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Biomedical subjects

R Pearce

Publications and source records attributed to R Pearce.

At least 55 records · Page 3Linked to original sources
PubMed1993

The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight-year study of 155 patients.

Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarial overall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses > 10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.

Adolescent↗
PubMed1993

Autologous bone marrow transplantation for pediatric Hodgkin's disease: a case-matched comparison with adult patients by the European Bone Marrow Transplant Group Lymphoma Registry.

PURPOSE: We analyzed the outcome of autologous bone marrow transplantation (ABMT) in pediatric and adult patients with Hodgkin's disease (HD) by means of a case-controlled study. PATIENTS AND METHODS: Eighty-one pediatric HD patients who had undergone ABMT and who had been reported to the European Bone Marrow Transplant Group (EBMTG) Lymphoma Registry were compared with a case-matched group of 81 adult patients who had undergone the same procedure. The case-matching was performed following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. RESULTS: The PFS rate was not significantly different between the groups (39% for the pediatric group v 48% for the adult group). The overall relapse/progression rates for the groups were 52% and 40%, respectively. This was not a statistically significant difference and the sites of relapse were similar. There was no significant difference in the incidence or causes of procedure-related morbidity or mortality of the two groups. CONCLUSION: This study suggests that patients with pediatric HD have the same outcome at ABMT as their adult counterparts; however, long-term complications will need to be carefully monitored.

Adolescent↗
PubMed1992

Genome diversity at the serA-linked capsule locus in Escherichia coli.

Individual isolates of Escherichia coli synthesize one of more than 70 chemically distinct polysaccharides which form the capsule. In this article we review the genetics of capsule production in E. coli and highlight what this is beginning to reveal in terms of the genetic basis of the structural diversity of polysaccharides. The serA-linked capsule locus can take three different allelic forms. Two of these are associated with capsule genes and are themselves internally variant, whilst the third form has not so far been implicated in capsule biogenesis. Thus the serA-linked region of the E. coli genome is strikingly polymorphic.

Carbohydrate Dehydrogenases↗
PubMed1992

Species differences and interindividual variation in liver microsomal cytochrome P450 2A enzymes: effects on coumarin, dicumarol, and testosterone oxidation.

Antibody against purified CYP2A1 recognizes two rat liver microsomal P450 enzymes, CYP2A1 and CYP2A2, that catalyze the 7 alpha- and 15 alpha-hydroxylation of testosterone, respectively. In human liver microsomes, this antibody recognizes a single protein, namely CYP2A6, which catalyzes the 7-hydroxylation of coumarin. To examine species differences in CYP2A function, liver microsomes from nine mammalian species (rat, mouse, hamster, rabbit, guinea pig, cat, dog, cynomolgus monkey, and human) were tested for their ability to catalyze the 7 alpha- and 15 alpha-hydroxylation of testosterone and the 7-hydroxylation of coumarin. Antibody against rat CYP2A1 recognized one or more proteins in liver microsomes from all mammalian species examined. However, liver microsomes from cat, dog, cynomolgus monkey, and human catalyzed negligible rates of testosterone 7 alpha- and/or 15 alpha-hydroxylation, whereas rat and cat liver microsomes catalyzed negligible rates of coumarin 7-hydroxylation. Formation of 7-hydroxycoumarin accounted for a different proportion of the coumarin metabolites formed by liver microsomes from each of the various species examined. 7-Hydroxycoumarin was the major metabolite (greater than 70%) in human and monkey, but only a minor metabolite (less than 1%) in rat. The 7-hydroxylation of coumarin by human liver microsomes was catalyzed by a single, high-affinity enzyme (Km 0.2-0.6 microM), which was markedly inhibited (greater than 95%) by antibody against rat CYP2A1. The rate of coumarin 7-hydroxylation varied approximately 17-fold among liver microsomes from 22 human subjects. This variation was highly correlated (r2 = 0.956) with interindividual differences in the levels of CYP2A6, as determined by immunoblotting. These results indicate that CYP2A6 is largely or entirely responsible for catalyzing the 7-hydroxylation of coumarin in human liver microsomes. Treatment of monkeys with phenobarbital or dexamethasone increased coumarin 7-hydroxylase activity, whereas treatment with beta-naphthoflavone caused a slight decrease. These results suggest that environmental factors can increase or decrease CYP2A expression in cynomolgus monkeys, which implies that environmental factors may be responsible for the large variation in CYP2A6 levels in humans, although genetic factors may also be important. In contrast to rats and mice, the expression of CYP2A enzymes in cynomolgus monkeys and humans was not sexually differentiated. Despite their structural similarity to coumarin, the anticoagulants dicumarol and warfarin do not appear to be substrates for CYP2A6. The overall rate of dicumarol metabolism varied approximately 5-fold among the human liver microsomal samples, but this variation correlated poorly (r2 = 0.126) with the variation observed in CYP2A6 levels and coumarin 7-hydroxylase activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
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↗