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Biomedical subjects

L J Rubinstein

Publications and source records attributed to L J Rubinstein.

At least 55 records · Page 3Linked to original sources

Expression of epithelial membrane antigen in perineurial cells and their derivatives. An immunohistochemical study with multiple markers.

Paraffin-embedded surgical pathology specimens from skin (5) and muscle (2) biopsies, from Morton's neuromas (3), traumatic neuromas (8), schwannomas (21), neurofibromas (12), and from one perineurioma and one neurothekeoma were studied by immunoperoxidase histochemistry and antibodies against epithelial membrane antigen (EMA), Leu 7 epitopes (Leu 7), S-100 protein (S-100) and cytokeratins. Normal, reactive and neoplastic perineurial cells stain consistently for EMA, whereas Schwann cells express Leu 7 and/or S-100 positivity. None of the immunoreactive cells stained for cytokeratin. Our findings indicate that perineurial and Schwann cells can easily be distinguished by their different patterns of immunoreactivity with the above markers.

Cell Line↗

Localization of neuron-specific (gamma gamma) enolase in proliferating (supportive and neoplastic) Schwann cells. An immunohisto- and electron-immunocyto-chemical study of ganglioneuroblastoma and schwannomas.

Neuron-specific (gamma gamma) enolase, a glycolytic enzyme used as a relatively specific marker for normal neurons and neuroendocrine cells, has recently been found in a variety of neoplastic cells and in reactive astrocytes. Its localization was investigated by immunohisto- and electron-immunocyto-chemistry, in the proliferating supportive Schwann cells of a peripheral ganglioneuroblastoma and in the neoplastic Schwann cells of four acoustic tumours. By light microscopy, the neoplastic Schwann cells showed moderate uneven diffuse immunopositivity for enolase. By electron-immunocytochemistry, both types of Schwann cells demonstrated immunopositivity discretely limited to their cell surface membranes. The neoplastic ganglion cells and axons of the ganglioneuroblastoma and the normal neurons and axons included in the schwannomas were, as expected, intensely immunopositive. The visualization of gamma gamma enolase on the cell surface membranes of both neoplastic and non-neoplastic proliferating Schwann cells suggests that increased glycolytic activity may occur on the surface of these proliferating cells irrespective of the nature of the proliferation.

Ganglioneuroma↗

Non-specificity of anti-carbonic anhydrase C antibody as a marker in human neurooncology.

Because the presence of carbonic anhydrase C (CA C) has been demonstrated in the oligodendrocytes of the mouse, rat and man, anti-CA C serum has been considered to be a possible specific marker for these cells. In order to determine its value in human neurooncology, specimens from 110 human tumors from the central and peripheral nervous systems as well as from five cases of cerebral infarction and two of multiple sclerosis were tested immunohistochemically by the peroxidase-antiperoxidase method with anti-CA C serum. Reactive astrocytes, oligodendrocytes in the neural parenchyma surrounding tumors, and neurons included in areas of neoplasia showed CA C immunopositivity. In 92% of the astrocytomas and 56% of the glioblastomas variable numbers of tumor cells were positive. Some tumor cells positive for glial fibrillary acidic protein in ependymomas and astroblastomas were also CA C-positive. Schwannomas (86%), neurofibromas (100%) and meningiomas (86%) showed CA C positivity of the tumor cells, as did choroid plexus papillomas and gangliogliomas. However, all the medulloblastomas, neuroblastomas, central neurocytomas or melanomas tested in this study were entirely CA C-negative. In some examples of squamous cell carcinoma, leiomyoma, leiomyosarcoma and fibrous histiocytoma, CA C-positive neoplastic cells were also demonstrated. Our findings indicate that since various types of neoplastic and reactive cells express CA C positivity, the anti-CA C serum cannot be used as a specific marker for any tumor in human neurooncology.

Animals↗

GFA protein reactivity in nerve sheath tumors: a polyvalent and monoclonal antibody study.

We studied glial fibrillary acidic (GFA) protein immunoreactivity in 30 schwannomas, including two intracerebral examples, 26 neurofibromas and 12 neuromas using the immunoperoxidase method with a polyvalent antiserum (PVAS) and three well-characterized monoclonal antibody (MAb) preparations. Twelve of the schwannomas, including both intracerebral tumors, two of the neurofibromas and none of the neuromas immunostained with PVAS. Except for one schwannoma, all the PVAS-positive tumors were positive with two of the MAb preparations. While both of the intracerebral schwannomas were positive with the third MAb, none of the extracerebral tumors were. Our results suggest that: 1) human nerve sheath tumors contain cells having polypeptides that share epitopes with GFA protein, but 2) these polypeptides differ from astrocytic GFA protein by at least one epitope, and 3) the location of the tumors in relation to the central nervous system may influence GFA protein immunoreactivity.

Antibodies↗

Desmoplastic supratentorial neuroepithelial tumors of infancy with divergent differentiation potential ("desmoplastic infantile gangliogliomas"). Report on 11 cases of a distinctive embryonal tumor with favorable prognosis.

Eleven cases of supratentorial neuroepithelial tumor presenting in infancy are reported. The tumors were characterized by their voluminous size, their intense desmoplasia, and the frequent presence of divergent astrocytic and ganglionic differentiation as demonstrated by special neurohistological and immunohisto- and immunocytochemical techniques. All the tumors presented in subjects below the age of 18 months, usually within the first 4 months of life. They most often involved the frontal and parietal regions and were composed predominantly of a dense desmoplastic tissue superficially resembling a moderately cellular fibroma. The fibroblastic elements were admixed with variable numbers of pleomorphic neuroepithelial cells. Divergent astrocytic and neuronal differentiation was demonstrable in nine of the 11 tumors. All showed astrocytic differentiation. The study of one example by electron microscopy, immunocytochemistry, and tissue culture disclosed that the astrocytic tumor cells were partly invested by a pericytoplasmic basal lamina. Successful total or near-total surgical resection has been followed by a favorable postoperative course extending in some cases over many years of tumor-free survival. The name "desmoplastic infantile ganglioglioma" is proposed for this apparently distinct clinicopathological entity, whose massive size is indicative of a pre- or perinatal origin. Its identification can be achieved by careful histological analysis and is of obvious prognostic significance.

Brain Neoplasms↗

Recent applications of immunoperoxidase histochemistry in human neuro-oncology. An update.

In this review, we describe some of the most commonly used antibodies and discuss their immunohistochemical applications to human neuro-oncology. We stress the importance of determining the spectrum of antibody immunoreactivity in a wide panel of normal, reactive, and neoplastic tissues, and the caution with which immunopositivity needs to be interpreted in atypical and aberrant cases. Whether the detection of a well-characterized, cell-type-specific marker in a tumor reflects histogenesis or solely differentiation potential is discussed in several examples.

Antibodies, Monoclonal↗

Non-specific binding of mouse myeloma IgM immunoglobulins by human myelin sheaths and astrocytes. A potential complication of nervous system immunoperoxidase histochemistry.

The immunoreactivity of purified mouse myeloma IgM immunoglobulins (mouse IgM) to human myelin sheaths and astroglial cells was evaluated with the peroxidase-antiperoxidase method on paraffin-embedded tissues from human gliomas and areas of multiple sclerosis, and from normal human cerebrum, spinal cord and spinal nerve roots. The mouse IgM reacted positively with central and peripheral myelin sheaths and, as shown independently by others, with the cytoplasm of neoplastic and reactive astroglia. Parallel immunostaining of successive sections with an anti-glial fibrillary acidic protein (GFAP) serum and/or the anti-Leu 7 monoclonal antibody was of considerable assistance in identifying the immunoreactive elements and in distinguishing specific from non-specific immunostaining of myelin sheaths and astroglia. Pretreatment with normal human serum inhibited the non-specific binding by mouse IgM without altering GFAP and Leu 7 reactivities. The non-specific binding of mouse IgM to human myelin sheaths and astroglia can therefore be overcome, and the specificity of mouse IgM monoclonal antibodies retained, by the parallel immunostaining of successive sections with mouse IgM. If non-specific binding by mouse IgM is found to occur, it can then be inhibited by preincubation with normal human serum without loss of specific antigenicity.

Animals↗

Immunohistochemical characterization of oligodendrogliomas: an analysis of multiple markers.

Twenty-eight oligodendrogliomas and seven oligoastrocytomas were immunotested by the peroxidase-antiperoxidase (PAP) method with antiglial fibrillary acidic protein (GFAP) serum, anti-Leu 7 monoclonal antibody (Mab), anti-myelin-associated glycoprotein (MAG) Mab, anti-myelin basic protein (MBP) serum, anti-carbonic anhydrase C (CA C) serum and anti-neuron-specific enolase (NSE) serum. The immunoreactivity of their vascular pattern was studied with Ulex europaeus type I lectin (UEA I). According to their morphology and distribution GFAP-positive cells were respectively interpreted as reactive astrocytes, neoplastic astrocytes and neoplastic oligodendrocytes. Reactive astrocytes were found in the tumor, around the tumor and surrounding the supporting blood vessels. Neoplastic astrocytes were mainly found in the oligoastrocytomas and usually closely intermingled with neoplastic oligodendrocytes. GFAP-positive neoplastic oligodendrocytes were found in the typical oligodendrogliomatous areas. They had central nuclei and GFA positivity was mainly found in the perinuclear cytoplasm. They correspond to the "gliofibrillary oligodendrocytes" described by Herpers and Budka. Of the oligodendrogliomas 91% displayed Leu 7 positivity, but anti-Leu 7 cannot be considered as a specific marker for oligodendrogliomas since other neuroepithelial tumors have been reported to react with this antibody. MAG-, CA C- and NSE-positivities were found in a number of tumor cells in a few oligodendrogliomas. All the tumor cells were MBP-negative, but myelin sheaths and fragments of myelin in the infiltrated white matter were clearly demonstrated by this antiserum. UEA I strikingly demonstrated the vascular pattern of the tumors, and its usefulness as a discriminating marker for the supportive endothelial cells was confirmed.

Antigens, Differentiation, T-Lymphocyte↗

S-antigen immunoreactivity in human pineal glands and pineal parenchymal tumors. A monoclonal antibody study.

Using a four-step immunoperoxidase (PAP) method and the monoclonal antibody MAbA9-C6 (MAbA9-C6), which defines an epitope of the retinal S-antigen (S-Ag), we investigated the S-Ag immunoreactivity in human fetal, newborn, infantile and adult pineal glands and in 13 human pineal parenchymal tumors. S-Ag immunoreactivity was demonstrated in a few cells in one of the four fetal and in both infantile glands. Eight of nine adult pineal glands contained isolated MAbA9-C6-positive cells. In two of seven pineocytomas showing neuronal or gangliogliomatous differentiation a few scattered cells displayed S-Ag positivity; two of four pineoblastomas contained small groups of strongly immunoreactive neoplastic cells; two malignant pineocytomas did not demonstrate any S-Ag immunoreactivity. Our results indicate that isolated cells in human pineal gland retain some of the cytochemical characteristics of photoreceptor cells recognized by the MAbA9-C6, and that S-Ag immunoreactivity may be occasionally expressed in pineal parenchymal tumors.

Adult↗

Immunohistochemical recognition of human neuroepithelial tumors by anti-Leu 7 (HNK-1) monoclonal antibody.

The immunoreactivity of the anti-Leu 7 (HNK-1) monoclonal antibody, a marker for natural killer cells, was evaluated with the peroxidase-anti-peroxidase (PAP) method on sections of human paraffin-embedded tissues from 135 tumors of the central nervous system and five esthesioneuroblastomas. As shown independently by others, the antibody was found to react with most types of neoplastic neuroepithelial cells. Our findings indicate that the reaction is most often localized on the cytoplasmic membranes. The immunoreactive cell membranes were generally those of well-differentiated tumor cells and of neoplastic cells found in tumors that usually were not embryonal in nature. Parallel immunostaining either of the same or of successive sections with an anti-glial fibrillary acidic protein serum was of considerable assistance in discriminating between different immunoreactive cells, e.g., between astrocytes and cells presumed to be oligodendrocytes. Despite its cross-recognition of cells of various histogenesis, the anti-Leu 7 monoclonal antibody can, in well-defined circumstances, elucidate specific differential diagnostic problems involving neurogenic neoplasms that cannot be resolved with routine staining techniques.

Antibodies, Monoclonal↗

Electron-immunocytochemical localization of neuron-specific enolase in cytoplasm and on membranes of primary and metastatic cerebral tumours and on glial filaments of glioma cells.

A series of primary and metastatic human brain tumours was evaluated immunocytochemically for the electron microscopic localization of neuron-specific enolase (NSE). All contained cells which, regardless of the cell type, demonstrated an irregular distribution of NSE in their cytoplasm and on membranes. This was in contrast to the staining pattern in normal central nervous system (CNS) cells which, as previously reported (Vinores et al. 1984b), show only diffuse cytoplasmic staining usually not associated with membranes. In the tumours, the interior of nuclei and the cristae and matrices of mitochondria were consistently negative, as in normal CNS cells. Except in one low-grade fibrillary astrocytoma, the cytoplasmic filaments in neoplastic astrocytes were often, but not invariably, stained for NSE. The fine structural localization of NSE in neoplastic cells suggests that the conversion of 2-D-glycerophosphate to phosphoenolpyruvate by enolase may occur on the membrane and, in the case of astrocytic tumours, on the cytoplasmic filaments as well as in the cytoplasm. When cells which contain only the non-neuronal form of enolase (NNE) transform to neoplastic cells, they may acquire the ability to produce NSE. This presumably enables them to accommodate the increased metabolic demands of neoplasia by allowing them to elude the regulatory controls that are specific for NNE.

Adolescent↗

The malformative central nervous system lesions in the central and peripheral forms of neurofibromatosis. A neuropathological study of 22 cases.

The neuropathological features of 22 autopsied cases of NF have been reviewed, with special reference to the malformative and proliferative lesions implicating the intracranial and intraspinal neural structures. Eleven cases represented examples of the central form of the disease, and 11 examples of the peripheral form. The central form is defined by the association and multiplicity of cranial and spinal meningeal, nerve-sheath, and glial neoplasms (astrocytomas and ependymomas). Bilateral acoustic schwannomas are a frequent, but not invariable, component of the disease. Central NF is also characterized by the very frequent incidence (9 out of 11 cases) of distinctive malformative CNS lesions, which included intramedullary and perivascular schwannosis, meningioangiomatosis, discrete ependymal ectopias, atypical glial cell nests in the grey matter, and, less frequently, syringomyelia. Many of these hamartomatous changes were closely associated topographically with florid neoplastic lesions. Five of the 11 cases of peripheral NF showed involvement of the CNS by cellular proliferative changes that included subependymal gliofibrillary nodules in 3 cases (causing aqueduct stenosis in 2, with resulting hydrocephalus in 1); hyperplastic meningioencephalic gliosis involving the pons and the cerebellum in 1 case; and micronodular capillary and arteriolar proliferations typical of the vascular form of NF in 1 case. Whereas some of the glial proliferations are probably hamartomatous in nature, others may represent an abnormal productive neuroglial response to adjacent pathological conditions, such as antecedent cerebral hemorrhage or infarct, known to stimulate a proliferative gliosis. Such a response may exhibit morphological features that are indistinguishable from those of an astrocytoma, including leptomeningeal and perivascular invasion. The incidence of proliferative CNS lesions in both the central and the peripheral form of NF indicates that the spectrum of tissues implicated extends beyond those derived solely from the neural crest.

Adolescent↗

[Contribution of immunohistochemical methods to the study of central nervous system tumors].

The contributions of the immunoperoxidase technique for the demonstration of glial fibrillary acidic (GFA) protein, neuron specific enolase (NSE) and the Leu-7 (HNK-1) monoclonal antibody in central nervous system (CNS) tumors are reviewed. GFA protein is expressed in normal, reactive and neoplastic cells of astrocytic lineage. Its presence in nonastrocytic CNS tumors is related either to the development of gliofibrillogenesis (ependymomas), to ontogenetic factors (oligodendrogliomas; choroid plexus papillomas), or to uptake of the protein from adjacent reactive astrocytes (capillary hemangioblastomas). It has permitted the recognition of new entities such as the pleomorphic xanthoastrocytoma, and of little known variants such as lipidized glioblastomas. NSE is of diagnostic importance in peripheral neuronal, endocrine and neuroendocrine tumors, but of considerably less value in CNS tumors, since it may be found in the cells of a variety of glial and other cerebral neoplasma as well as in reactive astrocytes. It has also been found to be present in a number of unrelated tumors outside the nervous system. The Leu-7 (HNK-1) monoclonal antibody, a hematological marker, has been found to cross-react with a number of cells of schwannian origin and may be helpful in the differential diagnosis of schwannomas and neurofibromas from other soft tissue neoplasms. Its recognition of oligodendroglial tumor cells has been confirmed, but it is also frequently recognized by both reactive and neoplastic astrocytes. In addition to its reactivity with cells of the immune system, a number of epithelial tumors, in particular adenocarcinomas of the prostate, will also be recognized by the antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Regulation of myeloma growth in mice by antigen and regulatory idiotopes.

The effect of antigen, activation of normal A48Id+ B-cell clones, and monoclonal antibodies sharing A48-UPC10 regulatory idiotopes on the in vivo growth of spleen adapted ABPC48 myeloma cells has been examined. Immunogenic doses of bacterial levan have no detectable effects, whereas tolerogenic doses substantially delay the growth of the myeloma. The activation of normal A48Id+ B cell clones also has no apparent effect on the growth of the ABPC48 myeloma cells. Among a panel of 15 monoclonal antibodies expressing A48-UPC10 regulatory idiotopes and expressing VH genes derived from the VH441-4 germ line gene family, 5 were able to provide a long lasting but not definitive idiotype specific protection against the ABPC48 myeloma cells.

Animals↗

Ependymoblastoma. A reappraisal of a rare embryonal tumor.

This article reviews the clinicopathologic features of 12 ependymoblastomas, including those of 7 previously unreported cases. The histologic characteristics included a high density of small to medium-sized neuroepithelial cells with a uniform cytologic appearance, frequent mitotic figures, and numerous diagnostic ependymal rosettes and tubules. Differentiation was restricted to glial precursor cells and to cells with the differentiating features of ependymal cells. Cytogenetically, the tumor cells with the differentiating hallmarks of ependymal cells but which have retained their mitotic activity were considered to be ependymoblasts. Many of the rosettes in the tumors were of the ependymoblastic type, but ependymal rosettes were also present. The absence of pleomorphism, giant cells, multinucleation and pseudopalisades, and the scanty proliferation of vascular endothelial cells are additional features that delineate this tumor from an anaplastic (malignant) ependymoma. The median age of the patients was 2 years. After surgical treatment the median survival time was 12 months. Because of the frequency of leptomeningeal involvement, whole neuraxis radiation should be considered.

Adolescent↗