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D Moore

Publications and source records attributed to D Moore.

At least 91 records · Page 5Linked to original sources
PubMed1993

Heterogeneity of erbB-2 gene amplification in bladder cancer.

erbB-2 amplification and overexpression have been suggested as potentially useful prognostic markers in bladder cancer. We examined 141 bladder tumor specimens (45 fresh tissue samples and 96 formalin fixed tissue blocks) for erbB-2 amplification using fluorescence in situ hybridization. A dual labeling hybridization using a repetitive pericentromeric probe specific for chromosome 17 and a cosmid probe for the erbB-2 locus was performed to analyze the erbB-2 copy number in relation to chromosome 17 copy number on a cell by cell basis. Amplification (more than twice as many erbB-2 signals as centromere 17 signals per tumor) was found in 10 of 141 tumors. There was considerable heterogeneity in erbB-2 amplification. In a given tumor there was a wide range of erbB-2 copy number in amplified cells. The arrangement of erbB-2 signals in clusters in all amplified cases suggests that erbB-2 amplification occurs intrachromosomally in bladder cancer. Amplification was found only in tumors with aneusomy of chromosome 17 and was more frequent in pT2-T4 tumors than in pTa/T1 tumors. Overexpression was present without amplification in 51 tumors. All tumors with erbB-2 amplification showed erbB-2 overexpression. However, in 5 samples the proportion of cells with amplification was significantly lower than the fraction of cells with overexpression, indicating coexistence of two different mechanisms leading to overexpression in these tumors.

Bromodeoxyuridine↗
PubMed1993

Synthesis and biological activities of angiotensin II, Sarilesin, and Sarmesin analogues containing Aze or Pip at position 7.

Analogues of [Sar1]angiotensin II, Sarilesin (type I antagonist), and Sarmesin (type II antagonist) with L-azetidine-2-carboxylic acid (Aze) and L-pipecolic acid (Pip) at position 7 have been prepared by the solid-phase method, purified by reverse-phase HPLC, and bioassayed in the rat uterus. Analogues of the superagonist [Sar1]ANGII with Aze or Pip at position 7 and sarcosine (Sar) or aminoisobutyric acid (Aib) at position 1 had high intrinsic activity in the rat isolated uterus assay (34-184%). Analogues of Sarilesin ([Sar1,Ile8]ANGII) with Aze or Pip at position 7 and Sar or Aib at position 1 retained high antagonist activity (pA2 = 7.1-8.3). Analogues of Sarmesin ([Sar1,Tyr-(OMe)4]ANGII) with Aze and Pip at position 7 had pA2 values of 7.4 and 6.5, respectively. [Aze7]-ANGII and [Pip7]ANGII had low activities (12% and 1%, respectively), and deletion of Sar at position 1 of Sarmesin analogues abolished binding (or affinity) as judged from pA2 values. Nuclear Overhauser effect (NOE) spectroscopy studies of [Sar1,Aze7]ANGII in DMSO-d6 have indicated a clustering of the three aromatic rings (Tyr, His, Phe) and proximity of Sar C alpha and Arg C delta protons to the Tyr/Phe ring protons. These data emphasize that replacement of Pro with the lower and higher homologs Aze and Pip does not greatly alter the structural requirements necessary for expression of agonist or antagonist activity, when sarcosine occupies position 1, but not when Asp occupies position 1, suggesting that there is an intimate relationship between the N-terminal and penultimate residues of the molecule in the biologically active conformation of the molecule.

Angiotensin II↗
PubMed1993

Systemic therapies for unresectable primary hepatic tumors.

Clinical trials evaluating systemic therapies for hepatocellular carcinomas (HCCs) must take into consideration prognostic factors that influence survival. Clinical features such as poor performance status, older age, and the presence of jaundice may be predictive of short survivals. Because patients with elevated alpha-fetoprotein (AFP) levels have short survivals, randomized clinical trials of therapy for HCC should stratify patients based on AFP levels. Numerous clinical trials of single-agent chemotherapy for HCC have examined alkylating agents, antitumor antibiotics, anthracyclines, hormonal therapies, and interferons. However, these trials have failed to demonstrate an agent that consistently produces response rates greater than 20% or that improves survival. Similarly, effective combination chemotherapy regimens for HCC have not been identified. Clinical trials have also failed to identify effective systemic therapies for cholangiocarcinomas, although these trials have had limited numbers of patients. These dismal results mandate an examination of phase II agents in untreated good-performance patients with HCC. Novel approaches to drug delivery should also be pursued.

Antineoplastic Agents↗
PubMed1993

Ras-transformed cells express both CD44 and RHAMM hyaluronan receptors: only RHAMM is essential for hyaluronan-promoted locomotion.

Hyaluronan (HA) is an important regulator of cell locomotion. We show that ras-transformed cells, termed 245 cells, respond to HA with an increase in random locomotion. We show that two HA receptors, RHAMM (receptor for hyaluronan-mediated motility) and CD44, are present on these ras-transformed fibroblasts. RHAMM is expressed as a 58-kDa protein and is distributed primarily as patches over lamellae. CD44 occurs largely as an 85- to 90-kDa protein that is distributed more or less evenly over the cell surface with small amounts concentrated at the tips of lamellae. CD44 and RHAMM both bind biotinylated HA in a transblot assay, indicating that they are both potential fibroblast HA receptors. CD44 binds approximately five times more HA than RHAMM as determined by densitometric analysis of transblots, indicating that this protein is the major HA receptor on fibroblasts. We assessed the role of these receptors in mediating the stimulatory effects of HA on cell motility by using antibody neutralization. Several antibodies to CD44 were used that inhibit HA/CD44 interactions. None of these had an effect on locomotory responses to HA, indicating that CD44 is not directly involved in mediating locomotion in response to HA on ras-transformed cells. In contrast, antibodies specific to RHAMM completely inhibited locomotion, indicating that RHAMM is the primary mediator of HA-promoted locomotion of ras-transformed cells.

Animals↗
PubMed1993

p53 and erbB-2 protein overexpression are associated with early invasion and metastasis in bladder cancer.

Overexpression of p53 and erbB-2 was studied by immunohistochemistry in formalin-fixed tissue samples of 179 patients with transitional cell carcinoma of the urinary bladder. p53 immunostaining was strongly correlated with tumour stage (P < 0.0001). This was driven by a marked difference in p53 expression between pTa (37% positive) and pT1 (71%) tumours, while there was no difference between pT1 and pT2-4 tumours. Similarly, a strong overall association between p53 expression and grade (P < 0.0001) was driven by a marked difference between grade 1 (28%) and grade 2 tumours (71%), and there was no significant difference between grade 2 and grade 3 tumours. Surprisingly, the frequency of erbB-2 overexpression was higher in pT1 tumours (74%) than in either pTa (49%; P = 0.0265) or pT2-T4 (56%; P = 0.0645) tumours. Both p53 and erbB-2 expression was also associated with metastasis. Metastases were found in 77% of patients with p53 positive primary tumours, but in only 50% of the patients with p53 negative primary tumours (P = 0.022). Metastases were found in 66% of patients with erbB-2 positive primaries, but in only 37% of the erbB-2 negative primaries (P = 0.020). Of 32 patients with positivity for both p53 and erbB-2, 84% developed metastases, as compared to 49% of patients with positivity for either one or neither positive (P = 0.002). We conclude that both p53 and erbB-2 overexpression are associated with early invasion in bladder cancer. Furthermore, p53 and erbB-2 may be important predictors for metastasis.

Biomarkers, Tumor↗
PubMed1993

Improved performance 4 hours after cocaine.

Cocaine (2 mg/kg) was given orally to 13 healthy volunteers and physiologic, subjective, attentional and performance effects were measured over a period of 4 h. Posner's reaction time paradigm measured the effects of cocaine on performance and on attention to visual cues. Cocaine increased heart rate, systolic blood pressure and pupil diameter and reduced skin temperature. Physiologic effects, subjective rating of intoxication, and cocaine levels in saliva peaked at approximately 75 min and returned to precocaine levels within 3 h. In contrast, a reaction time measure of performance speed on the visual attention task showed improvement for 4 h after cocaine. A measure of covert attention in the cocaine condition failed to show the improvement which occurred in the placebo condition. Less fatigue was reported 4 h after cocaine than after placebo. Cocaine users may experience the drug's stimulant effects considerably longer than the euphoriant effects.

Adult↗
PubMed1993

Young and old adults' ability to use different standards to evaluate understanding.

In Experiment 1 we examined young (mean age = 22.88 years) and old (mean age = 70.79 years) adults' ability to evaluate their understanding of texts. We examined ability to detect nonsense words (a lexical standard), violations of prior knowledge (an external consistency standard), and inconsistent sentences (an internal consistency standard) that were nonadjacent in texts. Adults with more education detected more problems than less educated adults, and older adults were less able than young to use an internal consistency standard. No age differences were found for lexical and external consistency standards. In Experiment 2, older adults' (mean age = 71.02 years) ability to use an internal consistency standard of evaluation was affected by the amount of material intervening between inconsistent sentences, with hindered performance for nonadjacent inconsistencies. This was not true for younger adults (mean age = 22.59 years). Results are discussed in terms of older adults' possible retrieval difficulty and failure to regulate comprehension.

Adolescent↗
PubMed1993

Social controls, harm minimisation and interactive outreach: the public health implications of an ethnography of drug use.

This is a report on ethnographic research with the members of a social network of young, recreational, illicit drug users in Perth, Western Australia, with whom I maintained close social interaction for over twelve months. Following the work of Zinberg, the article outlines some of the main social controls employed by these young drug users to reduce drug-related harm. These social controls are of two types: sanctions (the rules prescribing certain behaviours and proscribing others) and rituals (the stylised behaviour surrounding the use of drugs). There exists an ideology of harm minimisation amongst drug users which may provide the basis for innovative programs. The implications of these findings are discussed with reference to one particular public health strategy, outreach, and the possibility of a more active, reciprocal and beneficial engagement between drug users and researchers, health educators and policy makers is suggested.

Anthropology, Cultural↗
PubMed1993

The Escherichia coli K-12 F plasmid gene traX is required for acetylation of F pilin.

The Escherichia coli F plasmid gene required for amino-terminal acetylation of F-pilin subunits was identified. Using Western blots (immunoblots), we assayed the reaction of monoclonal antibodies with F-pilin polypeptides in inner membrane preparations from various F mutant strains. It was known that JEL92 recognizes an internal pilin epitope and JEL93 recognizes the acetylated amino-terminal sequence (L.S. Frost, J.S. Lee, D.G. Scraba, and W. Paranchych, J. Bacteriol. 168:192-198, 1986). As expected, neither antibody reacted with inner membranes from F- cells or Flac derivatives that do not synthesize pilin. Mutations that affected the individual activities of F tra genes traA, -B, -C, -D, -E, -F, -G, -H, -I, -J, -K, -L, -M, -N, -P, -R, -U, -V and -W or trb genes trbA, -B, -C, -D, -E, -G, -H, and -I did not prevent JEL92 or JEL93 recognition of membrane pilin. However, Hfr deletion mutants that lacked the most-distal transfer region genes did not express pilin that reacted with JEL93. Nevertheless, all strains that retained traA and traQ did express JEL92-reactive pilin polypeptides. Analysis of strains expressing cloned tra segments showed that traA and traQ suffice for synthesis of JEL92-reactive pilin, but synthesis of JEL93-reactive pilin is additionally dependent on traX. We concluded that the traX product is required for acetylation of F pilin. Interestingly, our data also showed that TraA+ TraQ+ cells synthesize two forms of pilin which migrate at approximately 7 and 8 kDa. In TraX+ cells, both become acetylated and react with JEL93. Preparations of wild-type F-pilus filaments contain both types of subunits.

Acetylation↗
PubMed1993

Near fatal ingestion of oil of cloves.

A case of ingestion of oil of cloves is presented, which resulted in coma, fits, a coagulopathy, and acute liver damage. This is not unlike the syndrome produced in the late stages of a substantial paracetamol overdose, and a similar treatment regimen is proposed.

Chemical and Drug Induced Liver Injury↗
PubMed1993

Effects of an orally active NO-releasing agent, CAS 936, and its active metabolite, 3754, on cardiac and coronary dynamics in normal conscious dogs and after pacing-induced heart failure.

The mechanism of action of nitrates, compounds that have been used classically in the treatment of heart failure, appears to be the stimulation of guanylate cyclase in vascular smooth muscle, perhaps the same physiologic action as endothelium-derived relaxing factor, now thought to be synonymous with nitric oxide (NO). Drugs that release NO either inside cells or in plasma have been developed recently. One such compound, CAS 936, when taken orally, is converted to an active metabolite, 3754. The goal of our studies was to determine the effects of CAS 936 and 3754 on cardiovascular function in conscious dogs before and after the development of pacing-induced heart failure. CAS 936 (10 mg/kg, p.o.) increased large coronary artery diameter 9.1 +/- 1.2% and reduced left ventricular end diastolic pressure (LVEDP) 2.5 +/- 0.5 mm Hg, but had no significant effects on coronary blood flow or vascular resistance. The metabolite 3754 caused dose-related increases in coronary artery diameter, and large reductions in LVEDP. The effect of these compounds on large coronary artery diameter was significantly greater (p < 0.05) than that of nitroglycerin (25 micrograms/kg). After heart failure, both CAS 936 and 3754 caused significant increases in large coronary artery diameter (10%) and a reduction in preload, up to 10 mm Hg, which was even larger than in normal dogs. Thus, these NO-releasing agents are potent selective large-vessel dilators that also reduce preload and maintain this unique vasodilator profile even in the failing heart.

Administration, Oral↗
PubMed1993

Tuberculosis of the small bowel with perforation and hematogenous spread in a renal transplant recipient.

A 41-year-old male was admitted because of acute abdomen. A flat plate of the abdomen suggested pneumoperitoneum and a chest X-ray an infiltrate in the right upper lobe. The patient was a renal allograft recipient and was on immunosuppressive therapy with azathioprine, cyclosporine and steroids. At laparatomy inflammatory thickening of the bowel wall was found in the terminal ileum with necrotic areas and two sites of perforation. The involved terminal ileum was removed together with a right hemicolectomy. The resected segment showed exudative ileal tuberculosis and fibrinous and purulent peritonitis. During the postoperative period rapid hematogenous spread of tuberculosis developed with progressive reduction of respiratory function followed by ARDS. Autopsy revealed tuberculosis in all organs including the transplanted kidney.

Adult↗
PubMed1992

Phase I trial of Taxotere: five-day schedule.

BACKGROUND: Taxotere, a semisynthetic compound structurally related to taxol, has a broad spectrum of activity in murine transplantable tumors; in the B16 melanoma model, it caused a total log cell kill 2.5 times greater than that caused by taxol at equitoxic doses. PURPOSE: We conducted a phase I study of Taxotere (a) to determine its qualitative and quantitative toxic effects and a starting dose for phase II trials, (b) to investigate its clinical pharmacology, and (c) to document its antitumor activity. METHODS: Taxotere was given as a 1-hour infusion at a starting dose of 1 mg/m2 per day for 5 consecutive days. The 5-day course of therapy was repeated every 21 days. Thirty-nine cancer patients with advanced disease were entered in the study; at least three patients were entered at each dose level. Initial dose escalations were planned at 100% increments until biologic activity was observed; subsequent escalations were planned at 50% increments until grade 2 toxicity (the National Cancer Institute's Common Toxicity Criteria) occurred and then at 25% increments until the maximum tolerated dose was established. RESULTS: Thirty-nine patients were entered in the study. Successive dose levels used were 1, 4, 8, 16, 12, and 14 mg/m2 per day. The dose-limiting toxic effects were granulocytopenia and concurrent mucositis. Grade 4 granulocytopenia associated with grade 3 mucositis developed in six of 12 patients treated at a dose of 16 mg/m2 per day, two of 10 treated at 12 mg/m2 per day, and two of eight treated at 14 mg/m2 per day. Because these toxic effects occurred concurrently, all patients so affected developed neutropenic fevers and required hospitalization. Neither cardiac nor neurologic toxic effects were noted. Anti-tumor activity was observed in six patients with ovarian cancer and in one with breast carcinoma. Although pharmacokinetic parameters were consistent between day 1 and day 5 for individual patients, considerable variation existed among those treated at the same dose level. A relationship was observed between the area under the curve for plasma concentration of drug x time (AUC) on day 1 and the percentage decrease in absolute granulocyte counts. CONCLUSION: Granulocytopenia associated with oral mucositis is the dose-limiting toxicity of this schedule. We recommended a starting dose of 14 mg/m2 per day for phase II studies of this 5-day schedule. Dose modifications on days 2-5 based on the day-1 AUC may allow individualized dosing.

Adult↗
PubMed1992

Heterogeneity for allelic loss in human breast cancer.

BACKGROUND: Loss of heterozygosity (LOH) at specific chromosomal regions in the tumor cells implicates the presence of tumor suppressor genes. However, it is also possible for an LOH to be randomly acquired and irrelevant to tumor development. PURPOSE: To determine whether a particular LOH in human breast carcinomas represents a loss of tumor suppressor gene or merely a random loss, we analyzed untreated primary breast cancers for LOH. METHODS: Ninety-eight primary human breast cancers from previously untreated patients were analyzed for LOH at 12 chromosomal regions including five randomly selected regions and seven regions previously reported in other cancer types and/or breast cancers. RESULTS: The baseline incidence of LOH was five out of 124 tests (4%) using randomly selected probes on chromosomes 1p, 2p, 4p, 11q, and Xq. Incidences of LOH significantly greater than background were seen in the following chromosomal regions: 22q (10 of 26 cases, 38%); 18p (five of 24 cases, 21%); 17p (30 of 59 cases, 51%); 13q (five of 14 cases, 36%); 3p (13 of 28 cases, 46%); and 1q (18 of 70 cases, 26%). In contrast to previous reports, the incidence of LOH was not significantly different from background for 11p15. In all cases, results were the same for metastatic lymph nodes and primary tumors, suggesting that the losses occurred early in the malignant progression. In cases with LOH at more than one locus, the same DNA sample often varied in degree of signal reduction for the missing alleles. CONCLUSION: These observations indicate the presence of both intertumor and intratumor heterogeneity for LOH.

Adult↗
PubMed1992

The complete nucleotide sequence of pepper mottle virus genomic RNA: comparison of the encoded polyprotein with those of other sequenced potyviruses.

The complete nucleotide sequence of a pepper mottle virus isolate from California (PepMoV C) has been determined from cloned viral cDNAs. The PepMoV C genomic RNA is 9640 nucleotides excluding the poly(A) tail and contains a long open reading frame starting at nucleotide 168 and potentially encoding a polyprotein of 3068 amino acids. Comparison of the PepMoV C presumptive polyprotein with those of other sequenced members of the potyvirus group, including tobacco etch virus (TEV), tobacco vein mottling virus (TVMV), plum pox virus (PPV), and potato virus Y (PVY), allowed localization of putative protein cleavage sites. A similar analysis was used to determine the position of conserved viral protein-coding regions along the viral genomic RNA. These analyses confirm previous work indicating that genome organization is conserved among members of the genus Potyvirus. The localization of one PepMoV C gene product, the nuclear inclusion body protein a (NIa protein), was analyzed by expressing PepMoV cDNA deletion clones in bacteria and assaying for appearance of mature-sized coat protein, a cleavage product of the NIa protease. Comparative sequence analyses of the putative PepMoV polyprotein with those of TEV, TVMV, PPV, and PVY served to identify regions of the potyviral polyproteins which have diverged within the genus, as well as highly conserved protein features which may play an important functional role in the potyviral life cycle.

Amino Acid Sequence↗
PubMed1992

Modulation of T-cell reactivity to synthetic peptide analogues of foot-and-mouth disease virus in sheep by amino acid substitutions.

The ability of synthetic peptide analogues of foot-and-mouth disease virus VP1 capsid protein to induce T-cell proliferation in vitro following immunization of sheep with the uncoupled peptides was assessed. Elevated T-cell responses were obtained to a 21-residue peptide containing VP1 residues 141-158, and a 40-residue peptide containing residues 200-213 and 141-158 linked via a diproline-serine spacer. In contrast, no significant T-cell response was obtained with a 19-residue peptide containing residues 200-213 alone. In an attempt to engineer T-cell reactivity to this peptide, a sequence motif found in many peptides recognized by human or mouse T-cells was introduced by amino acid substitution. Substitution of a glycine or an aspartic acid for an alanine at position 207 in the 19-residue peptide resulted in the introduction of two such motifs running consecutively. Immunization of sheep with these peptides resulted in significant T-cell proliferative responses and elevated antibody responses. Analysis of further sequence variants showed that T-cell responsiveness was maintained with peptides containing single amino acid changes within these motifs, provided position 207 was glycine. The results thus suggest that increased T-cell reactivity, might be engineered via sequence manipulation of the 200-213 component of the 40-residue synthetic peptide. Such an additional T-cell epitope in the 40-residue peptide could potentially result in superior neutralizing antibody responses directed against the major epitope in residues 141-160 of VP1.

Amino Acid Sequence↗
PubMed1992

Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility.

A cDNA encoding a unique hyaluronan receptor has been molecularly cloned from a lambda GT11 3T3 cDNA expression library. Immunoblot analyses of cell lysates, using antibodies to peptides encoded in the cDNA, specifically react with a 58-kD protein. This protein is regulated by the mutant H-ras gene in cells containing a metallothionein promoter H-ras hybrid gene. Further, antibodies to peptide sequences encoded in the cDNA block the increase in locomotion resulting from induction of the mutant H-ras gene in this cell line. In a transblot assay, the bacterially expressed protein binds to biotinylated hyaluronan. Antibodies to peptides encoded in the cDNA react in immunoblot assays with the 58- and 52-kD proteins of a novel hyaluronan receptor complex previously implicated in cell locomotion. Furthermore, antibodies specific to the 58- and 52-kD proteins, which block ras-induced locomotion, also cross-react with the expressed, encoded protein. The gene product described here appears to be a new type of hyaluronan receptor that is involved in cell locomotion. It is named RHAMM, an acronym for receptor for hyaluronan-mediated motility.

3T3 Cells↗