Biomedical subjects

W D Merritt

Publications and source records attributed to W D Merritt.

At least 19 recordsLinked to original sources

PubMed1996

Coexpression of GD3 ganglioside with CD45RO in resting and activated human T lymphocytes.

The ganglioside GD3 is preferentially expressed on the surface of malignant T cell lymphoblasts and on resting T cells which express the memory cell phenotype, CD45RA-CD29+. However, GD3 expression in activated T cells and its potential function in proliferating normal and malignant T cells are unclear. Utilizing three-color immunostaining and flow cytometry, we examined changes in the expression of GD3 in conjunction with the RA and RO isoforms of CD45 during in vitro T cell activation. GD3 was equally expressed in resting CD4 and CD8 cells and was specifically found in the CD45RO+RA population. Activation of T cells with PHA resulted in an increased percentage of GD3+ cells. This increase was evident by the first day and was observed in the CD45RO (naive cell) population; by 2 days, GD3 was expressed heterogeneously in a large population of CD45RO+RA+ cells. Further activation of T cells with PHA or anti-CD3 monoclonal antibody (OKT3) resulted in a further increase in GD3-expressing cells, and the increase in GD3 density correlated with increased CD45RO and loss of CD45RA. In contrast, increases in GD3 and interleukin-2 receptor (CD25) expression in response to PHA or OKT3 occurred independently, indicating that the GD3/ CD45RO coexpression observed was not a general consequence of cell activation. The results provide evidence for specific comodulation of GD3 and CD45RO during T cell mitogenesis, and thus suggest that these molecules may colocalize on the T cell surface.

Adult↗

PubMed1994

Increased GD3 ganglioside in plasma of children with T-cell acute lymphoblastic leukemia.

The presence of tumor-associated GD3 in the plasma of 12 patients with T-cell acute lymphoblastic leukemia (T-ALL) was determined utilizing microscale ganglioside isolation and thin layer chromatography (TLC) immunodetection with an anti-GD3 monoclonal antibody, R24. Immunostaining of control plasma gangliosides revealed two nearly equal subspecies groups of GD3, GD3U and GD3L. Plasma from those T-ALL patients with a high R24-positive lymphoblast count (> 60,000/mm3) had a significant increase in total GD3 and each of the GD3 subspecies groups, and a disproportionate increase in GD3L resulted in an increased ratio GD3L/GD3U in these samples. In contrast, total GD3, GD3 subspecies, and GD3L/GD3U was not increased in plasma from those cases with low R24-positive blast count (< 20,000/mm3) or in pre-B ALL plasma. The altered GD3 content in R24-positive T-ALL plasma was reversible, since total GD3 and GD3L/GD3U in plasma from a patient in remission from R24-positive T-ALL was near that of controls. Resorcinol staining of TLC-separated gangliosides confirmed the results observed with R24 detection methods. The results strongly suggest that GD3 is shed in vivo from T-ALL blasts in patients with R24-positive T-ALL, resulting in both qualitative and quantitative changes in circulating GD3 in these patients.

Biomarkers, Tumor↗

PubMed1992

Tunicamycin inhibits function and expression of the high-affinity IL-2 receptor in a murine IL-2-dependent cell line.

Murine interleukin-2-dependent T-lymphocytes (CT6) were treated with tunicamycin, an inhibitor of both glycoprotein and ganglioside synthesis, to study the involvement of glycosylation in the IL-2 proliferative response. Tunicamycin inhibited proliferation in a dose-dependent manner at concentrations which did not inhibit protein synthesis (10-50 ng/ml). Swainsonine, a glycoprotein processing inhibitor, had no effect on proliferation. Inhibition of proliferation by tunicamycin was accompanied by an inhibition of binding of 125I-IL-2 to its high-affinity receptor. Scatchard analysis showed that receptor number was decreased by tunicamycin treatment. On the other hand, tunicamycin did not affect either the binding of the monoclonal antibody 7D4, specific for the 55 kDa low-affinity protein subunit of the IL-2 receptor, or the recycling of the IL-2 receptor. To determine the specific effects of tunicamycin on the biosynthesis of particular CT6 glycoconjugates, cells were radiolabeled with 3H-glucosamine and incorporation into ganglioside, neutral glycolipid and glycoprotein fractions was measured. Low doses of tunicamycin inhibited ganglioside synthesis and glycoprotein glycosylation to the same extent, whereas no effect on neutral glycolipid synthesis was observed. These results suggest that glycosylation of glycoprotein and/or gangliosides might play an important role in the formation of a functional high-affinity IL-2 receptor complex in CT6 cells.

Animals↗

PubMed1992

The importance of the eosinophil in head and neck cancer.

In a previous study, we found tumor-associated tissue eosinophilia (TATE) to be a favorable prognostic indicator for squamous cell carcinoma of the head and neck (p less than 0.05). The present expanded study was undertaken to confirm this finding. The pathology of 120 head and neck tumors was examined for histologic features suggestive of poor prognosis. Ten descriptive histopathologic variables, including two malignancy grading scales, were correlated with DNA flow cytometric data and clinical outcome. No correlation was found between the malignancy grading scales and DNA flow cytometric data or clinical outcome. The present expanded study confirmed with greater statistical significance (p less than 0.001) that high-grade TATE is a favorable prognostic indicator for head and neck cancer. Furthermore, high-grade TATE was associated with the absence of distant metastasis (p less than 0.05). Using a stepwise logistic regression analysis of the clinicopathologic variables in the study, high-grade TATE was the most influential variable affecting clinical outcome, followed by border, stage, and perineural invasion. We conclude that the grade of TATE is a significant prognostic indicator for head and neck cancer. The significance and possible role of the eosinophil in the tumor-host interaction are discussed.

Eosinophils↗

PubMed1991

Immunoreactivity of leukemic lymphoblasts of T-cell and B-cell precursor origin with monoclonal anti-GD3 and anti-GM3 antibodies.

The glycosphingolipids GD3, GM3, and alpha 2, 3-sialosylparagloboside (SPG) are major gangliosides of lymphoid leukemia cells. The reactivity of two monoclonal anti-ganglioside antibodies, an anti-GD3 (R24) and an antibody cross-reactive to GM3 and SPG (M2590), to blasts of patients with T-cell acute lymphoblastic leukemia (ALL) and B-cell precursor ALL (pre-B-ALL), were compared using indirect immunofluorescence and flow cytometry. Results from 23 patients with T-ALL and eight with pre-B-ALL yielded four subclasses of T-ALL and two subclasses of pre-B-ALL. Blasts from most of the patients with T-ALL were R24+M2590- whereas most of the patients with pre-B-ALL were R24-M2590-. Seven of 23 patients with T-ALL had ganglioside immunophenotypes similar to that of pre-B-ALL, i.e. R24-M2590- or R24-M2590+. These subclasses could not be further characterized by additional cell surface immunophenotypic markers or by gene (immunoglobulin and T-cell receptor) rearrangement analysis. The ratio R24/M2590 was less than 1.0 in all patients with pre-B-ALL, and was greater than 1.0 in all patients with T-ALL who were R24 positive, but was not useful in characterizing the double negative T-ALL subclass. To assess whether cryptogenicity of gangliosides due to cell surface protein could account for the low binding of either R24 or M2590, blasts were treated with trypsin before antibody analysis. Whereas the binding of R24 was unchanged after trypsin treatment, binding of M2590 was increased in a number of samples, particularly in those samples which were originally M2590-positive. The results show that comparative staining of T-ALL and pre-B-ALL cells with both anti-GD3 and anti-GM3/SPG antibodies results in a further subclassification of ALL and provides a quantitative assessment of the expression of tumor-associated gangliosides on the blasts of this disease.

Antibodies, Monoclonal↗

PubMed1990

Anti-GD3 monoclonal antibody analysis of childhood T-cell acute lymphoblastic leukemia: detection of a target antigen for antibody-mediated cytolysis.

We have demonstrated in previous studies significant quantitative differences in the ganglioside content of leukemia cell membranes within immunological subclasses of acute lymphoblastic leukemia (ALL): The disialoganglioside GD3 (disialolactosylceramide) is increased in lymphoblasts with a T-cell immunophenotype compared to non-T-ALL blasts. Utilizing an indirect immunofluorescence assays with a monoclonal antibody to GD3(R24), pretreatment leukemic lymphoblasts from 80 children with ALL were assayed for GD3 expression. GD3 was observed in 75% of leukemic samples in which lymphoblasts exhibited a T-cell phenotype, whereas none of the 33 non-T-ALL samples tested exhibited GD3. Correlation between the expression of GD3 and various antigenic determinants of T-cell differentiation was restricted to CD2; 75% of CD2-negative T-cell ALL blasts failed to express GD3. Anti-GD3 immunoreactivity to T-ALL samples was not restricted to R24 in that two other monoclonal anti-GD3 antibodies were similarly reactive to T-ALL blasts. In vitro incubation of T-cell lymphoblasts with the anti-GD3 antibodies, R24 and C281 and human serum resulted in significant cytotoxicity, and R24 also mediated antibody-dependent cellular cytotoxicity by normal effector cells. Cytotoxicity was specific for those T-ALL blast cell populations which reacted with anti-GD3 as assessed by immunofluorescence microscopy. Since immunoreactivity with monoclonal antibody to GD3 was exclusively observed in a large population of immunophenotypically defined T-cell leukemic lymphoblasts, these studies suggest a possible immunodiagnostic and immunotherapeutic potential for anti-GD3 monoclonal antibodies in T-cell lymphoblastic malignancies.

Antibodies, Monoclonal↗

PubMed1990

Oncogene amplification in squamous cell carcinoma of the head and neck.

Cellular oncogenes appear to be involved in the control of normal cell growth and differentiation. The abnormal activation of these genes in naturally occurring and experimentally induced cancers may have an important role in the expression of the malignant phenotype in cancer cells. Mechanisms for the activation of these genes include chromosomal translocation, point mutation, and DNA amplification. The amplification of specific oncogenes correlates with clinical prognosis in several human malignancies, including breast cancer and neuroblastoma. We examined 21 fresh-frozen human squamous cell carcinomas of the aerodigestive tract for amplification of 10 known cellular oncogenes (c-myc, N-myc, L-myc, N-ras, H-ras, K-ras, erb-B, erb-B2, raf, and int-2), using Southern blotting techniques. Eleven of 21 tumors demonstrated a two-fold to 11-fold amplification of the int-2 oncogene, one member of a family of genes related to basic fibroblast growth factor. Amplification of c-myc, a gene that codes for a DNA-binding protein involved in the regulation of cell growth, was seen in two tumors. None of the other eight genes studied were amplified in any of the tumor specimens.

Carcinoma, Squamous Cell↗

PubMed1988

Detection of GD3 ganglioside in childhood acute lymphoblastic leukemia with monoclonal antibody to GD3: restriction to immunophenotypically defined T-cell disease.

We have recently reported that the disialoganglioside GD3 is found in cellular lipid extracts of T-cell acute lymphoblastic malignancies (T-ALL) but is not detectable by resorcinol staining in extracts of non-T acute lymphoblastic leukemia blasts (non-T-ALL). We have now extended this study to assess the detectability of GD3 in T-ALL vs non-T-ALL utilizing an anti-GD3 antibody, R24. Gangliosides isolated from T-ALL and non-T-ALL blasts by two different methods were separated by thin-layer chromatography and stained with anti-GD3 and a control antibody specific for GM3 and sialosylparagloboside (SPG). Anti-GD3 reactivity was observed in extracts from T-ALL cells in all cases, whereas GD3 was not detected in any of the non-T-ALL samples. The anti-GM3/SPG antibody stained GM3 in all of the leukemic samples analyzed as well as SPG in the non-T-ALL samples. Indirect immunofluorescence was used to assess the expression of GD3 at the surface of leukemic blasts. Fluorescence-activated cell sorting analysis with R24 showed that whereas T-ALL blasts were highly reactive with this antibody, non-T-ALL blasts were totally unreactive. In an analysis of a larger number of leukemia patients by fluorescence microscopy, 20 out of 28 samples with the T-ALL phenotype were positive for R24, whereas zero out of 11 non-T-ALL samples were reactive. These results confirm our earlier finding of the specificity of GD3 to the T-ALL subclass of childhood leukemias and furthermore suggest the potential value of anti-GD3 as an immunological tool for the diagnosis and therapy of T-cell ALL.

Antibodies, Monoclonal↗

PubMed1988

Psychogenic vocal cord dysfunction masquerading as asthma.

The authors present a case of a depressed woman who had a long history of episodic respiratory distress that had been diagnosed as asthma. Psychiatric and otolaryngological evaluation revealed that the patient was suffering from paradoxical motion of the vocal cords (PMVC) which was associated temporally with psychological factors. The authors suggest that in some patients PMVC may be psychogenic and could be misdiagnosed as asthma. With early recognition of PMVC unnecessary respiratory treatment might be avoided and appropriate psychiatric assessment and treatment could be provided.

Asthma↗

PubMed1987

Expression of GD3 ganglioside in childhood T-cell lymphoblastic malignancies.

Lymphoblasts from seven children with T-cell lymphoblastic malignancies and three children with non-T, non-B acute lymphoblastic leukemia (ALL) were analyzed for ganglioside content. Nonmalignant T-cells from thymus served as controls. Both ganglioside and glycoprotein sialic acid were increased approximately 3-3.5-fold in T-cell disease compared to thymic tissue when expressed on a per cell basis, but not on a per milligram protein basis. Thin-layer chromatography of the isolated ganglioside fraction from T-cell lymphoblasts revealed two major resorcinol-positive bands. One ganglioside comigrated with II3-alpha-N-acetylneuraminosyllactosylceramide (GM3), the major ganglioside in normal lymphoid tissue, and the other ganglioside comigrated with authentic II3-alpha-N-acetylneuraminosyl-alpha 2----8-N-acetylneuraminosyllactosylceramide (GD3) in three different solvent systems. Neuraminidase treatment of the latter ganglioside yielded GM3 and lactosyl ceramide, hydrolysis products of GD3. Scanning densitometry revealed that whereas thymus cells contained 97% GM3 and 3% GD3, T-cell lymphoblasts contained from 22 to 86% GD3 and a corresponding decrease in GM3. The shift to increased GD3 was observed in the blasts from all seven T-cell patients, but not in the blasts from the non-T, non-B patients studied. Only trace quantities of GD3 were detected from two continuous T-ALL cell lines, HSB2 and RPMI 8402. The results demonstrate a consistently significant increase in ganglioside GD3 in uncultured, patient-derived T-cell ALL lymphoblasts when compared to non-T-cell ALL and normal lymphoid tissue. Therefore, GD3 may represent a tumor-associated antigen for the T-cell subclass of childhood lymphoblastic malignancy.

Adolescent↗

PubMed1986

Adaptation to cold antagonizes neurotensin-induced hypothermia in mice.

Intracerebrally-administered neurotensin produces a marked hypothermia in a variety of mammals. In this study, prior adaptation to a cold environment was found to significantly antagonize the hypothermia produced by intracisternally-administered neurotensin in mice. This antagonism required both previous exposure to cold ambient temperatures and cold exposure immediately prior to, or simultaneously with, neurotensin administration. The antagonism of neurotensin-induced hypothermia by prior cold-adaptation was blocked by indomethacin, but not by acetylsalicylic acid, suggesting that brain prostaglandin synthesis may be essential for this newly-discovered phenomenon.

Adaptation, Physiological↗

PubMed1984

Inhibition of interleukin-2-dependent cytotoxic T-lymphocyte growth by gangliosides.

Previous work has shown that exogenous gangliosides suppress lectin-induced T-lymphocyte mitogenesis in mixed populations of immune cells. As one potential cellular site of this inhibition, the influence of gangliosides on interleukin-2-dependent T-cell proliferation was tested, using cultures of cytotoxic T cells (strain CT-6). Incubation of CT-6 cells with mixed bovine brain gangliosides resulted in a dose-dependent inhibition of cell proliferation. Cell viability was unaffected by gangliosides, and the inhibition was totally reversed when the gangliosides were removed. Individual purified gangliosides were tested and GM2 was most inhibitory (I50 = 15 microM). GD1a and GT1b were somewhat less potent, whereas GM1 and GM3 were only weakly inhibitory. Various nonpolar lipids, sulfatides, and sialic acid did not inhibit CT-6 cell growth. The results suggest that a primary mechanism whereby gangliosides inhibit lectin-induced lymphocyte mitogenesis is by inhibition of the interleukin-2-stimulated proliferation of T cells in these cultures.

Animals↗

PubMed1980

Glycolipids modulate glycosyl transfer to endogenous protein acceptors.

Regulation by gangliosides of glycosylation of endogenous membrane glycoproteins is indicated from in vitro studies in which incorporation of radioactive sugars into endogenous protein acceptors was measured and from in vitro studies where transferase activities of membranes were correlated with ganglioside content during hepatic tumorigenesis. Galactosyl transfer from UDP galactose exhibited a complex response pattern and was stimulated by lactosyl ceramide and the ganglioside N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GM2) but was inhibited by higher gangliosides. Except for N-acetylneuraminylgalactosylglucosylceramide (GM3), which had no effect, inhibition was proportional to ganglioside complexity. Inhibition of glycosylation of the exogenous acceptor, ovomucoid, by ganglioside was slight by comparison. While marked structure-linked latency was observed with the high molecular weight exogenous acceptor, no latency was observed for incorporation into endogenous acceptors suggesting that the membranes were permeable to sugar nucleotides. Membrane disruption with detergents lessened rather than enhanced inhibition by gangliosides. Sialyl transfer from CMPsialic acid, on the other hand, was unaffected or stimulated by gangliosides. Stimulation by galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GM1) was proportional to concentration and reached 2-fold at 240 micrograms/mg protein. The results suggest that the ganglioside content of membrane may affect glycosylation of membrane glycoproteins.

Animals↗

PubMed1980

Gangliosides of liver tumors induced by N-2 fluorenylacetamide III. Galactosyl and sialyl transferases in single carcinomas and nodules.

The specific activities of UDP-galactose : GM2 galactosyltransferase and CMP-NAN : GM1 sialyltransferase were measured in total particulate fractions of individual hepatocellular carcinomas (hepatomas) and hepatic nodules, induced in the rat by a carcinogenic diet of 0.05% N-2-fluorenylacetamide alternating with a low protein basal diet. In all tumors except the smallest nodules, galactosyltransferase specific activities were increased compared to those of control livers from rats fed only basal diet. When relative specific activities were related to wet weight of nodules larger than 0.1 g were in two populations. Specific activities of nodules in one population overlapped those of poorly differentiated hepatomas whereas specific activities of the second population those of well differentiated hepatomas. Specific activities of the sialyltransferase were also increased above those in control livers but not with the same frequency or to the same extent as for the galactosyltransferase. As with galactosyltransferase, nodules were found in two major populations when specific activities were related to nodule wet weight. The data suggest that increased specific activities of galactosyltransferase and sialyltransferase in hepatic nodules may provide an early phenotypic indicator of diverging differentiation in hepatocarcinogenesis.

2-Acetylaminofluorene↗

PubMed1979

Lipoprotein secretion by rat liver Golgi apparatus. Lipoprotein particles and lipase activity.

Lipoprotein particles of the size range of very low density lipoproteins in smooth endoplasmic reticulum, peripheral elements of the Golgi apparatus, and secretory vesicles of the immature Golgi apparatus face are 55 to 80 nm in diameter. Particles in mature secretory vesicles are smaller (45 nm). Concomitant with the change in particle size, the lumina of mature vesicles increase in electron density. A technique to fractionate immature and mature secretory vesicles was based on precipitation of a cupric-ferrocyanide complex (Hatchett's brown) through the action of a NADH-ferricyanide oxido-reductase resistant to glutaraldehyde which is characteristic of the membranes of mature secretory vesicles and of the plasma membrane of liver. Mature secretory vesicle fractions so isolated were enriched in cholesterol and depleted in triglycerides relative to immature vesicles on a phospholipid basis. Lipase activity was present in secretory vesicle fractions of the Golgi apparatus as shown by biochemical analysis and by cytochemistry. Cytochemical studies showed lipase to be present in both mature and immature vesicles but most evident in immature vesicles. The findings suggest that some very low density lipoprotein particles are converted to particles of smaller diameter during transit through Golgi apparatus. A lipase-mediated hydrolysis of triglycerides may relate to the transformation.

Animals↗

PubMed1978

Enzymatic synthesis of trisialoganglioside by particulate fractions of rat liver.

Rat liver contains a particulate (membrane-bound) glycosyl transferase, concentrated in Golgi apparatus fractions, which catalyzes the synthesis of a trisialoganglioside from the ganglioside precursor disialohematoside (GD3). Sialic acid was not incorporated into exogenous GD1a from CMP-N-acetylneuraminic acid suggesting that GD1a is an endproduct of the monosialoganglioside pathway. Thus, the disialoganglioside pathway may be a primary source of trisialoganglioside and higher ganglioside homologs in adult rat liver.

Animals↗

PubMed1978

Glycolipids as indicators of tumorigenesis.

Hyperplastic liver nodules and hepatocellular carcinomas were induced in rats by oral administration of the carcinogen N-2-fluorenylacetamide. Neoplastic tissue was compared with control, fetal, neonatal, and precancerous liver tissues. The development of the tumors was slow, such that temporal changes in the biochemical and morphologic development of carcinogenesis could be identified. Ganglioside sialic acid levels were elevated in all but the most poorly differentiated tumors. Experiments to monitor individual enzymes suggested that the alterations in glycolipid composition were a direct effect of alterations in biosynthetic activities. The pattern during tumorigenesis was the inverse of that during normal development. Also, ganglioside patterns showed a progressive simplification from hyperplastic nodules to well-differentiated hepatomas and through two grades of poorly differentiated hepatomas. An increase in the activity of the branchpoint enzyme of ganglioside biosynthesis preceded both a decrease in the branchpoint enzyme of the disialoganglioside pathway and a marked increase in the galactosyltranferase of GM1 formation. The results indicate that ganglioside deletions are the end result of a cascade of events in the tumorigenic transformation. The onset of ganglioside deletions but not of the cascade per se may correlate with the onset of malignancy. Glycolipid levels are elevated early in certain surrounding tissues especially in the blood. In rats bearing transplantable hepatomas, serum levels of lipid-bound sialic acid were elevated 2.5-fold. Similar results were obtained with sera of mice bearing transplantable mammary carcinomas and of cancer patients. These findings provide new emphasis for gangliosides in both cancer detection and as regulatory signals for growth and multiplication of cells.

Animals↗

PubMed1978

Gangliosides of liver tumors induced by N-2-fluorenylacetamide. I. Ganglioside alterations in liver tumorigenesis and normal development.

Hyperplastic nodules and hepatocellular carcinomas were induced in livers of rats by a low-protein diet containing 0.05% of the carcinogen N-2-fluorenylacetamide. Ganglioside amounts and composition were determined for histologically different hepatocellular carcinomas and compared with those for control livers, hyperplastic nodules, and liver tissue surrounding hepatomas and nodules as well as those for livers of fetal, newborn, 1-week-old, weanling, and adult Sprague-Dawley rats. Ganglioside sialic acid levels were elevated above those of normal adult liver in all liver tissues following the carcinogen treatment regimen. Livers of fetal and newborn rats contained nearly twice the amount of ganglioside sialic acid on a protein or DNA basis as did livers of adult rats. Analyses of individual nodules and hepatomas revealed two populations of tumors in which the levels of ganglioside sialic acid were 2.3 and 3.8 times normal. Ganglioside sialic acid content was at hepatoma levels in small nodules. Individual gangliosides were evenly distributed between products of the monosialoganglioside and disialoganglioside pathways in normal liver with a ratio of [N-acetylneuraminic acid (sialic acid)] (NAN)-galactose (Gal)-N-acetylgalactosamine (GalNAc)-(NAN)-Gal-glucose (Glc)-ceramide (Cer) (GD1a) to Gal-GalNAc-(NAN)2-Gal-Glc-Cer (GD1b) of about one. In contrast, the monosialogangliosides predominated in liver tissues following administration of the carcinogen. Increased levels of specific monosialogangliosides were present in nodules, in liver of carcinogen-treated animals prior to the appearance of tumors, and in the liver tissues surrounding nodules and hepatomas. In single hepatomas, ganglioside patterns correlated with tumorigenicity. A well-differentiated hepatoma had a normal complement of most gangliosides but was deficient in trisialogangliosides. In a poorly diferentiated but well-circumscribed hepatoma, the relative levels of all higher gangliosides were reduced. The monosialoganglioside Gal-GalNAc-(NAN)-Gal-Glc-Cer (GM1) accounted for 80% of the total ganglioside in a poorly circumscribed and poorly differentiated hepatoma. The ganglioside pattern of fetal livers most closely resembled that of a poorly differentiated hepatoma. During the first week post natum, levels of all higher monosialogangliosides and disialogangliosides declined, but the decline was most pronounced for gangliosides GM1 and GD1a. The ratio of GM1 + GD1a to GD1b + NAN-Gal-GalNAc-(NAN)2-Gal-Glc-Cer or (NAN)3-Gal-Glc-Cer (GT), used as an index of the relative predominance of the monoslaloganglioside and disialoganglioside pathways, fell from 2.7 for fetal liver to 0.4 for adult liver. Pools of precursor gangliosides increased during development, transiently for GalNAc-(NAN)-Gal-Glc-Cer and for more than 3 weeks for NAN-Gal-Glc-Cer. When hyperplastic nodules and hepatocellular carcinomas were compared, a reverse pattern was observed. The ratio of GM1 + GD1a to GD1b + GT rose steadily to values of 2.7 and 11...

2-Acetylaminofluorene↗