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Isabel Fonseca

Publications and source records attributed to Isabel Fonseca.

14 recordsLinked to original sources
PubMed2005

Peritoneal fast transport in incident peritoneal dialysis patients is not consistently associated with systemic inflammation.

BACKGROUND: The determinants of peritoneal fast transport status at the beginning of peritoneal dialysis (PD) are still under debate. The relationship between fast transport status and inflammation or co-morbidity, and its impact on patient survival are not fully elucidated. Our objective was to investigate if fast transport status in incident patients is associated with markers of inflammation and atherosclerosis, and its relationship to patient survival. METHODS: Seventy-three incident patients on PD performed a 3.86% peritoneal equilibrium test (PET) at 4.7+/-2.7 months after starting PD. Doppler carotid wall intima-media thickness (IMT) and the presence of carotid plaque were used as markers of atherosclerosis. C-reactive protein (CRP) and serum interleukin-6 (IL-6) were evaluated as markers of systemic inflammation. Baseline plasma levels of albumin, homocysteine, lipoprotein (a) [Lp(a)] and other lipid parameters were measured. Body mass index and residual renal function (RRF) were calculated. Patients were classified with the Davies co-morbidity score. RESULTS: The dialysate-plasma creatinine ratio (D/P creatinine) was 0.75 +/- 0.10; 26% were fast transporters (D/P > or = 0.85). In comparison with other transport categories, these had similar age, body mass index and RRF, and did not present a higher co-morbidity score than non-fast transporters. IMT did not significantly differ between groups. By multiple regression analysis, baseline peritoneal small solute transport was not related to systemic inflammation biomarkers. Fast transporters did not present higher levels of CRP or serum IL-6. Plasma levels of lipids, Lp(a), calcium x phosphorus product and albumin also did not differ between groups. Similar results were obtained when patients were grouped according to mass transfer area coefficient for creatinine. Patients with more than two co-morbidities had lower levels of plasma albumin (3.6 +/- 0.58 vs 3.9 +/- 0.9 g/dl, P = 0.054), significantly higher median levels of serum IL-6 (19.3 vs 9.2 pg/ml, P = 0.003) and wider IMT (0.90 +/- 0.36 vs 0.65 +/- 0.28 mm, P = 0.017). Multivariate analysis confirmed that baseline peritoneal transport was not a significant determinant of patient survival (P = 0.848), while the co-morbidity score remained significant (hazard ratio = 3.48, 95% confidence interval = 1.29-9.38, P = 0.014). CONCLUSION: Initial fast transport was not associated with systemic inflammation and atherosclerosis. In a population with preserved RRF and absence of baseline serious co-morbidity, it was not predictive of worse prognosis. Other determinants of early peritoneal fast transport deserve investigation.

Biological Transport↗
PubMed2005

Who takes the lead in the development of ulcerative colitis-associated colorectal cancers: mutator, suppressor, or methylator pathway?

Although several genetic alterations have been identified in patients with ulcerative colitis (UC), it remains unclear whether these changes indicate an increased risk for malignancy. This paper analyzes the involvement of suppressor, mutator, and methylator pathways in malignant transformation associated with UC. A total of 60 colonic samples (47 affected non-neoplastic mucosa, 7 dysplasia, and 6 carcinoma) from 51 UC patients were analyzed for 22 microsatellite markers. p53 gene exons 5-8 were analyzed by single-strand conformational polymorphism, and APC gene by denaturing gradient gel electrophoresis (exons 1-14) and protein truncation test (exon 15). Methylation studies for MLH1 and CSPG2 genes were also performed. Microsatellite instability was absent in all samples whereas allelic imbalance (AI) and loss of heterozygosity (LOH) were detected mainly in samples with neoplastic transformation (P<0.0001). AI and/or LOH at loci located on chromosomes 5, 9, and 18 were significantly more frequent in neoplastic samples (P<0.01), as were TP53 gene mutations (P<0.007). A single mutation was detected for APC gene in a cancer sample. MLH1 gene methylation was absent in all analyzed samples, whereas CSPG2 gene methylation was detected in a single non-neoplastic sample. Our results suggest that the suppressor pathway plays the main role in UC associated tumorigenic progression. LOH at specific loci located on chromosomes 5, 9, and 18 appears to be specifically associated with malignancy risk.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Sol-gel encapsulation: an efficient and versatile immobilization technique for cutinase in non-aqueous media.

Cutinase from Fusarium solani pisi was encapsulated in sol-gel matrices prepared with a combination of alkyl-alkoxysilane precursors of different chain-lengths. The specific activity of cutinase in a model transesterification reaction at fixed water activity in n-hexane was highest for the precursor combination tetramethoxysilane/n-butyltrimetoxysilane (TMOS/BTMS) in a 1:5 ratio, lower and higher chain lengths of the mono-alkylated precursor or decreasing proportions of the latter relative to TMOS leading to lower enzyme activity. Results obtained using combinations of three precursors confirmed the beneficial effect of the presence of BTMS in the preparations. Scanning electron microscopy of the 1:5 TMOS/n-alkylTMS gels showed a direct correlation between the macropore dimensions and the alkyl chain length of the alkylated precursor and revealed that TMOS/n-octylTMS gels suffered extensive pore collapse during the drying process. The specific activity of TMOS/BTMS sol-gel entrapped cutinase was similar to that exhibited by the enzyme immobilized by adsorption on zeolite NaY. However, the incorporation of different additives (zeolites, silica, Biogel, grinded sol-gel, etc.) having in common the capability to react with residual silanol groups of the sol-gel matrix brought about remarkable enhancements of cutinase activity, despite the fact that the global porosity of the gels did not change. The behavior of the gels in supercritical CO 2 (sc-CO 2) paralleled that exhibited in n-hexane, although cutinase activity was ca. one order of magnitude lower (i.e. sol-gel encapsulation did not prevent the deleterious effect of CO 2. The impact that functionalization of some of the additives had on cutinase activity indicates that the enzyme/matrix interactions must play an important role. Some of the best additives from the standpoint of enzyme activity were also the best from the standpoint of its operational stability (ca. 80% retention of enzyme activity at the tenth reutilization cycle). None of the additives that proved effective for cutinase could improve the catalytic activity of sol-gel encapsulated Pseudomonas cepacia lipase.

Carboxylic Ester Hydrolases↗
PubMed2005

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry.

Pleomorphic adenoma is the most common benign tumor of the salivary glands. It has marked histological diversity with epithelial, myoepithelial and mesenchymal-type cells arranged in a variety of architectural and differentiation patterns. Pleomorphic adenoma gene 1 (PLAG1), shown to be consistently rearranged in pleomorphic adenomas, is activated by chromosomal translocations involving 8q12, the chromosome region that is most frequently affected in these tumors. In this study, we evaluated PLAG1 involvement in salivary gland tumorigenesis by determining the frequency of its alterations in a selected group of 20 salivary gland tumors: 16 pleomorphic adenomas and four carcinomas ex-pleomorphic adenoma, having in common the presence of karyotypic chromosome 8 deviations, either structural, with 8q12 rearrangements, or numerical, with gain of chromosome 8. PLAG1 status was analyzed using in situ hybridization techniques, on metaphase cells, by fluorescence detection and/or interphase cells in paraffin sections, by chromogenic detection. Except for one pleomorphic adenoma case (5%) that lacked PLAG1 involvement, 17 tumors (85%), (14 pleomorphic adenomas and three carcinomas ex-pleomorphic adenoma) showed intragenic rearrangements of PLAG1 and the remaining two cases (10%), (one pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma), had chromosome trisomy 8 only. To further investigate the role of PLAG1 on pleomorphic adenomas tumorigenesis, as well as the putative morphogenesis mechanism, we attempted to identify the cell types (epithelial vs myoepithelial) carrying 8q12/PLAG1 abnormalities by a combined phenotypic/genotypic analysis in four cases (three pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma) characterized by 8q12 translocations and PLAG1 rearrangement. In these cases, both cells populations carried PLAG1 rearrangements. This finding further supports the pluripotent single-cell theory, which postulates that the tumor-initiated, modified myoepithelial cell, evolves into the varied somatic cell phenotypes present in pleomorphic adenoma, and reinforces the role of PLAG1 on the tumorigenesis of benign and malignant pleomorphic adenoma.

Adenoma, Pleomorphic↗
PubMed2004

Comparative genomic hybridization analysis of a pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare, aggressive dysontogenetic tumor of childhood. We report the comparative genomic hybridization (CGH) study performed on a case of PPB in a 3-year-old-boy. The tumor was characterized by several chromosomal imbalances. Gains observed affected regions: 1q12-q23, 3q23-qter, 8pter-q24.1, 9p13-q21, 17p12-p11, 17q11-q22, 17q23-q25, 19pter-p11, and 19q11-q13.3. Whole chromosome gains were detected at 2 and 7. Loss of genetic material was found at regions: 6q13-qter, 10pter-p13, 10q22-qter, and 20p13. To our knowledge, there have been no CGH reports on PPB, but it is interesting to note that 1) the alterations found confirm previous cytogenetic reports describing gains of chromosomes 2 and 8 as recurrent abnormalities in this type of tumor, suggesting that a gene or genes of putative relevance in PPB pathogenesis are mapped at 8p11-p12, and 2) the CGH profile of this case is very similar to those observed in embryonal rhabdomyosarcomas, in which gains of 2 or 2q, 7 or 7q, and 8 or 8p and loss of 10q22-qter are consistently found. This finding supports the hypothesis that PPB may be tumorigenetically related with embryonal rhabdomyosarcoma.

Child, Preschool↗
PubMed2004

A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands.

The t(11;19)(q21;p13) chromosomal translocation has been described in two distinct types of salivary gland neoplasms: mucoepidermoid carcinoma (MEC) and Warthin's tumor (WT). Since this translocation has been recently shown to generate a MECT1-MAML2 fusion gene, we evaluated 10 primary MEC and seven primary WT to further define the molecular association of these two entities using cytogenetic, as well as in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses directed against the fusion gene. A karyotype was established in all neoplasms except for two MEC cases. Of the eight karyotyped MECs, five showed the t(11;19)(q21;p13), two had a normal karyotype, and one case presented a -Y and +X. Three of the WT revealed a normal karyotype and four had several abnormalities which did not involve chromosomes 11 and 19. ISH analysis performed in cytogenetic suspension and/or in tumor paraffin sections demonstrated MAML2 rearrangement in 7 of 10 cases of MEC: all five cases with t(11;19), one case with normal karyotype, and one unkaryotyped case. RT-PCR analysis confirmed the expression of the MECT1-MAML2 gene in all MEC cases that were positive by ISH analysis. Neither the t(11;19) nor MECT1-MAML2 was detected in any case of WT, nor in control samples from polymorphous low-grade adenocarcinoma, acinic cell carcinoma, or normal parotid gland tissue. We have demonstrated that ISH and RT-PCR are sensitive methods for detecting MECT1-MAML2 in MEC. In contrast, we did not detect the t(11;19) nor MECT1-MAML2 expression in seven cases of WT.

Adenolymphoma↗
PubMed2004

End-stage renal disease and dialysis in hereditary amyloidosis TTR V30M: presentation, survival and prognostic factors.

Classical familial amyloid polyneuropathy may have a course with progressive renal impairment. We studied 62 patients (24 males, 38 females) with FAP, transthyretin variant V30M, and end-stage renal disease (ESRD) treated with hemodialysis, all referred to a single center over a period of 11 years. Clinical course, morbidity and survival after dialysis were analyzed. Patient's mean age at first dialysis was 51.5 +/- 10.7 years, and mean duration of neuropathy was 10.2 +/- 3.8 years. The most frequent form of presentation of FAP nephropathy was nephrotic proteinuria with renal dysfunction. In the year prior to dialysis, renal function declined rapidly, and fluid overload was the main indication to initiate treatment. The presence of decubitus ulcers, significant disability, venous catheter for definitive vascular access for long-term treatment, and permanent bladder catheter, were related to death during the first year of dialysis. The mean duration of renal replacement therapy was 21 months, with a 54.5% one year, and 38.4% two year treatment survival. However, when the duration of neurological symptoms at first dialysis exceeded 10 years, survival was significantly lower. Infections, (41% were decubitus ulcers with sepsis) were the cause of early, as well as late mortality. Early creation of vascular access for hemodialysis, surveillance of skin wounds, and intervention on neurogenic bladder are essential to improve the prognosis of ESRD in FAP.

Adult↗
PubMed2004

Kidney and anemia in familial amyloidosis type I.

BACKGROUND: Familial amyloid polyneuropathy (FAP) type I is caused by a mutated transthyretin (TTR V30M) and characterized by a sensorimotor and autonomic neuropathy. Renal, cardiac, and ocular abnormalities can also occur. Anemia has been described in previous reports, but its prevalence in Portuguese FAP patients is not precisely known. The aim of this study was to estimate the prevalence of anemia in FAP type I Portuguese patients and to evaluate the contribution of erythropoietin (Epo) to its genesis. METHODS: A retrospective cross-sectional study was undertaken to determinate the prevalence and characteristics of anemia in 165 FAP patients. For comparison analysis, 3 control groups were also evaluated, 1 group of 46 apparently healthy subjects, 1 group of 17 asymptomatic carriers of FAP-trait, and a group of 14 non-FAP patients with chronic renal insufficiency. Serum Epo levels were analyzed in all groups. RESULTS: Anemia was present in 24.8% of symptomatic FAP patients. Iron stores, B12 vitamin, and serum folate levels were normal. FAP patients presented significantly lower serum Epo levels than healthy controls (P= 0.003). Epo levels were found lower than expected for the degree of anemia and in 17.5% were undetectable. Low Epo values were observed independently of the presence of renal failure or anemia, and sometimes preceded clinical disease. CONCLUSION: Anemia in FAP type I is a common manifestation. The results clearly suggest a defective endogenous Epo production in the genesis of the anemia.

Adult↗
PubMed2004

Evaluation of effluent markers cancer antigen 125, vascular endothelial growth factor, and interleukin-6: relationship with peritoneal transport.

Peritoneal hyperpermeability has been associated with increased levels of effluent vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). Mesothelial cells can produce various vasoactive substances besides VEGF. A large mesothelial mass may possibly lead to high dialysate VEGF concentrations and may partly explain some cases of peritoneal hyperpermeability during a patient's early months on peritoneal dialysis (PD). Early peritoneal fast transport may therefore not necessarily be associated with systemic inflammation. To investigate the relationship of effluent markers and peritoneal transport, we measured the appearance rates of cancer antigen 125 (CA125), VEGF, and IL-6 in 4-hour effluents from 69 peritoneal equilibration tests (PETs) using 3.86% glucose solution. At the same time, we measured serum VEGF and IL-6. Our analyses included an early group (EG), whose members had been on PD for 4.6 +/- 3.3 months, and a later group (LG), whose members had been on PD for 30 +/- 17 months. In EG, dialysate-to-plasma creatinine at 4 hours (D/P(Cr240)) correlated significantly with effluent CA125/min (r = 0.51, p = 0.006) and VEGF/min (r = 0.57, p = 0.001), but not with serum VEGF or IL-6. The values of CA125/min and VEGF/min also correlated (r = 0.40, p = 0.034). Fast transporters in EG had higher effluent CA125 (p = 0.057) and VEGF (p = 0.0001), but not serum or effluent IL-6. In LG, D/P(Cr240) again correlated significantly with dialysate VEGF (r = 0.51, p = 0.009), but not with CA125. Fast transporters in LG tended to have higher levels of serum and effluent IL-6 and effluent VEGF. We conclude that fast solute transport rates at the beginning of PD are associated with signs of a large mesothelial cell mass and not consistently associated with higher systemic IL-6. The VEGF produced by mesothelial cells can mediate early peritoneal hyperpermeability in some populations. Later, mesothelial mass is lost and is no longer related to increased intraperitoneal VEGF or IL-6.

Adult↗
PubMed2003

Highly diastereoselective[3+2] cycloadditions between nonracemic p-tolysulfinimines and iminoesters: an efficient entry to enantiopure imidazolidines and vicinal diaminoalcohols.

A new procedure for the asymmetric synthesis of imidazolidines and vicinal diamines is reported. The 1,3-dipolar cycloaddition between nonracemic p-tolylsulfinimines and azomethine ylides generated in situ from alpha-iminoesters and LDA produces N-sulfinylimidazolidines with a high degree of stereocontrol. In contrast, the presence of Lewis acids promotes formation of the cycloadducts through a highly diastereoselective process with opposite stereochemistry. Subsequent transformations of the imidazolidines including oxidative, reductive, and hydrolytic processes that provide easy access to vicinal diaminoalcohols have been explored. Among these, reductive cleavage of the aminal with LiAlH4 is an extremely efficient and general reaction for the synthesis of enantiopure N-sulfinyl-N'-benzyldiaminoalcohols

Journal Article↗
PubMed2002

Hyalinizing clear cell carcinoma of salivary glands: a study of extracellular matrix.

Hyalinizing clear cell carcinoma (HCCC) is a recently described low-grade carcinoma of the salivary glands presenting two main histological features: clear neoplastic cells and prominent hyalinized stroma. Our aim was to characterize the composition of the hyalinized stroma in three cases of HCCC. An immuno-histochemical study using laminin and type I, III and IV collagens, fibronectin and tenascin antibodies was performed. In one case, electron microscopy study was also done. Collagen I and fibronectin were always present in tumoral stroma. Collagen III was documented in two cases and tenascin at the invasive front of the neoplasm. Collagen IV and laminin were found around neoplastic cells but not at the interstitial stroma. Foci of basal lamina reduplication and large deposits of long space collagen were observed in EM. This study demonstrates that the hyalinized stroma of HCCC is not formed by the accumulation of basement membrane-type material since it is mostly composed by collagen I and fibronectin.

Adenocarcinoma, Clear Cell↗
PubMed1999

Synthesis, X-ray Structure, and Electrochemical Oxidative Coupling Reactions of 1,5- and 2,6-Bis(1,4-dithiafulven-6-yl)naphthalenes.

Novel pi-extended tetrathiafulvalene (TTF) derivatives (12a-c, 13a-c, 15a-c) in which the two 1,3-dithiole units are connected through a naphthalene spacer have been prepared in high yields by Wittig-Horner olefination reaction from dialkoxy-substituted diformylnaphthalenes (11a,b, 14) and differently substituted phosphonate esters (10a-c). The electrochemical study revealed a similar behavior for the novel electron donor molecules (12a-c, 13a-c, 15a-c) regardless of the position of the 1,3-dithiole rings on the naphthalene core. The extended donors undergo an efficient electrooxidation process affording new oligomeric extended TTF species which exhibit lower oxidation potential values than their precursor donors. EPR experiments confirm the presence of the cation radical derived from the oligomeric TTF vinylogues and support an ECE process. The structural study has been carried out by X-ray analysis of 12a and semiempirical PM3 calculations and reveals a distorted geometry from the planarity with the naphthalene moiety forming an angle of approximately 35 degrees with the thiafulvalene rings. A good agreement was found between the experimental and calculated values, thus validating the PM3 method. The chemical oxidation of the synthesized donors (12a-c, 13a-c, 15a-c) with strong electron acceptors give rise to charge transfer complexes (CTC) which were characterized by UV-vis, FTIR, and EPR spectroscopy.

Journal Article↗
PubMedDate not supplied

[DNA flow cytrometry in solid tumors].

This brief overview outlines the fundamental principles of flow cytometry with emphasis on DNA measurements and cell cycle analysis in human solid tumors. Type of material used, sampling processing procedures and methods of analysis of data are discussed. DNA ploidy and proliferative activity (S-phase fraction) are the two biological parameters commonly measured by DNA flow cytometric analysis. The prime purpose of most studies in this area is the investigation of the prognostic value of DNA flow cytometry in addition to the information provided by conventional clinicopathological factors known to affect disease prognosis. Numerous studies concerning the predictive significance of DNA flow cytometry in some types of solid tumors are reviewed in this article. The general statement, for tumors in the same histopathological stage of the disease, is that diploid and/or low proliferative tumors have a more favourable prognosis than aneuploid and/or high proliferative tumors, suggesting an important role of DNA flow cytometry in the assessment of tumor behaviour and in the outcome evaluation of the disease. However, in some studies this association could not be substantiated, and the prognostic relevance of DNA analysis has been questioned. The potential reasons for conflicting results, namely the methodological pitfalls related to the cell preparation techniques and the histogram interpretation are discussed.

DNA, Neoplasm↗