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Biomedical subjects

E Perentes

Publications and source records attributed to E Perentes.

At least 37 records · Page 2Linked to original sources

Proliferating cell nuclear antigen immunoreactivity in human central nervous system neoplasms.

Formalin-fixed, paraffin-embedded surgical specimens from 140 primary human central nervous system tumors, including 51 meningiomas, 26 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 5 ependymomas, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained using a streptavidin/peroxidase method and the PC10 monoclonal antibody, which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above neoplasms: meningiomas, 3.80 +/- 7.35%; astrocytomas, 0.65 +/- 1.03%; anaplastic astrocytomas, 8.46 +/- 7.95%; glioblastomas, 10.26 +/- 11.21; gliosarcoma, 46.34%; oligodendrogliomas, 2.31 +/- 3.59%; ependymomas, 1.12 +/- 2.10%; medulloblastomas, 23.91 +/- 11.95%; and paragangliomas, 2.07 +/- 1.86%. Collectively, our findings indicate that while benign central nervous system tumors generally have low PCNA LI values, consistent over-expression of PCNA epitopes was noted in some examples, especially in a number of meningiomas. Among the malignant neuroectodermal tumors, medulloblastomas were found to have the highest PCNA LI values, corresponding to their histological grade of malignancy, and malignant glial tumors generally displayed significantly higher PCNA LI values, than their benign counterparts. Although in our study mean PCNA LI values seemed to reflect histological grading, large discrepancies were noted in all tumor groups. Our data, therefore, suggest than PCNA immunoreactivity can not be considered reliable for predicting the prognosis of the disease in individual cases.

Antigens, Neoplasm↗

p53 protein expression in central nervous system tumors: an immunohistochemical study with CM1 polyvalent and DO-7 monoclonal antibodies.

Formalin-fixed, paraffin-embedded surgical specimens from 137 primary central nervous system tumors, including 26 astrocytomas (21 fibrillary, 1 protoplasmic, 1 gemistocytic and 3 pilocytic), 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 4 ependymomas, 1 anaplastic ependymoma, 2 subependymomas, 3 paragangliomas, and 57 meningiomas, were immunostained with the CM1 polyclonal (pAb) and the DO-7 monoclonal (mAb) antibodies against the p53 protein, using the streptavidin/peroxidase method. In addition, two series of 17 and 9 medulloblastomas were also immunostained with the above pAb and mAb, respectively. p53 protein expression was observed in 7 fibrillary astrocytomas, 17 anaplastic astrocytomas, 5 glioblastomas, 1 gliosarcoma, 1 oligodendroglioma, 1 anaplastic ependymoma, and 4 meningiomas with the CM1 pAb. An additional 10 cases (i.e., 3 anaplastic astrocytomas and 7 meningiomas) were found to be p53 protein positive with the DO-7 mAb. Of the medulloblastomas, 8 (of the 17) and 4 (of the 9) were found to express p53 protein with CM1 pAb and DO-7 mAb, respectively. Our results indicate that p53 protein is expressed in a number of central nervous system neoplasms, and suggest that in astrocytic tumors a possible association may exist between p53 protein expression and tumor progression through increasing histological grades of malignancy.

Antibodies, Monoclonal↗

Neuron-associated class III beta-tubulin isotype, retinal S-antigen, synaptophysin, and glial fibrillary acidic protein in human medulloblastomas: a clinicopathological analysis of 36 cases.

Surgical specimens from 36 medulloblastomas (25 classic and 11 desmoplastic) were studied by peroxidase-antiperoxidase (PAP) immunohistochemistry with antibodies against the class III beta-tubulin isotype (beta-tubulin), synaptophysin, retinal S-antigen (S-Ag), and glial fibrillary acidic protein (GFAP). We found that neoplastic cells expressed beta-tubulin in 91% of the tumors (23 classic and 10 desmoplastic), synaptophysin in 75% (19 classic and 8 desmoplastic), S-Ag in 44% (11 classic and 5 desmoplastic), and GFAP in 11% of medulloblastomas (2 classic and 2 desmoplastic). Synaptophysin and beta-tubulin positivities were observed in undifferentiated neoplastic cells, in cells forming neuroblastic rosettes, and in pale islands, while S-Ag immunopositivity was noted in undifferentiated cells, occasionally in beta-tubulin-negative neuroblastic rosettes, and exceptionally in pale islands. Large pale islands, in two desmoplastic medulloblastomas, exhibited distinct patterns of immunoreactivity to the above markers, suggesting neuronal and glial differentiation in the central area, and intense neuritic development in the peripheral zone. Our findings confirm the predominant capacity of medulloblastoma cells to differentiate along neuronal cell lines and indicate that large pale islands, in desmoplastic medulloblastomas, represent well-organized areas for neuronal and, to a lesser degree, astroglial differentiation. Furthermore, it appears, in our cases, that immunohistochemical features do not represent clear-cut prognostic indicators in patients with medulloblastomas.

Adolescent↗

The growth of two murine hemangioendotheliomas intracranially, subcutaneously, and in culture, and their comparison with human cerebellar hemangioblastomas: morphological and immunohistochemical studies.

Two thorium dioxide-induced murine hemangioendotheliomas, 42021 TCT and 44347 TST, were grown subcutaneously (for up to 22 and 15 passages respectively) or intracranially (single passage) and were adapted to culture as a monolayer and, in a limited fashion, in an organ culture system or in rotary suspension. They remained viable and malignant following 20-21 years of storage in liquid nitrogen, and had ultrastructural similarities to human hemangioblastomas. The murine tumors were positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding, establishing their endothelial nature; however, unlike human hemangioblastic tumors, they did not cross-react with antisera to human factor VIII or fibronectin and they did not demonstrate Ulex europaeus type I lectin (UEA I) binding (as is also the case for non-neoplastic murine vascular endothelial cells). A variety of morphological cell types in cultures derived from the tumors were also positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding. Both murine hemangioendotheliomas, when implanted in the cerebrum, were potent inducers of reactive gliosis, but there was no evidence of uptake of glial fibrillary acidic protein. Unlike the human cerebellar hemangioblastomas, murine tumors were malignant and invasive and did not contain stromal cells, nor did they demonstrate Weibel-Palade bodies or extensive pinocytotic activity. Thus, the murine tumors appear to more closely resemble angiosarcomas or epitheloid hemangioblastomas than the cerebellar hemangioblastomas.

Animals↗

Morphological, immunohistochemical, stereological and nuclear shape characteristics of proliferative Leydig cell alterations in rats.

Proliferative Leydig cell (LC) alterations (hyperplasia, adenoma) of laboratory rats often pose diagnostic problems because the progression from normal to hyperplasia to neoplasia is continuous. The LC compartments of 130 Wistar rats (kfm: WIST strain) of approximately 2 years of age were examined. Ten typical cases conventionally classified as being normal or as showing diffuse or focal hyperplasia or small or large adenomata were investigated in more detail. In large adenomata, areas with large and small LC nuclei were identified. Immunohistochemical characterization, EM examination, as well as stereologic and planimetric investigations were performed. Hyperplastic and neoplastic LC essentially retained their normal appearance and immunohistochemical characteristics, but were found to contain more lipid droplets, fibroblast-like cells and patches of collagen than normal LC at the EM level. LC proliferation was accompanied by significant LC hypertrophy. LC nuclei of hyperplastic LC compartments were slightly larger while those of LC adenoma were markedly larger than nuclei of normal LC. The values for circle-related and ellipticity factors indicated that the nuclei of normal and hyperplastic LC were more markedly oval than nuclei of neoplastic LC. Concavity factor and bending energy measurements revealed that the small and oval nuclei of normal and hyperplastic LC had significantly more and deeper indentations than the larger and somewhat rounder nuclei of neoplastic LC. It is concluded that LC proliferations conventionally diagnosed as hyperplasia or adenoma on the basis of their size were composed of cytologically different LC populations.

Adenoma↗

In situ analysis of adenohypophysis proliferative activity in beagle dogs. Preliminary results.

In order to establish control data on adenohypophysis cell cycle in beagle dogs, two different approaches were used. In the first approach, the adenohypophysis mitotic index (percentage of cells in mitosis: MI) was determined using pituitary glands from 50 control beagle dogs, 10 to 25 months old, from retrospective regulatory safety assessment studies. We found that the MI in males was 0.024 +/- 0.007% and in females 0.068 +/- 0.019%. The second approach involved the determination of the adenohypophysis cell fraction in S phase by means of bromodeoxyuridine (BrdU) anti-BrdU method in 16 control beagle dogs, 8 to 20 months old, from ongoing safety assessment studies. We found that the BrdU labeling index (percentage of BrdU-positive cells per total number of cells: BrdU LI) was 0.053 +/- 0.009% in males and 0.059 +/- 0.015% in females. Analysis of our data indicated that the results obtained from the BrdU LI were more reliable (coefficient of variation [CV] less than 0.07) compared to those obtained from the MI (CV greater than 1.4). No clear difference was found between male and female beagle dogs, regarding adenohypophysis cell proliferation. In both studies, adenohypophysis cell proliferation was found to be age-dependent, with the highest value in immature dogs. No correlation between estrus cycle in females and adenohypophysis cell proliferation was noted.

Animals↗

[Loss of ganglion cells in the retina secondary to vincristine therapy].

We report the case of a 25-year-old black female from Zaire with AIDS diagnosed 2 years earlier. Nine months before her death, she was treated for a disseminated Kaposi sarcoma with vincristin, adryamycin and bleomycin. At that time, visual acuity was normal and ophthalmologic examination was unremarkable except for the presence of bilateral Drusen and a cotton wool spot OS. Three months after the onset of chemotherapy, the patient complained of progressive visual field constriction, which progressed to blindness within a 4 month period. Five months after the onset of the tri-therapy a bilateral CMV retinitis developed, which was successfully treated by intravitreous injections of ganciclovir. This therapy was stopped as soon as blindness was established, with subsequent massive bilateral recurrence of the CMV retinitis. Histologic examination showed complete atrophy of the retinal ganglion cells and areas of CMV retinitis. The optic nerve was demyelinated and exhibited astrocytic gliosis. Immunohistochemistry confirmed the presence of CMV in infected retina and revealed the absence in the optic nerve of the class III beta-tubulin isotype and of the 200 kd neurofilament subunit. In contrast, oculomotor nerves appeared intact. The presence of HIV in the eye and in the optic nerve was excluded using PCR technique. The retinal ganglion cell loss and optic nerve atrophy appeared to be purely degenerative in nature, since there was no evidence of vascular occlusion, inflammation or retrobulbar compressive process. We therefore conclude that blindness was caused by vincristine therapy. The patient actually received 22 mg of vincristin intravenously in 11 courses over 7 months, although discontinuation was recommended by us after 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Desmoplastic supratentorial neuroepithelial tumours of infancy.

The clinicopathological features of two infants with desmoplastic supratentorial neuroepithelial tumours are described. The cases were similar to the 26 cases reported previously as desmoplastic infantile ganglioglioma and superficial cerebral astrocytoma attached to dura. Neuronal differentiation was absent on routine stains, but was immunohistochemically established. We review the literature and suggest classifying this clinicopathological entity by using a general designation such as desmoplastic supratentorial neuroepithelial tumours of infancy, a term which indicates the variability in the amount and lines of differentiation.

Astrocytoma↗

Granular cell brain tumors of the laboratory rat: an immunohistochemical approach.

We have studied paraffin-embedded specimens of 17 rat granular cell brain tumors (GCBT) from four long-term drug safety carcinogenicity studies by peroxidase-antiperoxidase (PAP) immunohistochemistry with either polyvalent or monoclonal antibodies against glial fibrillary acidic protein (GFAP), S-100 protein (S-100), Leu-7 epitopes, vimentin (VIM), keratin, desmin, and myelin basic protein. We have found that 9 of the 17 GCBT contained GFAP-positive, S-100-positive, and VIM-positive astrocytes, while GFAP-positive and VIM-positive granular cells were observed in 5 of these 9 tumors. Our findings indicate that astroglial cells are involved in rat GCBT and suggest that an astrocytic origin should be considered for these neoplasms.

Animals↗

A brief review of modern toxicologic pathology in regulatory and explanatory toxicity studies of chemicals.

Macroscopic and histologic evaluation of animal studies for general toxicity and carcinogenicity are cornerstones of the risk assessment of new chemical entities. Standard toxicopathologic evaluation is mainly based on the study of paraffin sections stained with hematoxylin and eosin. There are, however, a number of new approaches and techniques which have improved the objectivity of evaluation and the accuracy of cell identification, and provided deeper insight into the molecular biological mechanisms of toxicity and carcinogenicity. Such approaches include the standardization of the nomenclature, the creation of data banks for morphological alterations, the use of computers to register pathological findings in toxicity studies and to statistically evaluate incidences, and the use of morphometry. Other modern techniques are immunohistochemistry, in situ hybridization, and the assessment of cell kinetics.

Animals↗

Morphologic and immunohistochemical characterization of Leydig cell tumor variants in Wistar rats.

During a routine long-term drug safety study, lasting approximately 2 1/2 yr, male Wistar rats, treated with a prolactin-inhibiting compound, developed an excess of Leydig cell tumors (LCTs). Most tumors were typical for the rat but a small number showed an unusual variation and some appeared malignant. The variation consisted of glandular and/or tubular structures within the tumor mass which occasionally anastomosed and contained an eosinophilic periodic-acid Schiff (PAS) positive material. In a few of these variants, malignant features such as cellular atypia, capsular, and lymphatic invasion and necrosis were seen. No metastases were detected. Detailed morphological and immunohistochemical investigations were conducted in order to establish the cell of origin of these variants. Glandular/tubular structures were found to stain with varying intensity for vimentin and cytokeratin, but were always negative for beta-tubulin. The results indicated that the cell of origin of these LCT variants was indeed the Leydig cell and that glandular and/or tubular structures within LCTs represented a form of Leydig cell metaplasia.

Animals↗

Neuron-associated class III beta-tubulin isotype, microtubule-associated protein 2, and synaptophysin in human retinoblastomas in situ. Further immunohistochemical observations on the Flexner-Wintersteiner rosettes.

We studied by immunohistochemistry 26 retinoblastomas in situ using monoclonal antibodies specific for the neuron-associated class III beta-tubulin isotype (h beta 4), microtubule-associated protein 2 (MAP2), and synaptophysin. Anti-h beta 4 and anti-MAP2 immunostaining was consistently obtained in the Flexner-Wintersteiner rosettes, in fleurettes, in Homer Wright (neuroblastic) rosettes, and also variably among poorly differentiated tumor cells. A similar pattern of antisynaptophysin immunopositivity was seen, but was especially pronounced in the adluminal borders of cells forming the Flexner-Wintersteiner rosettes. The demonstration of h beta 4, MAP2, and synaptophysin epitopes in poorly differentiated and maturing neoplastic phenotypes in retinoblastomas attests to the neuronal character of this embryonal tumor. Immunoreactivity toward h beta 4 and MAP2 epitopes by poorly differentiated neoplastic cells may indicate early neuronal commitment in retinoblastoma. The consistent immunostaining of Flexner-Wintersteiner rosettes with monoclonal antibodies to h beta 4 and MAP2 is in keeping with the previous ultrastructural documentation of microtubules with a neuronal-like spatial organization present in the cells of these structures.

Adult↗

Neuroblastic differentiation potential of the human retinoblastoma cell lines Y-79 and WERI-Rb1 maintained in an organ culture system. An immunohistochemical, electron microscopic, and biochemical study.

The differentiation potential of the human retinoblastoma cell lines Y-79 and WERI-Rb1 was evaluated in vitro for up to 120 days in a matrix system and in rotary suspension for 30 days. Matrix cultures were grown with 10% fetal calf serum (FCS), with and without differentiation-promoting agents. The latter were applied for a total of 5-45 days (usually 30 days) and included 7S nerve growth factor, dibutyryl cyclic AMP, sodium butyrate, retinoic acid, hydrocortisone, and ascorbic acid. Fully defined, serum-free medium and medium containing 5 or 15% FCS were also used for matrix cultures, and medium with 5 or 10% FCS for suspension cultures. By immunoperoxidase (performed on matrix cultures, both untreated and treated for 30 days with differentiation-promoting agents), the cells of both lines were positive for neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP2), class III beta-tubulin (human h beta 4) isotype, and synaptophysin. In addition, the WERI-Rb1 cells expressed 200 kd neurofilament protein (NFP-H) and retinal S-antigen. Both lines were invariably negative for glial fibrillary acidic (GFA) protein, myelin-associated glycoprotein, myelin basic protein, the epitope recognized by the Leu-7 monoclonal antibody, opsin, and hydroxy-indole-O-methyltransferase. In the Y-79 line the presence of NSE and the absence of NF proteins-H, -M and -L, of GFA protein, and of retinal S-antigen were confirmed biochemically. No differentiated features were found by electron microscopy in either line. Thus, in the matrix system employed, both lines exhibited solely a potential for neuroblastic differentiation, which was more advanced in the WERI-Rb1 line, as reflected by the antigenic expression of NFP-H and of retinal S-antigen.

Cell Differentiation↗

Glial fibrillary acidic protein in chondrocytes of elastic cartilage in the human epiglottis: an immunohistochemical study with polyvalent and monoclonal antibodies.

Glial fibrillary acidic protein (GFAP), an intermediate filament, was first discovered in the cytoplasm of reactive astroglia and to this date is regarded as a rather characteristic component of both non-neoplastic and neoplastic astrocytes. It has, however, been found in other glial elements also, as well as in a few types of tissues outside the central nervous system. Chondrocytes in hyaline and fibrocartilage do not express GFAP, but in the elastic cartilage of the human epiglottis we found GFAP to be regularly present when tested with either polyclonal or monoclonal antibodies. While most types of cartilage in humans are believed to be of mesenchymal origin, embryologic relationship between epiglottal cartilage and the neural crest may play a role in the curious phenomenon of the regular presence of GFAP in the chondrocytes of the epiglottis.

Adult↗

Immunohistochemical differences between intracranial germinomas and their gonadal equivalents. An immunoperoxidase study of germ cell tumors with epithelial membrane antigen, cytokeratin, and vimentin.

Twenty-six intracranial germ cell tumours (11 germinomas, 10 teratomas, 2 endodermal sinus tumours, 1 teratocarcinoma, and 2 undifferentiated embryonal carcinomas) and 26 gonadal germ cell tumours (13 testicular seminomas, 2 ovarian dysgerminomas, 9 ovarian teratomas, and 2 myometrial choriocarcinomas) were studied by immunoperoxidase with monoclonal antibodies (MAbs) against epithelial membrane antigen (EMA), cytokeratin, and vimentin. Typical tumour cells in three of the 11 germinomas (two of the latter being situated in the posterior fossa) expressed both EMA and cytokeratin, whereas those in the seminomas and dysgerminomas did not. In one seminoma, a few multinucleated giant cells expressed cytokeratin. In three of seven germinomas, vimentin-positive tumour cells were found, but all seminomas and dysgerminomas were negative. In the other forms of intracranial and gonadal germ cell tumours, epithelial and mesenchymal elements displayed the expected patterns of immunoreactivity to the respective determinants. The immunoperoxidase differences between the intracranial germinomas and their gonadal equivalents indicate that, in the former, early epithelial or mesenchymal differentiation of the primordial germ cells may be present. The findings draw attention to the heterogeneous cellular composition of these otherwise morphologically homogeneous-appearing tumours and, especially in the posterior fossa, to their transitional links to the immature teratomas.

Adolescent↗

Retinal S-antigen immunoreactivity in medulloblastomas.

A series of 16 cerebellar medulloblastomas were studied immunohistochemically using a four-step immunoperoxidase (PAP) method and a monoclonal antibody (MAbA9-C6) which defines an epitope of the retinal S-antigen, a protein known to occur in retinal photoreceptor cells and pinealocytes of the pineal gland as well as in retinoblastomas, pineocytomas and pineoblastomas. Immunopositivity was demonstrated in a variable number of tumor cells in 50% of the cases. This finding may be an indication of a differentiation potential of medulloblastomas along the photoreceptor cell lineage. Alternatively, it may simply indicate the non-specificity of the retinal antigen in the neoplastic state.

Antibodies, Monoclonal↗

Are intestinal endocrine cells affected in Hirschsprung's disease? An immunohistochemical study with anti-Leu 7 monoclonal antibody.

Specimens from 15 cases of Hirschsprung's disease and 22 control cases of normal guts were studied by the peroxidase-antiperoxidase (PAP) method with with anti-Leu 7 (Leu 7) monoclonal antibody (MAb). In the normal human gut, some satellite cells in the enteric plexuses and a few nerve fibers and ganglion cells in the intestinal wall were stained with Leu 7 MAb, while endocrine cells in the intestinal mucosa showed consistent and intense cytoplasmic Leu 7 positivity. In Hirschsprung's disease, the number of Leu 7-positive endocrine cells was significantly low. The mean value of the number of Leu 7-positive endocrine cells per one microscopic field (X300 magnification) was 4.6 +/- 0.6 (+/- SE) in controls and 0.7 +/- 0.3 (+/- SE) in Hirschsprung's disease (P less than .001 by Student's t test). Our findings suggest that the development of endocrine cells in the intestinal mucosa may be closely related to the development of ganglion cells in the enteric plexuses, and that the anti-Leu 7 MAb may be useful for the diagnosis of Hirschsprung's disease when biopsy specimens are limited to the mucosa only.

APUD Cells↗