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Biomedical subjects

L J Rubinstein

Publications and source records attributed to L J Rubinstein.

At least 37 records · Page 2Linked to original sources
PubMed1989

Relationship of the demonstration of intermediate filament protein to kinetics of three human neuroepithelial tumor cell lines. Lack of neural-related proteins in most cells in S phase: a double-labeled immunohistochemical study on matrix cultures.

The immunocytochemical demonstration of intermediate filament proteins in three human neuroepithelial tumor cell lines maintained in vitro on a three-dimensional matrix was correlated with the proportion of cells in S phase. The cell lines of a medulloblastoma (D283 Med), a retinoblastoma (WERI-Rb1), and an astrocytic glioma (U-251 MG) were cultured in an organ culture system, pulse-fed with bromodeoxyuridine, and double-labeled by immunoperoxidase and by the avidin-biotin peroxidase complex method for bromodeoxyuridine and for intermediate filament proteins [each triplet of neurofilament proteins, as well as vimentin and glial fibrillary acidic (GFA) protein] using eight different antibodies. The average percentages of bromodeoxyuridine-labeled cells for the D283 Med, WERI-Rb1, and U-251 MG lines were respectively, 25, 32, and 12% 30 minutes after pulse labeling. In the D283 Med line, 15- greater than 95% of the cells were positive for each neurofilament protein, and 80% of the cells were positive for vimentin; less than 10% of the cells in S phase were positive with each of the five antineurofilament protein monoclonal antibodies (Mabs), but 20% of the vimentin-positive cells were in S phase. In the WERI-Rb1 line, 44 and greater than 96% of the cells were positive for the high-molecular-weight neurofilament subunit and high- and middle-molecular-weight neurofilament subunits proteins, respectively, but only 5% of the high-molecular-weight neurofilament positive cells were in S phase. In the U-251 MG line, 37 and 98% of the cells were positive for GFA protein and vimentin, respectively; only 3% of the GFA protein-positive cells, but 13% of the vimentin-positive cells, were in S phase. The results indicate that, when maintained in a matrix culture system, most cells in S phase in these lines lack markers of neural differentiation.

Astrocytoma↗
PubMed1989

Cerebellar desmoplastic medulloblastomas. A further immunohistochemical characterization of the reticulin-free pale islands.

We studied by immunohistochemistry the features of differentiation in 24 desmoplastic and 16 classic medulloblastomas (median patient ages, 18 and 6.5 years, respectively) with the use of a panel of cytoskeletal and synaptosomal markers. A distinctive pattern of immunoreactivity with a series of monoclonal antibodies (Mabs) was documented in the polar tumor cells forming the reticulin-free pale islands of the desmoplastic variant, denoting overt neuritogenesis. These comprised the following: (1) Mab Tp-NFP1A3 recognizing an epitope in the high-molecular-weight (Mr) isoform of neurofilament protein; (2) Mab AP18 to the high-Mr microtubule-associated protein 2; (3) Mab TUJ1 recognizing the class III beta-tubulin isotype (human h beta 4); and (4) Mab SY38 to synaptophysin. Immunoblot analysis confirmed the expression of h beta 4 in three medulloblastomas, yielding strong single bands in two desmoplastic medulloblastomas and a considerably weaker band in one classic medulloblastoma. Glial fibrillary acidic protein-positive tumor cells frequently formed an integral component of the pale islands. Oligodendrogliallike areas in one classic and in three desmoplastic medulloblastomas were immunopositive for the Mabs to synaptophysin, microtubule-associated protein 2, and h beta 4, indicating a neuroblastic nature. We propose that the reticulin-free structures of desmoplastic medulloblastomas constitute neoplastic foci with features of predominantly neuronal and, to a lesser degree, astroglial differentiation.

Adolescent↗
PubMed1989

Astroblastomas: a pathological study of 23 tumors, with a postoperative follow-up in 13 patients.

Astroblastomas are rare, usually circumscribed, supratentorial tumors of young subjects and are characterized by a perivascular arrangement of the tumor cells. Their clinical behavior is unpredictable and their prognosis has been regarded as intermediate between that of astrocytomas and glioblastomas. A personal series of 23 astroblastomas was reviewed, adequate postoperative follow-up being available in 13 patients. Two distinct histological types were encountered: low-grade and high-grade. The low-grade type comprised tumors with better differentiated and more benign-appearing microscopical features. Five of the 8 patients with tumors of this type who were available for follow-up have survived from 3 to 20 years after treatment; in 1 patient the tumor converted into a fatal glioblastoma after 4 1/2 years. The high-grade type consisted of tumors with more anaplastic features. Three of the 4 patients with tumors of this type available for follow-up died after 1 1/2 to 2 1/2 years, the astroblastomas in 2 of them having converted into a glioblastoma and a gliosarcoma, respectively. One patient, however, has had an unexpected length of postoperative survival of 11 1/2 years. The best clinical results were obtained after total or subtotal resection of the tumor, followed by radiotherapy. The role of chemotherapy is still uncertain. This form of glioma illustrates the discrepancies that may sometimes be apparent between histopathological features and length of postoperative survival. The prognosis is also further complicated by the potential of the astroblastoma to convert into a more malignant type of glioma.

Adolescent↗
PubMed1989

Focal neuronal gigantism and cerebral cortical thickening after therapeutic irradiation of the central nervous system.

An exceptional type of cortical dysplasia is described in the brain of a 32-year-old woman who had received radiation therapy for a large pituitary adenoma 6 years before death. Markedly thickened gyri of the left inferior frontal, insular, and temporal cortex were found grossly. Microscopically, these gyri showed laminar disorganization and many unusually large and abnormally shaped ganglion cells. These neurons were heavily impregnated with silver preparations; were strongly reactive for neuron-specific enolase, synaptophysin, and neuronal cytoskeletal proteins (68- and 200-kd subunits of neurofilament protein, microtubule-associated protein 2, and tau); and ultrastructurally contained numerous perikaryal neurofilaments. Collectively, these findings suggest that the abnormally large, misshapen neurons contained excessive accumulations of cytoskeletal intermediate filaments. The present case and a similar one described in 1964 are the only two documented instances of neuronal gigantism apparently related to therapeutic irradiation of the brain.

Adenoma↗
PubMed1989

An immunohistochemical study of neuropeptides and neuronal cytoskeletal proteins in the neuroepithelial component of a spontaneous murine ovarian teratoma. Primitive neuroepithelium displays immunoreactivity for neuropeptides and neuron-associated beta-tubulin isotype.

Approximately one third of the female mice of the LTXBO strain develop spontaneous ovarian teratomas. These tumors contain a large neuroepithelial component, which includes primitive neural structures resembling embryonic neural tubes (medulloepithelial rosettes), ependymoblastic and ependymal rosettes, neuroblasts, mature ganglionic neurons, myelinated neurites, and astrocytes. The purpose of this study was to characterize these tumors according to the immunohistochemical location of some well-characterized trophic and regulatory neuropeptides and neurotransmitters, several neuronal-associated cytoskeletal proteins, and other proteins indicative of neuronal and glial differentiation. Medulloepithelial rosettes showed focal serotonin-like, opioid peptide-like and gamma-amino butyric acid-like immunoreactivity, and displayed immunostaining for the neuron-associated class III beta-tubulin isotype. The mature ganglion cells were also immunoreactive for these markers, and, in addition, for somatostatin, cholecystokinin, bombesin, glucagon, vasoactive intestinal peptide, and neuropeptide Y. Mature ganglion cells were also immunoreactive for proteins associated with the neuronal cytoskeleton (including microtubule-associated proteins, MAP2 and tau, and higher molecular weight phosphorylated and non-phosphorylated neurofilament subunits), neuron-specific enolase, and synaptophysin. Undifferentiated stem cells, ependymoblastic and ependymal rosettes, and astroglia all stained with a monoclonal antibody that recognizes all mammalian beta-tubulin isotypes, but did not react with antibodies to neuronal-associated cytoskeletal proteins or neuropeptides. Neuropeptide-like immunoreactivity and demonstration of the class III beta-tubulin isotype indicate early neuronal commitment in neoplastic primitive neuroepithelium. These patterns of immunoreactivity closely follow those encountered in the normal neurocytogenesis of the mammalian and avian forebrain, and increase the precision with which the early stages of progressive neuroepithelial differentiation can be analyzed in human embryonal tumors of the CNS.

Animals↗
PubMed1988

Murine immune response to the Neisseria meningitidis group C capsular polysaccharide. I. Ontogeny.

The immune response to polysaccharide Ag develops late in ontogeny and the underlying mechanisms of the infant unresponsiveness are poorly understood. The development of vaccines that will prove efficacious in infants has been hindered by the lack of animal systems suitable for studying immunity to human pathogens. We have examined the BALB/c murine response to the capsular polysaccharide of Neisseria meningitidis group C (MCPS), a homopolymer of alpha(2----9) sialic acid, as a model system for the development of immunity to bacterial polysaccharides in man. We have observed the appearance of natural antibody of both IgM and IgG classes which increases with age, and the transfer of maternal IgG to the offspring. Both the naturally occurring and postimmunization serum responses are restricted to the IgM and IgG3 isotypes, and include antibody titers to both MCPS as well as a natural O-acetyl-negative variant (OAc-). The preimmune anti-OAc- antibodies, in contrast to anti-MCPS, were restricted to the IgM class, whereas after immunization with MCPS both IgM and low titers of IgG3 antibodies to OAc- were produced. These studies demonstrate that the BALB/c mouse strain shows a markedly similar immune profile to that observed in man.

Aging↗
PubMed1988

Murine immune response to the Neisseria meningitidis group C capsular polysaccharide. II. Specificity.

As a means of further understanding the regulation of diversity and the development of protective immunity to the Neisseria meningitidis group C capsular polysaccharide (MCPS), we have generated and characterized, in detail, a panel of mAb against MCPS, a homopolymer of alpha(2----9)-sialic acid. Whereas the serum response to MCPS is restricted to the IgM and IgG3 isotypes, the panel of mAb includes, in addition, both IgG1 and IgG2b. Among 15 mAb of four isotypes, seven different specificities were observed based on direct binding in a fluorescence ELISA and precipitation in gel. Although all the mAb were derived from mice immunized with bacteria encapsulated with the native MCPS (strain C11), only 7 of 15 reacted with MCPS alone. Seven of 15 reacted with a natural O-acetyl-negative variant (OAc-, strain MC19) polysaccharide as well as with MCPS. Five of these reacted as much as 3 logs better with OAc- than MCPS and the other two reacted better with MCPS than OAc-. One mAb appeared to be alpha(2----9)-linkage specific as it reacted not only with MCPS and OAc-, but also with the capsular polysaccharide of Escherichia coli K92, a polymer of sialic acid linked alternately alpha(2----8) and alpha(2----9). None of the mAb reacted with the capsular polysaccharide of E. coli K1, a homopolymer of alpha(2----8)-sialic acid. In general, there was a good correlation between the ability to precipitate Ag in gel and to agglutinate bacteria; however, 3 of 15 mAb, all IgG3, did not conform to this rule in that they precipitated Ag but did not agglutinate bacteria of the relevant capsular specificity. Antibodies of both IgM and IgG isotypes and of both major specificities, MCPS-specific and those binding MCPS and OAc-, were bactericidal for strain C11, whereas only those reactive with OAc- were able to kill strain MC19.

Agglutination Tests↗
PubMed1988

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↗
PubMed1988

Patterns of epithelial metaplasia in malignant gliomas. I. Papillary formations mimicking medulloepithelioma.

Adenoid-like formations resembling ducts and glands or forming a cribriform pattern have previously been described in malignant gliomas, resulting in some cases in a confusion with metastatic adenocarcinoma. The interpretation of these structures as being composed of anaplastic glial cells rests partly on the presence of transitions to more differentiated neoplastic astrocytes and partly on the positivity of some of these cells for glial fibrillary acidic protein. In this report two cases are presented in which the adenoid pattern was associated with papillary formations mimicking the arrangement of a medulloepithelioma. These structures represent a form of aberrant neoplastic differentiation in a malignant glioma rather than the expression of an embryonal neuroepithelial neoplasm.

Adult↗
PubMed1988

Patterns of epithelial metaplasia in malignant gliomas. II. Squamous differentiation of epithelial-like formations in gliosarcomas and glioblastomas.

Six cases are reported (four gliosarcomas and two glioblastomas) in which the epithelial-like areas of glial anaplasia showed focal squamous cell differentiation, characterized by the development of epithelial whorls, keratin pearls and immunopositivity for cytokeratin. The expression of glial fibrillary acidic protein and the development of squamous metaplasia usually were mutually exclusive. Autopsy findings in two patients and clinical work-up in five failed to disclose a primary extraneural malignancy. It is suggested that squamous differentiation may represent an extreme form of epithelial metaplasia in a malignant glioma. This possibility should be kept in mind in the diagnostic evaluation of such cases, especially in view of the current emphasis on the immunomorphologic demonstration of intermediate filament tumor markers.

Adult↗
PubMed1988

Diagnostic markers in human neurooncology. A progress report.

In this progress report, some of the most commonly used antibodies are discussed in regard to their immunohistochemical application to human neurooncology. The importance of determining the spectrum of antibody immunoreactivity in a wide panel of normal, reactive, and neoplastic tissues is stressed. in atypical and aberrant cases, immunopositivity needs to be interpreted with caution and in the context of all other available data. The demonstration of a well-characterized, cell type-specific marker in a tumor reflects not so much its cytogenesis as its differentiation potential and its capacity for metaplasia. The relation of an abnormal or aberrant expression of antigenic determinants to the process of neoplasia raises a number of intriguing questions to which research in the next few years will likely provide answers.

Antigens, Differentiation↗
PubMed1987

Late multifocal gliomas in adolescents previously treated for acute lymphoblastic leukemia.

Three of 37 adolescents in long-term remission from childhood acute lymphoblastic leukemia (ALL) developed malignant multifocal gliomas several years after completing treatment that included central nervous system (CNS) prophylaxis with radiation (RT) and intrathecal methotrexate (IT-MTX). No recurrence of the leukemia was evident when the CNS tumors were discovered. Seventeen other similar cases have been recorded. The occurrence of second malignancies is reviewed in the context of this development and of the oncogenic effects of radiation. It is probable that prolonged exposure to IT-MTX may have had a synergistic effect with radiation in contributing to the unusual incidence of glial tumors in these patients.

Adolescent↗
PubMed1987

Immunohistochemical characterization of human retinoblastomas in situ with multiple markers.

We studied paraffin-embedded specimens from 18 surgically enucleated eyes with retinoblastoma by peroxidase-antiperoxidase immunohistochemistry with antibodies against glial fibrillary acidic protein, S-100 protein, Leu 7 epitopes, neuron-specific enolase, the 200-kilodalton subunit of the neurofilament triplet polypeptide, and retinal S-antigen. We found that (1) glial fibrillary acidic protein, S-100 protein, and Leu 7 epitopes were detected only in well-differentiated glial cells that were interpreted as reactive and not neoplastic, (2) undifferentiated neoplastic cells expressed both neuron-specific enolase and retinal S-antigen immunoreactivity, and (3) differentiated cells forming Flexner-Wintersteiner rosettes were found to express neuron-specific enolase, retinal S-antigen, and, occasionally, neurofilament protein. These results support the view that retinoblastomas are composed of neuron-committed cells and favor the origin of these tumors from photoreceptor progenitor cells. We did not find any morphologic or immunohistochemical evidence of glial differentiation from tumor cells that would support the concept that retinoblastoma arises from a primitive neuroectodermal cell capable of divergent differentiation along neuronal and glial lines.

Antibodies, Monoclonal↗
PubMed1987

Embryonal central neuroepithelial tumors: current concepts and future challenges.

While the embryonal central neuroepithelial tumors present complex conceptual and clinical problems, advances in cell type identification by special neurohistological, immunohisto- and immunocytochemical techniques have permitted discrimination of distinct cytomorphogenetic entities. These are based in part on their resemblance to the normal phases of neurocytogenesis. Four of these tumors, medulloepithelioma, desmoplastic infantile ganglioglioma, pineoblastoma and medulloblastoma, are designated as multipotential in light of their capacity to undergo divergent differentiation. Cytomorphogenetic, clinical and experimental data implicate fetal neural cell targets for transformation and raise the possibility that aberrant developmental regulatory mechanisms may contribute to the biologic behavior of these tumors. Growth factors and some neuroregulatory neurotransmitters (such as serotonin) are known to act as modulators of normal neuromorphogenesis. They could play a regulatory role in central neuroepithelial tumors on the hypothesis that the aberrant behavior of the embryonal neoplasms could either be modified by functional receptor responses or result from abnormal receptor responses to these substances. Future challenges include the definition of new cytomorphogenetic entities and subgroups of the currently defined forms of embryonal CNS tumors based on the presence of specific growth factors and neuroregulatory neurotransmitters, or their receptors, the characterization of neoplastic receptor responses mediating any modulatory role of the presently known growth factors or neuroregulatory neurotransmitters on the growth and maturation potential of the embryonal central neuroepithelial tumors and the further definition of developmental, stage-specific modulators that might be operative in these tumors.

Brain Neoplasms↗
PubMed1987

The correlation of neoplastic vulnerability with central neuroepithelial cytogeny and glioma differentiation.

The vulnerability of neuroepithelial cells in the central nervous system (CNS) to neoplastic transformation results from the interaction of several factors: the existence of a reserve population of stem cells, the capability of differentiated cells to reenter the kinetic cycle, the number of replicating cells at risk at a particular time, the length of time during which a particular cell population remains in the cycle, the state of differentiation and the further differentiation potential of that population, and the steps of differentiation that are achieved in successive cell generations. This concept explains many aspects of CNS tumor incidence and the relationship of central neuroepithelial embryonal tumors to tumors of adult cell type. The incidence of different types of central neuroepithelial tumors can be correlated with the width of the window of neoplastic vulnerability. Examples illustrating the existence of only a narrow window include such rare tumors as medulloepitheliomas, cerebral neuroblastomas, gangliogliomas and ependymoblastomas. By contrast, cerebellar medulloblastomas, astrocytomas, mixed astrocytomas and oligodendrogliomas, and glioblastomas exemplify instances in which a relatively wider window of vulnerability exists in the light of cellular neuro-ontogeny and of the capacity of glial cells for postnatal replication. The relationship that may occasionally be established between the development of a glioma and the production of cellular gliosis such as may follow brain injury or accompany multiple sclerosis can also be viewed in the light of that concept. Increasing awareness is needed concerning the development of postradiation gliomas, in particular after the apparently successful treatment of acute lymphocytic leukemia.

Astrocytoma↗