Toral and salazar reply:
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Journal Article↗
Biomedical subjects
R Salazar
Publications and source records attributed to R Salazar.
Tumor markers at the time of recurrence in patients with germ cell tumors.
BACKGROUND: alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) closely follow the course of germ cell tumors (GCTs) and are widely used for diagnosis, prognosis, and follow-up purposes. The objective of this study was to assess the concordance of tumor markers at the time of diagnosis and recurrence. METHODS: The authors reviewed the records of 794 patients with GCTs treated in three Spanish hospitals from 1977-1996 and analyzed the concordance between AFP, HCG, and LDH levels at diagnosis and first and second recurrence. A positive marker was defined as a level of AFP > 10 ng/mL, HCG > 5 IU/L, or LDH > the upper limit of normal. One hundred twenty-five patients were identified who developed a first recurrence (123 had marker levels recorded). The median age was 27 years (range, 14-78 years). Histology was seminoma in 36 patients (29%) and nonseminomatous GCT (NSGCT) in 87 patients (71%). RESULTS: Seventy-nine patients (64%) had elevated tumor markers at diagnosis and 76 (62%) at first recurrence. An elevated marker was present at first recurrence in 58 of 79 patients (73%) with initially positive markers and in 18 of 44 patients (41%) with initially negative markers. In 84 of 123 patients (68%), the same marker pattern (positive or negative) was present at the time of diagnosis and at first recurrence, 78% in seminomas and 64% in NSGCTs. The earliest indicator of recurrence was an elevated marker in patients with NSGCTs and a radiologic finding in patients with seminomas. Thirty patients developed a second recurrence, 27 of whom (90%) had the same marker pattern as at first recurrence. CONCLUSIONS: Tumor marker pattern at diagnosis is not a good predictor of the pattern at recurrence, particularly in patients with NSGCTs. Marker assessment should be included in the follow-up schedule regardless of levels at the time of diagnosis. Early detection of recurrence should not rely only on marker levels, even in patients with elevated levels at presentation.
Adolescent↗
Determination of beta-globin gene cluster haplotypes and prevalence of alpha-thalassemia in sickle cell anemia patients in Venezuela.
Sickle cell anemia and alpha-thalassemia have a heterogeneous distribution in Venezuela with a high frequency in the coastal area (sea level) and few cases in the mountains. Most of our population is an ethnic admixture of Europeans (Spaniards colonists), Africans (slaves), and Amerindians. The purpose of our study was to determine the origin of the beta(s) globin haplotype, age and survival dependency, and the admixture among the different African groups in our population. The alpha(3.7) globin gene deletion status was also studied and found in a very high frequency. DNA from peripheral blood of 191 non-related patients (81 with HbS homozygous and 15 patients compound heterozygous for HbS, HbC, HbD with beta-thalassemia, and 95 with sickle cell trait) were studied. The beta(s) chromosome was linked 51% to the Benin Haplotype, 29.5% with the CAR, 12.5% to the Senegal, and 2.5% to the Cameroon. We did not find any significant difference between the haplotype distribution among adults and children and among sickle cell patients and traits. Only 8.6% of the patients have homozygosity for the Benin haplotype. These results show a very high frequency of admixture in our African origin population.
Age Distribution↗
Bacteraemia caused by non-glucose-fermenting gram-negative bacilli and Aeromonas species in patients with haematological malignancies and solid tumours.
The clinical characteristics and outcome of bacteraemia caused by non-glucose-fermenting gram-negative bacilli and Aeromonas spp. were examined in 115 adults with haematological malignancies or solid tumours. The most aggressive pathogens were Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Aeromonas spp., Acinetobacter spp. and Burkholderia cepacia, all of which caused either septic syndrome or pneumonia in more than 40% of cases. Pseudomonas aeruginosa was involved less often in catheter-related bacteraemia than other species. Polymicrobial bacteraemia (n=28) was more often catheter-related than monomicrobial bacteraemia and more often required catheter removal for definitive cure. The most important predictors of catheter-related bacteraemia and its outcome were polymicrobial infection, the presence of pneumonia or septic syndrome and the species involved.
Adolescent↗
RGD-dependent vacuolation and lumen formation observed during endothelial cell morphogenesis in three-dimensional fibrin matrices involves the alpha(v)beta(3) and alpha(5)beta(1) integrins.
Recent data have revealed the involvement of the alpha(v)beta(3) integrin in angiogenesis. However, few studies to date have provided a convincing role for this receptor in in vitro assays of endothelial cell morphogenesis where defined steps can be examined. Here, we present data showing that two integrins, alpha(v)beta(3) and alpha(5)beta(1), regulate human endothelial cell vacuolation and lumen formation in three-dimensional fibrin matrices. Cells resuspended in fibrin formed intracellular vacuoles that coalesced into lumenal structures. These morphogenic events were completely inhibited by the simultaneous addition of anti-alpha(v)beta(3) and anti-alpha(5) integrin antibodies. Complete blockade was also accomplished with a combination of the cyclic Arg-Gly-Asp (cRGD) peptide and anti-alpha(5) integrin antibodies. No blockade was observed with the control Arg-Gly-Glu (RGE) peptide alone or in combination with control antibodies. Finally, we were able to demonstrate regression of vacuoles and lumens several hours after the addition of cRGD peptides combined with anti-alpha(5) integrin antibodies. These effects were not observed with control peptides alone or in combination with control antibodies. We report here the novel involvement of both the alpha(v)beta(3) and alpha(5)beta(1) integrins in vacuolation and lumen formation in a fibrin matrix, implicating a role for multiple integrins in endothelial cell morphogenesis.
Antibodies, Monoclonal↗
Purification and characterization of a 200 kDa fructosyllysine-specific binding protein from cell membranes of U937 cells.
Amadori-modified proteins are bound by macrophages and monocytes via fructosyllysine-specific receptors. Detergent extracts from U937 cell membranes were used to purify the binding proteins by affinity purification on glycated polylysine coated magnetic beads followed by SDS-PAGE. Two proteins of 200 and 100kDa were isolated. MS-analysis of the 200 kDa protein showed high homologies with cellular myosin heavy chain, type A. Both fructosyllysine specific binding proteins, cellular myosin heavy chain and nucleolin, are glycosylated.
Amino Acid Sequence↗
Rifampin does not improve the efficacy of quinolone antibacterial prophylaxis in neutropenic cancer patients: results of a randomized clinical trial.
PURPOSE: To determine whether the addition of rifampin to a quinolone-based antibacterial prophylactic regimen in patients undergoing high-dose chemotherapy (HDC) with peripheral-blood stem-cell transplantation (PBSCT) decreases the incidence of neutropenia and fever, Gram-positive bacteremia, and infection-related morbidity. PATIENTS AND METHODS: Patients with solid tumors undergoing HDC with PBSCT were randomized to receive prophylactic antibiotics with either ciprofloxacin 500 mg orally every 8 hours or the same ciprofloxacin regimen with rifampin 300 mg orally every 12 hours. Prophylaxis was started 48 hours before stem-cell reinfusion. Patients were monitored to document the occurrence of neutropenia and fever, incidence and cause of bacterial infection, time to onset and duration of fever, requirement for intravenous antimicrobials, and length of hospital admission. RESULTS: Sixty-five patients were randomized to receive ciprofloxacin and 65 to receive ciprofloxacin plus rifampin, and from these groups, 62 and 61 were assessable, respectively. The proportion of patients who developed neutropenia and fever was 87% in the group treated with ciprofloxacin and 78% in the group treated with ciprofloxacin and rifampin (P =.25). Although there was a trend toward a reduction in the overall incidence of bacteremia (12 v 4 patients), and Gram-positive bacteremia (8 v 2 patients) with the addition of rifampin, none of these comparisons was statistically significant (P =.05 and P =.09, respectively). CONCLUSION: The results of this study, which demonstrate that rifampin does not improve ciprofloxacin antibacterial prophylaxis in cancer patients undergoing HDC with PBSCT support but that it does increase the occurrence of undesirable side effects, do not support the routine use of rifampin in this setting.
Adult↗
Coordinate induction of the actin cytoskeletal regulatory proteins gelsolin, vasodilator-stimulated phosphoprotein, and profilin during capillary morphogenesis in vitro.
The formation of capillaries during development and tissue repair is likely to involve active reorganization of the actin cytoskeleton, although few studies have addressed this issue. Here, we have utilized an in vitro model of capillary morphogenesis whereby human umbilical vein endothelial cells are suspended within three-dimensional type I collagen gels. The cells undergo dramatic morphogenic changes to develop capillary lumens, tubes, and networks over 72 h of culture. Western blots using cell extracts of these gels over this time frame were performed using antibodies directed to various proteins associated with the actin cytoskeleton. Three proteins showed altered expression during the time course, and they were gelsolin, which increased fivefold; vasodilator-stimulated phosphoprotein (VASP), which increased twofold; and profilin, which increased threefold in expression between the 24- and the 72-h time points. Reverse transcriptase-polymerase chain reaction and Northern blot analysis revealed a similar increase in mRNA expression of the three proteins. After the onset of network formation, the differentiated endothelial cells (dECs) undergoing capillary morphogenesis were removed from collagen gels at 48 h of culture to compare their properties with untreated endothelial cells (uECs). These dECs showed two- to threefold increased spontaneous migration in Boyden chamber assays compared to uECs. The dECs also displayed a prominent spindle-shaped morphology and the novel presence of intranuclear gelsolin compared to uECs when both cell types were replated on type I collagen-coated microwells and glass coverslips. These data suggest that increased gelsolin, VASP, and profilin expression may play an important role in the regulation of capillary tube and network formation in three-dimensional extracellular matrix.
Actins↗
[High dose chemotherapy in germinal testicular tumors].
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Adult↗
Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.
The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.
Acyclovir↗
[Detection of beta thalassemia by the technique of refractory amplification of mutation systems (ARMS-PCR)].
beta Thalassemia (Thal) mutations were studied in DNA from 80/159 patients with hemolytic anemia and high levels of Hb A2 by the amplification refractory mutation system technique (ARMS-PCR). This method detects point mutations and insertions or deletions of just a few nucleotides in the beta globin gene by the polymerase chain reaction of allele-specific priming. In 43/80 patients with different clinical presentations of beta Thalassemia and 37/80 compound heterozygous for hemoglobinopathies and beta Thalassemia the most frequent mutation found was the -29 (of African origin), followed by the CD39 (of Mediterranean origin) and in a lower frequency also was found the -88, the IVSI-6 and the IVSI-110. We conclude that this technique is an useful approach in determining the beta thalassemia mutations in population surveys, because it allows to make a differential diagnosis between beta Thalassemia minor and individuals with high levels of Hb A2. It helps to clarify the diagnosis of patients with structural hemoglobinopathies that also presents high levels of Hb A2.
Base Sequence↗
Giant neurofibromatosis of the chest wall: two patient reports.
Two patients with severely deforming giant neurofibromatosis of the chest wall secondary to von Recklinghausen's disease are presented. Pain, respiratory compromise, recurrent ulcerations, cosmetic considerations, and the malignant potential of these lesions indicated wide excision and reconstruction. It is impossible to completely eradicate all neurofibromas, which may affect virtually every nerve within the chest wall including the mediastinum. However, excision of the primary mass may reduce the possibility of malignant degeneration into neurofibrosarcoma or malignant schwannoma. This type of major, full-thickness chest wall resection is now possible using musculocutaneous flaps to achieve satisfactory closure with a single-stage procedure with minimal morbidity and a short hospital stay. At the 10-year follow-up, neither patient exhibited evidence of recurrence.
Adult↗
Evidence for binding of in vitro glycated low-density lipoproteins by fructosyllysine-specific sites on macrophages and U937 monocyte-like cells.
Early development of arteriosclerosis is a main late complication of diabetes mellitus. Although its uptake by LDL receptors is impaired, glycated LDL is thought to play a role in foam cell formation from macrophages. In the present study we show binding of glycated LDL (8-9 mol fructosyllsine/mol apo B) to macrophages and to the monocyte-like cell line U937. The binding involves fructosyllysine-specific binding sites, as well as LDL and scavenger receptors. Fructosyllysine and glycated albumin were competitors for binding of 125I-labelled glycated LDL by macrophages and U937 cells. Scatchard analysis of binding data using a two ligands binding model showed a linear plot with Ka = 2.6 x 10(7) M-1 for U937 cells, which lack scavenger receptors. On U937 cells only the 200 kDa fructosyllysine-specific receptor protein and the 165 kDa LDL receptor were involved in binding glycated LDL as evidenced by ligand blotting. U937 cell uptake and degradation of glycated LDL was mediated by fructosyllysine-specific and LDL receptors. Binding of glycated LDL by macrophages via fructosyllysine-specific sites could be demonstrated in only 6 from 35 rats investigated, indicating that the receptor is not expressed in each individual. Whether the fructosyllysine-specific receptor mediated pathway is relevant for uptake and degradation of glycated LDL in vivo is yet to be determined.
Animals↗
Factor XII-induced mitogenesis is mediated via a distinct signal transduction pathway that activates a mitogen-activated protein kinase.
Clotting factor XII (Hageman factor) contains epidermal growth factor (EGF)-homologous domains and is reported to be a potent mitogen for human hepatoma (HepG2) cells. In this study, we tested whether factor XII exhibits growth factor activity on several other EGF-sensitive target cells, including fetal hepatocytes, endothelial cells, alveolar type II cells, and aortic smooth muscle cells. We found that factor XII significantly enhanced [3H]thymidine incorporation in aortic smooth muscle cells (SMCs) and all other cells tested. Tyrphostin, a growth factor receptor/tyrosine kinase antagonist, inhibited both EGF- and factor XII-induced responses. However, differences in the levels of magnitude of DNA synthesis, the observed synergism between EGF and factor XII, and the differential sensitivity to tyrphostin suggest that the EGF receptor and the factor XII receptor may be nonidentical. The factor XII-induced mitogenic response was achieved at concentrations that were 1/10th the physiologic range for the circulating factor and was reduced by popcorn inhibitor, a specific factor XII protease inhibitor. Treatment of aortic SMCs with factor XII, as well as activated factor XII, resulted in a rapid and transient activation of a mitogen-activated/extracellular signal-regulated protein kinase with peak activity/tyrosine phosphorylation observed at 5 to 10 min of exposure. Taken together, these data (i) confirm that clotting factor XII functions as a mitogenic growth factor and (ii) demonstrate that factor XII activates a signal transduction pathway, which includes a mitogen-activated protein kinase.
Animals↗
Bacteremia due to glucose non-fermenting gram-negative bacilli in patients with hematological neoplasias and solid tumors.
Twenty-six patients with hematological or solid tumors who developed bacteremia caused by Stenotrophomonas maltophilia (n = 10), Pseudomonas putida (n = 6), Sphingomonas paucimobilis complex (n = 4) or Alcaligenes xylosoxidans (n = 6) in the period between 1993 and 1995 were studied. Seventeen patients were neutropenic during the infection, and 13 were undergoing bone marrow or peripheral blood stem cell transplantation. Twenty-three patients had catheter-related infections; only 3 of the 26 patients developed septic complications (all due to Stenotrophomonas maltophilia). Twenty patients were cured following catheter removal, either as primary measure (n = 8) or salvage measure (n = 12). Four responded to antibiotic therapy only, and two died of septic complications. Such infections in hematological and oncological patients have increased in this hospital from no cases in 1975 to 11 cases in 1995.
Adolescent↗
[Intellectual property rights in Costa Rica in the light of the Biodiversity Convention].
This report analyzes intellectual property rights and acquisition of biological samples in light of the Biological Diversity Convention, with emphasis on Costa Rica. It examines the legal framework which exists for the protection of biological resources in this country, especially evaluating the law regarding protection of biota, which was approved in 1992. This includes information regarding access to genetic resources, and regulation for the aforementioned law. It examines the Biological Diversity Convention which was signed at the Rio Summit in 1992, whose objectives and goals, above all, emphasize the subject of distribution of benefits to be derived from the utilization of biological resources.
Animals↗
Expression of fructosyllysine receptors on human monocytes and monocyte-like cell lines.
Short-term exposure of human serum albumin to glucose in vitro results in the formation of fructosyllysine residues. Using short-term glucose-modified albumin the interactions with human monocytes and with the human monocyte-like cells U937, MonoMac 6, HL60, and THP1 were studied. Short-term glycated albumin was specifically bound by monocytes, U937 and MonoMac 6 cells, but not by HL60 and THP1 cells. This specific binding of short-term glycated albumin was inhibited by fructosyllysine, but not by hexitollysine. Short-term glycated albumin did not compete for binding of albumin, modified by advanced glycation end products. Scatchard analysis of the binding data indicated that there are 10,000 binding sites per cell in monocytes or U937 cells and 2000 sites per cell on MonoMac 6 cells with affinity constants of 9 x 10(6) M-1. Specific binding of short-term glycated albumin to human monocytes was observed in 29% of the 101 human subjects investigated. Ligand-receptor cross-linking and ligand blotting experiments revealed two binding proteins of 100 to 110 and 190 kDa in SDS-PAGE after membrane protein solubilization of U937 and MonoMac 6 cells. The binding of short-term glycated albumin to MonoMac 6 cells induced the production of the cytokines IL-1 and TNF.
Binding Sites↗
Purification and partial amino acid sequencing of a fructosyllysine-specific binding protein from cell membranes of the monocyte-like cell line U937.
The ability of short-term in vitro glycated albumin to react with monocytes or the monocyte-like cells U937 is due to the Amadori adduct fructosyllysine. Two binding proteins of about 100 and 200 kDa have been previously described to interact specifically with the monocyte-like cell line U937. Detergent extracts from U937 cell membranes were used to purify the 100kDa protein by ion exchange chromatography, fructosyllysine-Sepharose affinity chromatography and SDS-PAGE. Six amino acids from the N-terminal end and two peptide sequences of 14 and 15 amino acids were identical with the N-terminus and the positions 349 to 362 and 610 to 624 of the major nuclear protein nucleolin. However, ligand blotting experiments with nuclear extracts from U937 and RIN cells showed no binding of glycated albumin with nucleolin. The reported amino acid sequences of the 100kDa fructosyllysine specific binding protein do not show any homologies with AGE-receptors. This receptor protein as a nucleolin-like polypeptide belongs to the superfamily of RNA-binding proteins.
Amino Acid Sequence↗