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R Morgan

Publications and source records attributed to R Morgan.

At least 145 records · Page 8Linked to original sources
PubMed1993

A more efficient and specific strategy in the ablation of mRNA in Xenopus laevis using mixtures of antisense oligos.

Previously, antisense oligodeoxyribonucleotides (oligos) have been used to ablate specific mRNAs from the maternal RNA pool of Xenopus laevis oocytes. However, this strategy is limited by the dose of oligo which can be used and the fact that 100% cleavage of the target RNA is rare. Further, non-specific cleavage of other RNAs can also occur. We demonstrate that the use of several oligos against the histone H4 RNA results in a marked improvement in the efficiency of target degradation, due to synergistic action between oligos and the existence of RNA in at least two different secondary structures. We show, by using a set of overlapping oligos complementary to the entire H4 RNA, that the amount of oligo required for efficient target ablation is greatly lowered and non-specific effects are reduced.

Animals↗
PubMed1993

Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations.

BACKGROUND: Translocations involving chromosome band 11q23 are very frequent in both acute lymphoblastic and acute myeloid leukemias and are the most common genetic alteration in infants with leukemia. In all age groups and all phenotypes of leukemia, an 11q23 translocation carries a poor prognosis. A major question has been whether one or several genes on band 11q23 are implicated in these leukemias. Previously, we identified the chromosomal breakpoint region in leukemias with the common 11q23 translocations and subsequently cloned a gene named MLL that spans the 11q23 breakpoint. METHODS: We isolated a 0.74-kb BamHI fragment from a complementary DAN (cDNA) clone of the MLL gene. To determine the incidence of MLL rearrangements in patients with 11q23 abnormalities, we analyzed DNA from 61 patients with acute leukemia, 3 cell lines derived from such patients, and 20 patients with non-Hodgkin's lymphoma and 11q23 aberrations. RESULTS: The 0.74-kb cDNA probe detected DNA rearrangements in the MLL gene in 58 of the patients with leukemia, in the 3 cell lines, and in 3 of the patients with lymphoma. All the breaks occurred in an 8.3-kb breakpoint cluster region within the MLL gene. The probe identified DNA rearrangements in all 48 patients with the five common 11q23 translocations involving chromosomes 4, 6, 9, and 19, as well as in 16 patients with uncommon 11q23 aberrations. Twenty-one different chromosomal breakpoints involving the MLL gene were detected. CONCLUSIONS: MLL gene rearrangements were detected with a single probe and a single restriction-enzyme digest in all DNA samples from patients with the common 11q23 translocations as well as in 16 patients or cell lines with other 11q23 anomalies. The ability to detect an MLL gene rearrangement rapidly and reliably, especially in patients with limited material for cytogenetic analysis, should make it possible to identify patients who have a poor prognosis and therefore require aggressive chemotherapy or marrow transplantation.

Acute Disease↗
PubMed1993

Telomeric structure in cells with chromosome end associations.

End-to-end associations of metaphase chromosomes have been observed in a variety of human tumors, ageing cells, and several chromosome instability syndromes. Since telomeres of tumor cells and ageing tissues are often reduced in length, it has been suggested that chromosome end associations may be due to loss of telomeric repeats. We report the molecular structure of telomeres of two human tumor cell lines with frequent end-to-end associations of metaphase chromosomes. These telomeres were shown to be severely reduced compared with most other human cells with functional telomeres. However, we also describe two cell lines with severely shortened telomeres that are not detectably compromised in their function. We suggest that telomeric length is not the only determinant of the fusigenic behavior of human telomeres in tumor cells.

Base Sequence↗
PubMed1993

Two microsatellite repeat polymorphisms flanking opposite ends of the human glucokinase gene: use in haplotype analysis of Welsh Caucasians with type 2 (non-insulin-dependent) diabetes mellitus.

The purpose of this study was to evaluate the role of potential glucokinase defects contributing to susceptibility to Type 2 (non-insulin-dependent) diabetes mellitus in Welsh Caucasians. For this analysis, two microsatellite repeat polymorphisms flanking opposite ends of the gene were employed. For a recently described microsatellite (GCK2), located 6 kilobases upstream of islet exon 1, six different sized alleles were observed, with heterozygosity of 0.50 and polymorphism information content 0.44. Combined heterozygosity with another microsatellite repeat (GCK1) was 0.72. Significant linkage disequilibrium was noted between GCK2 and GCK1, suggesting that haplotypes may be a better predictor of Type 2 diabetes than analysis with either microsatellite alone. Using these two markers, the association with Type 2 diabetes was examined. The frequencies of alleles and genotypes at GCK1 did not differ between the patients with Type 2 diabetes (n = 157) and control subjects (n = 73). Similarly no differences were observed in GCK2 alleles or genotypes. The frequencies of haplotypes, derived from the two markers, also did not differ between the two groups. To investigate the possibility of minor metabolic effects of glucokinase defects, we also studied the association between the GCK alleles or haplotypes and the response profiles to meal tolerance tests. No association was observed between plasma glucose or insulin responses to meal tolerance tests with GCK haplotypes or alleles. These results suggest that glucokinase mutations in Welsh Caucasians are not major determinants of susceptibility to the common type of Type 2 diabetes.

Aged↗
PubMed1993

Multicenter phase II study of brequinar sodium in patients with advanced lung cancer.

A total of 53 patients with advanced lung cancer [non-small-cell (NSC), 21; small-cell (SC), 32] were treated with brequinar sodium. All of the NSC patients were chemotherapy-naive, but 31/32 (97%) SC patients had failed a multiagent chemotherapy program prior to study entry. Brequinar was given intravenously at a median weekly dose of 1200 mg/m2. The toxicity was moderate, with 19 patients (36%) experiencing grade 3 or 4 toxicity. Objective responses were observed in one NSC and two SC patients. We conclude that at this dose and on this schedule, brequinar does not have sufficient activity in patients with NSC or in patients with previously treated SC to warrant further evaluation. However, since responses were observed in previously treated SC lung-cancer patients, further evaluation in chemotherapy-naive patients may be warranted.

Aged↗
PubMed1993

FISH: a useful technique in the verification of clonality of random chromosome abnormalities.

Random chromosome abnormality is an important issue in clinical cytogenetics, especially in cancer cytogenetics. The significance of random abnormalities needs to be well defined. In the present study, ten patients with malignant hematologic disorders were analyzed by classical cytogenetic techniques and fluorescence in situ hybridization (FISH) procedures. Cytogenetic studies showed all ten patients to have a single cell with trisomy, i.e., +8, +8 (5 cases), +12, +15, +18, +20, and +21, respectively. FISH necessitated revision of the cytogenetic diagnosis and confirmed the clonality of these "random" abnormalities.

Adult↗
PubMed1993

Radiological aspects of solvent dissolution of gall-stones.

Twenty-five patients were referred for solvent dissolution of gall-stones using methyl tertiary butyl ether (MTBE). All patients were assessed beforehand by ultrasound and oral cholecystography. Computed tomography was performed in 23 patients to assess stone calcification and gall-bladder anatomy. Successful stone dissolution was achieved in 15 patients and partial dissolution in six patients. Failure to catheterize the gall-bladder occurred in four patients. There were four biliary leaks, two requiring cholecystectomy. The CT appearances of the gall-bladder may have predicted problems with catheterization in three of the four cases, and the results suggest that cover of the gall-bladder by the liver of greater than 50% is a favourable predictor of successful catheterization. A thick-walled gall-bladder and excess fat between the liver and the lateral abdominal wall are adverse predictors of successful gall-bladder catheterization. Both tubography and ultrasound should be used to assess progress of dissolution. Newer, more effective solvents together with increased expertise in interventional techniques may encourage the more widespread use of solvent dissolution of gall-stones as an alternative to surgery in a selected population.

Adult↗
PubMed1993

Overexpression of Her-2/neu may be an indicator of poor prognosis in prostate cancer.

Previous reports have shown that Her-2/neu oncogene expression in human breast cancer and ovarian cancer may be associated with poorer prognosis. We report the expression of Her-2/neu on fresh samples of known prostatic adenocarcinoma but not on those of benign prostatic hypertrophy. Using a monoclonal antibody (TA1) directed against human Her-2/neu oncogene product and an immunohistochemical staining method, no Her-2/neu expression was noted with benign prostatic hypertrophy (15 samples). With prostatic adenocarcinoma samples, a subset (9 of 25) showed overexpression of Her-2/neu. Such overexpression is correlated with higher histological grade, higher stage of disease, and high S phase and aneuploidy on flow cytometric analysis. These findings suggest that Her-2/neu may be a prognostic marker in prostate cancer as well.

Adenocarcinoma↗
PubMed1993

Effects of retroviral infections on immune function in African-American intravenous drug users.

OBJECTIVES: To determine the effect of retrovirus infection and co-infection, and intravenous substance use, on immune function in African-Americans. DESIGN: A cohort of South Florida street-recruited African-American intravenous drug users formed the study population. The cohort consisted of 90 HIV-negative & human T-lymphotropic virus (HTLV)-negative, one HIV-negative & HTLV-I-positive, 11 HIV-negative & HTLV-II-positive, 79 HIV-positive & HTLV-negative, one HIV-positive & HTLV-I-positive and 21 HIV-positive & HTLV-II-positive individuals. The results reported are for the cross-sectional, baseline assessment of immune parameters. METHODS: Lymphocyte phenotypic distributions and functional markers, including proliferative response to mitogens and natural killer cell cytotoxicity, were determined. Serum immunoglobulin (Ig) levels were determined as a measure of B-cell activity. RESULTS: HTLV-II infection was associated with increases in CD8 lymphocyte count and serum Ig, but with no other significant immunologic changes. The distribution of CD4 and CD8 percentages, CD4:CD8 ratio, phytohemagglutinin (PHA) and pokeweed mitogen (PWM) reactivity, IgA and IgG for the four retrovirus serostatus groups suggested the possibility of interactive effects in the co-infected group, as demonstrated by a trend toward lower medians for CD4 and for PHA and PWM response and higher medians for IgG, IgA and CD8. Retrovirus-seronegative intravenous drug users had significantly impaired immune status compared with non-drug-using control individuals. CONCLUSIONS: Immunologic dysfunction attributable to HTLV-II infection was minor compared with HIV infection in this population. Study subjects who were co-infected with HIV and HTLV demonstrated more impairment of immune function than individuals with single retrovirus infections.

Adult↗
PubMed1993

Phase I trial of interleukin-2 plus doxorubicin.

Interleukin-2 (IL-2) and doxorubicin have synergistic antitumor activity in selected animal models and may interact favorably in the therapy of human tumors. In order to explore the interactions between these agents and to define a maximum tolerated dosage for the combination, we performed a phase I clinical trial of IL-2 administered by continuous intravenous infusion (c.i.) plus doxorubicin given by intravenous bolus. Fifteen patients were treated on one of two schedules; the first seven patients received IL-2, 9 mIU/m2/day (3 patients) or 13.5 mIU/m2/day (4 patients) by c.i. on days 1-5, 8-12, and 15-19 with doxorubicin, 25 mg/m2 on day 14. Eight patients received IL-2, 18 mIU/m2/day by c.i. on days 1-5 and 8-12 with doxorubicin, 25 mg/m2 (4 patients) or 50 mg/m2 (4 patients) on day 7. The toxicities of the combination were no greater than those expected from each agent individually. Patients at all three planned IL-2 dosage levels received similar percentages of the planned total dosage (median 100%; > 95% in 60% of cycles), and all patients received the planned dosages of doxorubicin with only one brief delay for resolution of hyperbilirubinemia. The doses recommended for further study are IL-2, 18 mIU/m2/day, on days 1-5 and 8-12 with doxorubicin, 50 mg/m2 on day 7, a regimen which is not associated with significant organ toxicity.

Adult↗
PubMed1993

Apolipoprotein (a) concentrations and susceptibility to coronary artery disease in patients with peripheral vascular disease.

OBJECTIVE: To investigate the relation between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with atheromatous peripheral vascular disease. DESIGN: 40 consecutive patients were recruited at the time of admission for peripheral vascular surgery. All underwent clinical assessment and coronary arteriography. Apolipoprotein(a) concentrations were measured by an immunoradiometric assay. SETTING: Tertiary referral centre. SUBJECTS: Patients requiring surgical intervention for large vessel peripheral vascular disease. MAIN OUTCOME MEASURES: Presence or absence and severity and distribution of angiographically defined coronary artery disease. Measurement of circulating contractions of apolipoprotein(a) and other lipid indices. RESULTS: Coronary artery disease was absent in 11 patients (group 1), mild to moderate in 12 (group 2), and severe in 17 (group 3). The distribution of peripheral vascular disease and of standard lipid indices was similar in these three groups of patients. There was a significant difference in apolipoprotein(a) concentrations between the three groups, with concentrations progressively increasing with the severity of coronary artery disease (mean (95% confidence interval): group 1, 112 U/1 (52 to 242); group 2, 214 U/1 (129 to 355); group 3, 537 U/1 (271 to 1064) (analysis of variance p < 0.005). The prevalence of coronary artery disease was increased 7.4 fold in patients with apolipoprotein(a) concentrations that were greater than the cohort median (206 U/1) (p < 0.01). CONCLUSIONS: The results show an association between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with large vessel peripheral vascular disease. The findings imply differences in the pathogenesis of coronary and peripheral atheroma and suggest that the measurement of apolipoprotein(a) may prove a useful additional tool in the risk factor assessment of patients undergoing peripheral vascular surgery.

Aged↗
PubMed1993

Vagus nerve stimulation for complex partial seizures: surgical technique, safety, and efficacy.

Electrical stimulation of the vagus nerve has shown efficacy in controlling seizures in experimental models, and early clinical trials have suggested possible benefit in humans. Eleven patients with complex partial seizures were subjected to implantation of vagus nerve stimulators. Electrode contacts embedded in silicone rubber spirals were placed on the left vagus nerve in the low cervical area. A transcutaneously programmable stimulator module was placed in an infraclavicular subcutaneous pocket and connected to the electrode. One patient required replacement of the system due to electrode fracture. Another patient developed delayed ipsilateral vocal-cord paralysis; the technique was then modified to allow more tolerance for postoperative nerve edema. A third patient showed asymptomatic vocal-cord paresis on immediate postoperative laryngoscopy. Vagus nerve stimulation produces transient vocal-cord dysfunction while the current is on. Nine patients were randomly assigned to receive either high- or low-current stimulation, and seizure frequency was recorded. The high-current stimulation group showed a median reduction in seizure frequency of 27.7% compared to the preimplantation baseline, while the low-current stimulation group showed a median increase of 6.3%. This difference approached statistical significance. The entire population then received maximally tolerable stimulation. The high-current stimulation group showed a further 14.3% reduction, while the low-current stimulation group showed a 25.4% reduction compared to the blinded period. The efficacy of vagus nerve stimulation seemed to depend on stimulus parameters, and a cumulative effect was evident. These results are encouraging, and further study of this modality as an adjunct treatment for epilepsy is warranted.

Adult↗
PubMed1993

Establishment of cell lines from B-cell precursor acute lymphoblastic leukemia.

In an attempt to establish permanent cell lines from children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), 123 clinical samples from 117 patients were cultured in vitro. Using a method which was successful for the growth of ALL with T-cell phenotype, 3% (2/74) of BCP-ALL samples from patients at diagnosis and 31% (9/29) of BCP-ALL samples from patients at relapse were established as cell lines. However, in most cultures, leukemic cells survived for only a few weeks and the majority of viable cells present after 28 days of culture were esterase-positive mononuclear cells. Based on the hypothesis that mononuclear cells inhibited leukemic cell growth, we evaluated the effect of a monocyte toxin, L-leucine methyl ester (Leu-OMe), on the growth of four frozen BCP-ALL samples. Thawed leukemic cells treated with Leu-OMe, but not untreated control cells, proliferated in three samples and one new cell line was established. Subsequently, when Leu-OMe was added to fresh leukemia cells in culture, leukemic cell lines were grown from 29% (4/14) of samples at diagnosis and 66% (4/6) of relapse samples. Overall, 20 BCP-ALL cell lines were established, all were Epstein-Barr virus (EBV)-negative, and authenticity of each cell line was verified by a direct comparison of the immunophenotype, karyotype, and genotype with the patient's tumor cells. This improved method of cell culture permits a higher success rate of cell line establishment from patients with BCP-ALL thereby aiding in analysis of B-lymphocyte transformation and neoplasia.

Adolescent↗
PubMed1993

Abnormal pituitary-adrenocortical response in early HIV-1 infection.

The corticotropin-adrenocortical response to cold pressor challenge was investigated in a study of human immunodeficiency virus (HIV) infection. Data obtained from 16 HIV-1-positive and 28 HIV-1-negative subjects are presented in this report. After the insertion of a venicatheter and following 30 min of rest, the subjects immersed one of their hands in an ice-water mixture for 2 min, and serial blood samples were obtained for the determination of ACTH and cortisol levels. The results show a significant blunting in the ACTH response and marginally lower levels of cortisol, over all time points, in HIV-1-positive subjects compared to that in HIV-1-negative subjects.

Adrenocorticotropic Hormone↗