Biomedical subjects

W H Peters

Publications and source records attributed to W H Peters.

At least 55 records · Page 3Linked to original sources

PubMed1999

Glutathione and glutathione-related enzymes in decidua and placenta of controls and women with pre-eclampsia.

Pre-eclampsia is a major complication of pregnancy with high morbidity and mortality rates. The aetiology is still unclear but impaired detoxification or enhanced levels of reactive (oxygen) metabolites may contribute to the development or maintenance of pre-eclampsia. Glutathione and glutathione-related enzymes, as one of the major detoxificating and free-radical scavenging systems, may play a role in controlling the disease. Seventeen normotensive pregnant women and 24 pre-eclamptic women were investigated prospectively with respect to placental and decidual levels of total glutathione (GSH), glutathione S-transferase activity (GST), selenium-dependent glutathione peroxidase (SeGPX) and total glutathione peroxidase activity (TGPX, both selenium- and non-selenium-dependent GPX). Decidual levels of glutathione and related enzymes were compared with placental levels, and the investigated parameters in pre-eclampsia were compared with those in normotensive pregnancy by the Mann-Whitney U -test. Clinical data were correlated with biochemical parameters by Spearman's correlation test. Glutathione levels were significantly higher in decidua as compared with placenta. Glutathione levels were elevated in pre-eclampsia and HELLP (haemolysis, elevated liver enzymes, low platelets) as compared to normotensive pregnancy for decidua and in the placenta of patients with pre-eclampsia only. Glutathione S-transferase activity was not different between the two groups. In the placenta of patients with pre-eclampsia+HELLP, total glutathione peroxidase activity was elevated versus controls. Selenium-dependent glutathione peroxidase activity was higher in decidua versus placenta and in decidua of pre-eclamptic versus control subjects. Enhanced glutathione concentrations and glutathione peroxidase activities were often found in placenta and decidua in pre-eclampsia, probably as a compensatory mechanism to prevent further damage by peroxides, (oxygen) radicals or other toxins in the placenta or in the feto-placental interface.

Adult↗

PubMed1999

Expression of glutathione S-transferase theta class isoenzymes in human colorectal and gastric cancers.

Glutathione S-transferases (GSTs) are a superfamily of detoxification enzymes, which play an important role in the protection of tissues against potentially harmful compounds. In humans, two theta class isoenzymes, GSTT1-1 and GSTT2-2, have been described so far. Both enzymes were claimed to have an important role in human carcinogenesis. In colorectal and gastric tissues, the expression of the other isoenzymes changes after malignant transformation. No data on the expression levels of the theta isoenzymes in these tissues are available. The aim of this study was to determine the protein levels of the two theta class isoenzymes in human colorectal and gastric cancers and paired normal tissue. Cytosolic fractions of normal and matched tumor tissue samples from 20 patients with colorectal or gastric adenocarcinomas were analyzed on immunoblots using specific antibodies against GSTT1-1 and GSTT2-2, respectively. In addition paraffin-embedded sections of these tissues were examined immunohistochemically for GSTT1-1 expression. In both types of tissue, theta class isoenzymes were highly expressed. Expression of GSTT1-1 was higher in gastric than in colorectal tissues. The GSTT2-2 levels were comparable in both tissues. A great interindividual difference in expression was demonstrated. In colon, there was no change in the theta class isoenzyme levels after malignant transformation. Gastric tumors had significantly lower expression of both theta class isoenzymes compared with the normal mucosa. In colon, GSTT1-1 was expressed in the enterocytes and goblet cells. In gastric tissues, staining was seen in upper and deeper mucous cells, chief cells and, to a lesser extent, in parietal cells. In both types of tumors, staining was seen in adenomatous cells. In conclusion, in both normal human colonic and gastric mucosa, GSTT1-1 and GSTT2-2 are present at high levels, whereas after malignant degeneration, expression is not influenced or is even downregulated.

Adenocarcinoma↗

PubMed1999

Low glutathione and glutathione S-transferase levels in Barrett's esophagus as compared to normal esophageal epithelium.

Patients with Barrett's esophagus, wherein squamous epithelium has been replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma as compared to the general population. Glutathione S-transferase (GST), a family of detoxification enzymes consisting of class alpha, mu, pi, and theta isoforms, is involved in detoxification of carcinogens and low levels of these enzymes correlated with high cancer risk. We have now compared GST enzyme activity, GST isoenzyme composition and glutathione (GSH) content of Barrett's mucosa with that of adjacent normal squamous epithelium. Biopsy specimens of 98 patients with Barrett's esophagus were taken from both Barrett's and adjacent normal squamous epithelium. GST enzyme activity towards 1-chloro-2,4-dinitrobenzene was measured, and GST isoenzyme levels were determined by densitometrical analyses of western blots after immunodetection with monoclonal antibodies. Total GSH content was determined by high-performance liquid chromatography after conjugation with monobromobimane. Wilcoxon's signed rank test and Spearman correlation analyses were used for statistical evaluation. As compared with adjacent normal squamous epithelium, GST enzyme activity in Barrett's epithelium was reduced by 35%, and GST mu, GST pi and GSH levels were reduced by 24%, 30%, and 63%, respectively. However, the minor GST alpha and GST theta levels were higher in Barrett's epithelium (by 625% and 33%, respectively). High levels of GSH and GSTs in general are correlated with protection against cellular or cytogenetic damage. The observed reduction in GSTs and GSH in Barrett's epithelium may therefore contribute to the increased cancer risk in this tissue.

Adult↗

PubMed1999

Immunohistochemical localization of glutathione S-transferase alpha and pi in human esophageal squamous epithelium, Barrett's epithelium and carcinoma.

High tissue levels of glutathione S-transferases (GSTs), a family of detoxification enzymes, are inversely correlated with cancer risk in the human gastrointestinal tract. Patients with Barrett's esophagus, wherein squamous epithelium is replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma. Biochemical analyses revealed that Barrett's epithelium contains lower levels of GST enzyme activity as well as some GST isoforms, as compared with squamous epithelium. So far, little information on the immunohistochemical distribution of the GST alpha and pi isoforms in normal squamous epithelium, in Barrett's metaplastic epithelium or in adeno- and squamous cell carcinomas of the esophagus is available. Tissues were fixed in formalin and embedded in paraffin. Three 4 microm thick sections were used for hematoxylin and eosin staining and for immunostaining with antibodies against GST alpha and pi. GST alpha and pi were seen in normal squamous epithelium (0% and 75%, respectively), Barrett's epithelium (75% and 100%), adenocarcinoma (25% and 100) and squamous cell carcinoma (27% and 91%). Staining was mainly cytoplasmic, though some nuclear staining with the GST pi antibody was apparent. The varying expression of GST alpha and pi in normal and (pre)neoplastic esophagus may have consequences for the treatment of these diseases and may contribute to an understanding of the development of these esophageal disorders.

Adenocarcinoma↗

PubMed1999

Glutathione S-transferase alpha levels in epileptic and healthy women preconceptionally and throughout pregnancy.

We studied plasma GSTA1-1 concentrations in preconceptionally recruited epileptic women who received antiepileptic drugs (n = 99) and a control group of healthy women (n = 106). Mean plasma GSTA1-1 concentrations in the control group did not show significant changes preconceptionally and throughout pregnancy. Six weeks postpartum, however, a significant increase in the mean plasma GSTA1-1 concentration (p < 0.001) was found as compared to preconceptional levels and levels during pregnancy. The mean plasma GSTA1-1 concentration in epileptic women was significantly higher in the 4th gestational week compared to those determined in healthy pregnant women (1.68 versus 1.08 microg/l, p < 0.001). Values between the groups in the second and third trimester and postpartum period showed no significant differences.

Anticonvulsants↗

PubMed1999

Plasma glutathione S-transferase Pi 1-1 measurements in the study of hemolysis in hypertensive disorders of pregnancy.

OBJECTIVE: To investigate the value of plasma glutathione S-transferase Pi1-1(GSTP1-1) measurements in the assessment of hemolysis in hypertensive disorders of pregnancy. METHODS: Plasma GSTP1-1 and haptoglobin levels and serum lactate dehydrogenase (LDH) activity were measured in 81 healthy nonpregnant female blood donors between 20 and 40 years of age, 41 women during uncomplicated normotensive pregnancy, 35 women with pregnancy-induced hypertension, 67 women with preeclampsia, and 34 women with the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Levels in hypertensive pregnancies were compared to levels in normotensive pregnancy, and levels in normotensive pregnancy were compared to levels in blood donors by the Mann-Whitney U-test. RESULTS: Median GSTP1-1 and LDH levels were significantly increased (p < 0.01) and haptoglobin significantly decreased (p < 0.01) in preeclampsia and the HELLP syndrome as compared to normotensive pregnancy. Both GSTP1-1 and LDH levels were significantly higher in normotensive pregnant women as compared to nonpregnant women (p < 0.0001). The percentage of preeclamptic patients (26.9%) or patients with the HELLP syndrome (73.5%) with elevated GSTP1-1 levels was lower than those with elevated LDH (38.8% and 100%, respectively) or decreased haptoglobin levels (41.8% and 97%, respectively). CONCLUSIONS: We conclude that plasma GSTP1-1 levels may provide useful information on hemolysis in hypertensive disorders of pregnancy in addition to serum LDH activity and plasma haptoglobin levels and that the degree of hemolysis in hypertensive disorders of pregnancy, especially in the HELLP syndrome, is probably less prominent than generally assumed.

Adult↗

PubMed1999

Variability of glutathione S-transferase alpha in human liver and plasma.

BACKGROUND: Glutathione S-transferases are a family of enzymes involved in the binding, transport, and detoxification of a wide variety of endogenous and exogenous compounds. Little information is available about the variability of class alpha glutathione S-transferases in human liver, where they are highly expressed, or in serum. METHODS: Both total class alpha glutathione S-transferase (GST-alpha, composed of GSTA1-1, GSTA1-2, and GSTA2-2) as well as GSTA1-1 concentrations were measured by specific and sensitive ELISA in liver cytosols of 35 organ donors and in plasma samples of 350 healthy controls. RESULTS: The mean total GST-alpha and GSTA1-1 in liver cytosols were 25.1 +/- 9.4 and 10.7 +/- 5.3 microg/mg protein, respectively, and did not correlate with activities of aspartate aminotransferase or alanine aminotransferase. The mean total GST-alpha in liver was significantly higher in females compared with males (28.8 +/- 10.0 vs 22.0 +/- 7.8 microg/mg protein; P <0.05). In contrast, the median total GST-alpha in plasma was lower in females compared with males (2.0 and 2.8 microg/L, respectively; P <0.0001). The median ratios for GSTA1-1/total GST-alpha in liver and plasma were 0.42 and 0.58, respectively. CONCLUSIONS: GSTA1-1 constitutes approximately one-half of the total amount of alpha class GSTs in human plasma and liver. Total GST-alpha values are higher in female liver but lower in plasma compared with the respective values in males.

Adolescent↗

PubMed1998

Nonsteroidal anti-inflammatory drugs enhance glutathione S-transferase theta levels in rat colon.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been claimed to reduce cancer rates in oesophagus, stomach and colon of humans and laboratory animals. Recently we showed that dietary administration of NSAIDs enhanced glutathione S-transferase (GST) class alpha, mu and pi levels in the upper part of the rat gastrointestinal tract, with minor effects in the colon. Enhancement of GSTs, a family of detoxification enzymes consisting of class alpha, mu, pi and theta isoforms, might be one of the mechanisms leading to cancer prevention. The recently cloned GST class theta levels have not yet been studied in this respect. We now investigated whether the NSAIDs indomethacin, relafen, sulindac, ibuprofen, piroxicam, and acetyl salicylic acid (ASA), incorporated individually into the diet at 25, 200, 320, 400, 400 and 400 mg/kg, respectively, affect gastrointestinal GSTT1-1 and GSTT2-2 levels in male Wistar rats. GSTT1-1 and GSTT2-2 levels were determined in cytosolic fractions of oesophagus, gastric, small intestinal and colonic mucosa and liver by densitometrical analyses of Western blots after immunodetection with a monoclonal (GSTT1-1) or a polyclonal (GSTT2-2) antibody. Gastric GSTT2-2 levels were induced by ibuprofen (1.6x) and indomethacin (1.5x), and colonic levels were induced by ASA (1.7x). Colonic GSTT1-1 levels were elevated by all NSAIDs tested except for relafen (1.5-6.4x). In conclusion, enhancement of colonic GSTT1-1 levels seems to be a common working mechanism of NSAIDs. Enhanced enzyme activity, which may result from these higher GSTT1-1 levels, might lead to a more efficient detoxification of potential carcinogens and hence contribute to the prevention of colon carcinogenesis.

Animals↗

PubMed1998

Plasma glutathione S-transferase P1-1 levels in patients with head and neck squamous cell carcinoma.

BACKGROUND: Many tumors contain high amounts of the detoxification enzyme glutathione S-transferase P1-1 (GSTP1-1). Elevated levels of GSTP1-1 have also been detected in serum and plasma from patients with gastrointestinal, lung, or head and neck tumors. The authors of this report evaluated the role of GSTP1-1 as a plasma tumor marker in patients with head and neck squamous cell carcinoma (HNSCC) of the larynx, hypopharynx, or oropharnyx and in patients with benign head and neck lesions (BHNL). METHODS: GSTP1-1 levels were measured in EDTA plasma combined with ethylenediaminetetraacetic acid using a recently developed sensitive and specific sandwich enzyme-linked immunoadsorbent assay. A normal reference level with an upper limit of 21.8 microg GSTP1-1 per liter of plasma was calculated from results obtained with samples from 230 blood donors. RESULTS: Median GSTP1-1 levels in samples from 53 patients with oral/oropharyngeal SCC (10.6 microg/L; range, 3.7-46.1 microg/L), 12 patients with hypopharyngeal SCC (11.9 microg/L; range, 5.2-146.6 microg/L), and 28 patients with laryngeal SCC (14.4 microg/L; range, 6.4-141.5 microg/L) were significantly elevated when compared with plasma GSTP1-1 levels in samples from 45 patients with BHNL (8.1 microg/L; range, 3.3-32.3 microg/L; P < 0.0001, P < 0.01, and P < 0.0001, respectively). However, only 6 of 53 patients (11%) with oral/oropharyngeal SCC, 1 of 12 patients (8%) with hypopharyngeal SCC, and 6 of 28 patients (21%) with laryngeal SCC had plasma GSTP1-1 levels above the upper limit of the normal reference level. Thus, only 13 of 93 patients (14%) with HNSCC had elevated plasma GSTP1-1 levels overall. No significant relation between plasma GSTP1-1 levels and TNM classification of the tumors was observed. CONCLUSIONS: GSTP1-1 is not a suitable plasma tumor marker for HNSCC.

Adult↗

PubMed1998

Effects of the sulforaphane analog compound 30, indole-3-carbinol, D-limonene or relafen on glutathione S-transferases and glutathione peroxidase of the rat digestive tract.

Several dietary compounds have been demonstrated to reduce gastrointestinal cancer rates in both humans and animals. We showed that high human gastrointestinal tissue levels of glutathione S-transferase (GST), a family of detoxification enzymes consisting of class Alpha, Mu, Pi and Theta isoforms, were inversely correlated with cancer risk. We now investigated whether the sulforaphane analog compound 30, indole-3-carbinol, D-limonene or relafen, supplemented in the diet for two weeks at 1450, 250, 10,000, and 200 ppm, respectively, influenced (i) GST activity, (ii) GST isoenzyme levels, (iii) GSH levels, or (iv) glutathione peroxidase (GPx) activity in the gastrointestinal tract of male Wistar rats. Sulforaphane analog compound 30 enhanced GST activity in all organs studied (1.2-2.4 x). It induced GST Alpha levels in small intestine and liver, GST Mu levels in stomach and small intestine, GST Pi levels in stomach and small and large intestine, and GSH levels in stomach and proximal and middle small intestine. Indole-3-carbinol induced gastric GST Mu and hepatic GST Alpha levels. D-limonene induced hepatic GST Alpha, colonic GST Pi levels and proximal small intestinal GST enzyme activity and GST Pi levels. Relafen induced hepatic GST Alpha levels, distal small intestinal and gastric GST Pi levels, and oesophageal and proximal small intestinal GSH levels. GPx activity was enhanced by relafen in oesophagus, and in distal small intestine by sulforaphane analog compound 30. Enhancement of GSTs and to a lesser extent GPx and GSH, resulting in a more efficient detoxification, may explain at least in part the anticarcinogenic properties of sulforaphane analog compound 30, and to a much lesser extent of indole-3-carbinol and D-limonene.

Animals↗

PubMed1998

Identification of a novel murine glutathione S-transferase class mu gene.

Screening of a genomic mouse DNA library with a glutathione S-transferase class mu cDNA probe resulted in the identification of mGSTM5, a novel member of the murine glutathione S-transferase class mu gene family. Here we present the sequence of the promoter region, the exon-intron organization of the gene and the isolation and characterization of its complete cDNA. Conceptual translation of the cDNA sequence revealed that several amino acid positions have been changed in 'invariant' mu class signature sequences in mGSTM5. Reverse transcriptase polymerase chain reaction using gene specific primers revealed that mGSTM5 is uniquely expressed in mouse liver, stomach and small intestine.

Amino Acid Sequence↗

PubMed1998

Glutathione S-transferase M1 and T1 and cytochrome P4501A1 polymorphisms in relation to the risk for benign and malignant head and neck lesions.

BACKGROUND: Susceptibility to head and neck cancer in a particular individual may depend in part on the metabolic balance between Phase 1 enzymes, such as cytochromes P450 (CYPs), and Phase II enzymes, such as glutathione S-transferases (GSTs). Genetic variability in CYP and GST isoenzymes may contribute to individual differences in susceptibility to chemical carcinogenesis. GSTM1 and GSTT1 null genotypes as well as polymorphic variants in the CYP1A1 gene that may help determine the risk for head and neck cancer have been described in previous reports. METHODS: Polymorphisms of GSTM1, GSTT1, and CYP1A1 in whole blood were detected by polymerase chain reaction (PCR) in 185 patients with head and neck squamous cell carcinoma (HNSCC), 78 patients with benign head and neck lesions (BHNL), and 207 blood donors. RESULTS: GSTM1 null genotype was demonstrated to be equally frequent in patients with HNSCC (50.8%), patients with BHNL (47.4%), and blood donors (51.7%). GSTT1 null genotype occurred significantly more often in patients with BHNL (33.3%) as compared with blood donors (20.3%), demonstrating that lack of GSTT1 may be a risk factor for BHNL. Presence of the rare valine in the CYP1A1/Nco1 site was found in 33 patients with HNSCC (17.8%), in 20 patients with BHNL (25.6%), and in 34 blood donors (16.4%). The frequencies with which the presence of the rare cytosine nucleotide in the CYP1A1/Msp1 site was detected were 17.8%, 15.4%, and 15.9%, respectively. CONCLUSIONS: The occurrence of polymorphic variants in the GSTM1, GSTT1, and CYP1A1 genes did not differ between the groups investigated, therefore indicating no significant contribution to the development of head and neck cancer.

Adult↗

PubMed1998

Plasma glutathione S-transferase alpha 1-1: a more sensitive marker for hepatocellular damage than serum alanine aminotransferase in hypertensive disorders of pregnancy.

OBJECTIVE: Our purpose was to investigate the value of plasma glutathione S-transferase Alpha 1-1 measurements in the assessment of hepatocellular damage in hypertensive disorders of pregnancy. STUDY DESIGN: Patients were recruited at the Department of Obstetrics and Gynecology of the University Hospital, Nijmegen, The Netherlands. Five groups of patients were studied: normotensive pregnancy (n = 87), pregnancy-induced hypertension (n = 48), preeclampsia (n = 79), the syndrome of hemolysis, elevated liver enzymes, and low platelets (n = 39), and serially studied normotensive pregnancy (n = 21). Blood was collected for assessment of plasma glutathione S-transferase Alpha 1-1 levels and serum alanine aminotransferase activity. Levels in hypertensive pregnancies were compared with levels in normotensive pregnancy by the Mann-Whitney U test. Patients were categorized according as to whether their values are below (normal) or above (elevated) the upper normal reference level. The difference in relative magnitude of elevation between the two factors was determined by the Wilcoxon matched-pairs signed-rank test. RESULTS: Plasma levels in the longitudinally studied normotensive pregnancy group did not differ between gestational ages and were not significantly different from those of the normotensive control group. Median levels of glutathione S-transferase Alpha 1-1 and alanine aminotransferase were significantly increased (p < 0.01, p < 0.0001, respectively) in all subgroups of hypertensive pregnancies compared with normotensive pregnancies. When both levels were elevated, the relative magnitude of the increase of glutathione S-transferase Alpha 1-1 levels was significantly higher than that of alanine aminotransferase activity in preeclampsia (p < 0.01) and the syndrome of hemolysis, elevated liver enzymes, and low platelets (p < 0.0001). Almost half the patients with preeclampsia showed elevated levels of alanine aminotransferase and/or glutathione S-transferase Alpha 1-1. CONCLUSION: Plasma glutathione S-transferase Alpha 1-1 measurements may provide a more sensitive indicator of acute hepatic damage in preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets compared with the assessment of aminotransferase activity and therefore may allow earlier recognition of these syndromes. The clinical benefits of plasma measurements of glutathione S-transferase Alpha 1-1 for monitoring the hepatic condition in the management of these patients need to be elucidated in further studies.

Adolescent↗

PubMed1998

Umbilical cord plasma glutathione S-transferase alpha 1-1 levels as a marker of neonatal hepatocellular integrity.

OBJECTIVE: To investigate possible delivery-related impaired neonatal hepatocellular integrity by assessment of arterial and venous umbilical cord plasma levels of glutathione S-transferase Alpha 1-1. METHODS: Glutathione S-transferase Alpha 1-1 levels were assessed in arterial and venous umbilical cord, and maternal venous plasma samples. The influence of maternal, delivery, and neonatal characteristics on arterial umbilical cord glutathione S-transferase Alpha 1-1 levels was studied, using linear regression analysis after log-transformation. RESULTS: Median (range) arterial umbilical cord glutathione S-transferase Alpha 1-1 plasma levels were higher than venous umbilical cord levels (9.68 [0.64-1125] microg/L and 7.66 [0.78-987.5] microg/L, respectively, P < .005). Median (range) arterial and venous umbilical cord glutathione S-transferase Alpha 1-1 levels were higher than, and did not correlate with, maternal venous plasma levels (8.79 [1.79-183] microg/L and 6.47 [1.58-164.5] microg/L versus 1.47 [0.46-10.4] microg/L, P < .001). Neonates born vaginally demonstrated higher median (range) levels than those delivered by cesarean (13.41 [1.02-1125] microg/L and 5.73 [0.64-172.90] microg/L, respectively, P < .001). Neonates with unfavorable pH (arterial pH under 7.20) demonstrated higher median (range) levels than those with normal pH (arterial pH at least 7.20) (15.15 [0.77-1125] microg/L and 8.82 [0.64-120.90] microg/L, respectively, P < .001). Stepwise multiple linear regression analysis showed that birth weight had the largest influence on arterial umbilical cord glutathione S-transferase Alpha 1-1 levels, followed by arterial base deficit, and route of delivery. CONCLUSION: Arterial umbilical cord glutathione S-transferase Alpha 1-1 plasma levels, being unrelated to maternal venous levels, might give a reliable impression of early neonatal hepatocellular integrity and may become an additional indicator of neonatal condition immediately after birth.

Adolescent↗

PubMed1998

Low whole blood glutathione levels in pregnancies complicated by preeclampsia or the hemolysis, elevated liver enzymes, low platelets syndrome.

OBJECTIVE: To investigate the pathophysiologic involvement of glutathione in pregnancies complicated by preeclampsia or the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. METHODS: Total whole blood glutathione levels were measured by high performance liquid chromatography in 23 women with pregnancies complicated by preeclampsia or the HELLP syndrome and in 22 normotensive gravidas. Total glutathione levels and the total glutathione/hemoglobin ratios of patients were compared with those of controls by the Mann-Whitney U test. RESULTS: Median total glutathione levels were lower in preeclamptic pregnancies or those complicated by the HELLP syndrome than in normotensive pregnancies (647 [range 268-986] and 750 [range 495-1572] micromol/L, P = .05). The median total glutathione/hemoglobin ratios were significantly lower in preeclamptic pregnancies or in those complicated by the HELLP syndrome than in normotensive pregnancies (0.079 [range 0.033-0.122] and 0.101 [range 0.073-0.210], P = .02). CONCLUSION: Decreased total glutathione levels in maternal whole blood might indicate decreased detoxificating or free radical scavenging capacity in pregnancies complicated by preeclampsia or the HELLP syndrome.

Adult↗

PubMed1998

Significance of cell proliferation measurement in gastric cancer.

Cell kinetic data may be important indicators of clinical behaviour in many types of cancer. Recently, several antibodies to cell-cycle associated antigens have been characterised. This overview summarises the advantages and disadvantages of different methods for the assessment of cell proliferation. Moreover, the prognostic value of proliferative activity in gastric cancer is discussed and suggestions for future research are given.

Antigens, Nuclear↗

PubMed1998

Characterization of human soft-tissue sarcoma xenografts for use in secondary drug screening.

We have established ten transplantable human soft-tissue sarcoma (STS) xenografts grown as subcutaneous tumours in the nude mouse. Nine xenografts originated from patients that needed chemotherapy in the course of their disease. The xenografts were tested for their sensitivity to maximum tolerated doses of five anti-cancer agents. Growth of treated tumours was expressed as a percentage of control tumour growth and a growth inhibition > 75% was measured for doxorubicin in 20% of the STS xenografts, for cyclophosphamide in 30%, for ifosfamide in 20%, for vincristine in 20%, whereas etoposide was not effective in the STS xenografts. In three out of ten STS xenografts MDR1 mRNA was detectable, but this was not related to the resistance against doxorubicin, vincristine or etoposide. Topoisomerase IIalpha mRNA expression levels did not reflect sensitivity to doxorubicin or etoposide. In all STS tissues, however, these levels were lower than topoisomerase IIalpha mRNA in a drug-sensitive human ovarian cancer xenograft. Glutathione concentrations and the activities of glutathione S-transferase, glutathione peroxidase and glutathione reductase were not related to resistance against the alkylating agents or doxorubicin. Of interest, in all STS tissues, glutathione S-transferase pi was the predominant isoenzyme present. In conclusion, chemosensitivity of the STS xenografts reflects clinical response rates in phase II trials on the same compounds in adult STS patients. Relatively low levels of topoisomerase IIalpha mRNA may partly account for intrinsic resistance against, for example, doxorubicin. Additional factors must contribute to moderate responsiveness to alkylating agents.

Animals↗

PubMed1998

Age and gender dependent levels of glutathione and glutathione S-transferases in human lymphocytes.

Glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of a wide range of chemicals including chemical carcinogens. Human cytosolic GSTs are divided into four major classes; alpha, mu, pi and theta. This study was performed to evaluate the influence of age and gender on the GST isoenzyme expression and glutathione (GSH) content in lymphocytes. Blood was collected from 124 healthy controls, which were divided into age groups of 20-40 years (21 females, 20 males), 40-60 years (20 females, 21 males) and 60-80 years (20 females, 22 males). Lymphocytes were isolated by density centrifugation on Histopaque-1077. After homogenization, cytosolic fractions were isolated. Herein, GST isoenzyme levels were determined by densitometrical analysis of western blots after immunodetection with monoclonal antibodies. Total GSH content was determined by high performance liquid chromatography after conjugation with monobromobimane. Spearman rank correlation and Wilcoxon rank sum tests were used for statistical evaluation. Lymphocytic GSTmu and pi levels were not correlated with age or gender. GSTalpha was not detectable in lymphocytes. GSH contents were not different in males and females, but decreased with age in both males and females. In age group 60-80, GSH content was significantly lower as compared with age groups 20-40 and 40-60 in both sexes. Since high GSH is an essential factor in the detoxification of many compounds, these data indicate that the detoxification potential of the GSH/GST system in lymphocytes may decrease with age in man.

Adult↗