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C Carda

Publications and source records attributed to C Carda.

At least 19 recordsLinked to original sources

Ultrastructural patterns of human dentinal tubules, odontoblasts processes and nerve fibres.

The structure of the dentin, consists of the following elements: the odontoblastic processes, dentinal tubules and their periodontoblastic spaces. The odontoblasts are aligned in a single layer in the periphery of the dental pulp and secrete the organic components of dentin. The vitality of dentin is mediated too by the nerve fibres. The ultrastructure of the trigeminal sensory nerves in dentin, especially in relation to odontoblasts remains to be clarified. We studied the third molars and young premolars. The specimens were fixed in glutaraldehyde immediately after extraction. Our investigations give evidence to prove that the distribution of the dentinary tubules is homogeneous, containing a principal odontoblastic prolongation in the regions of the inner dentine, and only in special cases more than one. The area of the dentinary tubules and the odontoblastic prolongations' area were studied. The nervous fibres appeared accompanying 30-70% of the odontoblastic prolongations and their synapsis-like relation with the odontotoblastic processes was demonstrated. The existence of very few periodontoblastic spaces, and intradentinal sensory axons, as well as the intercellular connections will allow us to discover more about the mechanisms of the dentinary permeability, and its significance in maintenance and repair of the human pulpodentinal complex.

Adolescent↗

Osteoprotegerin (OPG) and RANKL expression and distribution in developing human craniomandibular joint.

During embryogenesis the bone tissue of craniomandibular joint (CMJ) is formed through two pathways: intramembranous ossification and endochondral ossification. The development process is under the control of regulatory factors. The osteoprotegerin (OPG) and the receptor activator of nuclear factor (NF)-kappaB ligand are key regulators of osteoclastogenesis. The aim of this study is the localization of OPG and RANKL mRNA and protein in the foetal CMJ by immunohistochemistry (IHC) and in situ hybridization (ISH). The main results were: OPG and RANKL mRNA and protein were co-localized in the same cell types; OPG and RANKL were specially immunolocated in osteogenic cells; immunolabeling was often seen in the nucleus and cytoplasm of otherwise negative hypertrophic chondrocytes; IHC and ISH labeling decreased from proliferative to hypertrophic chondrocytes; early osteocytes showed dual protein expression and some of the mature osteocytes were ISH-negative; periosteal osteoclasts and chondroclasts were mostly stained by IHC and variably labeled by ISH; the new bone matrix and trabecular borders showed intense immunolabeling. The co-expression of OPG and RANKL in the same bone cell types confirms their strictly coupled action in the regulation of bone metabolism in the CMJ development and their extracellular presence in the new bone matrix and trabecular borders suggests a local regulatory role.

Carrier Proteins↗

Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers.

AIMS: To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers. METHODS AND RESULTS: Clinical data and follow-up, histopathological features (pattern, cell size, thickness, mitoses, vascular invasion, lymphocytic infiltration) and immunohistochemical detection [CK20, thyroid transcription factor (TTF-1), chromogranin A, synaptophysin, p53, Ki67, Fli-1, CD99, c-Kit] were evaluated in 20 cases of MCC. Fli-1 and CD99 were detected in 90% and 55% of cases, respectively. Tumour size>30 mm, stage II, 'absent' lymphocytic infiltration, and the presence of>50% of Ki67+ tumour cells, were found to be prognostic indicators of disease-free interval (DFI), but only 'absent' lymphocytic infiltration constituted an independent prognostic factor of DFI after multivariate analysis. For overall survival, the same variables, together with local recurrence and lymph node involvement, had prognostic significance, with only local recurrence as an independent prognostic factor after multivariate analysis. CONCLUSIONS: Absence of lymphocytic infiltration and Ki67 immunoreactivity in more than 50% of tumour cells should be evaluated in conjunction with other well-known prognostic markers in MCC. Furthermore, recognizing that Fli-1 and CD99 expression is commonly found in MCC by immunohistochemistry may avoid misinterpretation in the differential diagnosis of MCC with other small round cell tumours.

12E7 Antigen↗

Ultrastructural and immunohistochemical characterization of the so-called giant multinucleate cells in cutaneous collagenomas.

AIMS: This study was undertaken to compare the histopathological, immunohistochemical and ultrastructural features of the so-called giant multi nucleate cells in cutaneous collagenomas: giant-cell collagenoma and solitary sclerotic fibroma. METHODS AND RESULTS: We studied four collagenomas: one giant-cell collagenoma and three solitary sclerotic fibromas. All the cases showed an indolent clinical presentation and were histologically constituted by a well-demarcated dome-shaped proliferation of coarse collagen bundles with a varying number of interspersed giant multinucleate cells and stellate mononuclear cells. The immunohistochemical study on paraffin sections revealed that neoplastic cells in both collagenomas were vimentin and CD34-positive, whereas FXIIIa was only expressed in solitary sclerotic fibromas. In regard to the so-called giant multinucleate cells, we have ultrastructurally found that these cells were 'real' multinucleate cells in giant-cell collagenoma, whereas in solitary sclerotic fibromas they consisted of closely packed aggregates of individual stellate mononuclear cells. Moreover, perinuclear cisternae focally containing finely textured material of moderate density were unexpectedly found in giant cells of giant-cell collagenoma, a finding which was not observed in solitary sclerotic fibromas. Additionally, a characteristic cell-cell interaction between tumour cells and mast cells was encountered in all collagenomas. CONCLUSIONS: This study supports a distinctive immunohistochemical and overall ultrastructural profile of giant multinucleate cells in giant-cell collagenoma and solitary sclerotic fibroma, which suggests a different pattern of differentiation for these two related cutaneous lesions.

Adult↗

Molecular analysis of the 9p21 locus and p53 genes in Ewing family tumors.

SUMMARY: The EWS-ETS rearrangements, and their respective fusion gene products, are specifically associated with histopathologically Ewing family tumors (EFT). These translocations are implicated in generating malignant transformation of EFT, but the presence of additional genetic alterations must be considered in the pathogenesis of such tumors. We analyzed 26 samples (biopsies and/or nude mice xenotransplants) collected from 19 patients with an EFT to determine whether molecular and cytogenetic alterations of the G(1)/S checkpoint genes are implicated in the pathogenesis of EFT. We found inactivating p53 mutations in three (16%) cases, which correlated with a loss of p21(WAF1/Cip1) expression and with a monosomy of chromosome 17 in two cases. Homozygous deletion of the p16(INK4A)/p14(ARF) gene was detected in four (21%) cases, three with codeletion of the p15(INK4B) gene and with chromosome 9 abnormalities. In all of these cases, expression of the implicated genes was absent. Hypermethylation of the p16(INK4A) and p15(INK4B) genes was detected in two (10%) and three (16%) cases, respectively, and was correlated with a low level of gene expression. Neither cyclin D1, nor MDM2 and CDK4 amplification was observed. Kaplan-Meier analysis showed that patients with tumors carrying homozygous deletion of the 9p21 locus, or point mutations of the p53 gene, had poorer outcomes than those without these molecular alterations (p = 0.005). In conclusion, 58% (11 of 19) of the analyzed patients showed genetic or epigenetic alterations in either the 9p21 locus or p53 tumor suppressor genes, defining a subgroup of patients with poor clinical outcome. This fact points to an important role of the G(1)/S cell cycle checkpoint dysregulation in the pathogenesis of EFT.

Adolescent↗

Translocation (10;11;22)(p14;q24;q12) characterized by fluorescence in situ hybridization in a case of Ewing's tumor.

It is well recognized that the identification by classic cytogenetics of t(11;22)(q24;q12) is a useful aid in the accurate diagnosis of Ewing's sarcoma and related tumors. This translocation induces the EWS/FLI-1 fusion transcript, which can be detected by reverse transcription-polymerase chain reaction. Recent studies have also used fluorescence in situ hybridization (FISH) to demonstrate the translocation. The authors coupled classic cytogenetics and FISH on tumor cells from the original specimen, the local recurrence, and the pulmonary metastasis as well as from the xenografted tumors in a case of extraosseous Ewing's sarcoma. FISH analysis not only confirmed the cytogenetic results but also allowed the identification of a tumor-specific chromosome change, consistent with a complex translocation, t(10;11;22), as well as revealed other chromosomal rearrangements on both metaphases and interphase nuclei of each material. In addition this technique served to identify, in the interphase nuclei of the original tumor, the clone that became dominant, from the cytogenetic point of view, in the lung metastasis and in the nude mice xenografted tumors. Current results indicate that the use of FISH on metaphases and interphase nuclei is an easy and reliable approach to complement or even to substitute classic cytogenetic studies for the detection of specific chromosomal rearrangements, especially for determining complex translocations and for describing tumoral clones with different cytogenetic markers.

Bone Neoplasms↗

Characterization of a new rat cell line established from 2'AAF-induced combined hepatocellular cholangiocellular carcinoma.

A rat cell line-nominated CC-62 derived from a combined hepatocellular and cholangiocellular carcinoma obtained by administration of 2-acetylaminofluorene to male Wistar rats, has been established. Using light and electron microscopy it was determined that morphologically the tumor consisted of a mixed population of hepatocytes and cholangiolar neoplastic cells, intermingled with small, undifferentiated oval-like cells. The CC-62 line has been maintained through 90 passages in culture adopting a paving stone arrangement. Doubling time at the 12th passage was 23 h. Immunostaining with a panel of antisera was performed to identify the cytological profiles of the cell line. There was no k-ras or p53 expression by immunohistochemistry, and molecular biology failed to detect mutations. Molecular analysis by reverse transcriptase-polymerase chain reaction revealed transcripts for c-met but no expression of HGF messenger ribonucleic acid. Three cell lines cloned from CC-62 showed the same immunohistochemical and molecular pattern as the parental line. Cytogenetic analysis revealed a chromosome number ranging from 74 to 82 with a modal number of 79 but no clonal structural abnormalities were found. Deoxyribonucleic acid ploidy analysis showed an aneuploid peak. CC-62 caused tumors 1 mo after subcutaneous transplantation into nude mice, with morphological patterns of mucosecretory solid and spindle-shaped carcinoma. This cell line is the first established from a primary rat combined hepatocellular and cholangiocellular neoplasm. The resulting cells expressed biological and morphological markers of hepatocytes and cholangiolar cells. Therefore this cell line may contribute to a better understanding of the histogenesis of liver cancer.

2-Acetylaminofluorene↗

Clear cell syringoid carcinoma: an ultrastructural and immunohistochemical study.

Syringoid carcinoma (syringoid "eccrine" carcinoma or eccrine epithelioma) is a rare cutaneous tumor with some controversy regarding its correct definition. It may also be difficult to differentiate from its benign counterpart (syringoma), other adnexal carcinomas, and cutaneous metastasis from adenocarcinomas. We present a case of a syringoid carcinoma of the clear cell variant complemented with an immunohistochemical and ultrastructural study, the latter revealing cytoplasmic accumulation of glycogen and presence of intercellular and intracellular lumina in clear tumor cells, as well as diverse hallmarks of malignancy (i.e., perineural invasion, tumor necrosis, and deep invasion). Clear tumor cells showed cytoplasmic and membranous immunoreactivity to epithelial membrane antigen, carcinoembryonic antigen, keratins, and S-100. Our ultrastructural and immunohistochemical results support the ductal differentiation of the glycogen-filled clear cell tumor population.

Aged↗

Soft tissue Ewing sarcoma--peripheral primitive neuroectodermal tumor with atypical clear cell pattern shows a new type of EWS-FEV fusion transcript.

This study describes a new case of Ewing sarcoma (ES)-peripheral primitive neuroectodermal tumor (pPNET) with unusual phenotype and fusion gene structure. The tumor located in the inguinal area of a 15-year-old boy showed a highly aggressive behavior with hematogenous metastases after intensive chemotherapy and bone marrow transplant, causing death 28 months after diagnosis. The tumor displayed a clear cell pattern, and several neuroectodermal markers proved positive both in the original tumor and in xenografts. This neuroectodermal character was confirmed by electron microscopy. Moreover, cytogenetically the tumor has an unusual chromosomal rearrangement, t(2;22)(q13;q22,t(3;18)(p21;q23); representing a new EWS-FEV fusion type in which exon 7 of EWS gene is fused with exon 2 of FEV gene. This is the third published study of an ES-pPNET showing EWS-FEV fusion described, but it is the first study of a tumor with the aforementioned fusion points. These findings support the genetic and morphologic heterogeneity existing within the group of ES-pPNET tumors.

Adolescent↗

Near-haploidy in a malignant sacrococcygeal teratoma.

Cytogenetic analysis of a malignant sacrococcygeal teratoma in an adult patient revealed near-haploid (77%), near-diploid (19%), and polyploid (4%) cells. The near-haploid cells had a karyotype of 25,XX,der(5)t(5;7)(p15;p13),+7,der(9)t(6;9)(p21;q34),r(17)(p13q25) . In the near-diploid and polyploid cells identical copies of the structural chromosomal changes were found. Although some of the anomalies observed appear unique to this case, a common breakpoint in chromosome 6 was previously reported as specific in a subgroup of extragonadal germ cell tumors of adults.

Aged↗

Endometrial stromal sarcomas: immunohistochemical, electron microscopical and cytogenetic findings in two cases.

Uterine sarcomas are approximately 3% of all malignant uterine corpus tumours. Of these, the tumours that originate solely in the stromal elements of the uterine wall are infrequent and have not been well characterized cytogenetically. We report two cases of endometrial stromal sarcomas (ESS), one low grade and one high grade, diagnosed by conventional histology, immunocytochemistry, electron microscopy and cytogenetics. Morphologically clear-cut differential structures were seen at optical, immunohistochemical, and electron microscopic levels, permitting a clear differential diagnosis. The low-grade ESS expressed hormonal receptors and vimentin, whereas the high-grade ESS showed no hormone receptors, high Ki-67 activity, and occasional cytokeratin-positive cells. Ultrastructurally, no malignant epithelial differentiation was seen in the tumour cells, but cilia were found in both cases. Cytogenetic study of the low-grade ESS showed pseudodiploid karyotype with chromosomes 6 and 20 rearranged. The high-grade ESS showed a complex karyotype with clonal numerical and structural anomalies. The chromosomes involved in the structural rearrangements were 1, 3, 6, 7, 13, 14, 15, 17, 19, and 21.

Aged↗

Analysis of p53 and mdm2 proteins in malignant fibrous histiocytoma in absence of gene alteration: prognostic significance.

TP53 and MDM2 genes and their protein expression were evaluated in frozen and paraffin-embedded tissue from 27 patients with malignant fibrous histiocytoma to elucidate the relationship between them, their implication in tumor progression mechanisms and their possible diagnostic-prognostic value in malignant fibrous histiocytoma. Single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA were used to establish two TP53 mutations (7.4%): a point mutation and a 63-bp duplication. Amplification of the MDM2 gene was observed in two tumors (7.4%) by means of Southern-blot analysis, one of them also carrying the TP53 point mutation. Immunohistochemical and Western-blot techniques were used to study nuclear accumulation of p53 and mdm2 proteins: 11 cases (40.7%) with p53 protein expression and thirteen cases (48.1%) with mdm2 protein expression were detected. We confirmed overexpression of mdm2 protein in eight of ten cases (80%) with p53 protein expression without TP53 gene mutation. Statistical analysis shows that simultaneous co-expression of p53 and mdm2 in malignant fibrous histiocytoma is significantly correlated with survival in absence of gene alteration in contrast to the lack of statistical correlation with survival of p53 protein expression alone.

Animals↗

Toxicological assessment of recombinant xylanase X(22) in wine.

Toxicological evaluation of xylanase X(22) from Aspergillus nidulans expressed in a wine yeast strain was carried out. The safety of the X(22) intake was assessed by digestibility, bioinformatic, and mouse short-term repeated dosing studies, although X(22) shows resistance to proteolytic degradation in the gastrointestinal system, is a minority protein component (<0.5 10(-)(6) %) of the produced wine, and shows no significant amino acid sequence homology to any known food allergens. The 4-week oral toxicity study was performed in Swiss mice at a dose level of 0.01, 0.1, or 1 mg/kg/day (these dosages correlate to 8, 80, and 800 times, respectively, the enzyme amount contained in 250 mL of wine). Body weight, food and fluid intake, urinalysis, and hematology data were obtained. Postmortem examinations and histopathology by both light and electron microscopy were performed. According to the results of this study, no adverse effects were detected by oral administration of X(22).

Allergens↗

New type of chimeric fusion product between the EWS and ATFI genes in clear cell sarcoma (malignant melanoma of soft parts).

We report a new case of clear cell sarcoma (CCS) harboring the t(12;22)(q13;q12). Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the presence of a chimeric transcript between the EWS and ATFI genes, both in primary and metastatic tissue. Sequencing studies disclosed an in-frame fusion between EWS gene codon 265 and ATFI gene codon 110. This breakpoint has not been reported previously and indicates an important in vivo loss of EWS and ATFI gene domains, which could be associated with the unusually aggressive behavior of this tumor.

Adult↗

Nasal mucociliary transport and ciliary ultrastructure in cystic fibrosis. A comparative study with healthy volunteers.

Cystic fibrosis (CF) is a deadly hereditary disease that produces an abnormally thick, viscous and abundant secretion in the respiratory tract. This secretion in turn leads to the development of recurrent respiratory infections and irreversible lung damage. We have studied nasal mucociliary transport by means of an isotopic technique in 12 patients with CF and in 12 healthy volunteers. Nasal mucociliary transport was repeated at 12-18 months in the patients. In five randomly selected patients ciliary ultrastructure was studied. The velocity of nasal mucociliary transport was significantly slower than in healthy persons (P < 0.001) and no significant differences were observed in both studies (P < 0.05). No significant differences were either observed in the CF group between the homo- and heterozygotes (P < 0.5), or in those six patients infected by Pseudomonas aeruginosa (P < 0.05). Ciliary ultrastructure was normal in one patient. In another patient the sample showed no cilia, while the remaining three exhibited changes similar to those observed in chronic respiratory infections: supernumerary peripheral tubules, ciliary disorientation and ciliary complexes.

Adolescent↗

Erythrophagocytic tumour cells in melanoma and squamous cell carcinoma of the skin.

AIMS: Erythrophagocytosis is a characteristic feature of tumour cells in malignant histiocytosis, some leukaemias, lymphomas, and also reactive histiocytes in the haemophagocytic syndrome associated with a variety of infections and neoplasms. It has also been found exceptionally in metastatic malignant epithelial cells in bone marrow and lymph nodes. We present two cases, a cutaneous malignant melanoma and an acantholytic squamous cell carcinoma, in which erythrophagocytosis by tumour cells was demonstrable by both light and electron microscopy. METHODS AND RESULTS: The melanocytic and squamous nature of these cells was supported by the immunohistochemical detection of HMB45, S100, and NKI-C3 in the former, and cytokeratin and EMA in the latter, and at ultrastructural level by the presence of melanosomes and tonofilaments, respectively. CONCLUSIONS: This is, to our knowledge, the first documented report of erythrophagocytic tumour cells in human melanomas and primary carcinomas. Biological considerations apart, this unusual feature can prove to be of value to avoid a misdiagnosis of a variety of haematopoietic malignancies.

Aged↗