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Papers by Isabel Fonseca

The Journal of Physical Chemistry C, 2014

The molecular mobility of ibuprofen confined to a mesoporous silica host (MCM-41) of 3.6 nm pore ... more The molecular mobility of ibuprofen confined to a mesoporous silica host (MCM-41) of 3.6 nm pore diameter is investigated by dielectric relaxation spectroscopy. It is confirmed that crystallization is suppressed; therefore, depending on the temperature, the guest exists in the glassy and supercooled state inside of the pores. A detailed relaxation map is provided where multiple processes are dynamically characterized, comprised of three processes that are also found for the bulk and two additional ones. The bulk-like processes include two secondary processes, a simple thermally activated one, a γ process and a Johari−Goldstein β JG process, and the one associated with the dynamic glass transition of molecules located in the pore center (α process). In confinement, all of these processes display deviations in its dynamical behavior relative to the bulk, the most dramatic one undergone by the α process, which exhibits Arrhenius-like temperature dependence upon approaching the glass transition instead of Vogel/Fulcher/ Tammann/Hesse (VFTH) scaling as obeyed by the bulk. The two additional relaxations are associated with the dynamical behavior of hydrogen-bonded ibuprofen molecules lying in an interfacial layer near the pore wall, an S process for which the mobility is strongly reduced relative to the α process and a Debye-like D process for which the dynamics is closely correlated to the dynamics of the interfacial process, both exhibiting VFTH temperature dependencies. The comparison with the behavior of the same guest in the analogous host, SBA-15, with a higher pore diameter (8.6 nm) leads to the conclusion that the bulk-like mobility associated with the dynamic glass transition undergoes finite size effects being accelerated upon a decrease of the pore size with a concomitant reduction of the glass transition temperature relative to the bulk, 22 and 32 K, respectively, for the 8.6 and 3.6 nm pore diameters. The continuous decrease in the separation between the αand β JG -trace with pore size decrease allows one to conclude that confined ibuprofen is a suitable guest molecule to test the Coupling Model that predicts a transformation of the α process into a β JG -mode under conditions of an extreme nanoconfinement. The overall behavior inside of pores is consistent with the existence of two distinct dynamical domains, originated by ibuprofen molecules in the core of the pore cavity and adjacent to the pore wall, from which a clear picture is given by molecular dynamics simulation.

Journal of Chemical Thermodynamics, 2005

Densities of the binary systems of 1,1-dimethylethyl methyl ether (MTBE) with allyl methacrylate,... more Densities of the binary systems of 1,1-dimethylethyl methyl ether (MTBE) with allyl methacrylate, butyl methacrylate, methacrylic acid, and vinyl acetate have been measured as a function of the composition, at 298.15 and 308.15K and atmospheric pressure, using an Anton Paar DMA 5000 oscillating U-tube densimeter. The calculated excess molar volumes were correlated with the Redlich–Kister equation and with a series

Background. The determinants of peritoneal fast transport status at the beginning of peritoneal d... more 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.

Nephron Clinical Practice, 2008

Anemia with low serum erythropoietin (EPO) is common in Portuguese transthyretin V30M amyloid pol... more Anemia with low serum erythropoietin (EPO) is common in Portuguese transthyretin V30M amyloid polyneuropathy (FAP). Low EPO production can be observed before clinical disease. Renal amyloidosis is observed in FAP, mainly in the medulla. Renal manifestations correlate with glomerular and vascular involvement, but not with tubulointerstitial deposition. To evaluate the potential role of renal amyloid deposits in the genesis of the EPO defect in FAP, we analyzed the renal biopsies of 12 patients (5 males, 7 females, aged from 29 to 54 years) with a clinical evolution varying from 3 to 12 (mean 5.4 +/- 2.8) years. Formalin-fixed, paraffin-embedded sections of renal biopsies were stained by Congo red. Amyloid deposits were assessed by a semiquantitative method based on the percentage of amyloid deposition in each renal structure. Hemoglobin, creatinine, urea, EPO and proteinuria were concomitantly evaluated and correlated with the pathological findings. Renal amyloid deposits were observed in all biopsies analyzed, independently of the neuropathy score. Low serum EPO levels were not related with either the amount of amyloid deposition or the renal clinical manifestations. Impairment of EPO production in FAP is not directly related to renal amyloid deposits and more studies are needed to clarify this question.

Oral Surgery, Oral Medicine, Oral Pathology, 1991

During a 30-year period 24 epithelial salivary gland tumors were diagnosed in children and adoles... more During a 30-year period 24 epithelial salivary gland tumors were diagnosed in children and adolescents less than 18 years of age. The cases were retrieved from a series of 759 consecutive cases of salivary gland tumors (3.2%) from the area corresponding to southern Portugal during the same period of time. The mean age of the patients was 13.4 years, and one case was congenital. There was a slight female predominance (male/female ratio 1: 1.7). The parotid gland was affected in most cases (70.8%). Seventeen neoplasms were benign, and the remaining seven were malignant. As in the adult group, pleomorphic adenoma was the most frequent benign tumor (68.8%), with similar histologic findings and clinical course. Mucoepidermoid carcinoma was the prevalent malignant tumor (20.8%), had a high grade of differentiation, and had a favorable outcome. The histologic pattern of the congenital neoplasm was similar to that of adult epithelial-myoepithelial carcinoma. (ORAL SURC ORAL MED ORAL PATHOL 1991;72:696-701)

International Journal of Oral and Maxillofacial Surgery, 1991

A submandibular endodermal sinus (yolk sac) tumor (EST-YST) is reported. The patient was a 1.5-ye... more A submandibular endodermal sinus (yolk sac) tumor (EST-YST) is reported. The patient was a 1.5-year-old girl exhibiting a rapidly growing tumor in the submandibular region. The lesion showed the typical microscopic features including Schiller-Duval bodies and colloid bodies. Alpha-fetoprotein immunoreactivity was expressed by most tumor cells. There was no clinical or radiological evidence of the presence of this tumor elsewhere in the body.

Ultrastructural Pathology, 1996

Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with peripheral radiating f... more Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with peripheral radiating filaments. These structures, which were formerly observed in only three cases of proliferative breast epithelial lesions, appeared in 0.5-1% of the neoplastic cells of a case of dedifferentiated acinic cell carcinoma of the parotid gland. Helioid bodies are related to rough endoplasmic reticulum cisternae, which suggests that they are the result of the condensation and partial crystallization of their contents when sequestrated into the nuclear compartment of the cell. The presence of helioid bodies may be related to secretory dysfunction of the tumor cells associated with the process of neoplastic dedifferentiation.

Journal of Pathology, 1993

We studied the AgNOR counts in 30 cases of adenoid cystic carcinoma from salivary glands (n = 18)... more We studied the AgNOR counts in 30 cases of adenoid cystic carcinoma from salivary glands (n = 18) and non-salivary sites (n=12) in an attempt to correlate them with the evolution of the disease. AgNOR counts per nucleus varied between 1·96 and 6·12 (mean value 4·2 ± 0·99) as compared with 1·21 ± 1·4 in normal salivary tissue. There was no significant difference between cases that had an unfavourable clinical outcome (recurrence, metastases, and/or died of the disease) and cases without disease complications (4·31 vs. 4·03 AgNORs per nucleus). No difference was found between tumours located at salivary and non-salivary sites or between major and minor salivary glands. AgNOR counts also did not correlate with the grade of differentiation of the neoplasms. In adenoid cystic carcinoma, AgNOR counts do not seem to be a prognostic indicator, in contrast to the usefulness of this method in other tumour types.

Genes Chromosomes & Cancer, 1999

We report the finding of clonal chromosome abnormalities in 13 short-term cultured squamous cell ... more We report the finding of clonal chromosome abnormalities in 13 short-term cultured squamous cell carcinomas (SCCs) of the skin. Intratumor heterogeneity, in the form of cytogenetically related (subclones) or unrelated clones, was detected in six tumors. Whereas clones with complex karyotypic changes were found in 6 tumors, clones with simple anomalies were observed in 10 tumors, and sometimes these clones coexisted with highly abnormal clones. Rearrangement of chromosome 8, in the form of isochromosome i(8q) or whole arm translocation, was the most common aberration, found predominantly in complex clones. Another recurrent feature, i.e., the centromeric rearrangement of chromosome 1, as isochromosome i(1q) or i(1p), or whole arm translocations, was always part of a complex karyotype. Homogeneously staining regions were found in two cases, one with a highly complex karyotype and the other with a simple karyotype. In order to obtain an overall karyotypic picture in SCC of the skin, the cytogenetic findings in 10 SCCs reported earlier were reviewed. The chromosomes most commonly affected were, in decreasing order, chromosomes 1, 11, 8, 9, 5, 3, and 7. Chromosomal sites most frequently rearranged were almost all pericentromeric: they were 8q10-q11, 1p10-q12, 5p10-q11, 11p15, and 9p10-q10. Recurrent anomalies were i(1q), i(8q), i(5p), i(1p), i(9p), and i(9q). Among them, only i(8q) and i(9q) might be assumed to be early genetic events, considering the fact that they could occasionally be identified in simple clones. The most frequent losses included part of or the entire chromosomes 2, 4, 9, 11, 14, 18, and 21, arm 8p, and chromosomes X, Y, and 13. Overrepresentation most frequently involved 1q, chromosome 7, and 8q. The characteristic karyotypic pattern observed in skin SCC was in line with the experience in several other carcinomas. Genes Chromosomes Cancer 26:295-303, 1999.

Oral Surgery, Oral Medicine, Oral Pathology, 1991

During a 30-year period 24 epithelial salivary gland tumors were diagnosed in children and adoles... more During a 30-year period 24 epithelial salivary gland tumors were diagnosed in children and adolescents less than 18 years of age. The cases were retrieved from a series of 759 consecutive cases of salivary gland tumors (3.2%) from the area corresponding to southern Portugal during the same period of time. The mean age of the patients was 13.4 years, and one case was congenital. There was a slight female predominance (male/female ratio 1: 1.7). The parotid gland was affected in most cases (70.8%). Seventeen neoplasms were benign, and the remaining seven were malignant. As in the adult group, pleomorphic adenoma was the most frequent benign tumor (68.8%), with similar histologic findings and clinical course. Mucoepidermoid carcinoma was the prevalent malignant tumor (20.8%), had a high grade of differentiation, and had a favorable outcome. The histologic pattern of the congenital neoplasm was similar to that of adult epithelial-myoepithelial carcinoma. (ORAL SURC ORAL MED ORAL PATHOL 1991;72:696-701)

Journal of Surgical Oncology, 1995

Cytogenetic findings of 21 benign salivary gland tumors, including 14 pleomorphic adenomas, 5 War... more Cytogenetic findings of 21 benign salivary gland tumors, including 14 pleomorphic adenomas, 5 Warthin's tumors, 1 myoepithelioma, and 1 cystadenoma, are reported. The present study confirms that pleomorphic adenomas characteristically have highly specific rearrangements involving only a few chromosome regions (3p21, 8q12 and 12q13–15) which suggests their specific role in the mixed tumors genesis. Warthin's tumors also show nonrandom numerical and structural alterations that were concurrent in one of the cases studied. To our knowledge no cytogenetic data are available in myoepitheliomas and cystadenomas. The former reveals a normal karyotype and the latter shows only clonal numerical alterations (gain of chromosomes 2 and 18). © 1995 Wiley-Liss, Inc.

European Journal of Cancer. Part B: Oral Oncology, 1996

A group of 19 malignant salivary gland neoplasms of various histological types (mucoepidermoid ca... more A group of 19 malignant salivary gland neoplasms of various histological types (mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, myoepithelial carcinoma, basal cell adenocarcinoma, carcinoma ex-pleomorphic adenoma, ductal carcinoma, adenocarcinoma not otherwise specified and undifferentiated carcinoma) were cytogenetically investigated. Previous karyotypic information revealed deletion of the long arm of chromosome 6, loss of chromosome Y and the gain of chromosome 8 as the most recurrent deviations found in these neoplasms. Clonal chromosome aberrations were detected in 11 cases of this series. In 7 of them there were only numerical deviations (gain of chromosomes 2, 7, 8, 10 and X and loss of chromosomes 18, 21 and Y) without concomitant structural anomalies. Structural rearrangements such as t(2;7), t(6;16), t(6;9) and t(1;1) translocations were found in two mucoepidermoid carcinomas, one adenoid cystic carcinoma and one ductal carcinoma, respectively. The wide spectrum of changes found in this group of neoplasms may reflect the diversity in their histogenesis and differentiation phenotypes.

Human Pathology, 1999

Laminin and collagen have been studied in several tumor types and their immunomorphological expre... more Laminin and collagen have been studied in several tumor types and their immunomorphological expression correlated with tumor morphogenesis, local invasiveness, and metastatic behavior. In a series of 53 cases of pleomorphic adenomas (PA) and 16 cases of carcinomas ex-pleomorphic adenoma (Ca ex-PA), we investigated by immunohistochemistry the distribution pattern of laminin (lam) and collagen IV (col IV) at the basement membrane (BM) and the interstitial compartments, and their potential relationship with the metastatic behavior of Ca ex-PA. At the BM compartment, lam and col IV were expressed in 37 and 41 of all cases, respectively. In PA, there were lam and col IV around cell aggregates in 47.2% and 56.6% of the cases, respectively, and around isolated cells in 30.2% and 26.4%, respectively. In Ca ex-PA cases, both antigens were expressed in 56.3% and in 18.8% of the cases around cell aggregates and isolated cells, respectively. At the interstitial compartment, the fibro-hyaline matrix contained few lam in PA (19.2%) in contrast to Ca ex-PA (75%), including the benign areas of the neoplasms (90%), being the difference statistically significant (P < .001). In the Ca ex-PA group, a statistically significant difference was found on col IV deposits around tumor cell aggregates between metastasizing and nonmetastasizing neoplasms (P < .001). These findings support that laminin and collagen IV are involved in the process of malignant transformation of pleomorphic adenomas and their biological progression.

Journal of Clinical Pathology, 1997

To evaluate whether the immunoexpression of c-erbB-2 and p53 is involved in the pathogenesis and ... more To evaluate whether the immunoexpression of c-erbB-2 and p53 is involved in the pathogenesis and progression of salivary tumours with myoepithelial differentiation. 233 tumours from 211 patients were studied. These included 76 primary and 24 recurrent adenocarcinomas (polymorphous low grade adenocarcinoma, 13; epithelial-myoepithelial carcinoma, 19; adenoid cystic carcinoma, 56; and basal cell adenocarcinoma, 12) and 133 pleomorphic adenomas and myoepitheliomas, 96 being primary and the remaining recurrent tumours. All cases were formalin fixed and paraffin wax embedded. A StrepABC peroxidase method and polyclonal c-erbB-2 and p53 specific antisera were used. Cell membrane staining of c-erbB-2 was not found in any benign or malignant tumour. There was p53 protein accumulation in one primary and one recurrent pleomorphic adenoma and in 10 adenocarcinomas (polymorphous low grade adenocarcinoma, one; epithelial-myoepithelial carcinoma, one; adenoid cystic carcinoma, five; and basal cell adenocarcinoma, three), three of them being recurrences. The c-erbB-2 and p53 proteins are not involved in the pathogenesis of pleomorphic adenoma and myoepithelioma and do not constitute biomarkers in assessing the risk of recurrence. c-erbB-2 is not involved in the genesis of low grade salivary neoplasia with myoepithelial differentiation. The percentage of this type of neoplasia with p53 accumulation is low (10%) and does not appear to be related to tumour recurrence.

Histopathology, 1996

A series of 19 cases of carcinoma ex-pleomorphic adenoma was studied for the immuno-expression of... more A series of 19 cases of carcinoma ex-pleomorphic adenoma was studied for the immuno-expression of c-erbB-2 oncoprotein. Twelve tumours showed a malignant component with only one histological type; in the remaining seven there was co-existence of areas of various carcinoma types, adenocarcinoma NOS being the most frequent. Membranous c-erbB-2 reactivity was found in 21.1% of the cases, all corresponding to high-grade adenocarcinomatous areas. The low-grade carcinoma types that formed the malignant mixed tumours components were negative. Benign pleomorphic adenoma areas, either adjacent or intermingled with carcinomatous areas, were also consistently negative, proving that c-erbB-2 accumulation is associated with the acquisition of the malignant phenotype. The finding of a preferential association between c-erbB-2 overexpression and high-grade malignant mixed tumour may indicate prognostic implications for the oncogene protein and may also be indicative of its specific relationship with the putative pathway of malignant transformation in pleomorphic adenomas.

Genes Chromosomes & Cancer, 2001

Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 sali... more Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 salivary gland tumors that had been investigated by banding analysis. Five cases were pleomorphic adenoma (PA), three were adenoid cystic carcinoma, and one case each was mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma (CaPA), and adenocarcinoma. All 11 cases were selected on the basis that they had shown rearrangement of 6q or 9p or had unresolved aberrations after karyotyping. The COBRA-FISH and FISH analyses led to a revised karyotype in all informative cases and made it possible to clarify almost all chromosomal rearrangements occurring in the tumors. Of particular note were the confirmation of the existence of 6q deletions, a common change in salivary gland carcinomas, and the demonstration that a seemingly balanced t(6;9) resulted in del(6q). Other rearrangements that were revealed by FISH included amplification of 12q sequences (MDM2 and CDK4) in one PA. We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements. Only in the former two cases were the FISH results compatible with intragenic rearrangements. Overall, the results of the study show that, even with good banding quality and in karyotypes of modest complexity, much new information will be gained by supplementing the banding analysis with a multicolor FISH approach, such as COBRA-FISH.

Oncogene, 1998

Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed ... more Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed in salivary gland carcinomas. To better de®ne the location of these deletions we investigated loss of heterozygosity (LOH) for 23 polymorphic markers within 19 salivary gland carcinomas covering several histological subtypes. LOH was observed in 47% of tumors, con®rming previous reports that such losses are frequent and occur in almost all histological subtypes of tumors. The highest frequency of LOH was found at, or distal to, D6S437. Seven tumors had allelic losses for D6S297 and/or D6S37. A second peak of loss was also observed at D6S262 and D6S32. In some tumors we observed LOH in one or the other of these two regions. In other tumors we observed loss of both regions with retention of intervening loci. These data suggest that two small deletions commonly occur, one between D6S262 and D6S32 (estimated to cover less than 1.5 Mb) and another between D6S297 and D6S446 (estimated to cover *2 Mb). These results extend previous studies by sublocalizing the regions of LOH and suggest that inactivation of one or more tumor suppressor genes located in these regions may be an important step in salivary gland carcinogenesis.

Virchows Archiv, 1997

We used three markers of cell proliferationmitotic counts, mitotic index and expression of prolif... more We used three markers of cell proliferationmitotic counts, mitotic index and expression of proliferating cell nuclear antigen -to assess the proliferative activity of a series of 78 low-grade salivary adenocarcinomas with myoepithelial participation classified according to: their histological type, the predominant architectural type, and the predominant cytological type. The series included adenoid cystic carcinomas (40), epithelial-myoepithelial carcinomas , polymorphous low-grade adenocarcinomas (12) and basal cell adenocarcinomas . The proliferation indicators were found to be similar in the first three groups, being significantly lower than in the last. Tumours formed by basal cells had statistically significant higher mitotic indexes than those predominantly composed of clear cells of myoepithelial type and ductal cells. Tubular tumours, irrespective of the histological classification of the neoplasm, had proliferation indexes similar to those found in cribriform neoplasms. Solid tumours, whether formed by ductal or clear myoepithelial-type cells, had higher indexes than the neoplasms with differentiated (cribriform and tubular) patterns. The highest mean values for every proliferation indicator used were found in tumours with solid organization that were predominantly formed by basal cells. These results agree with the hypothesis that cell proliferation is inversely related to neoplastic diflTerentiation. The identification of the prevalent cell phenotype and architecture may extend our knowledge from adenoid cystic carcinoma, whose solid variant carries a worse prognosis, and supports that the usual classification of this group of salivary adenocarcinomas would benefit to be I. TeL/Fax: complemented with information on tumour architecture and cellular composition.

Ultrastructural Pathology, 1996

Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with peripheral radiating f... more Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with peripheral radiating filaments. These structures, which were formerly observed in only three cases of proliferative breast epithelial lesions, appeared in 0.5-1% of the neoplastic cells of a case of dedifferentiated acinic cell carcinoma of the parotid gland. Helioid bodies are related to rough endoplasmic reticulum cisternae, which suggests that they are the result of the condensation and partial crystallization of their contents when sequestrated into the nuclear compartment of the cell. The presence of helioid bodies may be related to secretory dysfunction of the tumor cells associated with the process of neoplastic dedifferentiation.

Oncogene, 1998

Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed ... more Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed in salivary gland carcinomas. To better de®ne the location of these deletions we investigated loss of heterozygosity (LOH) for 23 polymorphic markers within 19 salivary gland carcinomas covering several histological subtypes. LOH was observed in 47% of tumors, con®rming previous reports that such losses are frequent and occur in almost all histological subtypes of tumors. The highest frequency of LOH was found at, or distal to, D6S437. Seven tumors had allelic losses for D6S297 and/or D6S37. A second peak of loss was also observed at D6S262 and D6S32. In some tumors we observed LOH in one or the other of these two regions. In other tumors we observed loss of both regions with retention of intervening loci. These data suggest that two small deletions commonly occur, one between D6S262 and D6S32 (estimated to cover less than 1.5 Mb) and another between D6S297 and D6S446 (estimated to cover *2 Mb). These results extend previous studies by sublocalizing the regions of LOH and suggest that inactivation of one or more tumor suppressor genes located in these regions may be an important step in salivary gland carcinogenesis.

The Journal of Physical Chemistry C, 2014

The molecular mobility of ibuprofen confined to a mesoporous silica host (MCM-41) of 3.6 nm pore ... more The molecular mobility of ibuprofen confined to a mesoporous silica host (MCM-41) of 3.6 nm pore diameter is investigated by dielectric relaxation spectroscopy. It is confirmed that crystallization is suppressed; therefore, depending on the temperature, the guest exists in the glassy and supercooled state inside of the pores. A detailed relaxation map is provided where multiple processes are dynamically characterized, comprised of three processes that are also found for the bulk and two additional ones. The bulk-like processes include two secondary processes, a simple thermally activated one, a γ process and a Johari−Goldstein β JG process, and the one associated with the dynamic glass transition of molecules located in the pore center (α process). In confinement, all of these processes display deviations in its dynamical behavior relative to the bulk, the most dramatic one undergone by the α process, which exhibits Arrhenius-like temperature dependence upon approaching the glass transition instead of Vogel/Fulcher/ Tammann/Hesse (VFTH) scaling as obeyed by the bulk. The two additional relaxations are associated with the dynamical behavior of hydrogen-bonded ibuprofen molecules lying in an interfacial layer near the pore wall, an S process for which the mobility is strongly reduced relative to the α process and a Debye-like D process for which the dynamics is closely correlated to the dynamics of the interfacial process, both exhibiting VFTH temperature dependencies. The comparison with the behavior of the same guest in the analogous host, SBA-15, with a higher pore diameter (8.6 nm) leads to the conclusion that the bulk-like mobility associated with the dynamic glass transition undergoes finite size effects being accelerated upon a decrease of the pore size with a concomitant reduction of the glass transition temperature relative to the bulk, 22 and 32 K, respectively, for the 8.6 and 3.6 nm pore diameters. The continuous decrease in the separation between the αand β JG -trace with pore size decrease allows one to conclude that confined ibuprofen is a suitable guest molecule to test the Coupling Model that predicts a transformation of the α process into a β JG -mode under conditions of an extreme nanoconfinement. The overall behavior inside of pores is consistent with the existence of two distinct dynamical domains, originated by ibuprofen molecules in the core of the pore cavity and adjacent to the pore wall, from which a clear picture is given by molecular dynamics simulation.

Journal of Chemical Thermodynamics, 2005

Densities of the binary systems of 1,1-dimethylethyl methyl ether (MTBE) with allyl methacrylate,... more Densities of the binary systems of 1,1-dimethylethyl methyl ether (MTBE) with allyl methacrylate, butyl methacrylate, methacrylic acid, and vinyl acetate have been measured as a function of the composition, at 298.15 and 308.15K and atmospheric pressure, using an Anton Paar DMA 5000 oscillating U-tube densimeter. The calculated excess molar volumes were correlated with the Redlich–Kister equation and with a series

Background. The determinants of peritoneal fast transport status at the beginning of peritoneal d... more 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.

Nephron Clinical Practice, 2008

Anemia with low serum erythropoietin (EPO) is common in Portuguese transthyretin V30M amyloid pol... more Anemia with low serum erythropoietin (EPO) is common in Portuguese transthyretin V30M amyloid polyneuropathy (FAP). Low EPO production can be observed before clinical disease. Renal amyloidosis is observed in FAP, mainly in the medulla. Renal manifestations correlate with glomerular and vascular involvement, but not with tubulointerstitial deposition. To evaluate the potential role of renal amyloid deposits in the genesis of the EPO defect in FAP, we analyzed the renal biopsies of 12 patients (5 males, 7 females, aged from 29 to 54 years) with a clinical evolution varying from 3 to 12 (mean 5.4 +/- 2.8) years. Formalin-fixed, paraffin-embedded sections of renal biopsies were stained by Congo red. Amyloid deposits were assessed by a semiquantitative method based on the percentage of amyloid deposition in each renal structure. Hemoglobin, creatinine, urea, EPO and proteinuria were concomitantly evaluated and correlated with the pathological findings. Renal amyloid deposits were observed in all biopsies analyzed, independently of the neuropathy score. Low serum EPO levels were not related with either the amount of amyloid deposition or the renal clinical manifestations. Impairment of EPO production in FAP is not directly related to renal amyloid deposits and more studies are needed to clarify this question.

Oral Surgery, Oral Medicine, Oral Pathology, 1991

During a 30-year period 24 epithelial salivary gland tumors were diagnosed in children and adoles... more During a 30-year period 24 epithelial salivary gland tumors were diagnosed in children and adolescents less than 18 years of age. The cases were retrieved from a series of 759 consecutive cases of salivary gland tumors (3.2%) from the area corresponding to southern Portugal during the same period of time. The mean age of the patients was 13.4 years, and one case was congenital. There was a slight female predominance (male/female ratio 1: 1.7). The parotid gland was affected in most cases (70.8%). Seventeen neoplasms were benign, and the remaining seven were malignant. As in the adult group, pleomorphic adenoma was the most frequent benign tumor (68.8%), with similar histologic findings and clinical course. Mucoepidermoid carcinoma was the prevalent malignant tumor (20.8%), had a high grade of differentiation, and had a favorable outcome. The histologic pattern of the congenital neoplasm was similar to that of adult epithelial-myoepithelial carcinoma. (ORAL SURC ORAL MED ORAL PATHOL 1991;72:696-701)

International Journal of Oral and Maxillofacial Surgery, 1991

A submandibular endodermal sinus (yolk sac) tumor (EST-YST) is reported. The patient was a 1.5-ye... more A submandibular endodermal sinus (yolk sac) tumor (EST-YST) is reported. The patient was a 1.5-year-old girl exhibiting a rapidly growing tumor in the submandibular region. The lesion showed the typical microscopic features including Schiller-Duval bodies and colloid bodies. Alpha-fetoprotein immunoreactivity was expressed by most tumor cells. There was no clinical or radiological evidence of the presence of this tumor elsewhere in the body.

Ultrastructural Pathology, 1996

Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with peripheral radiating f... more Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with peripheral radiating filaments. These structures, which were formerly observed in only three cases of proliferative breast epithelial lesions, appeared in 0.5-1% of the neoplastic cells of a case of dedifferentiated acinic cell carcinoma of the parotid gland. Helioid bodies are related to rough endoplasmic reticulum cisternae, which suggests that they are the result of the condensation and partial crystallization of their contents when sequestrated into the nuclear compartment of the cell. The presence of helioid bodies may be related to secretory dysfunction of the tumor cells associated with the process of neoplastic dedifferentiation.

Journal of Pathology, 1993

We studied the AgNOR counts in 30 cases of adenoid cystic carcinoma from salivary glands (n = 18)... more We studied the AgNOR counts in 30 cases of adenoid cystic carcinoma from salivary glands (n = 18) and non-salivary sites (n=12) in an attempt to correlate them with the evolution of the disease. AgNOR counts per nucleus varied between 1·96 and 6·12 (mean value 4·2 ± 0·99) as compared with 1·21 ± 1·4 in normal salivary tissue. There was no significant difference between cases that had an unfavourable clinical outcome (recurrence, metastases, and/or died of the disease) and cases without disease complications (4·31 vs. 4·03 AgNORs per nucleus). No difference was found between tumours located at salivary and non-salivary sites or between major and minor salivary glands. AgNOR counts also did not correlate with the grade of differentiation of the neoplasms. In adenoid cystic carcinoma, AgNOR counts do not seem to be a prognostic indicator, in contrast to the usefulness of this method in other tumour types.

Genes Chromosomes & Cancer, 1999

We report the finding of clonal chromosome abnormalities in 13 short-term cultured squamous cell ... more We report the finding of clonal chromosome abnormalities in 13 short-term cultured squamous cell carcinomas (SCCs) of the skin. Intratumor heterogeneity, in the form of cytogenetically related (subclones) or unrelated clones, was detected in six tumors. Whereas clones with complex karyotypic changes were found in 6 tumors, clones with simple anomalies were observed in 10 tumors, and sometimes these clones coexisted with highly abnormal clones. Rearrangement of chromosome 8, in the form of isochromosome i(8q) or whole arm translocation, was the most common aberration, found predominantly in complex clones. Another recurrent feature, i.e., the centromeric rearrangement of chromosome 1, as isochromosome i(1q) or i(1p), or whole arm translocations, was always part of a complex karyotype. Homogeneously staining regions were found in two cases, one with a highly complex karyotype and the other with a simple karyotype. In order to obtain an overall karyotypic picture in SCC of the skin, the cytogenetic findings in 10 SCCs reported earlier were reviewed. The chromosomes most commonly affected were, in decreasing order, chromosomes 1, 11, 8, 9, 5, 3, and 7. Chromosomal sites most frequently rearranged were almost all pericentromeric: they were 8q10-q11, 1p10-q12, 5p10-q11, 11p15, and 9p10-q10. Recurrent anomalies were i(1q), i(8q), i(5p), i(1p), i(9p), and i(9q). Among them, only i(8q) and i(9q) might be assumed to be early genetic events, considering the fact that they could occasionally be identified in simple clones. The most frequent losses included part of or the entire chromosomes 2, 4, 9, 11, 14, 18, and 21, arm 8p, and chromosomes X, Y, and 13. Overrepresentation most frequently involved 1q, chromosome 7, and 8q. The characteristic karyotypic pattern observed in skin SCC was in line with the experience in several other carcinomas. Genes Chromosomes Cancer 26:295-303, 1999.

Oral Surgery, Oral Medicine, Oral Pathology, 1991

During a 30-year period 24 epithelial salivary gland tumors were diagnosed in children and adoles... more During a 30-year period 24 epithelial salivary gland tumors were diagnosed in children and adolescents less than 18 years of age. The cases were retrieved from a series of 759 consecutive cases of salivary gland tumors (3.2%) from the area corresponding to southern Portugal during the same period of time. The mean age of the patients was 13.4 years, and one case was congenital. There was a slight female predominance (male/female ratio 1: 1.7). The parotid gland was affected in most cases (70.8%). Seventeen neoplasms were benign, and the remaining seven were malignant. As in the adult group, pleomorphic adenoma was the most frequent benign tumor (68.8%), with similar histologic findings and clinical course. Mucoepidermoid carcinoma was the prevalent malignant tumor (20.8%), had a high grade of differentiation, and had a favorable outcome. The histologic pattern of the congenital neoplasm was similar to that of adult epithelial-myoepithelial carcinoma. (ORAL SURC ORAL MED ORAL PATHOL 1991;72:696-701)

Journal of Surgical Oncology, 1995

Cytogenetic findings of 21 benign salivary gland tumors, including 14 pleomorphic adenomas, 5 War... more Cytogenetic findings of 21 benign salivary gland tumors, including 14 pleomorphic adenomas, 5 Warthin's tumors, 1 myoepithelioma, and 1 cystadenoma, are reported. The present study confirms that pleomorphic adenomas characteristically have highly specific rearrangements involving only a few chromosome regions (3p21, 8q12 and 12q13–15) which suggests their specific role in the mixed tumors genesis. Warthin's tumors also show nonrandom numerical and structural alterations that were concurrent in one of the cases studied. To our knowledge no cytogenetic data are available in myoepitheliomas and cystadenomas. The former reveals a normal karyotype and the latter shows only clonal numerical alterations (gain of chromosomes 2 and 18). © 1995 Wiley-Liss, Inc.

European Journal of Cancer. Part B: Oral Oncology, 1996

A group of 19 malignant salivary gland neoplasms of various histological types (mucoepidermoid ca... more A group of 19 malignant salivary gland neoplasms of various histological types (mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, myoepithelial carcinoma, basal cell adenocarcinoma, carcinoma ex-pleomorphic adenoma, ductal carcinoma, adenocarcinoma not otherwise specified and undifferentiated carcinoma) were cytogenetically investigated. Previous karyotypic information revealed deletion of the long arm of chromosome 6, loss of chromosome Y and the gain of chromosome 8 as the most recurrent deviations found in these neoplasms. Clonal chromosome aberrations were detected in 11 cases of this series. In 7 of them there were only numerical deviations (gain of chromosomes 2, 7, 8, 10 and X and loss of chromosomes 18, 21 and Y) without concomitant structural anomalies. Structural rearrangements such as t(2;7), t(6;16), t(6;9) and t(1;1) translocations were found in two mucoepidermoid carcinomas, one adenoid cystic carcinoma and one ductal carcinoma, respectively. The wide spectrum of changes found in this group of neoplasms may reflect the diversity in their histogenesis and differentiation phenotypes.

Human Pathology, 1999

Laminin and collagen have been studied in several tumor types and their immunomorphological expre... more Laminin and collagen have been studied in several tumor types and their immunomorphological expression correlated with tumor morphogenesis, local invasiveness, and metastatic behavior. In a series of 53 cases of pleomorphic adenomas (PA) and 16 cases of carcinomas ex-pleomorphic adenoma (Ca ex-PA), we investigated by immunohistochemistry the distribution pattern of laminin (lam) and collagen IV (col IV) at the basement membrane (BM) and the interstitial compartments, and their potential relationship with the metastatic behavior of Ca ex-PA. At the BM compartment, lam and col IV were expressed in 37 and 41 of all cases, respectively. In PA, there were lam and col IV around cell aggregates in 47.2% and 56.6% of the cases, respectively, and around isolated cells in 30.2% and 26.4%, respectively. In Ca ex-PA cases, both antigens were expressed in 56.3% and in 18.8% of the cases around cell aggregates and isolated cells, respectively. At the interstitial compartment, the fibro-hyaline matrix contained few lam in PA (19.2%) in contrast to Ca ex-PA (75%), including the benign areas of the neoplasms (90%), being the difference statistically significant (P < .001). In the Ca ex-PA group, a statistically significant difference was found on col IV deposits around tumor cell aggregates between metastasizing and nonmetastasizing neoplasms (P < .001). These findings support that laminin and collagen IV are involved in the process of malignant transformation of pleomorphic adenomas and their biological progression.

Journal of Clinical Pathology, 1997

To evaluate whether the immunoexpression of c-erbB-2 and p53 is involved in the pathogenesis and ... more To evaluate whether the immunoexpression of c-erbB-2 and p53 is involved in the pathogenesis and progression of salivary tumours with myoepithelial differentiation. 233 tumours from 211 patients were studied. These included 76 primary and 24 recurrent adenocarcinomas (polymorphous low grade adenocarcinoma, 13; epithelial-myoepithelial carcinoma, 19; adenoid cystic carcinoma, 56; and basal cell adenocarcinoma, 12) and 133 pleomorphic adenomas and myoepitheliomas, 96 being primary and the remaining recurrent tumours. All cases were formalin fixed and paraffin wax embedded. A StrepABC peroxidase method and polyclonal c-erbB-2 and p53 specific antisera were used. Cell membrane staining of c-erbB-2 was not found in any benign or malignant tumour. There was p53 protein accumulation in one primary and one recurrent pleomorphic adenoma and in 10 adenocarcinomas (polymorphous low grade adenocarcinoma, one; epithelial-myoepithelial carcinoma, one; adenoid cystic carcinoma, five; and basal cell adenocarcinoma, three), three of them being recurrences. The c-erbB-2 and p53 proteins are not involved in the pathogenesis of pleomorphic adenoma and myoepithelioma and do not constitute biomarkers in assessing the risk of recurrence. c-erbB-2 is not involved in the genesis of low grade salivary neoplasia with myoepithelial differentiation. The percentage of this type of neoplasia with p53 accumulation is low (10%) and does not appear to be related to tumour recurrence.

Histopathology, 1996

A series of 19 cases of carcinoma ex-pleomorphic adenoma was studied for the immuno-expression of... more A series of 19 cases of carcinoma ex-pleomorphic adenoma was studied for the immuno-expression of c-erbB-2 oncoprotein. Twelve tumours showed a malignant component with only one histological type; in the remaining seven there was co-existence of areas of various carcinoma types, adenocarcinoma NOS being the most frequent. Membranous c-erbB-2 reactivity was found in 21.1% of the cases, all corresponding to high-grade adenocarcinomatous areas. The low-grade carcinoma types that formed the malignant mixed tumours components were negative. Benign pleomorphic adenoma areas, either adjacent or intermingled with carcinomatous areas, were also consistently negative, proving that c-erbB-2 accumulation is associated with the acquisition of the malignant phenotype. The finding of a preferential association between c-erbB-2 overexpression and high-grade malignant mixed tumour may indicate prognostic implications for the oncogene protein and may also be indicative of its specific relationship with the putative pathway of malignant transformation in pleomorphic adenomas.

Genes Chromosomes & Cancer, 2001

Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 sali... more Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 salivary gland tumors that had been investigated by banding analysis. Five cases were pleomorphic adenoma (PA), three were adenoid cystic carcinoma, and one case each was mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma (CaPA), and adenocarcinoma. All 11 cases were selected on the basis that they had shown rearrangement of 6q or 9p or had unresolved aberrations after karyotyping. The COBRA-FISH and FISH analyses led to a revised karyotype in all informative cases and made it possible to clarify almost all chromosomal rearrangements occurring in the tumors. Of particular note were the confirmation of the existence of 6q deletions, a common change in salivary gland carcinomas, and the demonstration that a seemingly balanced t(6;9) resulted in del(6q). Other rearrangements that were revealed by FISH included amplification of 12q sequences (MDM2 and CDK4) in one PA. We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements. Only in the former two cases were the FISH results compatible with intragenic rearrangements. Overall, the results of the study show that, even with good banding quality and in karyotypes of modest complexity, much new information will be gained by supplementing the banding analysis with a multicolor FISH approach, such as COBRA-FISH.

Oncogene, 1998

Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed ... more Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed in salivary gland carcinomas. To better de®ne the location of these deletions we investigated loss of heterozygosity (LOH) for 23 polymorphic markers within 19 salivary gland carcinomas covering several histological subtypes. LOH was observed in 47% of tumors, con®rming previous reports that such losses are frequent and occur in almost all histological subtypes of tumors. The highest frequency of LOH was found at, or distal to, D6S437. Seven tumors had allelic losses for D6S297 and/or D6S37. A second peak of loss was also observed at D6S262 and D6S32. In some tumors we observed LOH in one or the other of these two regions. In other tumors we observed loss of both regions with retention of intervening loci. These data suggest that two small deletions commonly occur, one between D6S262 and D6S32 (estimated to cover less than 1.5 Mb) and another between D6S297 and D6S446 (estimated to cover *2 Mb). These results extend previous studies by sublocalizing the regions of LOH and suggest that inactivation of one or more tumor suppressor genes located in these regions may be an important step in salivary gland carcinogenesis.

Virchows Archiv, 1997

We used three markers of cell proliferationmitotic counts, mitotic index and expression of prolif... more We used three markers of cell proliferationmitotic counts, mitotic index and expression of proliferating cell nuclear antigen -to assess the proliferative activity of a series of 78 low-grade salivary adenocarcinomas with myoepithelial participation classified according to: their histological type, the predominant architectural type, and the predominant cytological type. The series included adenoid cystic carcinomas (40), epithelial-myoepithelial carcinomas , polymorphous low-grade adenocarcinomas (12) and basal cell adenocarcinomas . The proliferation indicators were found to be similar in the first three groups, being significantly lower than in the last. Tumours formed by basal cells had statistically significant higher mitotic indexes than those predominantly composed of clear cells of myoepithelial type and ductal cells. Tubular tumours, irrespective of the histological classification of the neoplasm, had proliferation indexes similar to those found in cribriform neoplasms. Solid tumours, whether formed by ductal or clear myoepithelial-type cells, had higher indexes than the neoplasms with differentiated (cribriform and tubular) patterns. The highest mean values for every proliferation indicator used were found in tumours with solid organization that were predominantly formed by basal cells. These results agree with the hypothesis that cell proliferation is inversely related to neoplastic diflTerentiation. The identification of the prevalent cell phenotype and architecture may extend our knowledge from adenoid cystic carcinoma, whose solid variant carries a worse prognosis, and supports that the usual classification of this group of salivary adenocarcinomas would benefit to be I. TeL/Fax: complemented with information on tumour architecture and cellular composition.

Ultrastructural Pathology, 1996

Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with peripheral radiating f... more Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with peripheral radiating filaments. These structures, which were formerly observed in only three cases of proliferative breast epithelial lesions, appeared in 0.5-1% of the neoplastic cells of a case of dedifferentiated acinic cell carcinoma of the parotid gland. Helioid bodies are related to rough endoplasmic reticulum cisternae, which suggests that they are the result of the condensation and partial crystallization of their contents when sequestrated into the nuclear compartment of the cell. The presence of helioid bodies may be related to secretory dysfunction of the tumor cells associated with the process of neoplastic dedifferentiation.

Oncogene, 1998

Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed ... more Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed in salivary gland carcinomas. To better de®ne the location of these deletions we investigated loss of heterozygosity (LOH) for 23 polymorphic markers within 19 salivary gland carcinomas covering several histological subtypes. LOH was observed in 47% of tumors, con®rming previous reports that such losses are frequent and occur in almost all histological subtypes of tumors. The highest frequency of LOH was found at, or distal to, D6S437. Seven tumors had allelic losses for D6S297 and/or D6S37. A second peak of loss was also observed at D6S262 and D6S32. In some tumors we observed LOH in one or the other of these two regions. In other tumors we observed loss of both regions with retention of intervening loci. These data suggest that two small deletions commonly occur, one between D6S262 and D6S32 (estimated to cover less than 1.5 Mb) and another between D6S297 and D6S446 (estimated to cover *2 Mb). These results extend previous studies by sublocalizing the regions of LOH and suggest that inactivation of one or more tumor suppressor genes located in these regions may be an important step in salivary gland carcinogenesis.