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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 127 records · Page 7Linked to original sources

Identification of second malignancies on effusions and fine-needle aspirates using a panel of monoclonal antibodies.

The longer survival of neoplastic patients achieved through improvements of therapeutic regimens has increased the relative risk of developing a second primary tumour (SPT). In this context, conventional cytopathology can define tumour histotype only in a small fraction of cases. In this study, we have evaluated whether selected combinations of monoclonal antibodies (MAbs) to tumour-associated antigens (TAAs) can increase the accuracy of conventional morphology in detecting second primary tumours (SPTs) in two particularly difficult areas of cytodiagnosis, namely that of effusions and pulmonary fine-needle aspirates (FNAs). The immunocytochemical (ICC) analysis of 334 cytological specimens demonstrated that the use of our selected panel of MAbs could allow a more efficient identification of SPTs in comparison with conventional morphology. This diagnostic improvement was statistically significant (P < 0.0001). The present findings show that the immunophenotyping of effusions and FNAs, providing a more accurate and objective identification of SPTs, may have significant therapeutic and epidemiological relevance.

Antibodies, Monoclonal↗

Microheterogeneity of the oligosaccharides carried by the recombinant bovine lactoferrin expressed in Mamestra brassicae cells.

The development of therapeutic glycoprotein production using the baculovirus expression system depends on the ability of insect cell lines to reproduce site specific mammalian-like N-glycans. A combination of 1H-NMR and mass spectrometry techniques (MALD-MS, ES-MS, and CID-MS-MS) allowed us to elucidate the N-linked oligosaccharides microheterogeneity on three different N-glycosylation sites, Asn233, Asn476, and Asn545, of a baculovirus-expressed recombinant bovine lactoferrin produced in Mamestra brassicae. Two families of N-glycan structures have been found: first, oligomannosidic glycans (Man[9-5]GlcNAc2) and secondly, short truncated partially fucosylated glycans (Man(3-2)[Fuc(0-1)]GlcNAc2). These results indicate that Mamestra brassicae cell line is not able to synthesize complex N-glycans, even if an alpha1,6-linked fucose residue is frequently present on the asparagine-bound N-acetylglucosamine residue of short truncated structures. Nevertheless, we have shown that Mamestra brassicae ensures the same N-glycosylation pattern as found on natural bovine lactoferrin showing the same distribution between complex and high-mannose type glycans on the different glycosylation sites. Sites which are naturally occupied by high-mannose glycans (Asn233 and Asn545) are substituted essentially by the same type of N-glycans in the recombinant counterpart, and the site Asn476,which carries sialylated complex type chains in the natural glycoprotein, is substituted by short, truncated, partially fucosylated chains in Mamestra brassicae-expressed bovine lactoferrin. These various results lead us to the conclusion that bovine lactoferrin is an interesting model to determine the potential of glycosylation of the baculovirus/insect cell expression systems.

Amino Acid Sequence↗

Risk stratification after myocardial infarction. A reappraisal in the era of thrombolysis. The Groupe d'Etude du Pronostic de l'Infarctus du Myocarde (GREPI)

OBJECTIVES: The present study was performed to evaluate whether the modalities of risk stratification after myocardial infarction were still operative in the thrombolytic era. BACKGROUND: Prediction of fatal events in the aftermath of myocardial infarction relies on tests which aim to assess myocardial function, residual ischaemia and propensity for ventricular arrhythmias. Recent data on improved myocardial infarction prognosis have led to the view that risk stratification needs to be updated. METHODS: In this multicentre, prospective study, 471 acute myocardial infarction patients, 45% of whom were given thrombolytic therapy, were enrolled from the 10th day and underwent all or part of the following tests exercise test, radionuclide ventriculography (resting and exertional ejection fraction). Holter monitoring, signal-averaged electrocardiography and programmed electrical stimulation. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: One year and long-term (mean follow-up 31.4 months) mortality rates were 5.5% and 8.4%, respectively. Prediction of mortality was assessed and the role of the following variables was thus determined: age over 56 years (P = 0.01), previous coronary attacks (P < 0.001), history of heart failure (P < 0.001), early heart failure after myocardial infarction (P = 0.017), maximum workload of lest than 120 W at exercise test (P = 0.014), ineligibility to perform exercise (P = 0.002), depressed left ventricular ejection fraction (P = 0.013), late potentials as identified using 50 Hz high pass filtering (P = 0.012), mean night-time cycle length of less than 750 ms (P < 0.001), standard deviation of day time RR intervals of less than 100 ms (P = 0.04), the last two measures reflecting heart rate variability. In this population, neither ventricular ectopic activity nor inducibility of sustained monomorphic ventricular tachycardia at electrophysiological study carried any prognostic significance. Multivariate analyses showed that decreased heart rate variability, presence of late potentials and low ejection fraction (< 30%) made an independent contribution to the survival models. CONCLUSION: In the current context of management of acute coronary patients, the basis for risk stratification after myocardial infarction remain roughly unchanged.

Adult↗

Altered expression of insulin-like growth factor II receptor in human pancreatic cancer.

The insulin-like growth factor-II (IGF-II) receptor (IGF-IIR) is a single-chain transmembrane protein identical to the mannose-6-phosphate receptor. In the present study we examined IGF-IIR expression in normal and cancerous human pancreatic tissues. In the normal pancreas, moderately strong IGF-IIR immunoreactivity was present in the cytoplasm of islet cells, and mild cytoplasmic immunoreactivity was evident occasionally in ductal and acinar cells. Some ductal cells also exhibited nuclear IGF-IIR immunoreactivity. In the pancreatic cancers, regions of strong IGF-IIR immunoreactivity were present in the duct-like cancer cells within the tumor mass, often exhibiting nuclear localization. Expression of IGF-IIR mRNA in the cancer cells was confirmed by in situ hybridization. By comparison with normal pancreatic tissues, 7 of 12 pancreatic cancers exhibited a 5.6-fold increase in IGF-IIR mRNA levels, whereas in 3 cancers the IGF-IIR transcript was below the level of detection. Furthermore, all six tested cultured human pancreatic cancer cell lines expressed the IGF-IIR mRNA transcript. Our data indicate that IGF-IIR is overexpressed in a significant number of human pancreatic cancers, where it has a tendency to localize in the nucleus, and raise the possibility that IGF-IIR may contribute to the pathobiology of pancreatic cancer.

Adolescent↗

ABO antigen blood-group compatibility in corneal transplantation.

Our objective was to evaluate the effect of ABO antigen blood-group compatibility on corneal allograft rejection. The 199 penetrating keratoplasties performed between 1985 and 1994 were analyzed retrospectively for ABO compatibility and the occurrence of irreversible allograft rejection. Of these, 72 were considered high-risk transplants, as there was significant vascularization of the recipient cornea or a history of irreversible corneal allograft rejection or both. One hundred twenty-seven were low-risk transplants. The data were analyzed by using the Kaplan-Meier method and compared with the log-rank test. Overall, the estimated 1-year graft survival was 83.9% in the low-risk group and 61.4% in the high-risk group (p = 0.001). The estimated 1-year rejection-free graft survival was 89.8% in the low-risk group and 67.1% in the high-risk group (p = 0.0002). In the high-risk group, graft survival (p = 0.008) and rejection-free graft survival (p = 0.0002) were higher in the ABO-compatible subgroup than in the ABO-incompatible subgroup. In the low-risk group, graft survival and rejection-free graft survival of the ABO-compatible and ABO-incompatible subgroups were similar. ABO compatibility may be effective in preventing irreversible allograft rejection in high-risk recipients.

ABO Blood-Group System↗

Evaluation of the deswelling period in dextran-containing medium after corneal organ culture.

PURPOSE: To evaluate corneal structural modifications induced by the deswelling period in dextran-containing medium following organ culture. METHODS: Twenty human corneas were organ-cultured for 2 weeks and subsequently incubated in Exosol deswelling medium (Opsia, Toulouse, France) for 1-4 days. Corneas were studied by means of light microscopy, morphometry, and transmission electron microscopy. RESULTS: The deswelling period induced a statistically significant 8.4% endothelial cell loss and a 27.4% increase in the coefficient of variation. The endothelial layer remained intact. The basal epithelial cells displayed a flat appearance. Thin endothelial cells were observed in addition to dark vacuoles (the number of which increased with incubation time) with dense material and no mitochondrial swelling. Some basal epithelial cells and keratocytes were damaged on day 3 or 4. CONCLUSIONS: Preservation injuries induced by 1 or 2 days of incubation in deswelling medium are moderate. Three or 4 days of incubation result in more severe dextran-induced injuries. Consequently, the deswelling period should not exceed 2 days.

Aged↗

HLA class I and class II alleles and haplotypes in Mexican mestizos established from serological typing of 50 families.

We describe new information on the frequency and association of class II antigens (HLA-DR and HLA-DQ) of the major histocompatibility complex (MHC) in Mexicans. The study includes HLA-B typing and its association with the HLA-DR antigens determined in 50 families, which included 100 individuals. This family study allowed the establishment of the precise composition of the 200 HLA haplotypes, which cannot be obtained from unrelated individuals. The predominant antigens in decreasing order of frequency were B35, B39, and B61 at the B locus; DR4, DR5, and DR8 at the DR locus; and DQ3 at the DQ locus. The most common HLA-B,HLA-DR haplotype (considering broad specificities) was B16,DR4, with a frequency of 8.0%. Five HLA-B,HLA-DR haplotypes showed significant delta values (observed vs. expected frequencies) after correcting for the number of comparisons. On the other hand, the most common HLA-DR,HLA-DQ haplotypes were DR4,DQ3 and DR5,DQ3 with a frequency higher than 10%. Ten of the 17 HLA-DR,HLA-DQ haplotypes had significant postcorrection delta values.

Ethnicity↗

Technetium-99m-MIBI scintigraphy in the assessment of neoadjuvant chemotherapy in breast carcinoma.

UNLABELLED: Presurgical neoadjuvant chemotherapy (PSNC) is the treatment of choice for patients with locally advanced breast carcinoma (LABC). Accurate assessment of tumor response is important in planning subsequent treatments. Conventional response assessment by mammography and clinical evaluation is not fully reliable. This study evaluates the diagnostic yield of serial 99mTc-MIBI scintigraphy in the assessment of LABC response to PSNC. METHODS: Twenty-nine patients affected by LABC underwent clinical, mammographic and 99mTc-MIBI scintigraphy before and after 3 cycles of FEC (500 mg/m2 5-fluorouracil, 50 mg/m2 epirubicin and 400 mg/m2 cyclophosphamide) on Days 1 and 8. Surgery was planned for 15 days after the third cycle of chemotherapy. Pathological status was obtained after surgery in all patients. RESULTS: Sensitivities (i.e., true-positive ratios) for a correct prediction of tumor presence after PSNC were 65% for scintigraphy, 35% for clinical evaluation and 69% for mammography. Specificities (i.e., true-negative ratios) for a correct prediction of tumor absence after PSNC were 100% for scintigraphy, 67% for clinical evaluation and 33% for mammography. Technetium-99m-MIBI uptake in this series did not correlate with P-170 expression, proliferating cell nuclear antigen, Her-2/neu oncogene protein, antihuman endothelial cell CD31 antigen and estrogenic and progestinic receptor status. CONCLUSION: Technetium-99m-MIBI scintigraphy is effective in monitoring the response to PSNC in LABC patients. Its diagnostic yield is clearly superior to clinical evaluation alone. Scintigraphy performs as does mammography in patients with negative response, but it is clearly superior in patients with positive response.

Antineoplastic Combined Chemotherapy Protocols↗

Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173-194 from bovine adrenal medullary chromaffin granules.

Recently, we have isolated from bovine chromaffin granules and identified two natural peptides possessing antibacterial activity: secretolytin (chromogranin B 614-626) and enkelytin (proenkephalin-A 209-237). Here, we characterize a large natural fragment, corresponding to chromogranin A 79-431, that inhibits growth of both Gram-positive and Gram-negative bacteria. The aim of the present work was to determine the shortest active peptide located in the 79-431 chromogranin A region. Three peptides, which shared the same 173-194 chromogranin A sequence (YPGPQAKEDSEGPSQGPASREK) but differed in post-translational modifications, including O-glycosylation and tyrosine phosphorylation, were isolated. A detailed study using microsequencing and mass spectrometry allowed us to correlate their antibacterial activity with these post-translational modifications. The chromogranin A precursor fragment (79-431) and the active glycosylated and phosphorylated peptides were, respectively, named prochromacin and chromacin (P, G, and PG for phosphorylated, glycosylated, and phosphorylated-glycosylated form).

Adrenal Medulla↗

Phase I/II trial of autologous activated macrophages in advanced colorectal cancer.

Autologous activated macrophage (AAM) therapy is an adoptive cellular therapy based on ex vivo differentiation and activation of autologous peripheral blood monocytes. This study was undertaken to evaluate the tolerance, efficiency and biological effects of AAMs in chemoresistant progressive colorectal cancers. From January 1993 to May 1995, 15 patients were treated. Mononuclear cells were collected six times by weekly apheresis, cultured for 7 days, and activated with interferon-gamma. AAMs were then separated by elutriation and re-infused intravenously, with a mean total of 7.95 x 10(9) macrophages per patient. Clinical tolerance was good: toxicity consisted only of a World Health Organisation grade 2 fever after 28% of the infusions. Responses were not seen in the 14 evaluable patients, as expected with very bulky tumours: in 11, the tumours continued to progress, but disease was stabilised in 3 patients who experienced progression-free survival for 14, 12 and 12 weeks, respectively.

Aged↗

Evaluation of household dust mite exposure and levels of specific IgE and IgG antibodies in asthmatic patients enrolled in a trial of immunotherapy.

BACKGROUND: Monitoring the response to immunotherapy entails understanding exposure to relevant allergens. For the major indoor allergens, this requires sampling of dust from the patient's house. The objectives of this study were to measure indoor allergen levels during a controlled trial of dust mite immunotherapy for asthma and to relate these results to serum antibody levels. METHODS: Eighty-eight asthmatic patients with mite allergy from seven geographic areas in the United States were enrolled in and completed a course of immunotherapy with Dermatophagoides extract or placebo control. Sensitization was evaluated by quantitative measurements of IgG and IgE antibodies. Dust samples were assayed for group I mite (Der p 1 and Der f 1), cat (Fel d 1), and cockroach (Bla g 1) allergens by monoclonal antibody-based ELISA. RESULTS: Over the 4 years of the study, each of the houses had at least one sample that contained more than 2 micrograms of group I mite allergen per gram of dust. Mean mite allergen levels, however, varied over a wide range, from 0.2 microgram/gm or less to more than 50 micrograms/gm. IgE antibodies to mite were present in sera from 78% of the patients, whereas IgE antibodies to cat and cockroach allergens were found in sera from 34% and 11% of patients, respectively. Sixty-four percent of the patients had exposure and sensitization to mite, whereas the comparable figure for each of the other allergens was 5%. CONCLUSIONS: Examination of the results suggested that allergen exposure, relative to a trial of immunotherapy, could be expressed as (1) the maximum level found in the house, (2) the percentage of sites having greater than 2 micrograms/gm, or (3) the mean value at the site with the maximum level. This report provides a background for evaluating the clinical results of immunotherapy in these patients and a model for the way in which sensitization and exposure should be monitored in studies of this kind.

Adolescent↗

Immune therapy with macrophages: present status and critical requirements for implementation.

Adoptive transfer of activated macrophages has been validated in animal experimental tumor models; clinical trials are ongoing (70 patients up to now). The mechanisms involved are reviewed as well as improved and standardized procedures for macrophage differentiation and activation. New developments including specific Ag presentation and gene therapy are discussed.

Animals↗