did not return to the normal range (P < 0.001 and P < 0.001). In all patients, serum thyroid hormone concentrations were inversely correlated with basal plasma t-PA (T4: r = -0.549, P < 0. 001; T3: r = -0.463, P < 0.001) and released t-PA by endothelial cells (T4: r = -0.505, P < 0.001; T3: r = -0.450, P < 0.001) but strongly correlated with plasma PAI-1 (T4: r = 0.613, P < 0.001; T3: r = 0.577, P < 0.001) and vWF (T4: r = 0.457, P < 0.001; T3: r = 0. 564, P < 0.001). CONCLUSION: Hyperthyroid patients may experience vascular endothelial dysfunction and reduced fibrinolytic activity in blood.
Adult↗
Epididymectomy in the management of intrascrotal disease: a critical reappraisal.
OBJECTIVE: To assess the outcome of epididymectomy as a method of treating epididymal pathology. PATIENTS AND METHODS: Forty-one patients who underwent epididymectomy between 1990 and 1995 were analysed retrospectively; their clinical records were reviewed and their satisfaction with the outcome and relief of symptoms assessed using a questionnaire and/or telephone interview. RESULTS: Twenty-nine patients with pain were subdivided into three categories depending on the indication for epididymectomy, i.e. post-vasectomy epididymal engorgement (eight patients), complex cystic disease (11) or 'chronic epididymitis' (10). The outcome was satisfactory in 27 of the 29 patients. The best results were obtained in the group who underwent epididymectomy after vasectomy, where seven of eight improved after the procedure. Those with chronic epididymitis had the least favourable outcome, with only seven reporting any improvement in symptoms. CONCLUSIONS: Epididymectomy has a valuable role in the management of epididymal pathology in appropriately selected patients.
Cysts↗
Proton-decoupled 31P magnetic resonance spectroscopy reveals osmotic and metabolic disturbances in human hepatic encephalopathy.
Quantitative proton and quantitative proton-decoupled 31P magnetic resonance spectroscopy (MRS) of the brain was performed in 16 patients with liver disease (10 with and six without chronic hepatic encephalopathy) and four patients with hyponatremia, as well as 20 age-matched normal subjects. Patients with hepatic encephalopathy were distinguished from controls by significant reduction in levels of cerebral nucleoside triphosphate (2.45 +/- 0.20 vs. 2.91 +/- 0.21 mmol/kg of brain; p < 0.0003), inorganic phosphate (p < 0.03), and phosphocreatine (p < 0.04). In addition of increased levels of cerebral glutamate plus glutamine and decreased concentrations of myo-inositol, patients with hepatic encephalopathy showed a reduction of total visible choline and of glycerophosphorylcholine (0.67 +/- 0.13 vs. 0.92 +/- 0.20 mmol/kg of brain in controls; p < 0.005) in 1H MRS, and of glycerophosphorylethanolamine (0.40 +/- 0.12 vs. 0.68 +/- 0.12 mmol/kg of brain in controls; p < 0.0003) in proton-decoupled 31P MRS. Of the reduction of "total choline," 61% was accounted for by glycerophosphorylcholine, a cerebral osmolyte. Similar metabolic abnormalities were seen in hyponatremic patients. The results are consistent with disturbances of cerebral osmoregulation and energy metabolism in patients with chronic hepatic encephalopathy.
Adenosine Triphosphate↗
The three-quarters vein anastomosis: a teaching tool for microsurgery.
Explore the source record for details and available documents.
Anastomosis, Surgical↗
Interferon-gamma-inducing factor elicits antitumor immunity in association with interferon-gamma production.
Interferon-gamma-inducing factor (IGIF) is a novel cytokine that stimulates T-cell proliferation, augments natural killer (NK) cell lytic activity, and induces interferon-gamma (IFN-gamma) production in established type 1 T-helper (Th1) cells in the presence of anti-CD3 antibody. The in vitro induction of IFN-gamma by recombinant murine IGIF in these cells was more potent than that induced by murine interleukin-12 (IL-12) and occurred apparently independent of murine IL-12. Here we report that subcutaneous injection into mice of tumor cells transfected with murine IGIF complementary DNA (cDNA) resulted in > or = 10-fold increase of mitogen-stimulated IFN-gamma production in cultured splenocytes. In addition, IGIF-transfected Renca and K1735 tumor cells can be rejected in vivo. The IGIF antitumor effect was abrogated in mice that were sublethally irradiated or depleted of both CD4+ and CD8+ T cells but not in mice depleted of either subpopulation alone. The antitumor effect mediated by IGIF appears to be dependent on IFN-gamma production, because in vivo neutralization of IFN-gamma was accompanied by growth of IGIF-transfected tumors in 100% of the animals. Taken together, our results show that murine IGIF can elicit T-cell-dependent antitumor immunity associated with IFN-gamma induction.
Animals↗
Inhibitory effect of enalapril on neurally mediated syncope in elderly patients.
A dramatic increase in catecholamine (CA) concentration is believed to be a primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The hypercontractile state of the heart might be alleviated by angiotensin-converting enzyme (ACE) inhibitor through depression of CA release from the sympathetic nerve ending. Thus ACE inhibitor might have positive effect on the prevention of NMS. In this study, 24 elderly subjects who had reproducible NMS induced with head-up tilt test (HUT) were randomized and double-blind divided into placebo and ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS were observed in the two groups. Before administration of enalapril, plasma CA concentrations were significantly increased during HUT compared with those in the supine position; In contrast, administration of the enalapril (10 mg/day) for >1 year inhibited the concentration of plasma CA increase and prevented syncope in all 12 patients (p < 0.05); however, placebo had no effect on plasma CA concentrations and syncope disappeared in only two of 12 patients after administration of placebo. From this study, we conclude that enalapril can prevent NMS in patients, presumably because of its part in the inhibition of CA release from sympathetic nerve endings.
Aged↗
Ambulatory pH measurements at the upper esophageal sphincter.
Explore the source record for details and available documents.
Adult↗
The tissue effects of ultrasound-assisted lipoplasty.
The objective of our study was to investigate the effects of ultrasonic energy on tissues, using a porcine model, performed under various instrumental and procedural parameters. Domestic pigs were anesthetized and prepared for surgery. An incision was made on the side of the hip randomly assigned to the right or left side. Tumescence solution was infiltrated via a blunt tip, small diameter cannula, followed by performance of standard liposuction. On the contralateral side, a similar incision was made. For ultrasonic liposuction experiments without the sheath, a percutaneous introducer was inserted into the incision, which was protected at the entry site from contact with the cannula. Tumescence solution was infiltrated via a blunt tip, small diameter cannula, and then the site was treated with ultrasonic energy at maximum output from the machine with liposuction concurrent through the hollow cannula. The experiments with the sheath did not require a pretreatment with tumescence solution but consisted of tumescence solution pumped through the sheath at a low infusion rate, with concurrent treatment utilizing ultrasonically assisted liposuction through the central lumen of the cannula. In all cases, the lipoaspirate was preserved for biochemical analysis. After treatment, the pigs were euthanized, and samples for histopathology were taken. The pigs were then perfused with a radio-opaque solution through the left ventricle following preperfusion with saline. The groups were ultrasound-assisted liposuction with sheath (n = 3), ultrasound-assisted without sheath (n = 4), and tumescence alone (n = 1), with standard liposuction performed on the contralateral side for all ultrasound-assisted liposuction animals. The lipoaspirates from the ultrasonically assisted liposuction with the sheath showed significantly less blood loss (measured as hemoglobin in the aspirate) than standard liposuction (p = 0.012) at comparable levels of fat (measured as triglycerides in the aspirate). The lipoaspirates from ultrasound-assisted liposuction without the sheath showed blood loss comparable to that experienced with standard liposuction. The ratio of hemoglobin to triglyceride was lowest in the ultrasound-assisted group with (p = 0.01) and without (p = 0.06) the sheath when compared to traditional liposuction. In both of these treated groups, the radiograms of the perfused areas showed significantly less vascular disruption when compared with suction-assisted liposuction. Histopathologic examination of specimens taken from various treated areas showed substantial tissue damage comparable in ultrasound- and suction-assisted liposuction treated groups. This preliminary experimental study showed that ultrasound-assisted lipoplasty is comparable to traditional suction-assisted lipoplasty. Treatment with ultrasound provided more significant hemoglobin/triglyceride ratios, indicative of more lipid aspirated per hemoglobin lost, and better preservation of vascular tissues as demonstrated by our perfusion studies. Treatment with the sheath showed a significantly lower hemoglobin release with a diminished volume infused into the subcutaneous space during the procedure.
Acetylcholinesterase↗
Prevalence of heart disease diagnosed de novo in pregnancy in a West London population.
OBJECTIVES: To determine the prevalence of heart disease diagnosed de novo in pregnancy in a West London population and to re-examine the current role of routine cardiovascular examination in antenatal care in the UK. DESIGN: Retrospective study. SETTING: Obstetric medical clinics at Queen Charlotte's and Chelsea Hospital, University College Hospital and Northwick Park Hospital. POPULATION: Three hundred and twenty women referred for cardiac evaluation during pregnancy. RESULTS: The majority of the 139 women referred specifically for evaluation of murmurs during pregnancy were found to have physiological murmurs (97%). Only four women (3%) were found to have significant cardiac lesions de novo in their pregnancy. Three of these four women were immigrants who had no previous history of heart disease. The only woman from the UK was already known to have a murmur from childhood. CONCLUSIONS: Our study shows that heart disease diagnosed de novo in pregnancy in a West London population is an uncommon problem with low prevalence. It also appears to be a problem seen mainly in the immigrant population. The results emphasise the importance of taking a thorough medical history in all pregnant women. However, our results if they are confirmed, would suggest that only immigrants and those with significant symptoms or a known history of heart murmur or heart disease need undergo cardiovascular examination during pregnancy. These findings need to be confirmed in a larger group in other parts of the UK before further recommendations on selective cardiovascular examination can be made. This will have significant implications for midwifery-led care.
Adult↗
Abnormal cervical cytology in pregnancy: experience of 811 cases.
This paper reviews our hospital's experience spanning 15 years and involving 811 women referred with abnormal cervical cytology in pregnancy. It supports the safety and accuracy of managing dysplasia in pregnancy with colposcopy, directed punch biopsy and deferral of treatment until the postpartum period. The histologically-proven progression in pregnancy to a higher grade of dysplasia postpartum was 7%. None of the women are known to have developed microinvasive or invasive cancer between antenatal assessment and postpartum review. Of these 811 women, 16% were lost to follow-up, 1 of whom subsequently represented 4 years later with invasive cervical cancer.
Adult↗
Quantitative analysis of amelogenin solubility.
Amelogenins are a group of extracellular enamel matrix proteins which are believed to be involved in the regulation of the size and habits of forming enamel crystals. The aim of this study was to compare the solubility properties of several amelogenins at various pH (from 4.0 to 9.0) at constant ionic strength (IS), and to examine the influence of buffer composition, IS, and divalent metal ions (including Ca2+, Mg2+, and Zn2+) on amelogenin solubility. The solubility of the recombinant murine amelogenin ("rM179") was minimum near its isoelectric point and increased rapidly below and above, regardless of buffer composition. A similar trend was observed for the native porcine ("25K") amelogenin. Porcine "23K" amelogenin was only sparingly soluble from pH of 4.0 to 9.0, in contrast to the analogous recombinant "rM166", which was more soluble in acidic solutions. The synthetic amelogenin polypeptide "TRAP" was extremely insoluble, while synthetic LRAP was readily soluble. Porcine "20K" amelogenin solubility increased strikingly as the solution pH was lowered from 7.0 to 6.0. Increasing IS decreased the solubility of rM179. While Zn2+ reduced rM179 solubility, Ca2+ and Mg2+ showed no significant effects. We conclude that the solubility of amelogenin was dependent on the primary structure, solution pH, and IS, and the low solubility of amelogenins under physiological conditions may result from their tendency to form quaternary (aggregate) structures in vivo.
Amelogenin↗
Differential spatiotemporal regulation of lactoferrin and progesterone receptor genes in the mouse uterus by primary estrogen, catechol estrogen, and xenoestrogen.
Many xenobiotics are considered reproductive toxins because of their ability to interact with the nuclear estrogen receptors (ERalpha and ERbeta). However, there is evidence that these xenobiotics can regulate gene expression in the reproductive targets by mechanisms that do not involve these ERs. To examine this further, we compared the effects of estrogenic (o,p'-DDT [1-(o-chlorophenyl)-1-(p-chlorophenyl)2,2,2-trichloroethane] and Kepone, chlordecone) and nonestrogenic (p,p'-DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], a metabolite of p,p'-DDT) xenobiotics with those of 17beta-estradiol (E2) and 4-hydroxyestradiol-17beta (4-OH-E2), a catechol metabolite of E2, on uterine expression of lactoferrin (LF) and progesterone receptor (PR). These genes are estrogen responsive in the mouse uterus. Normally, LF is expressed in the uterine epithelium, whereas PR is expressed in both the epithelium and stroma in response to estrogenic stimulation. Ovariectomized mice were injected with xenobiotics (7.5 mg/kg), E2 (10 microg/kg), 4-OH-E2 (10 microg/kg), or the vehicle (oil, 0.1 ml/mouse), and uterine tissues were processed for Northern blot and in situ hybridization. The pure antiestrogen ICI-182780 (ICI; 1 or 20 mg/kg) was used to interfere with estrogenic responses that were associated with the ERs. The results of Northern and in situ hybridization demonstrated increased uterine levels of PR and LF messenger RNAs (mRNAs) by all of these xenobiotics, but quantitatively the responses were much lower than those induced by E2 or 4-OH-E2. The results further showed that the E2-inducible epithelial LF mRNA accumulation was markedly abrogated by pretreatment with ICI (20 mg/kg). In contrast, this treatment retained the epithelial expression of PR mRNA, but down-regulated the stromal expression. In contrast, ICI had negligible effects on LF and PR mRNA responses to 4-OH-E2, indicating that this catechol estrogen exerted its effects primarily via a mechanism(s) other than the ERs. The heightened accumulation of LF mRNA in the epithelium in response to Kepone and o,p'-DDT was also severely compromised by pretreatment with ICI, but this antiestrogen had little effect on responses to p,p'-DDD. Similar to E2, Kepone increased the expression of PR mRNA in both uterine epithelium and stroma. However, pretreatment with ICI decreased stromal cell expression, whereas epithelial cell expression remained unaltered or increased. These responses were not noted in mice treated with o,p'-DDT or p,p'-DDD. Collectively, the results demonstrate that catechol estrogens or xenobiotics can alter uterine expression of estrogen-responsive genes by mechanisms that are not totally mediated by the classical nuclear ERs, and these alterations are cell type specific. We conclude that an interaction of a compound with the nuclear ERalpha and/or ERbeta is not an absolute requirement for producing specific estrogen-like effects in the reproductive target tissues.
Animals↗