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J Buesa

Publications and source records attributed to J Buesa.

At least 19 recordsLinked to original sources
PubMed2007

Inhibitory activities of bovine macromolecular whey proteins on rotavirus infections in vitro and in vivo.

Rotavirus is a major cause of infantile viral gastroenteritis and can lead to severe and sometimes lethal dehydration. Previous studies have shown that breast-fed children are better protected against symptomatic infections, and that the milk fat globule protein lactadherin might be at least partly responsible for this effect. In vitro studies have shown that human lactadherin, in contrast to the bovine ortholog, could inhibit rotavirus infectivity, and that bovine MUC1 and a commercially available bovine macromolecular whey protein (MMWP) fraction proved to be effective. The present work describes the versatility of MMWP against the infection of 2 human intestinal cell lines (Caco-2 and FHs 74 Int) by 4 different rotavirus strains (Wa, RRV, YM, RF). Isolation of a protein fraction (CM3Q3) from MMWP that effectively inhibits rotavirus infectivity in vitro is documented. Purification was achieved by monitoring the rotaviral inhibitory activity in fractions obtained from 2 consecutive steps of ion-exchange chromatography. The major component of CM3Q3 was shown to be bovine IgG, and the attenuating capacity of this fraction is most properly linked to this component. The capacity of MMWP, MUC1, lactadherin, and the CM3Q3 fraction to inhibit the infectivity of the murine EMcN rotavirus strain was analyzed in adult BALB/c mice by using 2 different amounts of virus (10 and 100 times more than 50% the viral shedding doses). Only CM3Q3 was able to significantly affect the shedding of rotavirus in the stools of experimentally infected mice when the high viral dose was given. Detection of rotavirus-specific serum antibodies showed that the high dose infected all groups of mice. Experiments with the low dose of virus implied that all the tested milk proteins could affect the viral shedding in stools; in addition, use of MUC1, MMWP, and CM3Q3 prevented the appearance of serum viral antibodies. The advantages of using bovine immunoglobulins to induce passive immunity against rotavirus have been substantially investigated, although studies have mainly focused on the use of derivatives from immunized cows, especially colostrum. This report associates considerable activity against rotavirus infectivity with an ordinary whey product, suggesting that there might be alternatives to colostral-derived products.

Animals↗
PubMed2005

An outbreak of food poisoning due to a genogroup I norovirus.

Norovirus infection is associated with approximately 90% of epidemic non-bacterial acute gastroenteritis. The objective of this study is to describe an outbreak of norovirus genogroup I gastroenteritis which affected workers in a hospital and was attributed to food prepared by an infected food handler. Forty cases were detected, of whom 80% were interviewed. The index case was the cook employed in the hospital cafeteria. The following symptoms were observed: abdominal pain in 90.6%, vomiting in 71.9%, diarrhoea in 71.9%, general indisposition in 62.5%, headaches in 53.1% and fever in 32.4% of cases. The initial symptoms were abdominal pain in 37% and vomiting in 28%. Of the 14 samples analysed by RT-PCR, 12 (86%) were positive for a genogroup I norovirus. After sequencing the strain was identified as genotype Desert Shield. Many of the foodstuffs consumed were made by hand, favouring transmission from the index case to the cafeteria users.

Adult↗
PubMed2002

Molecular epidemiology of caliciviruses causing outbreaks and sporadic cases of acute gastroenteritis in Spain.

The molecular epidemiology of human caliciviruses (HuCVs) causing sporadic cases and outbreaks of acute gastroenteritis around eastern Spain (Catalonia and the Valencian Community) was studied by reverse transcription-PCR (RT-PCR) and by sequencing part of the RNA polymerase gene in open reading frame 1. HuCVs were detected in 44 of 310 stool specimens (14.19%) negative for other enteric pathogens obtained from children with acute gastroenteritis. Norwalk-like viruses (NLVs) were the most common cause of the gastroenteritis outbreaks investigated here. They were detected in 14 out of 25 (56%) outbreaks with an identified pathogen. Genotypes producing both sporadic cases and outbreaks were diverse, with a predominance of GGII strains related to genotypes Melksham and Lordsdale. Five strains clustered with a "new variant" designated GGIIb, which was detected circulating throughout quite a few European countries in the years 2000 and 2001. The emergence mechanism of these strains might be the occurrence of intertypic recombinations between different viruses. The nucleotide sequence of part of the capsid gene (ORF2) from three of these strains demonstrated their relationship with Mexico virus.

Acute Disease↗
PubMed2001

Secretion of the rotavirus VP8* protein in Lactococcus lactis.

Secretion of the VP8* subunit of the VP4 capsid protein of rotavirus by Lactococcus lactis has been achieved. For this purpose, a secretion vector has been constructed with the lactococcal signal sequence AL9 and the VP8*-encoding gene fragment. The amount of VP8* secreted by L. lactis in the culture supernatant was quantified and visualised by Western blot. Furthermore, it was shown to retain its hemagglutination capability, indicating that the conformation of the secreted peptide may be retaining its biological activity.

Amino Acid Sequence↗
PubMed2001

A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma.

The aim of this study was to examine the strategy, feasibility and outcome of neo-adjuvant chemotherapy, with doxorubicin and ifosfamide, in adult patients with 'high-risk' soft-tissue sarcomas. Patients with 'high-risk' soft-tissue sarcomas, defined as tumours > or =8 cm of any grade, or grade II/III tumours <8 cm, or grade II/III locally recurrent tumours, or grade II/III tumours with inadequate surgery performed in the previous 6 weeks and therefore requiring further surgery, were randomised between either surgery alone or three cycles of 3-weekly doxorubicin 50 mg/m(2) intravenous (i.v.) bolus and ifosfamide 5 g/m(2) (24 h infusion) before surgery. The type of surgery had to be planned at randomisation. Tumours were to be amenable to surgery by amputation, compartmental resection, wide or marginal excision. If chemotherapy was given, surgery had to be performed within 21 days after the last chemotherapy. Patients received postoperative radiotherapy in cases of marginal surgery, microscopically incomplete resection and no further possibility for surgery, and in cases of surgery because of local recurrence. 150 patients were entered into the study and 134 were eligible, 67 in each arm. The most frequent side-effects of chemotherapy were alopecia, nausea and vomiting (95%), and leucocytopenia (32%). One patient died of neutropenic fever after the first cycle of chemotherapy. Chemotherapy did not interfere with planned surgery and did not affect postoperative wound healing. Limb-salvage was achieved in 88%, amputation was necessary in 12% (all according to the plan at randomisation). The trial was closed after completion of phase II, since accrual was too slow to justify expanding the study into the scheduled phase III study. At a median follow-up of 7.3 years, the 5 year disease-free survival is estimated at 52% for the no chemotherapy and 56% for the chemotherapy arm (standard error: 7%) (P=0.3548). The 5 year overall survival for both arms is 64 and 65%, respectively (standard error 7%) (P=0.2204). Neo-adjuvant-chemotherapy with doxorubicin and ifosfamide at these doses and with this schedule was feasible and did not compromise subsequent treatment, surgery with or without radiotherapy. Although not powered to draw definitive conclusions on benefit, but with an at least 7 year median follow-up, the results render it less likely that major survival benefits will be achieved with this type of chemotherapy.

Adolescent↗
PubMed2000

VP7 and VP4 genotypes among rotavirus strains recovered from children with gastroenteritis over a 3-year period in Valencia, Spain.

Between September 1996 and May 1999, the incidence and distribution of the main human rotavirus G genotypes (VP7 associated: G1-G4) and P genotypes (VP4 associated: P[8], P[4], P[6] and P[9]) among children with rotavirus gastroenteritis were determined using reverse transcription and polymerase chain reaction (RT-PCR)-based genotyping methods. From a total of 145 rotavirus strains examined, we identified the G type in 131 (90.3%) and the P type in 127 (87.5%) of the samples. An overall predominance of genotypes P[8] G1 (42.7%) and P[8] G4 (32.4%) was found during the period of study, with much lower incidence of genotypes P[4] G2 (5.5%) and P[8] G3 (2%). P[6] and P[9] types were not detected, neither were unusual combinations of P and G types. A significant genotypic shift was observed: whereas P[8] G4 was the most prevalent genotype during the first year of the study (60%), the genotype P[8] G1 gradually increased to account for 62.3% of the strains analysed in the following winter season. Mixed G types revealing dual infections G1/G4 and G3/G4 were found at low frequency (2%).

Acute Disease↗
PubMed2000

Homotypic protection against rotavirus-induced diarrhea in infant mice breast-fed by dams immunized with the recombinant VP8* subunit of the VP4 capsid protein.

The outer capsid proteins VP4 and VP7 induce neutralizing antibody against rotavirus. We have investigated in a mouse model the protection mediated by immunization with VP8*, the amino-terminal tryptic fragment of VP4. BALB/c female mice immunized with simian rotavirus SA11 VP6 and VP8* proteins expressed in Escherichia coli were mated with seronegative males. Litters were orally challenged with the SA11 strain (P5B[2], G3) or with the murine rotavirus strain EDIM (P10[16], G3) to verify the degree of protection against diarrhea induced in the newborns. Only those pups born to dams immunized with VP8* did not develop diarrhea after having been orally challenged with the SA11 strain. Pups born to naive dams but foster nursed by VP8*-immunized dams did not develop diarrhea after having been orally infected with the SA11 strain, but they suffered diarrhea when challenged with the EDIM strain. These results support the concepts that (1) VP8* is a highly immunogenic polypeptide that induces effective homotypic protection against disease in pups born to dams immunized with this antigen and (2) in newborn mice the protection against disease is mediated by neutralizing secretory antibodies present in the milk rather than by serum antibodies transferred through the placenta to the offspring.

Animals↗
PubMed2000

Randomized phase II study of docetaxel versus doxorubicin in first- and second-line chemotherapy for locally advanced or metastatic soft tissue sarcomas in adults: a study of the european organization for research and treatment of cancer soft tissue and bone sarcoma group.

PURPOSE: To assess antitumor response and time to progression (TTP) with docetaxel compared with doxorubicin in first-line treatment of advanced and/or metastatic soft tissue sarcoma. PATIENTS AND METHODS: Patients with measurable soft tissue sarcoma lesions and adequate bone marrow, liver, and renal function were entered onto the study. They were randomized to either docetaxel 100 mg/m(2) given as a 1-hour intravenous infusion every 3 weeks or doxorubicin 75 mg/m(2) given as a bolus injection every 3 weeks. A maximum of seven cycles of treatment were scheduled. The study was designed as a randomized phase III study evaluating TTP by log-rank model. There was a clause for premature closure of the trial if fewer than five responses were observed among the first 25 assessable patients in the docetaxel treatment arm. RESULTS: Eighty-six patients were entered onto the study; 85 were assessable for toxicity and 83 for response. The rate of severe granulocytopenia was not significantly different between the two arms. Nausea (P =.001), vomiting (P <.001), and stomatitis (P =.005) were more common with doxorubicin therapy, whereas neurotoxicity was more frequent with docetaxel treatment. The response rate to doxorubicin therapy was 30% (95% confidence interval, 17% to 46%), whereas no responses to docetaxel therapy were seen (P <.001). In view of this, the trial was closed prematurely and the phase III study part was not conducted. CONCLUSION: Docetaxel is inactive in soft tissue sarcomas and cannot be recommended for further use in treatment of this disease.

Adult↗
PubMed1999

Rotavirus-specific cytotoxic T lymphocytes recognize overlapping epitopes in the amino-terminal region of the VP7 glycoprotein.

Rotavirus-specific cytotoxic T lymphocytes (CTL) play an important role in the resolution of rotavirus infection. The outer capsid glycoprotein, VP7, elicits a class I MHC-restricted CTL response. Vaccinia virus recombinants expressing the VP7 genes from simian rotavirus SA11 (serotype G3) and from the RF strain of bovine rotavirus (serotype G6) were used to analyze the CTL activity to this antigen in BALB/c (H-2(d)) and C57BL/6 (H-2(b)) mice neonatally infected with homologous and heterologous rotaviruses. A vaccinia virus recombinant expressing the first amino-terminal 88 amino acids of VP7 was constructed and used to search for cross-reactive CTL against this region of the protein. By using synthetic Kb, Db, and Kd motif-fitting peptides two overlapping CTL epitopes have been identified located in the first hydrophobic domain (H1) of VP7. Splenocytes obtained from rotavirus SA11-infected C57BL/6 mice induced the strongest CTL response against target cells sensitized with a peptide containing a Kb-restricted CTL epitope (amino acids 8-16). A second Kd-restricted epitope (residues 5-13) was recognized by splenocytes derived from rotavirus-infected BALB/c mice. These findings reveal the existence of CTL epitopes in the H1 signal sequence of the VP7 glycoprotein that coexist with a CTL epitope (residues 31-40) previously described within the H2 region.

Animals↗
PubMed1999

Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study.

PURPOSE: A total of 2,185 patients with advanced soft tissue sarcomas who had been treated in seven clinical trials investigating the use of doxorubicin- or epirubicin-containing regimens as first-line chemotherapy were studied in this prognostic-factor analysis. PATIENTS AND METHODS: Overall survival time (median, 51 weeks) and response to chemotherapy (26% complete response or partial response) were the two end points. The cofactors were sex; age; performance status; prior therapies; the presence of locoregional or recurrent disease; lung, liver, and bone metastases at the time of entry onto the trial; long time period between the initial diagnosis of sarcoma and entry onto the study; and histologic type and grade. RESULTS: Univariate analyses showed (a) a significant, favorable influence of good performance status, young age, and absence of liver metastases on both survival time and response rate, (b) a significant, favorable influence of low histopathologic disease grade on survival time, despite a significantly lower response rate, (c) increased survival time for patients with a long time period between the initial diagnosis of sarcoma and entry onto the study, despite equivalent response rates, and (d) increased survival time with liposarcoma or synovial sarcoma, a decreased survival time with malignant fibrous histiocytoma, a lower response rate with leiomyosarcoma, and a higher response rate with liposarcoma (P < .05 for all log-rank and chi2 tests). The Cox model selected good performance status (P < .0001), absence of liver metastases (P = .0001), low histopathologic grade (P = .0002), long time lapse since initial diagnosis (P = .0004), and young age (P = .0045) as favorable prognostic factors of survival time. The logistic model selected absence of liver metastases (P < .0001), young age (P = .0024), high histopathologic grade (P = .0051), and liposarcoma (P = .0065) as favorable prognostic factors of response rate. CONCLUSION: This analysis demonstrates that for advanced soft tissue sarcoma, response to chemotherapy is not predicted by the same factors as is overall survival time. This needs to be taken into account in the interpretation of trials assessing the value of new agents for this disease on the basis of response to treatment.

Adult↗
PubMed1998

Viral proteins VP2, VP6, and NSP2 are strongly precipitated by serum and fecal antibodies from children with rotavirus symptomatic infection.

Rotavirus-specific IgA has been correlated with immune protection against rotavirus reinfection and symptomatic disease. Systemic and mucosal antibody responses were determined by an enzyme-linked immunosorbent assay in 11 infants with severe rotavirus gastroenteritis. Geometric mean titers of antirotavirus serum IgG and IgA antibodies were significantly higher during the convalescence of the disease (P < 0.001 vs. acute-phase titers). Rotavirus-specific fecal sIgA antibodies increased 4 times during the convalescence in 9 (81.8%) children (P < 0.001). The serum IgG and IgA antibody and fecal sIgA antibody responses to individual rotavirus polypeptides were characterized by radioimmunoprecipitation assay (RIPA) using Staphylococcus aureus protein A and the lectin jacalin to precipitate IgG- and IgA-immune complexes, respectively. The main IgG response was directed toward the structural viral proteins VP2, VP4, and VP6 and toward the nonstructural protein NSP2. Serum IgA reactivity was detected by RIPA in all serum samples, with major responses to VP2, VP6, and NSP2. Interestingly, fecal sIgA in convalescent samples reacted strongly toward NSP2 and VP6. These data reinforce the antigenic importance of rotaviral proteins other than VP4 and VP7, such as VP2, VP6, and NSP2, as main targets in the immune response to rotavirus.

Antibodies, Viral↗
PubMed1998

High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas. A study of the EORTC soft tissue and bone sarcoma group.

The activity and toxicity of single-agent standard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin. A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received (A) doxorubicin 75 mg m(-2) on day 1 (112 patients), (B) epirubicin 150 mg m(-2) on day 1 (111 patients) or (C) epirubicin 50 mg m(-2) day(-1) on days 1, 2 and 3 (111 patients); all given as bolus injection at 3-week intervals. A median of four treatment cycles was given. Median age was 52 years (19-70 years) and performance score 1 (0-2). Of 314 evaluable patients, 45 (14%) had an objective tumour response (eight complete response, 35 partial response). There were no differences among the three groups. Median time to progression for groups A, B and C was 16, 14 and 12 weeks, and median survival 45, 47 and 45 weeks respectively. Neither progression-free (P = 0.93) nor overall survival (P = 0.89) differed among the three groups. After the first cycle of therapy, two patients died of infection and one owing to cardiovascular disease, all on epirubicin. Both dose schedules of epirubicin were more myelotoxic than doxorubicin. Cardiotoxicity (> or = grade 3) occurred in 1%, 0% and 2% respectively. Regardless of the schedule, high-dose epirubicin is not a preferred alternative to standard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas.

Adult↗
PubMed1998

[Virus-specific serum and fecal antibodies response in children with acute rotavirus gastroenteritis].

BACKGROUND: The analysis of the immune response to rotavirus infection and the characterization of the viral antigens recognized by specific antibodies are of great concern in evaluating the protection against rotavirus. MATERIAL AND METHODS: The levels of rotavirus-specific fecal (sIgA) and serum antibodies (IgM, IgG and IgA) were evaluated by ELISA in 25 children with acute gastroenteritis for rotavirus, in 11 of them during the acute and convalescent phases. The specificity of serum antibodies to viral polypeptides was characterized by immunoblotting. RESULTS: Serum IgM antibodies with a geometric mean titer (GMT) of 1/3,973 were the predominant antibodies detected during the acute phase. In comparison, IgG and IgA serum antibodies and sIgA coproantibodies levels were higher in the convalescent phase (GMT = 1/5,799, 1/257 and 1/137 respectively). Significant differences were observed for all the isotypes of immunoglobulins evaluated during the infection and in the convalescence (p < 0.01). Rotavirus-specific serum antibodies recognized mainly the structural VP6, VP7 and VP3/VP4 proteins. Other polypeptides also detected were VP1, VP5 and the non-structural NS34 protein. CONCLUSIONS: Rotavirus infection produce an intense humoral immune response both in serum and in the gut. Specific antibodies react against structural proteins of the internal (VP6) and external (VP7) capsids of rotavirus.

Antibodies, Viral↗
PubMed1997

[Corneal ulcer caused by Nocardia asteroides after penetrating keratoplasty].

We report the case of a 43-years-old patient, to whom a corneal transplantation was made because he presented a Salzmann nodular degeneration in his left eye. The patient was observed every week and his development during the following months was good. Nine weeks later he was attended at the emergency room of the hospital, with an intensive secretion and partial loss of vision in the operated eye. It was detected a peripheral ulcer of a diffused borders with a loss of epithelium and anterior stroma in the superior temporal part of the cornea. Five days later, the microbiological cultures confirmed the presence of Nocardia asteroides. In spite of the initial good evolution of the ulcer treated topically with a 20% sulfacetamide and trimetoprim-sulfadiacine p.o., the graft ended unsuccessfully.

Adult↗
PubMed1995

Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

PURPOSE: The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas. PATIENTS AND METHODS: This was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C). RESULTS: The overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm A, 51 weeks on arm B, and 55 weeks on arm C). The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens. Cardiotoxicity was also more frequent in this arm, but other toxicities were similar. CONCLUSION: In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

PURPOSE: To evaluate the benefit of adjuvant chemotherapy in adult patients with soft tissue sarcomas. The principal end points were freedom from local recurrence and/or metastases and overall survival. PATIENTS AND METHODS: Between January 1977 and June 1988, 468 patients entered this randomized study and 317 were considered eligible. Following complete surgical resection with or without radiotherapy, outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses was compared with that in 172 control patients. RESULTS: With a median follow-up duration of 80 months (range, 39 to 165), actuarial percentage survival figures at 7 years were compared. Relapse-free survival rates were higher for CYVADIC, 56% versus 43% (P = .007), and local recurrence was significantly reduced in the CYVADIC arm at 17% versus 31% (P = .004). In contrast, distant metastases occurred with similar frequency in both arms, 32% for CYVADIC versus 36% for control patients (P = .42), and overall survival rates were not significantly different at 63% versus 56% (P = .64). A reduction in local recurrence was only apparent in the group of head, neck, and trunk sarcomas (P = .002), but not in limb tumors (P = .31). CONCLUSION: Adjuvant chemotherapy with CYVADIC cannot be recommended outside the context of a clinical trial. Experience from this study has been used to plan a trial of neoadjuvant chemotherapy with doxorubicin/ifosfamide, which is currently in progress.

Adolescent↗