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R Pearce

Publications and source records attributed to R Pearce.

49 records · Page 3Linked to original sources
PubMed1992

Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data.

PURPOSE: A case-controlled study of patients who reported to the European Bone Marrow Transplant Group (EBMTG) was performed to investigate the relative roles and efficacy of allogeneic (alloBMT) and autologous bone marrow transplantation (ABMT) in non-Hodgkin's lymphoma. PATIENTS AND METHODS: Of 1,060 patients who reported to the lymphoma registry, 938 patients underwent ABMT and 122 patients underwent alloBMT. A case-controlled study was performed by matching 101 alloBMT patients with 101 ABMT patients. The case matching was performed after the selection of the main prognostic factors for progression-free survival by a multivariate analysis. RESULTS: The progression-free survival was similar in both types of transplants (49% alloBMT v 46% ABMT). The overall relapse and progression rate for the alloBMT patients was 23% compared with 38% in the ABMT patients. This difference was not significant statistically. In the lymphoblastic lymphoma subgroup, alloBMT was associated with a lower relapse rate than ABMT (24% alloBMT v 48% ABMT; P = .035). The progression-free survival, however, was not significantly different because patients with lymphoblastic lymphoma who underwent alloBMT had a higher procedure-related mortality (24% alloBMT v 10% ABMT; P = .06). A significantly lower relapse/progression rate was also observed in patients with chronic graft-versus-host disease (cGVHD) compared with those patients without (0% cGVHD v 35% no cGVHD; P = .02). Fourteen of 18 patients who had cGVHD also had lymphoblastic lymphoma. CONCLUSION: This study suggests that ABMT and alloBMT for non-Hodgkin's lymphoma are comparable, with the exception of lymphoblastic lymphoma in which a graft-versus-lymphoma effect may account for the lower relapse rate for patients who underwent alloBMT.

Adolescent↗
PubMed1990

Molecular cloning, expression and nucleotide sequence of the rcsA gene of Erwinia amylovora, encoding a positive regulator of capsule expression: evidence for a family of related capsule activator proteins.

A gene encoding a positive activator of the expression of extracellular polysaccharide (EPS) synthesis in the phytopathogen Erwinia amylovora has been isolated from a genomic library in Escherichia coli. The presence of the cloned gene in E. coli stimulated transcription of the genes encoding colanic acid biosynthesis and could complement rcsA mutations. Introduction of the gene on a multicopy plasmid into Er. amylovora caused a threefold increase in EPS expression. The nucleotide sequence of the gene (designated rcsA) was determined. This revealed a single open reading frame encoding an RcsA protein of 23-7 kDa. This was confirmed by minicell analysis in E. coli. The predicted amino acid sequence of this RcsA protein showed a high degree of homology to the RcsA protein of Klebsiella aerogenes, demonstrating the existence of a family of related RcsA activator proteins capable of stimulating EPS expression. The protein had no significant homology to known DNA-binding activator proteins, indicating, for the first time, that the RcsA family of activator proteins may stimulate expression of EPS synthesis indirectly by acting on other regulatory proteins.

Amino Acid Sequence↗
PubMed1984

Analysis of hyaluronic acid in the diagnosis of malignant mesothelioma.

Using a modified papain digestion cetylpyridinium salt precipitation method, glycosaminoglycans were isolated from 21 mesotheliomas, 34 primary lung carcinomas, 12 carcinomas of other sites, and 7 soft tissue sarcomas. Qualitatively, hyaluronic acid (HA) was present in 20 of 21 mesotheliomas, about half of the primary lung adenocarcinomas, and all of the soft tissue sarcomas. On the average, HA constituted 45% of the total glycosaminoglycans in the mesotheliomas and 28% of the total in the lung cancers. Quantitatively, mesotheliomas contained statistically greater amounts (mean value, 0.74 mg/g) of HA than primary lung adenocarcinomas (mean value, 0.08 mg/g), but were not statistically different from soft tissue sarcomas (mean value, 2.01 mg/g) or primary ovarian serous neoplasms (mean value, 0.92 mg/g). The study concludes that, contrary to previous reports, HA is neither the sole nor the predominant glycosaminoglycan in most mesotheliomas, but, given the proper clinical and histologic setting, the finding of sufficiently high levels (greater than 0.4 mg/g dry tissue extract) supports the diagnosis of mesothelioma when the alternative diagnosis is primary adenocarcinoma of lung.

Adenocarcinoma↗
PubMed1984

Mapping midbrain sites for circling using current-frequency trade off data.

Electrical stimulation applied near the medial longitudinal fasciculus (MLF) produces ipsiversive circling. In this experiment we examined the spatial and temporal properties of this substrate in rats by determining the current required to produce a constant amount of circling at frequencies from 15 to 500 Hz. In general, when frequency was high, the required current was low and vice versa, but there were deviations from a reciprocal relationship. Frequencies above 200 Hz failed to reduce the current needed to reach criterion. Electrodes placed distant from the MLF required more current, and deviated from reciprocity in a systematic way. A geometric model of the overlap between substrate and stimulation field is proposed that allows estimation of spatial properties of the two regions: (1) the location of the center of the substrate for circling (0.7 mm lateral, 7.0 mm below dura in the coronal plane 1.0 mm posterior to ear bars); (2) the radius of the substrate (0.77 mm); and (3) the radius of excitation at each current. Current-frequency trade off data can provide an in vivo estimate of the behavioral effectiveness of a given electrode, and hence its placement relative to a behavioral substrate.

Animals↗
PubMed1979

Correlation between the growth inhibitory effects, partition coefficients and teratogenic effects of lipophilic acids.

The inhibition of cell duplication by many lipophilic acids was measured in Bacillus subtilis and in the following mammalian cell lines, the human epithelial-type cell lines HeLa, strain R and strain L-132, the human fibroblast cell line VA-13, and the rat glial cell line C. The results were correlated to the partition coefficient and the distribution coefficient (= apparent partition coefficient at pH 7.2) of the compounds, using octanol/water partition coefficients and pKa values either from the literature or measured for this work. For B. subtilis, the logarithm of the inhibitory potency of most compounds increases linearly with the logarithm of the partition coefficient. Exceptional high potencies were observed for compounds that can efficiently delocalize the charge of the negative ion over the whole molecule. Most compounds inhibit tissue cultures at least as potently as they inhibit B. subtilis. But some compounds are significantly more potent in tissue cultures than would have been expected from the B. subtilis data; such compounds (analgesics/antipyretics, anti-inflammatory compounds, butyrate, norepinephrine) presumably inhibits mammalian cells by specific reactions with certain cell components. However, most compounds inhibit the different cell lines to a similar degree, indicating no cellular specificity; exceptions to this rule are chlorambucil, chlortetracycline and dexamethasone. Many of the lipophilic acids that are potent inhibitors of mammalian cell replication are also teratogenic. Exceptional compounds may not reach the embryo. We propose that a number of other lipophilic acids that are potenta inhibitors and to which humans are frequently exposed should be tested for their teratogenic effect.

Animals↗
PubMed1978

Adenovirus type 21 keratoconjunctivitis.

A case of keratoconjunctivitis caused by adenovirus type 21 in London has been described. A 59-year-old woman attented hospital in August 1974 complaining of a 3-week history of redness, grittiness, watery discharge, and photophobia in her left eye and a slight upper respiratory infection. Clinical examination showed a moderate follicular conjuctivitis mainly in the lower and upper fornices, which lasted for 6 weeks. In the cornea a moderate amount of epithelial and subepithelial punctate keratitis was observed. The subepithelial opacities were coarse, discrete, and round and lasted for 4 months. The course of follicular conjunctivitis and the subepithelial punctate keratitis in this patient was similar to epidemic keratoconjunctivitis caused by adenovirus 8. A conjunctival swabbing collected from this patient was positive for adenovirus serotype 21.

Adenoviridae Infections↗
PubMedDate not supplied

Metabolism of the antimammary cancer antiestrogenic agent tamoxifen. I. Cytochrome P-450-catalyzed N-demethylation and 4-hydroxylation.

Previous studies suggested that the therapeutic effect of the antimammary cancer agent tamoxifen might be related to its metabolism. This study examined the cytochrome P-450 enzymes in rat and human liver catalyzing the metabolism of tamoxifen. Incubations of tamoxifen with rat liver microsomes yielded three major polar metabolites identified as the N-oxide, N-desmethyl, and 4-hydroxy derivatives. N-Oxide formation was catalyzed by the flavin-containing monooxygenase (see part II). Carbon monoxide, SKF-525A, metyrapone, and benzylimidazole strongly inhibited N-demethylation and 4-hydroxylation, indicating the participation of P-450 monooxygenase in these reactions. Antibodies to NADPH-P450 reductase inhibited N-demethylation and 4-hydroxylation. Comparison of the metabolism of tamoxifen in untreated male and female rats demonstrated some sexual dimorphism. N-Demethylation was higher in the male rat and 4-hydroxylation was higher in the female. Treatment of rats with phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), and methylcholanthrene (MC) enhanced N-demethylation, demonstrating the potential participation of multiple P-450s in N-demethylation. Evidence strongly indicates that CYP3A enzyme(s) catalyzes N-demethylation in liver microsomes of PB- and PCN-treated rats (PB and PCN microsomes, respectively): i) N-demethylation was inhibited by cortisol and erythromycin (alternate substrates) and a time-dependent inhibition was observed with troleandomycin (TAO) in vitro; ii) treatment of female rats with TAO, followed by dissociation of the microsomal TAO-P-450 complex, elevated N-demethylation; iii) treatment of PCN-induced female rats with chloramphenicol inhibited N-demethylation; and iv) polyclonal antibodies (PAbs) to CYP3A1 inhibited N-demethylation in PCN- and PB-treated female rats. Although we were unable to reconstitute the N-demethylation activity with purified CYP3A1, which is difficult to reconstitute, collectively the evidence demonstrated that CYP3A enzymes catalyze N-demethylation in PB and PCN microsomes. By contrast, antibodies against CYP2B1/B2 did not inhibit N-demethylation and reconstituted 2B1 did not catalyze N-demethylation of tamoxifen, indicating that 2B1 was not involved. The increase in N-demethylation by MC treatment appears to be due to elevation of CYP1A1/1A2 (P-450c/d). Alternate substrates of CYP1A1/1A2 inhibited N-demethylation and reconstituted rat CYP 1A1-catalyzed N-demethylation. Surprisingly, monoclonal antibodies (MAbs) against CYP1A1/1A2 only partially inhibited, and PAbs against CYP1A1 did not inhibit N-demethylation in MC microsomes, indicating that in MC microsomes, 1A1 does not contribute significantly to that reaction. Mab anti-CYP2C11/2C6 (P-450h/k) inhibited N-demethylation in PB, PCN, and control male rat liver microsomes, suggesting that CYP2C11 and/or CYP2C6 catalyze this reaction to some extent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗