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Biomedical subjects

L J Rubinstein

Publications and source records attributed to L J Rubinstein.

At least 91 records · Page 5Linked to original sources

Mixed capillary hemangioblastoma and glioma. A redefinition of the "angioglioma".

The histopathologic features of four cases of mixed capillary hemangioblastoma and glioma are described. In three cases, two of which arose in the cerebellum and one in the spinal cord, the hemangioblastic component may have originated from a neoplastic proliferation of the exuberant vascular stroma in a glial tumor. In a fourth case, a cerebellar hemangioblastoma was surrounded by a peripheral rim of atypical neoplastic-looking astrocytes ("reactive glioma"). The controversial concept of the "angioglioma" is reviewed, and it is proposed that the term be used to designate only true mixed tumors of glial and vascular tissue origin whose histologic features conform to the examples described in this report.

Aged↗

Idiotype-anti-idiotype network. II. Activation of silent clones by treatment at birth with idiotypes is associated with the expansion of idiotype-specific helper T cells.

BALB/c mice immunized with bacterial levan (BL) produce a vigorous antibody response that fails to include antibodies expressing the idiotype of the beta 2 leads to 6 fructosan-binding myeloma protein ABPC48 (A48). Treatment of newborn BALB/c mice at 1 d of age with 0.1-10 microgram of either the A48 myeloma protein or monoclonal proteins that share idiotopes with the A48 family, followed by immunization with BL 2-4 wk later, produces an anti-BL response that is dominated by the A48Id. Various degrees of activation of the A48Id BL response were observed by injecting mice with A48 monoclonal protein only up until 3 wk of age. Activation of the A48Id clones by treating with A48 monoclonal protein was ineffective in mice who were older than 4 wk. Elicitation of an A48Id BL response required specific antigenic stimulation with either beta 2 leads to 6 or beta 2 leads to 1 fructosan epitopes, because it does not occur after injection with TNP-Ficoll in spite of the A48 treatment. The expansion of A48Id clones in mice treated at birth with A48 monoclonal protein is associated with an increase in A48Id-specific helper T cells. The binding specificity of these cells was demonstrated by infusing them into nu/nu BALB/c mice and observing that they rendered help that enalbed the animal to mount an anti-TNP response after immunization only with A48-TNP, but not with MOPC384-TNP conjugates. The helper activity of these cells is sensitive to the effects of treatment with anti-Lyt-1.2 antibodies plus complement. A predominantly A48Id BL-specific response can be transferred into lethally irradiated mice by infusing them with purified T and B cells from A48-treated mice. The transfer of this response can be ablated by treating the T cells with anti-Lyt-1.2 antibodies plus complement. These results indicate that A48Id-specific helper cells possess the ability to select the A48Id-bearing B cell precursors for expression, thus exerting a fine-tuning effect on the idiotypic expression of the anti-BL repertoire. We propose that this idiotype-induced idiotype response, which can be, in principal, induced by idiotypes provided by the mother, plays an important role in the expansion of precursors of antibody-forming cells during embryonic as well as postnatal life.

Aging↗

Pigmented olfactory neuroblastoma: a new example of melanotic neuroepithelial neoplasm.

The light and electron microscopic features of a pigmented olfactory neuroblastoma are described. The neuroblastic nature of the tumor was confirmed by the demonstration of axons, some of which originated from the neoplastic cells, and by the presence of dense-core vesicles in the perikarya and processes of the tumor cells. The tumor contained a large amount of pigment, most of which had the histochemical reactions of melanin, but some of which had that of lipofuscin. Electron microscopy failed to demonstrate the presence of melanosomes or premelanosomes: the pigment showed some of the features of neuromelanin, although the fine structural appearances were not typical. The pigment was interpreted in this case as presumably representing a modified catecholamine degradation product, perhaps related to lipofuscin. The presence of melanotic pigment in an example of olfactory neuroblastoma, unreported until now, augments the list of neurogenic neoplasms in which an association with melanin formation has been described. The significance of this association in tumors originating from the nervous system or its coverings needs further investigation, as the nature of pigment appears to be heterogeneous. These tumors may contain either melanosomal pigment or pigment identified as neuromelanin (or a related substance), seemingly regardless of the derivation of the pigment-bearing cells.

Adult↗

Malignant gliomas with heavily lipidized (foamy) tumor cells: a report of three cases with immunoperoxidase study.

Three cases of heavily lipidized malignant glioma are reported. Large amounts of intracellular lipid gave the tumor cells a vacuolated, foamy appearance that generally obscured their glial nature. The latter was, however, confirmed by the demonstration of glial fibrillary acidic protein (GFAP) by immunoperoxidase. These tumors, which were situated deeply in the brain and contained areas of necrosis, must be distinguished from the relatively benign pleomorphic meningocerebral xanthoastrocytomas, which are characteristically superficial in their location and lack necrotic foci. The malignant nature of the presently described tumors is shown by the death of all three patients within one year of surgery. Thus, in the biologic sense these tumors represent glioblastomas; however, their morphologic peculiarities in the form of massive lipidization of tumor cells, apparently not caused by necrobiosis, set them aside as a histologic subgroup.

Adult↗

Glial fibrillary acidic protein in stromal cells of some capillary hemangioblastomas: significance and possible implications of an immunoperoxidase study.

Thirty-nine hemangioblastomas from 26 patients were studied by the immunoperoxidase method for GFA protein. Reactive gliosis in the form of trapped GFA protein-positive astrocytes or astrocytic cell processes penetrated the margins of all the neuraxial tumors and none of those occurring on nerve roots or in the tumor explants maintained in an organ culture system. Gliosis was especially prominent in tumors recurring after surgical excision or in patients with a long history of tumor. In six tumors, representing both the reticular and the cellular variants of hemangioblastoma, GFA protein-positive stromal cells were also found, chiefly in the periphery of the neoplasma: all these tumors were surrounded by dense reactive gliosis. Four hypotheses accounting for the presence of GFA protein-positive stromal cells are considered: (1) The tumors are astrocytomas. (2) The GFA protein-positive cells are not neoplastic but lipidized or altered reactive astrocytes. (3) The tumors are mixed and partly composed of neoplastic astrocytes. (4) The stromal cells are capable of taking up extracellular GFA protein derived from the adjacent reactive astrocytes. The last of these hypotheses is the most consistent with the collective evidence derived from the histological findings. It implies that the presence of GFA protein in the cytoplasm of a cell does not necessarily establish that the cell is glial. The possibility of uptake of GFA protein by non-glial cells must be considered if dense gliosis is present in the vicinity.

Adolescent↗

Focal ependymal differentiation in choroid plexus papillomas. An immunoperoxidase study.

Choroid plexus papillomas are usually easily distinguishable from papillary ependymomas by their delicate fibrovascular stroma and their cytologic similarity to normal choroid plexus epithelium. Exceptionally, however, examples are met which give rise to diagnostic difficulty. We therefore tested 22 choroid plexus papillomas for the presence of glial fibrillary acidic (GFA) protein using the immunoperoxidase technique. Positivity for the protein was found focally in epithelial tumor cells in nine of the 22 papillomas. All were in adults ranging from 19-66 years of age. Eight of the nine tumors originated in the 4th ventricle or one of its lateral recesses. In six papillomas showing GFA protein in the cells, intracellular fibrils were found in a small number of elongated epithelial cells with the PTAH and/or Masson trichrome stains; in all these six cases, the GFA protein-positive cells were considerably more numerous than cells containing fibrils. Normal choroid plexus epithelium lacks GFA protein, but pathologically altered ependymal cells are often GFA protein-positive. Our findings therefore suggest that focal divergent glial (presumably ependymal) differentiation may be expressed in neoplastic choroid plexus epithelium, consistent with the origin of this epithelium from primitive neuroepithelial (ventricular) cells.

Adolescent↗

Cytogenesis and differentiation of pineal neoplasms.

Our knowledge of pineal neoplasms is still fragmentary, but a pattern is beginning to emerge in this highly challenging area of neuro-oncology. In vitro studies and more complete morphologic and biochemical characterization are still needed for these very rare neoplasms. Follow-up data from appropriate clinical series are still almost nonexistent for the evaluation of therapeutic effectiveness. As an illustration of neoplastic development, the demonstration of divergent differentiation in pineal parenchymal tumors represents a most intriguing phenomenon in light of the origin, structure, and function of the pineal gland.

Brain Neoplasms↗

Rat C-6 glioma cells maintained in an organ culture system: a study of kinetic parameters.

Rat C-6 glioma cells were grown on a sponge foam matrix in an organ culture system and the cell cycle parameters, including the growth fraction (GF), were assessed after autoradiography. The zones of growth consisted of a compact upper layer (UL) at the gaseous interface, a central necrotic layer and a deeper lower layer (LL) which invaded the matrix. The fraction of continuously labeled mitoses (FCLM) was similar in both the UL and LL cells. The derivatives of the FCLM curves obtained in three experiments gave an average modal TG2 of 5 hr. A mathematical model relating GF, TG2, TC and labeling index as a function of time, LI(t), was devised for cells in a steady state exposed continuously to tritiated thymidine and was applied to data obtained from UL cells. A mean GF of 9% (range: 8-10%) and a mean cell cycle time (TC') of 27 hr (range: 13-47 hr) were obtained. The mean TS was calculated to be 11 hr (range: 8-16 hr) by the method of grain counts per mitotic figure or grain index (GI). Knowledge of TS permitted alternative calculation of the cell cycle time from the equation Ts/TC = LI(0)/GF:this gave a mean cell cycle time (TC") of 29 hr (range: 20-45hr). Except for the GF, the cell kinetics were comparable to those of the same cell line grown in monolayer culture. The GF in the in vitro system described is in the lower range reported in some human malignant gliomas in vivo.

Animals↗

Reactive glioma in intracranial sarcoma: a form of mixed sarcoma and glioma ("sarcoglioma"): report of eight cases.

The clinicopathologic features of eight new cases of combined intracranial sarcoma and glioma are described. This type of mixed cerebral tumor is histologically characterized by a peripheral distribution of the gliomatous elements in relation to a more centrally situated meningeal or intracerebral sarcoma, and by the frequent presence of gradual transitions from reactive to frankly neoplastic astrocytes. In six of the eight cases, the additional development of either infiltrating astrocytoma or frank glioblastoma in the adjacent brain was demonstrated; this was interpreted as a further expression of malignant glial reaction. It is suggested that these tumors be termed "sarcogliomas" to distinguish them from the type of mixed glioma and sarcoma that has recently been redesignated "gliosarcoma."

Adolescent↗

Pleomorphic xanthoastrocytoma: a distinctive meningocerebral glioma of young subjects with relatively favorable prognosis. A study of 12 cases.

Twelve cases of a distinctive form of supratentorial astrocytoma occurring in young subjects (ages 7 to 25) are reported. The tumors were superficial and involved the leptomeninges extensively. The tumor cells display marked pleomorphism, including bizarre giant cells and a number of mitotic figures, but no necrosis. Many contain large amounts of lipid in their cytoplasm and are surrounded by reticulin fibers, thus simulating a mesenchymal tumor. For these reasons, some examples of this tumor have been previously interpreted to represent meningocerebral fibrous xanthomas. Immunoperoxidase technique performed in nine of the twelve cases has, however, established the presence of glial fibrillary acidic protein in the tumor cells, which are therefore considered to be astrocytic. By electron microscopy many tumor cells are surrounded by basal laminae, accounting for the abundant reticulin network demonstrable in silver preparations. Since subpial astrocytes are known to be partly covered by a basal lamina, it is likely that they are the cells of origin for this neoplasm. In contrast to its pleomorphic cytology, the biological behavior of this tumor appears to be relatively favorable, and long survival times (up to 25 years) have been recorded in some cases. (These tumors are distinct from intracranial fibrous xanthomas of mesenchymal derivation. Cells of the latter are negative on GFAP stain.)

Adolescent↗

The cytological differentiating potential of pineal parenchymal neoplasms (true pinealomas). A clinicopathological study of 28 tumours.

A series of 28 pineal parenchymal tumours is described, with special reference to the potential of some of these neoplasms to differentiate along glial or ganglionic lines, or both. The more undifferentiated tumours (pineoblastomas, 11 cases) were the most frequent: they are histologically similar to medulloblastomas. One example showed focal differentiation to retinoblastoma at the primary site. The histological features of pineoblastomas merged with those of pineocytomas (7 cases), in which the lobular architecture is reminiscent of that of the mature pineal gland. In addition, 10 further examples in the group of pineocytomas showed more advanced differentiation as follows: towards astrocytes only (2 cases), towards ganglion cells only (1) case) and towards both astrocytes and ganglion cells (gangliogliomas) (7 cases). Confirmation of the pineal parenchymal nature of these neoplasms and of their differentiating potential was provided by a modification of the Achúcarro-Hortega's silver carbonate impregnation technique for pineal parenchymal cells, by specific silver impregnations for axonal processes, and by an immunoperoxidase stain for glial fibrillary acidic (GFA) protein. Electron microscopy of one new example of pineocytoma with neuronal and astrocytic differentiation demonstrated the presence of numerous microtubules, of clear-centred and dense-core vesicles, and of synaptic complexes. Seven illustrative clinical histories with pathological findings are presented. The identification of special features of cellular differentiation is of importance in evaluating the biological behaviour of these neoplasms since a definite correlation can be established between the patient's age, some of the cytological variants, and the malignant potential of the tumour. Pineoblastomas are highly malignant neoplasms of children and young adults which disseminate widely throughout the cerebrospinal fluid pathways. -ineocytomas without cellular evidence of further differentiation occur at any age and are also clinically malignant, but with a somewhat lesser tendency to metastasize than pineoblastomas. Pineobytomas with astrocytic differentiation occur in adults and may be either slowly growing or malignant. Pineocytomas with neuronal or with neuronal and astrocytic differentiation occur in later life, remain localized, and are relatively benign. Since the latter account for approximately one-third of pineal parenchymal tumours and are likely to be relatively radio-resistant, tissue diagnosis is imperative for a determination of the therapeutic approach. Radiation to the entire neuraxis should be administered to patients with pineoblastomas and malignant pineocytomas in view of their high frequency of cerebrospinal metastasis. An accurate histological classification of these tumours therefore carries important clinical and therapeutic implications...

Adolescent↗