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Biomedical subjects

M J Cooper

Publications and source records attributed to M J Cooper.

At least 19 recordsLinked to original sources
PubMed1995

Bcl-xL is expressed in neuroblastoma cells and modulates chemotherapy-induced apoptosis.

bcl-x is a new member of the bcl-2 gene family and is highly expressed in neural tissues. The present study was designed to determine the expression of the bcl-x gene products in neuroblastoma (NB) and their role in the modulation of chemotherapy-induced apoptosis. Twenty-seven NB cell lines were screened by quantitative immunoprecipitation for Bcl-xL, Bcl-xS, and Bcl-2 expression. None of the cell lines expressed Bcl-xS. Twenty-four of 27 (88%) of the NB cell lines expressed Bcl-xL and 21 of 27 (78%) were positive for Bcl-2. The level of Bcl-xL and Bcl-2 expression was variable among the lines analyzed. Bcl-2 expression was restricted to cells of chromaffin lineage, whereas Bcl-xL was seen in both chromaffin and nonchromaffin lines. To determine whether Bcl-xL could mediate chemotherapy resistance, a NB cell line expressing negligible levels of Bcl-xL was transfected with a bcl-xL expression vector, and unique clones were generated expressing variable levels of Bcl-xL. Cells were treated either with cisplatinum (CP), 4-hydroperoxy-cyclophosphamide (4-HC), or etoposide (VP-16) to induce apoptosis, and cell viability and DNA degradation were determined. Following treatment with CP or 4-HC, Bcl-xL-expressing cells showed significantly increased viability as compared to vector-transfected controls (P < 0.005). Flow cytometric analysis of propidium iodide-stained nuclei following CP or 4-HC treatment revealed significantly increased DNA degradation in controls as compared to Bcl-xL-expressing lines (P < 0.004). DNA analysis by pulsed-field gel electrophoresis revealed high molecular weight (approximately 40 kb) DNA degradation in controls, whereas the DNA in cells expressing Bcl-xL was largely intact. In contrast to CP and 4-HC, results with VP-16 revealed a short-term delay in the onset of apoptosis in Bcl-xL-expressing cells with no long-term survival advantage. The results of these studies indicate Bcl-xL is expressed in NB cells and functions in a manner analogous to Bcl-2 by inhibiting chemotherapy-induced apoptosis.

Animals↗
PubMed1995

Fetal echocardiography: retrospective review of clinical experience and an evaluation of indications.

OBJECTIVE: To assess the indications, use, and yield of fetal echocardiography. METHODS: We reviewed our 8-year experience with fetal echocardiography at a large health maintenance organization in northern California to assess the yield of abnormal findings for each indication and the accuracy of prenatal cardiac diagnosis. The study included 915 fetuses undergoing fetal echocardiography between 18-38 weeks' gestation because of accepted indications. All live-born infants had the presence or absence of congenital heart disease (CHD) confirmed postnatally. RESULTS: Family history of CHD led to 34% of all fetal echocardiography studies, with a detection rate of 0.7%. Maternal diabetes mellitus accounted for 28% of all studies, with a detection rate of 1.2%. Exposure of mothers to a potential teratogen led to 48 studies, but no abnormalities were detected. Only 4% of fetal echocardiograms were obtained because of a suspected heart defect noted on a screening obstetric sonogram; this indication had a detection rate of 68% and yielded by far the most cases of severe CHD. Based on the expected occurrence rate of severe CHD in our closed referral system, only about 15% were referred for fetal echocardiography and detected prenatally. CONCLUSION: Basing fetal echocardiography referral on risk factors misses most clinically significant detectable CHD.

Female↗
PubMed1995

Rapid intravenous infusion of d-1 sotalol: time to onset of effects on ventricular refractoriness, and safety.

d-1 sotalol is one of the most effective antiarrhythmic agents currently available for ventricular tachyarrhythmias, but the recommended infusion rate of 10-20 min is too slow for rapid pharmacological termination of sustained ventricular tachycardia (VT) or for use during cardiac arrest. The safety of the drug and time lag from its rapid administration to onset of significant effects on ventricular refractoriness is unknown. One hundred and nine patients with a history of spontaneous and inducible sustained ventricular tachyarrhythmias were studied. d-1 sotalol (1.5 mg.kg-1) was infused over 5 min in the first 57 patients (mean age 61 +/- 13 years, mean ejection fraction 37 +/- 15%, range 15-70%). d-1 sotalol was then given over 1 min in the next 52 patients (mean age 61 +/- 12 years, mean ejection fraction 35 +/- 11%, range 18-58%). The time course of change in right ventricular effective refractory period (RVERP) was measured in 15 consecutive patients following the 5 min infusion and in all 52 patients following the bolus injection. Following the 5 min infusion, RVERP increased rapidly from a baseline of 231 +/- 17 ms, reaching a plateau of 268 +/- 23 ms at 10 min. Following the 1 min injection, RVERP increased virtually immediately from a baseline of 237 +/- 25 ms to reach a plateau of 271 +/- 31 ms at 5 min. Two patients (one in each group) developed symptomatic hypotension; both responded to volume replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Can the electrophysiologic study predict treatment outcome in patients with sustained ventricular tachyarrhythmias unrelated to coronary artery disease?

UNLABELLED: Sustained ventricular tachyarrhythmias unrelated to coronary artery disease are uncommon. Currently there are no clear guidelines to aid selection of the most appropriate treatment strategy. Therefore, factors potentially predictive of arrhythmia recurrence and death and the ability of the electrophysiologic study to predict treatment outcome in patients with spontaneous sustained ventricular tachyarrhythmias unrelated to coronary artery disease were examined in 41 medically treated patients followed for a median of 25 (range 1-76) months. Examined factors were: syncope associated with the spontaneous arrhythmia, the morphology and cycle length of the presenting arrhythmia, underlying ventricular function, cardiac pathology, and the results of drug assessment at electrophysiologic study. Random variability in the ease of arrhythmia induction at electrophysiologic study was measured for the group as a whole and was allowed for in prediction of an effective drug response. The 95% confidence intervals for variability in the ease of repeat arrhythmia induction at the same study were < or = 1 extrastimulus and for variability in the ease of repeat arrhythmia inductions at different studies were < or = 2 extrastimuli. Poisson regression models were used for data analysis. Arrhythmia recurrence was most likely in: (1) patients on treatment not predicted to be anti-arrhythmic at electrophysiologic study; (2) patients whose treatment was not assessable at electrophysiologic study because the arrhythmia was not reliably inducible; (3) patients with impaired ventricular function; and (4) re-entered patients whose arrhythmia had recurred on previously allocated therapy. The risk of arrhythmia recurrence decreased with time from hospital assessment. All five deaths occurred in patients with impaired ventricular function. CONCLUSIONS: drug efficacy should be tested at electrophysiologic study in patients with reproducibly inducible clinical arrhythmias. Treatment not proven to be anti-arrhythmic at electrophysiologic study is usually ineffective. Patients with ventricular dysfunction are at highest risk of death from arrhythmia recurrence and should be considered for an implantable defibrillator, arrhythmia surgery, or heart transplantation if drug treatment is not predicted to be effective or is not assessable at electrophysiologic study.

Adolescent↗
PubMed1994

Changes in selective information processing with three psychological treatments for bulimia nervosa.

Data from a treatment trial were used to test whether interference with colour-naming eating, shape and weight related words on the Stroop colour-naming task changed with treatment. Interference decreased with treatment and there was no difference between three treatments in the size of this effect. These findings suggest that interference with colour-naming words related to eating, shape and weight in subjects with bulimia nervosa may be a useful objective measure of patients' concerns about these issues.

Adolescent↗
PubMed1994

A benign cultured colon adenoma bears three genetically altered colon cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-beta independence without inactivating the p53 tumor suppressor gene.

We describe the spontaneous progression of a colon adenoma cell line to tumorigenicity and growth factor independence. This system allows direct comparison of biologic stages of malignant progression with alterations of colon cancer suppressor genes and oncogenes. VACO-235, a human colon adenoma cell line, is at early passages nontumorigenic in the nude mouse, unable to grow in soft agar, growth stimulated by serum and EGF, and growth inhibited by TGF-beta. VACO-235 daughter passages 93 and higher have in culture spontaneously progressed to being weakly tumorigenic, but retain all other growth characteristics of VACO-235 early passages. A mouse xenograft from late passage VACO-235 was reestablished in culture as the granddaughter cell line, VACO-411. VACO-411 is highly tumorigenic, clones in soft agar, and is unresponsive to serum, EGF, and TGF-beta. Early passage VACO-235 bears a mutant K-ras allele, bears only mutant APC alleles, expresses no DCC transcripts, and expresses only wild type p53 transcripts. VACO-411 retains the identical genotype, still expressing only wild type p53. Colonic cells after ras mutation, APC mutation, and DCC inactivation remain nontumorigenic and growth factor dependent. Malignant progression involves at least two additional steps, and in VACO-411 can proceed by a novel pathway not requiring p53 inactivation.

Adenoma↗
PubMed1994

p53 mutations in bladder carcinoma cell lines.

Point mutations and deletions in the p53 tumor suppressor gene occur frequently in advanced stage bladder tumors. To extend these observations to an in vitro model of bladder tumorigenicity, we have evaluated the presence of p53 mutations in a panel of bladder carcinoma cell lines. p53 alleles were cloned using the reverse transcriptase-polymerase chain reaction method, and exons 2-11 were sequenced. Of 11 cell lines examined, 5 cell lines had missense point mutations, and each overexpressed p53 protein on western blot analysis. Except for the HT-1197 cell line, these point mutations occurred in evolutionarily conserved domains, which are characteristic hot spots for mutations. HT-1197 encodes an unusual C-terminal point mutation in codon 365, within the basic motif tetramerization domain, suggesting a linkage between induction of a mutant p53 conformation and alterations in protein oligomerization. Six of 11 cell lines had wild-type levels of p53 expression, with 4 producing p53 proteins having either internal deletions or truncations, and 2 producing wild-type p53. Presence of wild-type p53 was found only in cell lines derived from either a low-grade, papillary tumor (RT4) or fetal bladder (FHs 738Bl). The T24 cell line was found to contain a novel p53 mutant having an in-frame deletion of tyrosine 126. This p53 mutant does not bind SV40 large T antigen, yet is expressed at low levels, comparable to cell lines containing wild-type p53 alleles. Our findings characterize p53 mutations in a panel of bladder carcinoma cell lines, and provide a model for testing the role of wild-type or mutant p53 cDNA to suppress or induce tumorigenic properties.

Animals↗
PubMed1993

Comparison of number of extrastimuli versus change in basic cycle length for induction of ventricular tachycardia by programmed ventricular stimulation.

OBJECTIVES: The purpose of this study was to examine the effects of varying basic cycle lengths in a programmed stimulation protocol if up to seven extrastimuli were available at each basic cycle length. BACKGROUND: There is no uniformly accepted protocol for induction of ventricular tachycardia. Most protocols limit the number of extrastimuli to two or three but use several basic cycle lengths. METHODS: Twenty-eight patients with coronary artery disease and documented spontaneous sustained ventricular tachycardia or ventricular fibrillation were studied. In the absence of antiarrhythmic drugs, each patient underwent three inductions of ventricular tachycardia/ventricular fibrillation using sinus rhythm or right ventricular pacing at 600 or 400 ms as the basic cycle length. Up to seven extrastimuli were allowed at each basic cycle length. RESULTS: The maximal yield of clinical tachycardia (96%) was identical for each basic cycle length and was achieved using a maximum of seven, five and four extrastimuli for sinus rhythm and 600 and 400 ms, respectively. A basic cycle length of 400 ms required fewer extrastimuli (2.4 +/- 0.7) to induce ventricular tachycardia/ventricular fibrillation than did 600 ms (2.7 +/- 1.1, p = 0.014) or sinus rhythm (3.4 +/- 1.2, p < 0.001). There was no significant difference in the cycle lengths of the induced ventricular tachycardia, incidence of induced ventricular fibrillation or requirement for direct current countershock. CONCLUSIONS: The use of an adequate number of extrastimuli obviates the need for multiple basic cycle lengths for induction of ventricular tachycardia and does not increase induction of unwanted ventricular fibrillation. If only one basic cycle length is used, the ease of inducibility can be quantified in terms of the number of extrastimuli required. Fewer extrastimuli were required for induction of ventricular tachycardia if a basic cycle length of 400 ms was used. These data favor the use of ventricular pacing at a basic cycle length of 400 ms with up to at least four extrastimuli as the standard stimulation protocol for induction of ventricular tachycardia.

Adult↗
PubMed1993

Demographic and clinical correlates of selective information processing in patients with bulimia nervosa.

Demographic and clinical correlates of interference with color-naming words related to eating, weight, and shape were investigated in 75 patients with bulimia nervosa. Interference with color-naming was related to two measures, overall level of psychiatric symptoms and frequency of purging. Multiple regression analysis showed that frequency of purging, and not level of general psychiatric symptoms, was the best predictor of interference. Thus, as would be predicted by cognitive theories, interference appears to be most closely related to features specific to bulimia nervosa rather than to measures of general psychopathology.

Adolescent↗
PubMed1993

An experimental study of the relationship between thoughts and eating behaviour in bulimia nervosa.

This study tested the hypothesis that cognitive disturbance has a causal role in the maintenance of disturbed eating in bulimia nervosa. Thoughts about eating, weight and shape were activated in one group of patients with bulimia nervosa (the experimental group) but not in another (the control group). There was an increase in negative self-statements in the experimental group following the experimental manipulation. Food consumption was then measured in a taste test. As predicted, the experimental group ate less in the short term than the control group. Contrary to expectations, they did not subsequently report more objective bulimic episodes as a consequence of this decreased food intake. They did, however, report significantly fewer subjective bulimic episodes.

Adult↗
PubMed1993

Efficient episomal expression vector for human transitional carcinoma cells.

To develop an efficient expression vector for human transitional carcinoma cells, we evaluated the replication activity of episomal vectors derived from the BK virus (BKV) and the Epstein-Barr virus (EBV) in HT-1376 bladder carcinoma cells. Southern blot analysis of transient transfectants indicated that the BKV-derived episome replicated extrachromosomally whereas the EBV replicon did not appear to be functional in these cells. HT-1376 cells were stably transfected with BKV-derived episomes containing the neomycin resistance gene as a selectable marker. Southern analysis demonstrated that these stable transfectants contained approximately 150 copies of the BKV episome per cell. There was no evidence of integration of the BKV episome into genomic DNA following selection with G418 for 10 weeks. These stable episomal transfectants had approximately 20-fold higher levels of expression of neomycin resistance gene mRNA than clones of HT-1376 cells transfected with pSV2NEO which contained five integrated copies of this gene. In soft agar cloning experiments, BKV episomes were efficiently transferred to the progeny of these transfectants during cell division over multiple generations. Additionally, BKV episomal copy number is maintained in stable transfectants after withdrawal of selection pressure for over 2 months. These data demonstrate that BKV-derived episomes replicate efficiently in bladder carcinoma cells, yielding stable transfectants having a high episomal copy number and expressing encoded genes at high levels. BKV-derived episomes may be useful in gene therapy strategies to modulate the growth of bladder carcinoma cells.

BK Virus↗
PubMed1993

Gastric emptying and enterogastric reflux after conservative and conventional pancreatoduodenectomy.

BACKGROUND: Retention of the entire stomach during pancreatoduodenectomy should theoretically improve postoperative nutrition, but some studies have reported a high incidence of delayed gastric emptying (GE). An intact pylorus should also prevent enterogastric reflux and its attendant problems, provided that the operation does not impair sphincteric competence. METHODS: We studied pyloric function in 24 patients who underwent pylorus-preserving pancreatoduodenectomy (PPP) and 12 who underwent a conventional Whipple resection including distal hemigastrectomy. Resection had been performed for benign (n = 19) or malignant (n = 17) disease. A double isotope technique was used to measure liquid and solid GE, and enterogastric reflux was measured by means of cholescintigraphy. RESULTS: Only two patients who underwent PPP required nasogastric intubation beyond 8 days. At follow-up (median, 5 months; range, 2 to 42 months) one patient with persistent vomiting required remedial surgery after PPP (apart from two with recurrent carcinoma affecting the anastomosis); after Whipple resection there were three patients with intermittent vomiting and one with dumping. Median half-time for liquid GE was not significantly different (65 minutes for PPP vs 103 minutes for Whipple resection; n < 70 minutes); likewise, the median half-time for solid GE was not significantly different (140 minutes for PPP vs 180 minutes for the Whipple procedure; n < 110 minutes). Persistent enterogastric reflux was seen in three of 20 patients who underwent PPP and three of eight who underwent Whipple resection. CONCLUSIONS: Isotopic test results of GE are frequently abnormal after either type of pancreatoduodenectomy, but symptoms are uncommon. The retained pylorus is competent to prevent enterogastric reflux and does not itself impair emptying of the stomach.

Adult↗