PHARMAC and flutamide.
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Clinical Trials as Topic↗
Biomedical subjects
W Bennett
Publications and source records attributed to W Bennett.
CD30 and its ligand: possible role in regulation of teratoma stem cells.
Like the oocyte, the cells of the early embryo, and primordial germ cells, human teratocarcinoma stem cells are pluripotent, capable of giving rise to a wide range of somatic and extraembryonic tissues. Growth factors which regulate the growth of multipotent stem cells in the mouse have been identified, but none of these have been shown conclusively to have similar effects on human or primate multipotent stem cells. CD30 is a member of the tumour necrosis factor receptor superfamily with a restricted pattern of tissue distribution, limited to immune cells, decidual tissue, and human embryonal carcinoma: in common with other embryonal carcinoma markers, CD30 is found in foci of cells in a sub-population of seminomas. CD30 ligand is a transmembrane protein, structurally related to tumour necrosis superfamily members TNF alpha, TNF beta, and CD40. CD30 ligand is expressed by T and B lymphocytes, macrophages, and a variety of normal haematopoietic cells and tumours derived from them, and exerts pleiotropic effects on normal and malignant lymphoid cells, including death, differentiation, or cell division. Studies on cultured cell lines derived from human embryonal carcinomas and yolk sac carcinomas confirm CD30 expression in the former but not the latter, and show that CD30 expression is down-regulated during stem cell differentiation in vitro. Transcripts for CD30 ligand are found at highest levels in yolk sac carcinoma cell lines, but are also found in embryonal carcinoma. CD30 ligand protein is detected in yolk sac carcinoma and nullipotent embryonal carcinoma cell lines. Exogenous CD30 ligand has no effect on multipotent human stem cell growth in vitro. However, the receptor-ligand pair may function in autocrine regulation of embryonal carcinoma stem cells. CD30 and its ligand are candidate stem cell identity factors, juxtacrine regulators whose sole function is to identify a cell's position in a developmental hierarchy.
Animals↗
Use of statins. In New Zealand, subsidy of statins is limited to particular groups of patients.
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Cholesterol↗
Nephrology core curriculum. The American Society of Nephrology and the American Society of Nephrology Training Program Directors Committee.
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Curriculum↗
Expression of CD30 and CD30 ligand in cultured cell lines from human germ-cell tumors.
Embryonal carcinoma (EC) cells are the multipotent stem cells of human teratocarcinomas. EC cell lines isolated from human testicular teratocarcinomas retain pluripotentiality and show cell-surface marker phenotype and growth characteristics similar to those of primate embryonic stem cells. CD30, a member of the tumor necrosis factor superfamily of cytokine receptors, is expressed on the surface of human EC cells, but little is known regarding its function or the expression of its ligand in this context. Northern blot analysis, reverse transcriptase-PCR, and immunoprecipitation were used to study the expression of CD30 ligand and CD30 in cell lines representing multipotent and nullipotent EC as well as yolk sac carcinoma. Antibodies, recombinant CD30-Fc, and recombinant CD30 ligand were used in bioassays to assess the ability of exogenous CD30 ligand to promote the growth of multipotent human EC stem cells. Nullipotent and multipotent human EC cells, but not yolk sac carcinoma, expressed surface CD30, as demonstrated by immunoblotting and immunofluorescence; in multipotent cells, expression was decreased during differentiation induced by retinoic acid. Transcripts for CD30L were found at high levels in a yolk sac carcinoma cell line by Northern analysis and reverse transcriptase-PCR and were present at lower levels in EC cells as well. Immunoprecipitation confirmed expression of CD30 ligand protein in yolk sac carcinoma and in nullipotent embryonal carcinoma. Antibodies with CD30 cross-linking activity failed to promote the growth of multipotent EC cell line GCT 27 X-1. Anti-CD30 ligand antibodies and CD30-Fc both failed to block the promotion of EC cell growth induced by yolk-sac cell culture supernatants or feeder-cell monolayers. CD30 ligand is expressed in cell lines representative of human yolk sac carcinoma and nullipotent embryonal carcinoma. The membrane-bound cytokine may have an autocrine role in human EC stem-cell renewal, but other exogenous factors are required to maintain the growth of multipotent EC cells in vitro.
3T3 Cells↗
Reducing prescribing.
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Drug Prescriptions↗
Prospective risk stratification in renal transplant candidates for cardiac death.
In previous studies to predict future cardiac death of patients undergoing evaluation for renal transplantation, noninvasive or invasive testing of all, or nearly all, patients has been used. In an attempt to decrease the cost of cardiac risk assessment, we prospectively used a two-tiered cardiac risk assessment algorithm on 189 consecutive patients referred for renal transplant evaluation. First, patients were stratified by clinical characteristics of age > or = 50 years, history of angina, insulin-dependent diabetes, congestive heart failure, or abnormal electrocardiogram (excluding left ventricular hypertrophy). Patients having none of these risk factors (n = 94) were considered at low risk for cardiac events and underwent no further cardiac evaluation. Patients with one or more of the cardiac risk factors (n = 95) were considered to be in a high-risk group and were required to undergo further evaluation with thallium myocardial scintigraphy. Follow-up of patients was for 46 +/- 16 months. Cardiac mortality was significantly higher in the clinical high-risk group compared with the clinical low-risk group (17% v 1%, respectively; P < 0.001). Further cardiac risk stratification was evident by thallium myocardial scintigraphy. Patients with reversible thallium defects had significantly higher cardiac mortality rates than patients with no thallium defects (23% v 5%, respectively; P < 0.05). Fixed thallium defects also had predictive value for cardiac mortality (29%,; P < 0.05), but deaths in this fixed defect group tended to occur later in the follow-up period. The initial clinical stratification obviated the need for further noninvasive or invasive testing in nearly half of the renal transplant candidates.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Identification of UrinAid-adulterated urine specimens by fluorometric analysis.
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Drug Combinations↗
Biological consequences of overexpression of a transfected c-erbB-2 gene in immortalized human bronchial epithelial cells.
In order to examine the effects of the overexpression of c-erbB-2 (HER-2, neu) on human bronchial epithelial cells, a human c-erbB-2 expression vector was introduced into the simian virus 40 large T-antigen-immortalized human bronchial epithelial cell line BEAS-2B. Isolation of multiple clonal cell lines after selection revealed a wide range of expression of the gene product gp185erbB-2. While three of six clones tested expressed gp185erbB-2 at levels detectable by immunocytochemistry, only one, B2BE6, induced adenocarcinoma-like tumors in athymic nude mice. Both a nontumorigenic clone, B2BE2, and a tumorigenic clone, B2BE6, expressed comparable amounts of gp185erbB-2, which became phosphorylated on tyrosine in response to treatment with the c-erbB-2 ligands gp30 and p75. These data suggest that overexpression of c-erbB-2 in human bronchial epithelial cells can contribute to, but is not sufficient for, induction of tumorigenicity in this human model system.
Animals↗
p53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines.
A G:C-->T:A mutational hotspot at codon 249 of the p53 tumor suppressor gene has previously been identified in hepatocellular carcinoma (HCC) of patients from Qidong, China and southern Africa in which aflatoxin B1 (AFB1) and hepatitis B virus (HBV) are known synergistic risk factors. We have examined p53 mutation patterns of HCC from geographic areas in which the risk factors vary. Nine HCC lines and four hepatoblastoma lines (HB) were examined for p53 gene mutations and the relationship with HBV infection. Five of the nine HCC lines had homozygous mutation or deletion randomly distributed in exons 6-8, whereas none of the four HB cell lines had p53 mutations. One of the four HB lines (HepG2) had an N-ras mutation at codon 61 position 2. The p53 point mutations in the three HCC cell lines from Japan resulted in the amino acid changes of cysteine for tyrosine in cell line HuH 7 at codon 220 (A:T-->G:C), alanine for glycine in cell line HLF at codon 244 (G:C-->C:G), and serine for arginine in cell line HLE at codon 249 (G:C-->C:G). In addition, the deletion of 18 base pairs from codon 264 position 3 to codon 270 position 1 has resulted in the deletion of Leu-Gly-Arg-Asn-Ser-Phe from the amino acids sequences 256-270 in the Japanese cell line HuH 4. The cell line PLC/PRF/5 that showed p53 mutation at codon 249 (G:C-->T:A) with substitution of serine for arginine was derived from a South African patient. Our results indicate that whereas the p53 gene is not mutated in the HB cell lines, the HCC cell lines frequently contain an abnormal p53 gene. In addition, p53 point mutations were not detected in the four Japanese HCC cell lines that were positive for genomic integration of HBV X-gene and surface antigen gene. The three Japanese HCC cell lines with p53 mutations did not contain HBV sequences, indicating that hepatocarcinogenesis associated with p53 mutation does not require the genomic integration of HBV sequences.
Base Sequence↗
Cultured cell lines from human teratomas: windows into tumour growth and differentiation and early human development.
Cultured cell lines from human teratomas provide models to study molecules which might regulate tumour growth or normal embryonic development. Here, we describe efforts to delineate the role of transcription factors, extracellular matrix, and growth factors in controlling growth and differentiation of human embryonal carcinoma and yolk sac tumour.
Antigens, Differentiation↗
Efficacy of area under the curve cyclosporine monitoring in renal transplantation.
Previous studies suggest that area-under-the-curve (AUC) pharmacokinetic monitoring is superior to trough level monitoring for proper cyclosporin A (CSA) dosing, but AUC monitoring is expensive and unwieldy. The utility of a simplified AUC monitoring method was evaluated for predicting AUC on the basis of three timed levels. CSA pharmacokinetic profiles were studied in 27 renal transplant patients at steady state early (days), late (months), and in some patients, serially posttransplantation. Whole-blood RIA levels were obtained at 2, 4, 6, 10, 12, 14, and 24 h after a once-daily CSA dose. The 6- and 24-h levels were the best single-level predictors of AUC (r = 0.77 and 0.76, respectively). The best model predictive of AUC curves used three time points at 2, 6, and 24 h postdose: AUC predicted = 8.6 x (24 h) + 1.4 x (2 h) + 6.2 x (6 h) + 1.57 mg x h/L; r2 = 0.986, P = 0.00001. The greatest pharmacokinetic variability occurred between 0 and 10 h postdose (absorption and distribution) between patients and even within individual patients monitored serially over time. The 12- to 24-h postdose portion (elimination) of the curve was consistently flat and uniform among patients. AUC were not consistent in individual patients over time. An AUC of more than 13 mg x h/L correlated with nephrotoxicity, whereas a value of 8 mg x h/L correlated with protection from rejection in first-transplant recipients. This AUC, however, was not able to prevent rejection in reengrafted or highly sensitized patients.
Adult↗
A novel keratan sulphate proteoglycan from a human embryonal carcinoma cell line.
We describe here the purification and partial characterization of a 200 kDa keratan sulphate proteoglycan found in the pericellular matrix of human embryonal carcinoma cells. Previously we have shown that this molecule is recognized by a monoclonal antibody (GCTM-2). The antigen was isolated using ion-exchange chromatography and gel filtration, purification being monitored by e.l.i.s.a. using GCTM-2. Metabolic labelling of GCT 27 C-4 embryonal carcinoma cells with sodium [35S]sulphate resulted in the incorporation of [35S]sulphate into the purified molecule. Throughout the purification procedure, the peaks of 35S radioactivity were coincident with the peaks of immunoreactivity, and this label was released both by digestion with keratanase and chondroitinase, confirming the proteoglycan nature of the antigen. The intact molecule ran as a single broad band of 200 kDa, which has been identified by silver staining and immunoblotting following gel electrophoresis. Amino acid analysis of the purified antigen indicated a high content of serine, glycine and aspartic acid/asparagine residues. Visualization by rotary-shadowing electron microscopy suggests that the purified material forms large aggregates, even under denaturing conditions. Deglycosylation of this preparation with trifluoromethanesulphonic acid yielded a major band of 55 kDa and a minor band of 48 kDa. The biochemical nature of the molecule described here, along with tissue distribution studies using GCTM-2, indicates that the antigen is not related to previously described keratan sulphate proteoglycans.
Amino Acids↗
Review of the American College of Radiology--National Electrical Manufacturers' Association standards activity.
The American College of Radiology and the National Electrical Manufacturers' Association published the ACR-NEMA Digital Imaging and Communications Standard in 1985. Implementations are just now becoming available. During this time, working groups of the committee responsible for the standard have been very active. An expanded version of the standard was published in 1988 and a third version, to be known as Digital Imaging and Communications in Medicine (DICOM), is being prepared for publication in 1992. This paper briefly reviews the history of the standard, describes recent activities, outlines the extensions planned for the DICOM standard, and describes the participation of the committee in international radiological imaging standards activities.
Diagnostic Imaging↗
Comparison of UW and Euro-Collins solutions in paired cadaveric kidneys.
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Adenosine↗
Management of nephrotic syndrome in childhood.
Nephrotic syndrome is defined as proteinuria sufficiently severe to result in hypoalbuminaemia, oedema and hyperlipidaemia. The early modern history of this illness was characterised by the serendipitous development of renal biopsy technique at approximately the same time as the use of corticosteroids for nephrotic syndrome. The coincidence of these events set the stage for evaluating therapeutic response to corticosteroids and cytotoxic agents in relation to renal histology and ultimate clinical outcome. The International Study of Kidney Disease in Children (ISKDC) was initiated in the 1960s as a multicentre study examining these relationships in children. Over the next decade this study, as well as contributions from other investigators, helped define optimum therapy for these children. It was determined that a child with nephrotic syndrome under the age of 6 years, who did not present with hypertension, azotaemia, hypocomplementaemia or signs of systemic illness, had an approximately 85% chance of responding to corticosteroid therapy. If only those children who had minimal change histology on biopsy were considered, 94% responded. The original regimen which is still used today, was 60 mg/m2 bsa/day prednisone administered on a 3 times per day dosage schedule for 4 weeks, followed by an additional 4 weeks of therapy at a dose of 40 mg/m2 bsa given as a single oral dose every other day. Of those who respond roughly one-third will have no relapses, while almost half will have frequent relapses (greater than or equal to 2 in 6 months) and the rest will have infrequent relapses. Patients in relapse are treated as at presentation but are usually converted to the 40 mg/m2 bsa dose when the urine has been free of protein for 3 days, and are then tapered off or maintained on this dose for several weeks, depending on the individual's history of relapses and incidence of side effects from corticosteroids. For those children who are suffering frequent relapses and severe corticosteroid side effects (e.g. growth failure, morbid obesity, aseptic necrosis of bone), cytotoxic agents were identified as providing long term remission. After inducing remission with conventional corticosteroid dosages, cyclophosphamide is administered at a dose of 2 mg/kg/day given as a single dose for 8 weeks. This regimen was shown to lead to approximately 70% of patients being in remission 2 years after completion of this course of therapy. Chlorambucil given at a dose of 0.2 mg/kg/day as a single oral dose has been equally efficacious.(ABSTRACT TRUNCATED AT 400 WORDS)
Adrenal Cortex Hormones↗