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Biomedical subjects

F Reyes

Publications and source records attributed to F Reyes.

At least 55 records · Page 3Linked to original sources
PubMed1997

Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin's lymphoma: factors influencing chemotherapy administration. Groupe d'Etude des Lymphomes de l'Adulte.

The purpose of this study was to, assess the efficacy of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in the prevention of neutropenia and infection in patients receiving dose-intensive chemotherapy for non-Hodgkin's lymphoma (NHL). A second objective was to determine clinical predicators of delay to cytotoxic chemotherapy administration. One hundred-sixty two patients with intermediate- or high-grade NHL and at least one poor prognostic factor received a total of 4 cycles of the LNH-84-regimen every 2 weeks, with an open randomization to treatment with anthracyclines. Patients were randomized to receive subcutaneous lenograstim 5 micrograms/kg/day (n = 82) or placebo (n = 80) from day 6 to day 13 of each cycle. The incidence of severe neutropenia (absolute neutrophil count (ANC) < 0.5 x 10(9)/L) was reduced in the lenograstim group compared with placebo (52% vs 75%). A significant reduction (p < 0.001) in the median duration of ANC < 0.5 x 10(9)/L was also observed in patients treated with lenograstim during each cycle of chemotherapy (0-1 day vs 2-4 days in placebo recipients). Fever occurred in 66 patients in each treatment group. Thirty-four percent of placebo recipients had documented infections during ANC < 1.0 x 10(9)/L compared with 18.5% of lenograstim-treated patients (p < 0.05). Infections of > or = 2 severity were significantly less frequent (p = 0.001) among lenograstim recipients compared with placebo (25 vs 49). The most common adverse events among lenograstim recipients were headache, mild bone pain and injection site reactions. Although lenograstim significantly increased (p = 0.0001) relative dose intensity compared with placebo (93% vs 80%), no difference in CR rate (67% vs 71%) or 3-year survival (63% vs 55%) was observed. The results of this study suggest that patients treated with a chemotherapy regimen that induces severe neutropenia can benefit from treatment with lenograstim. Furthermore, lenograstim permits treatment to be delivered at full dose intensity at 2 week intervals, even in patients with bone marrow involvement, and may permit further dose escalation of the chemotherapeutic regimen used.

Adolescent↗
PubMed1997

Development of ELISA to estimate thymosin alpha1, the N terminus of prothymosin alpha, in human tumors.

We reported that tumor content of prothymosin alpha (ProT alpha) is a proliferation index of human breast tumors that might be used to identify patients at high risk for distant metastasis (Dominguez et al., Eur J Cancer 1993; 29A:893-7). In that study ProT alpha concentrations were measured by a RIA; here we present an alternative nonisotopic assay that could be used in a standard clinical laboratory. Main features of the ELISA are: (a) A recombinant fusion protein glutathione S-transferase (GST)-human ProT alpha was used to coat the microtiter plates; (b) we used a polyclonal antiserum raised in rabbits that detects thymosin alpha1, the NH2-terminal fragment of ProT alpha; (c) it is as sensitive as the RIA; (d) it is faster than the RIA. ProT alpha concentrations in various human tumors (skin, esophagus, colorectal, and breast) as assessed by ELISA were comparable with, although twofold greater than, the values previously estimated by RIA.

Antibody Specificity↗
PubMed1996

Molecular and Regulatory Properties of the Nitrate Reducing Systems of Rhodobacter

Phototrophic bacteria of the genus Rhodobacter possess several forms of nitrate reductase including assimilatory and dissimilatory enzymes. Assimilatory nitrate reductase from Rhodobacter capsulatus E1F1 is cytoplasmic, it uses NADH as the physiological electron donor and reduced viologens as artificial electron donors, and it is coupled to an ammonium-producing nitrite reductase. Nitrate reductase induction requires a high C/N balance and the presence of nitrate, nitrite, or nitroarenes. A periplasmic 47-kDa protein facilitates nitrate uptake, thus increasing nitrate reductase activity. Two types of dissimilatory nitrate reductases have been found in strains from Rhodobacter sphaeroides. One of them is coupled to a complete denitrifying pathway, and the other is a periplasmic protein whose physiological role seems to be the dissipation of excess reducing power, thus improving photoanaerobic growth. Periplasmic nitrate reductase does not use NADH as the physiological electron donor and is a 100-kDa heterodimeric hemoprotein that receives electrons through an electron transport chain spanning the plasma membrane. This nitrate reductase is regulated neither by the intracellular C/N balance nor by O2 pressure. The enzyme also exhibits chlorate reductase activity, and both reaction products, nitrite and chlorite, are released almost stoichiometrically into the medium; this accounts for the high resistance to chlorate or nitrite exhibited by this bacterium. Nitrate reductases from both strains seem to be coded by genes located on megaplasmids.

Journal Article↗
PubMed1996

Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen. Groupe d'Etudes des Lymphomes de l'Adulte.

PURPOSE: Results of a multidrug chemotherapy regimen consisting of cyclophosphamide, pirarubicin, teniposide, and prednisolone (CTVP) plus subcutaneous granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS: Between January and December 1992, 46 previously untreated patients older than 69 years with intermediate- and high-grade NHL received cyclophosphamide 750 mg/m2, teniposide 75 mg/m2, pirarubicin 50 mg/m2 day 1, and prednisolone 40 mg/m2 days 1 to 3. G-CSF, 5 micrograms/kg/day, was administered from day 4 up to day 14 or when the absolute neutrophil count reached 5 x 10(9)/l. Six cycles were scheduled every 3 weeks. RESULTS: Grade 3 or grade 4 neutropenia complicated 22% and 26% of chemotherapy cycles, respectively. Fever or/and clinical infection were observed in 4% and 14% of cycles. One toxic death related to a septic shock occurred. Eight cycles (4%) were delayed with a median duration of 7 days. Administered median dose intensity was 93.5%. Objective response rate was 74% and 46% of the patients achieved a complete response. The 2-year overall survival and event-free survival rates were 47% and 28%. CONCLUSION: In comparison with a previous group of patients treated with CTVP, G-CSF allows delivery of chemotherapy with a reduced neutropenia-induced morbidity in an outpatient setting in elderly patients with aggressive NHL without modifying response rate or survival.

Aged↗
PubMed1996

Isolation of periplasmic nitrate reductase genes from Rhodobacter sphaeroides DSM 158: structural and functional differences among prokaryotic nitrate reductases.

The phototrophic bacterium Rhodobacter sphaeroides DSM 158 has a periplasmic nitrate reductase which is induced by nitrate and it is not repressed by ammonium or oxygen. In a Tn5 mutant lacking nitrate reductase activity, transposon insertion is localized in a 1.2 kb EcoRI fragment. A 0.6 kb BamHI-EcoRI segment of this region was used as a probe to isolate, from the wild-type strain, a 6.8 kb PstI fragment carrying the putative genes coding for the periplasmic nitrate reductase. In vivo protein expression and DNA sequence analysis reveal the presence in this region of three genes, napABC, probably organized in an operon. These genes are required for nitrate reduction, as deduced by mutational and complementation studies. The napA gene codes for a protein with a high homology to the periplasmic nitrate reductase from Alcaligenes eutrophus and, to a lesser extent, to other prokaryotic nitrate reductases and molybdenum-containing enzymes. The napB gene product has two haem c-binding sites and shows a high homology with the cytochrome c-type subunit of the periplasmic nitrate reductase from A. eutrophus. NAPA and NAPB proteins appear to be translated with signal peptides of 29 and 24 residues, respectively, indicating that mature proteins are located in the periplasm. The napC gene codes for a 25 kDa protein with a transmembrane sequence of 17 hydrophobic residues. NAPC has four haem c-binding sites and is homologous to the membrane-bound c-type cytochromes encoded by Pseudomonas stutzeri nirT and Escherichia coli torC genes. The phenotypes of defined insertion mutants constructed for each gene also indicate that periplasmic nitrate reductase from R. sphaeroides DSM 158 is a dimeric complex of a 90 kDa catalytic subunit (NAPA) and a 15 kDa cytochrome c (NAPB), which receives electrons from a membrane-anchored tetrahaem protein (NAPC), thus allowing electron flow between membrane and periplasm. This nitrate-reducing system differs from the assimilatory and respiratory bacterial nitrate reductases at the level of cellular localization, regulatory properties, biochemical characteristics and gene organization.

Amino Acid Sequence↗
PubMed1996

Is the small non-cleaved-cell lymphoma histologic subtype a poor prognostic factor in adult patients? A case-controlled analysis. The Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To study the prognostic significance of the small non-cleaved-cell lymphoma (SNCCL) histologic subtype, we compared the outcome of adult patients with SNCCL with that of patients with aggressive lymphoma other than SNCCL by means of two case-controlled studies. PATIENTS AND METHODS: We analyzed the results of the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen used as a reference scheme in our cooperative study group (Groupe d'Etude des Lymphomes de l'Adult [GELA]) in 52 adult SNCCL patients with no bone marrow (BM) or CNS involvement. Forty-five SNCCL patients younger than 60 years could be compared with two separate case-matched groups of patients with aggressive lymphoma other than SNCCL undergoing the same therapeutic regimen. In the first case-controlled study, matching ensured identity of each risk factor of the age-adjusted International Index (ie, Ann Arbor stage, performance status, and lactate dehydrogenase [LDH] level); in the second study, matching was performed according to the number of presenting risk factors (zero, one, two, or three), regardless of their nature. RESULTS: The 5-year overall survival rates were not significantly different between SNCCL and control patients in both case-controlled studies: 48% versus 51% in the first study, and 48% versus 55% in the second study. CONCLUSION: These results support the thesis that in patients with no bone marrow or CNS involvement, the SNCCL histologic subtype does not confer a prognosis worse than that of other aggressive lymphoma.

Adolescent↗
PubMed1996

[Pleural exudate as presentation of constrictive pericarditis].

An exudative pleural effusion is a very infrequent form of presentation of constrictive pericarditis, and it can induce diagnostic difficulties. We present a 71 year-old woman with a pleural effusion attributed to be due to congestive heart failure which does not respond to the treatment. The pleural fluid had biochemical characteristics of an exudate. The echocardiographic study showed severe constrictive pericarditis, and after the pericardectomy the pleural effusion completely resolved. The diagnostic suspicion of constrictive pericarditis in cases of exudative pleural effusion is of special interest because an specific and effective treatment is available.

Aged↗
PubMed1995

Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma.

Intensive therapy, mainly with purged autologous bone marrow transplantation (ABMT), has been proposed in recent years as consolidation treatment in young patients with follicular lymphoma. Reported experience with transplantation of peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and the therapeutic efficacy of intensive therapy followed by unpurged autologous PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular lymphoma. Twelve patients were in first partial remission (PR), 34 were in second partial or complete remission (CR), and 14 were in subsequent progression. At the time of the procedure, 39 patients (65%) had persistent bone marrow involvement, 49 patients (82%) were in PR, and 16 patients had presented with a histologic transformation (HT). PBPC were collected after chemotherapy followed by granulocyte (G) colony-stimulating factor (CSF) or granulocyte-macrophage (GM)-CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen), or cyclophosphamide with or without etoposide plus total body irradiation (46 patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L was 13 days. There were five treatment-related deaths, with four being associated with a delayed engraftment and all occurring in patients in third or subsequent progression. At a median follow-up of 21 months, 48 patients were still alive, 18 relapsed, and seven died of lymphomas progression. Estimated 2-year overall survival (OS) and failure-free survival (FFS) rates were 86% and 53%, respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome. Patients with HT tended to have a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate of engraftment failure, the poor FFS observed in heavily pretreated patients suggests that intensive therapy should be performed early in the course of the disease. Given the high percentage of patients intensified in PR with residual bone marrow involvement, our results are comparable with those achieved with ABMT published to date. Prospective trials are warranted to compare this strategy with standard therapy in patients with relapsing or PR follicular lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Gibberellin biosynthesis in gib mutants of Gibberella fujikuroi.

The Ascomycete Gibberella fujikuroi synthesizes gibberellins, fujenal, carotenoids, and other terpenoids. Twelve gib mutants, isolated through the modified gibberellin fluorescence of their culture media, were subjected to chemical and biochemical analyses. Two mutants were specifically defective in the hydroxylation of carbon 13; their total gibberellin production was normal, but their main gibberellin was GA7 instead of GA3. Four mutants were blocked in the early reactions between geranylgeranyl pyrophosphate and 7-hydroxy-kaurenoic acid; two of them could not synthesize kaurene and another one was blocked in several oxidative steps. Six mutants had partial defects in early reactions, leading to the production of one-fifth to one-third of the wild type amounts of gibberellins and fujenal. Two of these produced considerable amounts of kaurenolides due to a defect in the conversion of kaurenoic acid to 7-hydroxykaurenoic acid. Another one produced no carotenoids, but attempts to isolate mutants of reactions shared by the carotenoid and gibberellin pathways failed. The gib mutations did not modify the ability of the fungus to live as a saprophyte.

Gibberella↗
PubMed1995

Purification of a heat-stable chitin deacetylase from Aspergillus nidulans and its role in cell wall degradation.

An extracellular chitin deacetylase activity has been purified to homogeneity from autolyzed cultures of Aspergillus nidulans. This enzyme is an acidic glycoprotein with a pI of 2.75 and a 28% (wt/wt) carbohydrate content. The apparent M(r) of the enzyme estimated by SDS/PAGE and Superose 12 (f.p.l.c.) was around 27,000. The enzyme had an optimum pH at 7.0 and was stable in the pH range 4.0-7.5. Its optimum temperature of reaction was 50 degrees C, and it was stable from 30 degrees to 100 degrees C after 1 h of preincubation. The enzyme hydrolyzed glycol chitin and oligomers of N-acetylglucosamine and to a lesser extent chitin, colloidal chitin, carboxymethylchitin, and an alpha-1-->3, 1-->6-N-acetylgalactosamine-galactan among other substances with amido groups, but the enzyme did not hydrolyze peptide bonds. The role of this enzyme could be deacetylation of chitin oligosaccharides during autolysis, after action of endochitinase on cell walls.

Amidohydrolases↗
PubMed1995

Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression.

PURPOSE: The treatment of low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma with prominent gastric expression is controversial. Total gastrectomy has been proposed, but is associated with significant morbidity. The aim of this monocentric study was to assess the efficacy of continuous oral chemotherapy with a single alkylating agent. PATIENTS AND METHODS: Twenty-four consecutive patients, 13 men and 11 women, were studied. Their mean age was 51 years (range, 22 to 79). Low-grade B-cell MALT lymphoma was diagnosed by histologic and immunohistologic examination of endoscopic biopsies. Seventeen patients had stage I disease and seven stage IV disease, with lung and gastric involvement. Two of these seven patients also had bone marrow involvement. The alkylating agent (cyclophosphamide or chlorambucil) was administered orally and daily for periods of 12 to 24 months. RESULTS: The median follow-up time was 45 months (range, 14 months to 14 years). Complete remission was obtained in 18 patients (75%) after a median treatment duration of 12 months. Five patients relapsed; two of them were successfully re-treated, and one died of MALT lymphoma that had transformed into large-cell lymphoma. Chemotherapy was stopped after 24 months for six patients who only achieved a partial remission; two of them required further treatment for progressive disease (surgery for a small-bowel localization in one case and cyclophosphamide rechallenge in the other). Nine patients had neutropenia that required a reduced chemotherapy dosage. CONCLUSION: In low-grade MALT lymphoma with prominent gastric expression, continuous monochemotherapy may constitute an efficient alternative to gastrectomy, regardless of disease stage.

Administration, Oral↗
PubMed1994

Comparison of autografting using mobilized peripheral blood stem cells with and without granulocyte colony-stimulating factor in malignant lymphomas.

Peripheral blood is becoming widely used as the only source of hematopoietic stem cells to support marrow ablative therapy in advanced lymphoma. We report data from 23 patients with high risk non-Hodgkin's (n = 19) and Hodgkin's lymphoma (n = 4) who underwent high-dose therapy with mobilized peripheral blood stem cell (PBSC) autografting. Peripheral blood progenitors were recruited using cytotoxic chemotherapy followed by administration of recombinant human G-CSF (filgrastim 5 micrograms/kg/day). Myeloablative treatment with autologous PBSC support was administrated to the 23 patients and followed by G-CSF at the same dose after cell reinjection. Hematopoietic reconstitution was compared with a control group of lymphoma patients who received chemotherapy mobilized PBSC transplantation but without G-CSF prior to leukaphereses or after high-dose therapy. The median time to neutrophil recovery > 0.5 x 10(9)/l was significantly shorter in study patients compared with the control patients (10 days and 17 days respectively) (p < 0.05). Self sustaining platelet counts of > 50 x 10(9)/l occurred at a median time of 17 days in both groups. Stable hemopoietic reconstitution was seen with a follow-up of 6 months after PBSC transplantation. In addition, a significant relationship was observed between the number of CFU-GM infused and the time to platelet recovery. We confirm the effectiveness of G-CSF given prior to PBSC harvesting in generating high numbers of progenitor cells. Hematologic recovery following high-dose therapy was improved after PBSC rescue and G-CSF.

Adolescent↗
PubMed1993

Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

BACKGROUND: Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin's lymphoma. In 1986, we designed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin's lymphoma. METHODS: The trial involved 242 patients with advanced low-grade follicular non-Hodgkin's lymphoma selected on the basis of clinical, radiographic, and biologic criteria. All patients were treated with a regimen consisting of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP), given monthly for six cycles and then every two months for one year. After randomization, 123 patients also received interferon alfa-2b at a dosage of 5 million units three times weekly for 18 months. The remaining 119 patients received chemotherapy alone. RESULTS: As compared with the patients treated with CHVP only, the patients treated with CHVP plus interferon alfa had a higher overall rate of response (85 percent vs. 69 percent, P = 0.006), a longer median event-free survival (34 months vs. 19 months, P < 0.001), and a higher rate of survival at 3 years (86 percent vs. 69 percent, P = 0.02). Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone. There were no treatment-related deaths. Interferon alfa had to be stopped because of toxic effects (fatigue and hepatitis) in 13 patients (11 percent). CONCLUSIONS: The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response, event-free survival, and overall survival in patients with advanced follicular non-Hodgkin's lymphoma, without serious toxicity, although some patients were unable to tolerate the side effects.

Aged↗
PubMed1993

Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus.

Recent evidence has shown that most nasal lymphomas (NL) are associated with a T-cell phenotype and are thus called nasal T-cell lymphomas (NTCL), but little information is available about the T-cell receptor (TCR) expression. The presence of Epstein-Barr virus (EBV) genome has been recently reported in NTCL in Oriental populations in which NL and EBV-associated tumors are more common and in occasional Occidental cases. This prompted us to investigate lymphoma biopsies from 7 non-Oriental patients with NTCL for the expression of natural killer (NK) and T-cell antigens, including TCR proteins, for the presence of EBV-encoded latent membrane protein (LMP) using immunohistochemistry and for the presence of EBV DNA and Epstein-Barr early region (EBER) RNA using in situ hybridization (ISH). Six cases displayed a CD3-, TCR alpha beta-, TCR gamma delta-, CD2+, CD7+, CD5-, CD4-, CD8-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas (PTCL) with extensive loss of T-cell antigens and expression of the NK-cell (CD56) antigen or, alternatively, NK-cell neoplasias. The remaining case was a gamma delta PTCL, as shown by the CD3+, TCR gamma delta+ phenotype and the biallelic gamma and delta TCR gene rearrangements. Using ISH, EBER RNA transcripts were detected in tumor cells in all cases and EBV DNA was shown in the 6 tested cases. In all cases, tumor cells expressed LMP. These findings support the concept that NTCL constitute a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibit an unusual TCR "silent" CD56+ or TCR gamma delta+ phenotype and harbor the EBV. In view of the LMP transforming potential, these data suggest that EBV may play a role in the pathogenesis of NTCL.

Adolescent↗