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Biomedical subjects

F T Vertosick

Publications and source records attributed to F T Vertosick.

30 records · Page 2Linked to original sources
PubMed1990

Brain stem and spinal metastases of supratentorial glioblastoma multiforme: a clinical series.

Although the spread of supratentorial glioblastoma multiforme to the brain stem and spine has been extensively described in published autopsy series, information on the diagnosis, treatment, and subsequent clinical course of patients manifesting symptoms of glioblastomatous dissemination ante mortem remains scant. We report a series of 11 patients having the signs and symptoms of neuraxis dissemination of supratentorial glioblastoma multiforme. All patients had radiographic documentation of metastases by either contrast-enhanced myelograms or enhanced magnetic resonance imaging scans. Ten presented with spinal involvement, whereas one presented with lower cranial neuropathies secondary to diffuse involvement of the basal cisterns. The mean age of the patients was 38.5 years, and the mean time interval between diagnosis of intracranial disease and diagnosis of metastases was 14.1 months. After diagnosis of tumor spread, subsequent mean survival time was 2.8 months. All patients received additional radiotherapy to the areas of metastasis, but the clinical response to radiotherapy was quite poor. This study confirms previous reports in the literature suggesting that metastases occur in younger patients and in patients with extended survival. The findings suggest that the relatively infrequent clinical incidence of the symptomatic spread of glioblastoma multiforme, as compared with the frequent incidental discovery of such spread at autopsy, may be the result of the limited survival of the affected patients, and not due to the biology of the tumor.

Adolescent↗
PubMed1990

Response of malignant glioma cell lines to activation and inhibition of protein kinase C-mediated pathways.

To evaluate the role of protein kinase C-mediated pathways in the proliferation of malignant gliomas, this study examined the effect of a protein kinase C (PKC)-activating phorbol ester (12-O-tetradecanoyl-13-phorbol acetate or TPA) and a protein kinase C inhibitor (polymyxin B) on deoxyribonucleic acid (DNA) synthesis of malignant glioma cells in vitro. A serum-free chemically defined medium, MCDB 105, was employed for all studies. Two established human malignant glioma cell lines (T98G and U138), two rat glioma lines (9L and C6), and two low-passage human glioma lines (obtained from surgical specimens) were studied. With the exception of the C6 line, all tumors responded in a dose-dependent fashion to nanomolar concentrations of TPA with a median effective dose that varied from 0.5 ng/ml for the U138 glioma to 1 ng/ml for the T98G glioma. At optimal concentrations (5 to 10 ng/ml), TPA produced a two- to five-fold increase in the rate of DNA synthesis (p less than 0.05) as assessed by incorporation of 3H-thymidine. However, TPA had no additive effect on the mitogenic response produced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF). Inhibition of PKC using the antibiotic polymyxin B (20 micrograms/ml) abolished the TPA-induced mitogenic response in the five responsive lines tested. In two tumors (U138 and 9L), polymyxin B also eliminated EGF-, PDGF-, and serum-induced DNA synthesis as well as abolishing baseline DNA synthesis. These cells remained viable, however, as assessed by trypan blue exclusion; after removal of polymyxin B from the medium, they were able to resume DNA synthesis in response to TPA and serum. In the three other tumors (T98G and the two low-passage human glioma lines), growth factor-induced and serum-induced DNA synthesis were inhibited by approximately 25% to 85%. It is concluded that PKC-mediated pathways affect DNA synthesis in the human malignant glial tumors studied. The response of the glioma cells to TPA is similar to the responses seen in fetal astrocytes, but differs significantly from those reported for normal adult glial cultures. Because the response of the 9L glioma to TPA is similar to the responses seen in the human tumors, the 9L rat glioma model may prove useful for examining the role of PKC-mediated pathways in controlling glioma growth in vivo.

Animals↗
PubMed1990

Response of malignant glioma cell lines to epidermal growth factor and platelet-derived growth factor in a serum-free medium.

The use of a serum-free culture system for assessing the growth factor responsiveness of malignant glial cells is described. The mitogenic properties of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) were examined in three human malignant glioma cell lines (T98G, U87, and U138). Each of the three had high-affinity EGF receptors and all responded in a dose-dependent fashion to physiological concentrations of EGF. These cell lines also showed a pronounced mitogenic response to PDGF which equaled or exceeded that achieved with EGF. Simultaneous stimulation with both factors produced an additive response, which approximated that obtained in medium supplemented with 10% fetal calf serum. The authors conclude that functional EGF and PDGF receptors were present in the human malignant glial tumors studied. The response of the human glioma lines to these growth factors in many respects parallels the response seen in fetal astrocytes tested under similar conditions. In contrast, the behavior of two chemically induced rat gliomas (9L and C6) differed significantly from that seen in the human lines, suggesting that the rat lines may not be entirely acceptable as models for studying the growth characteristics of human malignant glial tumors.

Brain Neoplasms↗
PubMed1989

A method for recovery of native, clonally-restricted immunoglobulins from agarose gels.

Multiple low level, clonally-restricted, immunoglobulins (Ig) are commonly encountered on routine serum protein electrophoresis by clinical laboratories using high resolution zone electrophoresis on agarose. We sought a method for recovering the clonally-restricted Ig, in native configuration, from clinical laboratory gels as a first step in the investigation of its clinical significance. We found that a two-stage electrophoretic procedure gave consistently good recoveries. After routine agarose gel electrophoresis, portions of the electropherogram, containing clonally-restricted Ig, were excised and subjected to flatbed isoelectric focusing in agarose to enhance separation of the individual antibody clonotypes. Multiple slabs, containing the same clonally-restricted Ig, could be cut from adjacent tracks (i.e., tracks loaded with the same specimen) on the zone electropherogram and applied to a single track on the focusing gel to improve separation and increase yields. The focused gels were cut to isolate slabs containing individual clonotypes. These slabs were washed to remove carrier ampholytes and held at -20 degrees C overnight. Ig was extracted from the thawed gels, with 61-68% recovery, by ultracentrifugation following physical disruption of the gel. Antigen binding activity of the recovered Ig was verified by rate nephelometry. Clonally-restricted antibodies were successfully isolated from an immune animal serum by this procedure and biotinylated for use as probes on Western blots.

Electrophoresis↗
PubMed1987

Antibodies to native and denatured DNA. Quantitation using an immuno-slot-blot technique.

The attachment of DNA to nitrocellulose by suction filtration has been used as a prelude to DNA hybridization experiments, and several filter manifolds for this purpose are available. One suction manifold, the 'Minifold II slot-blotter', creates small, rectangular slots of bound DNA which can be probed using immunoenzymatic techniques and then evaluated with quantitative scanning densitometry. We applied this technique to the detection and quantitation of naturally occurring anti-DNA antibodies. After probing slot-blots of native or denatured DNA with human sera, the slot-blots were stained using an alkaline phosphatase second antibody system. The serum concentration of anti-DNA antibodies was determined by comparing the peak areas of the positive blots to a standard IgG curve. When native DNA was used as a substrate, these serum concentrations correlated well with the anti-DNA titer as measured by the Crithidia luciliae indirect immunofluorescence assay.

Antibodies↗
PubMed1987

Stability of model immune complexes during zone electrophoresis and isoelectric focusing in agarose gels.

We evaluated the stability of model immune complexes, consisting of radioiodinated follitropin (125I-FSH), bound either to a mouse monoclonal antibody to FSH or to sheep polyvalent anti-FSH antiserum, during zone electrophoresis and isoelectric focusing in agarose gels. The complexes were relatively stable during zone electrophoresis at conventional voltages (less than 40 V/cm), about 80% of the initially bound antigen migrating in the gamma region. Highter voltages resulted in a linear increase in the antigen stripped from the gamma region. By contrast, isoelectric focusing very effectively dissociated the acidic 125I-FSH from the basic sheep immunoglobulins, even if the complexes were subjected to electromotive forces alone, i.e., by loading them onto the neutral region of the gel. The monoclonal complexes were not dissociated by high voltage alone. The monoclonal complexes could be completely dissociated by loading them at the anode, where gel acidification enhances complex dissociation. These observations can form the basis of a simple technique for isolating and dissociating human immune complexes before Western immunoblot analysis. Furthermore, the ease and rapidity with which bound and free antigen can be separated during zone electrophoresis in agarose suggests that this technique may have some application in clinical immunoassays.

Animals↗
PubMed1986

Systemic lupus erythematosus: a role for anti-receptor antibodies?

Systemic lupus erythematosus (SLE) is considered by many to represent the best example of human disease where immune complexes play a primary role in the pathogenesis. SLE is thought to have an autoimmune basis; a conclusion based largely upon the propensity of these patients to form antibodies to cell nuclear components. The etiology of SLE remains unknown, as does the mechanism by which nuclear components are rendered autoantigenic. Here we present an argument for considering SLE as an antireceptor autoimmune disease, analogous to Graves' disease or myasthenia gravis. The proposed target of autoimmune attack, the estrogen receptor (ER), is normally resident in the nucleus, physiologically more active in women, and shed from hormonally responsive tissues during the course of the menstrual cycle. Autoantigenicity of ER is enhanced in SLE patients owing to a biochemical abnormality of estrogen metabolism which favors ligand occupancy of the receptor. The spectrum of anti-nuclear antibodies characteristic of SLE arises via normally functioning immune network regulatory mechanisms.

Antigen-Antibody Complex↗
PubMed1985

Role of defective dopaminergic inhibition of prolactin secretion in the pathogenesis of prolactinoma.

Prolactinomas pose an increasingly frequent therapeutic dilemma for the clinician. The neurosurgeon caring for the prolactinoma-bearing patient must stay abreast of the most current basic research concerning the pathogenesis of these often difficult tumors. A fascinating and dynamic line of research involves the possibility that prolactinomas arise secondary to a flaw in the normally inhibitory dopaminergic neurohypophyseal axis. The details of this hypothesis are presented, the current literature surrounding this topic is reviewed, and a brief synthesis of the available theoretical models of prolactinoma pathogenesis is provided.

Autoantibodies↗
PubMed1983

Autoantigens in an immunological network.

An autoantigen network, consisting of all non-lymphoid cells and a subset of peripherally located autoregulatory lymphocytes, is proposed. By equilibrating a web of idiotypic stimulation (helper activity) and antiidiotypic inhibition (suppressor activity) directed at each tissue differentiation antigen, this network quantitatively limits autoantigen expression and thereby regulates the differentiation and growth homeostatic processes these autoantigens mediate. Perturbations of the network's dynamic equilibrium secondary to viral infection, somatic mutation, or interaction with environmental agents would clinically manifest themselves as autoimmune tissue destruction, benign or malignant nonlymphoid neoplasia, and lymphoproliferative disorders.

Antigens↗
PubMed1983

Unilateral hydrocephalus secondary to congenital atresia of the foramen of Monro. Case report.

Unilateral hydrocephalus is an uncommon entity which results from obstruction at the level of the foramen of Monro. It is usually brought about by tumors or inflammatory conditions. Congenital maldevelopment of the foramen of Monro is an often postulated, yet never proven, cause of unilateral ventricular enlargement. A case of unilateral hydrocephalus secondary to congenital atresia of the foramen of Monro is presented to document the occurrence of this condition.

Cerebral Ventricles↗