Biomedical subjects

P Fredman

Publications and source records attributed to P Fredman.

At least 73 records · Page 4Linked to original sources

PubMed1994

Sulphatide in islets of Langerhans and in organs affected in diabetic late complications: a study in human and animal tissue.

Sulphatide has been found in rat islets of Langerhans and anti-sulphatide antibodies have been demonstrated in patients with insulin-dependent diabetes mellitus. Using a specific monoclonal antibody, Sulph I, directed against sulphatide, we investigated the in situ distribution of this glycolipid immunohistochemically; furthermore, the sulphatide concentration was determined in several organs and cells by thin-layer chromatography. The islets of Langerhans in all species examined, mouse, rat, pig, and monkey were intensively stained but exocrine tissue remained unlabelled. The sulphatide concentration in human islets was 150 +/- 46 pmol/100 islets. The only glycolipid-antigen detected was sulphatide. Regarding other tissues, sulphatide was found to be located in distal tubules in the kidney, peripheral nerves, distinct scattered spot-like structures in the choreoid layer of the eye, the ovum, and peripheral granulocytes. Sulph I injection in mice showed homing to kidney tubules, Lung, heart, liver, adrenal, spleen, lymph node and thymus were not stained by Sulph I. Thus, the distribution of sulphatide shows an association with organs known to be affected in diabetes, either initially or in late complications.

Adult↗

PubMed1994

Formulas for the quantitation of intrathecal IgG production. Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis.

There are several formulas for the quantitative determination of intrathecal IgG production: Reiber and Felgenhauer's formula (IgG(loc)), the Extended IgG index, Tourtellotte's formula (TOURT), Schuller and Sagar's formula (SCHULL), the IgG index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To evaluate the utility of these formulas in the presence of blood-brain barrier (BBB) damage, we present the results from a study of serum and cerebrospinal fluid (CSF) samples from 125 healthy individuals, 18-88 years of age; 1072 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin ratio 9.8-30); and 106 patients with definite multiple sclerosis (MS). The relation between the CSF/S albumin ratio and the CSF/S IgG ratio was remarkably linear in both healthy individuals (r = 0.95; P < 0.0001) and patients without oligoclonal bands in the CSF (r = 0.95; P < 0.0001). Therefore, IgG(loc) and the Extended IgG index, two formulas based on a nonlinear relation between the CSF/S albumin ratio and the CSF/S IgG ratio, yielded biased results (lower values) in the presence of BBB damage. TOURT and SCHULL also yielded biased (higher) values in the presence of BBB damage, probably because of incorrect constants in these formulas. There were no significant correlations between the CSF/S albumin ratio (i.e. the BBB function) and the IgG index or the Log IgG index, two dimensionless quotients for the detection of intrathecal IgG production, or between the CSF/S albumin ratio and IGGPROD, an empirical formula for the determination of intrathecal IgG production in mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Detection of glioma-associated gangliosides GM2, GD2, GD3, 3'-isoLM1 3',6'-isoLD1 in central nervous system tumors in vitro and in vivo using epitope-defined monoclonal antibodies.

In this study, MAbs to the 'conventional' gangliosides expressed by human gliomas were generated and used to detect ganglioside species previously unisolated or defined in normal adult CNS tissue. Despite the marked phenotypic and genotypic heterogeneity shown by glioma cell lines (Bigner et al., 1981), the ganglioside phenotype of these cell lines is remarkably consistent qualitatively, if not quantitatively, in the ganglioside species expressed (Table V). The majority of cell lines and tumor samples express GM2, GD2 and GD3; this does not provide a diagnostic advantage (Vick et al., 1992). Nevertheless, as the relative amounts of these gangliosides in tumor as compared with normal adult CNS tissue is considerable, such reagents might be considered in compartmental immunotherapeutic approaches. Since GD2 and GD3 have been determined to mediate tumoricidal activity with human effector cells via specific antiganglioside epitope MAbs (Thurin et al., 1987; Kushner and Cheung, 1991; Barker et al., 1991; Reisfeld, 1993), cell-mediated approaches, as well as targeted immunoglobulin therapies, are also possible. The prospect of a more targeted approach with little or no effect on normal CNS tissue is now possible via the 'oncofetal' epitopes characteristic of 3'-isoLM1 and 3',6'-isoLD1. Several factors recommend the use of these moieties for compartmental immunotherapy; the inability to detect them within the adult CNS; the relatively high frequency of expression of 3'-isoLM1 and 3',6'-isoLD1, especially in human tumor samples (50-100%, depending upon the series and assay); and the existence of specific MAbs reactive with these epitopes. Current technology is being applied to these MAbs to transfer the specific recognition capacity of existing murine MAbs into various human framework structures of any desired immunoglobulin class, and thereby, biologic function. The variety of effector functions, the stability in affinity, labeling capacity, and the exquisite sensitivity of these MAbs for these glioma-distinctive epitopes is an exciting and promising approach for immunotherapy of human CNS tumors.

Antibodies, Monoclonal↗

PubMed1994

Gangliosides associated with primary brain tumors and their expression in cell lines established from these tumors.

Human primary brain tumors differ in their ganglioside composition when compared to adjacent tissues. One ganglioside found in all malignant glioma specimens, but not detected in normal adult brain, is 3'-isoLM1, a ganglioside of the lacto series. This ganglioside was also identified in medulloblastomas with astrocytic differentiation and in brain tissues containing benign proliferating astrocytes. The appearance of 3'-isoLM1 was seen over large regions of brain from glioma but was found mainly in areas either adjacent to the macroscopic tumor or areas corresponding to the tumor in the opposite hemisphere. A high concentration of 3'-isoLM1 was also seen in the corpus callosum, the anatomical structure along which glioma cells may migrate to the opposite brain hemisphere. Ganglioside expressed by cell lines established from primary malignant brain tumors varied widely among cell lines and within a given cell line propagated under different conditions. In in vitro-cultured glioma and medulloblastoma cell lines, gangliosides of the ganglio series dominated and the expression of the lacto series gangliosides, including 3'-isoLM1 was low if at all detectable. However, in vivo growth of solid subcutaneous tumors in nude mice or rats led to a significantly increased expression of the often dominant gangliosides of the lacto series and revealed a decreased expression of ganglio series gangliosides. In conclusion, these findings indicate that environmental factors could strongly influence the expression of gangliosides that may lead to a switch from the ganglio to the lacto series. These results also suggest that ganglioside 3'-isoLM1 is associated with proliferating astrocytes, of both neoplastic and non-neoplastic origin and that this ganglioside may be involved in cell-cell recognition and attachment during development and tumor cell migration.

Brain Chemistry↗

PubMed1994

Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report.

The Committee of the European Concerted Action for Multiple Sclerosis (Charcot Foundation) organised five workshops to discuss CSF analytical standards in the diagnosis of multiple sclerosis. This consensus report from 12 European countries summarises the results of those workshops. It is hoped that neurologists will confer with their colleagues in clinical chemistry to arrange the best possible local practice. The most sensitive method for the detection of oligoclonal immunoglobulin bands is isoelectric focusing. The same amounts of IgG in parallel CSF and serum samples are used and oligoclonal bands are revealed with IgG specific antibody staining. All laboratories performing isoelectric focusing should check their technique at least annually using "blind" standards for the five different CSF and serum patterns. Quantitative measurements of IgG production in the CNS are less sensitive than isoelectric focusing. The preferred method for detection of blood-CSF barrier dysfunction is the albumin quotient. The CSF albumin or total protein concentrations are less satisfactory. These results must be interpreted with reference to the age of the patient and the local method of determination. Cells should be counted. The normal value is no more than 4 cells/microliters. Among evolving optional tests, measurement of the combined local synthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation. Other tests that may have useful correlations with clinical indices include those for oligoclonal free light chains, IgM, IgA, or myelin basic protein concentrations.

Acute Disease↗

PubMed1994

A high-sensitivity immuno-chemiluminescence technique for detection of oligoclonal IgG and IgM in unconcentrated cerebrospinal fluid.

A method is described for detection of oligoclonal IgG and IgM in unconcentrated cerebrospinal fluid (CSF). The proteins were separated by agarose gel electrophoresis and transferred to cellulose nitrate membranes. A double antibody technique with a peroxidase conjugated secondary antibody was used to detect the protein. Bound secondary antibody was visualized by autoradiography using chemiluminescence (ECL) reagent. The procedure presented here allows examination of oligoclonal bands of IgG and IgM in less than 6h. The detection limit for a single band was approximately 10pg and the results were in complete agreement with those achieved by isoelectric focusing (Phast System) and subsequent immunofixation. In 9 of the samples oligoclonal IgM was also detected.

Electrophoresis, Agar Gel↗

PubMed1993

Sulphatide and sulphatide antibodies in insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) is associated with neurological disorders. Sulph I, a monoclonal antibody to sulphatide (a neural epitope), stained secretory granules in alpha and beta cells of rat islets of Langerhans, but not exocrine tissue. Sera from 88% of 57 newly diagnosed IDDM patients was anti-sulphatide positive, and 76% were positive 6 months later. All 135 healthy controls were negative. Sulphatide antibody may be an IDDM marker.

Adult↗

PubMed1993

Lactotetraose series ganglioside 3',6'-isoLD1 in tumors of central nervous and other systems in vitro and in vivo.

Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV3NeuAc,III6-NeuAcLcOse4Cer (3',6'-isoLD1), were found to define the minimum binding epitope NeuAc(or NeuGc)alpha 2-3Gal beta 1-3(NeuAc or NeuGc)alpha 2-6GlcNAc. The distribution of 3',6'-isoLD1 in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Only 4 of 26 cell lines, 3 teratomas and 1 pancreatic adenocarcinoma, expressed detectable 3',6'-isoLD1 when cultured in vitro; none of 14 tested glioma lines, including 2 that expressed the monosialo-precursor IV3NeuAcLcOse4Cer in vitro, expressed detectable levels. Expression of 3',6'-isoLD1 was more frequent when neoplastic cells were grown in xenograft form in athymic mice; 4 of 10 glioma and 2 of 2 teratoma xenograft ganglioside extracts were positive for 3',6'-isoLD1. The absence of 3',6'-isoLD1 in cultured tumor cells of the central nervous system and its proportional increased presence in tumor cells of the same origin grown in vivo further supports previous studies suggesting that ganglioside expression may be modified by environmental forces. The expression of lacto series gangliosides both in vitro and in vivo by teratoma and pancreatic adenocarcinoma cells, as opposed to only in vivo expression by glioma cells, suggests that tissue-specific forces may also exist. Immunohistochemical localization of 3',6'-isoLD1 in frozen sections of primary central nervous system neoplasms including those of glial and nonglial origin was performed; 20 of 30 (67%) of glial tumors were positive. Among nonglial tumors, 21 of 34 (62%) of epithelial cancers were reactive with anti-3',6'-isoLD1 monoclonal antibodies; notably negative were carcinomas of the ovary and lung carcinomas of all subtypes. Lymphomas and infiltrative lymphocytes were uniformly negative. The restriction of 3',6'-isoLD1 expression within the human central nervous system to periods of fetal-neonatal astroglial proliferation, to intense reactive astrocytosis, and to primary neoplasms, and the production of specific monoclonal antibodies to this epitope provide a specific complex for immunolocalization and, eventually, immunotherapy.

Animals↗

PubMed1993

Peripheral neuropathy associated with monoclonal IgM antibody to glycolipids with a terminal glucuronyl-3-sulfate epitope.

Twenty-nine patients with paraproteinaemia, 12 with neuropathy and 17 without a previous record of neurological symptoms were clinically characterized. All 12 neuropathy patients had a moderate to severe sensorimotor demyelinating neuropathy. The patients were examined with regard to serum antibodies to gangliosides, including GM1, GD1a, GD1b, GT1b, and LM1, and other acidic glycolipids, including LK1 and sulphatide, of human brain and peripheral nerve. Sera from 80 blood donors, 40 men and 40 women 20-60 years of age, were used as normal controls. The sera were analysed with an ELISA performed on thin-layer chromatography plates. At a dilution of 1/400 none of the control sera gave a detectable reaction and a titre of > or = 1:400 was considered as a positive test. In 11 of the 12 neuropathy patients the paraproteinaemia was of IgM type and 10 of them had a positive antibody titre against LK1 and Hex-LK1, acidic glycolipids with a terminal glucuronyl-3-sulphate group. The antibody titre against LK1 in 1 patient was 1:400 and varied between 1:5,000 and 1:3,200,000 in the other 9. One of the patients also had a positive titre, 1:64,000, to sulphatide. None of the sera from the 17 paraproteinaemia patients without a previous record of neurological symptoms contained antibodies to LK1 or to any glycolipid antigen examined, except for sulphatide. A positive titre (> or = 1:400) of antibodies to sulphatide was found in sera from 4 of these patients, the titres being < or = 3,200.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Expression of gangliosides GD3 and 3'-isoLM1 in autopsy brains from patients with malignant tumors.

Three autopsy brains from patients who succumbed to malignant gliomas have been analyzed in various regions with regard to their ganglioside content. The study focused on the gangliosides GD3 and 3'-isoLM1, which in a previous study of biopsies were found to be associated with these tumors. In particular, 3'-isoLM1, was suggested to be a marker for malignant gliomas. The highest concentrations (200-1,000 nmol of sialic acid/g wet weight) of GD3 was found in specimens of macroscopically pure tumor, where the proportion of GD3 was, at the most, 78% (range, 11-78%) of the total ganglioside sialic acid compared with < 10% in normal brain tissue. The proportion of the total ganglioside sialic acid made up by GD3 was also elevated in the periphery of the tumor and in the same region in the opposite hemisphere, where no tumor cells were detected. In four of eight brain metastases of various carcinomas, GD3 was > 10% of the total ganglioside sialic acid (range, 3-37%). The ganglioside 3'-isoLM1, as determined by TLC-enzyme-linked immunosorbent assay using a specific monoclonal antibody (SL-50), was not present at detectable levels in any of the macroscopically homogenous tumor areas. It was, however, found in the periphery of the tumor, in the corpus callosum, and at highest concentrations in the region of the opposite hemisphere corresponding to the tumor. The concentration varied between 0.1 and 6.0 nmol/g wet weight of tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Sulphatide antigen in islets of Langerhans and in diabetic glomeruli, and anti-sulphatide antibodies in type 1 diabetes mellitus.

Clinical coincidence between diabetes and neurological disorders, and sharing of antigen determinants between islets of Langerhans and neural tissue, has been suggested. Sulphatide is a neural epitope which can be visualized with a monoclonal antibody Sulph I. Different tissues were examined by immunohistological methods. Sulphatide and anti-sulphatide antibodies were determined by thin-layer chromatographic techniques. IgG was isolated using protein A columns. A specific staining by Sulph I was found of rat islets, assigned to the secretory granules of both alpha and beta cells. No labelling of the exocrine tissue or other body tissues was seen, except for nerve and kidney structures. The latter showed staining of the distal tubules and, in addition, but only in the diabetic kidney, of glomeruli located in the subendothelial area in the capillary loops and the mesangial space. Sera from 38% of 40 spontaneously diabetic BB rats displayed anti-sulphatide antibodies, mainly IgG, whereas all 30 control Lewis rats were negative. Most recently we have demonstrated anti-sulphatide antibodies in 88% of 57 patients with newly diagnosed Type 1 diabetes (titres of > 1:400); all 135 healthy control persons were negative. The sulphatide antibody reactivity was present in the IgG fractions of the patients' sera. Thus, sulphatide is demonstrated in islets of Langerhans and in kidney related to the diabetic lesion, and, furthermore, anti-sulphatide antibodies exist in Type 1 diabetes mellitus.

Adolescent↗

PubMed1993

Protein analyses in cerebrospinal fluid. I. Influence of concentration gradients for proteins on cerebrospinal fluid/serum albumin ratio.

Concentration gradients in lumbar cerebrospinal fluid (CSF) for albumin and IgG were studied in 8 healthy individuals and 44 neuropsychiatric patients by serial sampling of 6 successive portions of CSF, each containing 4 ml, in all 24 ml. Significant and identical decreases between the first (0-4th ml) and the last (21st-24th ml) portions were found for CSF-albumin (21% decrease, p < 0.0001) and CSF-IgG (21% decrease, p < 0.0001). Therefore, the CSF/serum albumin ratio also showed a significant gradient with a 21% decrease (p < 0.0001), while no gradients were found to the IgG index. These results imply that analyses of proteins in the CSF should be performed on a standardized volume of CSF, preferably the first 12 ml, to allow comparisons of scientific results between various patient groups and controls and between different laboratories and to increase the validity of protein analyses in clinical practice.

Adolescent↗

PubMed1993

Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age.

Analyses of the cerebrospinal fluid (CSF) to determine the blood-CSF barrier function and to detect intrathecal IgG production are used in the diagnosis of neurological and psychiatric diseases. Therefore, accurate reference values for these parameters are of utmost importance. However, current reference values are based on 'reference groups' consisting of patients with psychiatric and/or neurological symptoms but without positive clinical findings and on groups of young students. The present study presents reference values for CSF proteins in a large sample (n = 105) of healthy individuals, with a large age-span (18-88 years of age). The parameter for the determination of the blood CSF barrier function, the CSF/serum (CSF/S) albumin ratio, was found to show an increasing variability in individuals over 45 years of age, suggesting a less stable blood-CSF barrier function than in younger individuals. The upper reference limit for the CSF/S albumin ratio was 6.8 for individuals under 45 years of age and 10.2 for individuals over 45 years of age. The IgG index, a dimensionless quotient for the determination of intrathecal IgG production, showed only a minor correlation with age and had an upper reference limit of 0.63.

Adolescent↗

PubMed1993

Protein analysis in cerebrospinal fluid. III. Relation to blood-cerebrospinal fluid barrier function for formulas for quantitative determination of intrathecal IgG production.

To examine the possible influence of the blood-CSF barrier function on mathematical formulas for estimating intrathecal IgG production (IgG index, Tourtellotte's formula [TOURT], Schuller and Sagar's formula [Schull], and Reiber and Felgenhauer's formula [IgG(loc)]), we analysed serum and CSF samples from 105 healthy individuals, aged 18-88 years, and 816 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, aged 18-91 years. In healthy individuals there was no significant correlation between the CSF/serum (S) albumin ratio (i.e. blood-CSF barrier function) and the IgG index, a dimensionless quotient for determining intrathecal IgG production, and only a small correlation (r = -0.08, p < 0.05) in patients without OCBs. However, significant dependence on the blood-CSF barrier function was found, in both healthy individuals and patients without OCBs, for the formulas determining intrathecal IgG production in milligrams (per litre CSF or per day), i.e. for TOURT, SCHULL and IgG(loc). Therefore, we propose a new formula for the quantitative determination of intrathecal IgG production in mg/l, the IGGPROD, which is calculated as: CSF-IgG -[(0.51 x CSF-Alb x S-IgG)/S-Alb]. IGGPROD is an empirical formula, based on findings in 105 healthy individuals 18-88 years of age, and does not depend on the blood CSF barrier function.

Adolescent↗

PubMed1993

Glycosphingolipid tumor antigens.

Tumor-associated glycosphingolipids are a common finding in human tumors, and monoclonal antibodies directed to defined carbohydrate epitopes of these structures have been developed. A majority of the glycosphingolipid antigens are of the lacto series, types 1 and 2, and these epitopes are often also found on glycoproteins. The tumor-associated gangliosides of the ganglio series, preferentially found in tumors of neuroectodermal origin, have binding epitopes that have not been detected in glycoproteins. A large number of monoclonal antibodies, mainly murine but some human, have been produced, and their epitope specificity defined. These antibodies have been used for investigation of the role of tumor-associated glycosphingolipids in tumor cells. Some antibodies have been shown to inhibit the growth of tumor cell lines in vitro and in vivo and to influence the adhesion properties of tumor cells, and some antibodies have been shown to give a clinical response. Tumor cell lines are commonly used in tumor biology studies, but the expression of tumor-associated glycosphingolipids in tumor cell lines does not always reflect their expression in the tumor tissue from which the cell line originates. The expression of tumor-associated glycosphingolipids has also been shown to be different in cells grown in vitro or as solid tumors in nude mice or rats. In conclusion, monoclonal antibodies specific for tumor-associated glycosphingolipids may be valuable tools in diagnosis and, in addition, in therapy, glycosphingolipids may also be used in active immunotherapy. The availability of these antibodies also opens the possibility of studying the biological function of glycosphingolipids and may then lead to new approaches for the improved diagnosis and therapy of human tumors.

Animals↗

PubMed1992

Membrane lipids of human peripheral nerve and spinal cord.

Major membrane lipids were determined in specimens of human peripheral nerve (cauda equina) and spinal cord of 10 subjects aged 20-70 years. The same lipids were also assayed in myelin from the same tissues isolated with two different procedures and in myelin of cauda equina from 3 subjects aged 17-91 years isolated with a third method. The concentrations (mean and standard deviation) of phospholipids were 90 +/- 11 and 96 +/- 9 nmol/g fresh weight; of cholesterol 70 +/- 15 and 101 +/- 16; of cerebroside 19 +/- 3 and 41 +/- 7; of sulfatide 10 +/- 1 and 11 +/- l; and of gangliosides 0.80 +/- 0.08 and 0.40 +/- 0.05 N in cauda equina and spinal cord, respectively. The proportion of ethanolamine phosphoglyceride was lower and that of sphingomyelin higher in cauda equina than in spinal cord. The myelin of peripheral nerve and spinal cord contained almost the same proportions of lipids as the whole tissue. The protein-bound sialic acid content was 3-fold higher than the lipid-bound sialic acid content in cauda myelin. The fatty acid patterns of choline, ethanolamine, inositol and serine phosphoglycerides of spinal cord and its myelin, were very similar to those of cerebral white matter, while the phosphoglycerides of cauda equina had higher proportions of monoenoic acids and lower proportions of polyunsaturated fatty acids. The fatty acid patterns of sphingomyelin, cerebroside and sulfatide of spinal cord were similar to those of cerebral white matter, while those of cauda equina contained significantly more saturated fatty acids. This suggests that the lipid and fatty acid compositions of peripheral nerve are particularly suitable for the formation of a tightly packed myelin membrane which can be a powerful shield against infections and other injuries.

Adolescent↗

PubMed1992

Detection of oligoclonal IgG bands in cerebrospinal fluid by immunofixation after isoelectric focusing on polyacrylamide gels with the PhastSystem.

This paper describes the detection of oligoclonal bands of IgG immunoglobulins in cerebrospinal fluids (CSF) using isoelectric focusing (IEF) and immunofixation with the PhastSystem equipment. The proteins were separated by IEF on polyacrylamide gels, pH 3-9. The IgG immunoglobulins were then fixed by overlaying the gel with antihuman IgG antiserum. Fixed immunoglobulins were detected with silver staining in the PhastSystem Development Unit. One microliter of serum or CSF containing 15 mg/L of IgG was found to be optimal. The procedure had good reproducibility both with regard to IEF and silver staining of the fixed immunoglobulins. The manpower need was reduced, and the procedure has been found to be useful in the clinical laboratory.

Acrylic Resins↗

PubMed1992

Monoclonal antibodies to malignant human gliomas.

Operationally specific monoclonal antibodies (MAbs) reactive with tumor but not normal adult tissues offer great potential for diagnosis and therapy of CNS neoplasms. Two targets for specific MAb localization were chosen for this study: (1) glioma-associated gangliosides GM2 [II3NeuAc-GgOse3Cer], GD2 [II3(NeuAc)2-GgOse3Cer], GD3[II3(NeuAc)2-LacCer], 3'-isoLM1 [IV3NeuAc-LcOse4Cer], and 3',6'-isoLD1 [IV3NeuAc,III6NeuAc-LcOse4Cer] and (2) epidermal growth factor receptor (EGFR) variant molecules. Epitopic specificity of isolated ganglioside hybridomas was determined with FAB-MS defined ganglioside standards. All MAb are IgM. Assay of 14 cytologic specimens and 31 frozen sections of primary CNS neoplasms revealed staining with anti-GD3 (14/14, 31/31), anti-GM2 (9/14, 26/31), and anti-GD2 (6/14, 24/30), respectively. 3'-isoLM1 and 3',6' isoLD1, which exhibit a restricted oncofetal expression pattern and are not detectable in adult human brain, are present in 15/31 primary CNS neoplasms and in 1/8 human glioma xenografts, as detected by MAbs SL-50 and DMAb-14, respectively. EGFR proteins, the second target, have unique amino acid spans resulting from gene deletion in the amplified EGFR gene present in subsets of malignant human gliomas. Antibodies against EGFR deletion-mutant Type III show highly restricted activity with a subset of glioma biopsies (6/35) expressing the mutant EGFR. These reagents should be useful for in vitro and in vivo diagnosis and, potentially, for treatment of malignant brain tumors.

Adult↗