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N Gross

Publications and source records attributed to N Gross.

At least 19 recordsLinked to original sources
PubMed1992

Differentiation-related expression of adhesion molecules and receptors on human neuroblastoma tissues, cell lines and variants.

The expression of cellular adhesion molecules (CAM) involved in cell adhesion and immune recognition was measured on neuroblastoma tissue samples, on a neuroblastoma (NB) cell line, SK-N-SH, and on 3 phenotypically different variants, SH-SY5Y, SH-EP, SH-IN, representing neuronal, Schwannian/glial or intermediate NB-cell types. Immunohistochemical analysis of CAM expression by NB and related tumors at different stages of differentiation revealed a co-expression of several CAM (ICAM-1/CD54, LFA-3, VLA-2 and HLA-ABC) associated with low stages and more highly differentiated NB tumors and peripheral neuroepitheliomas (PN). In contrast, N-CAM was uniformly expressed on all NB tumors. Flow cytometric analysis of CAM surface expression by SK-N-SH and variant cells revealed highly variable phenotypes. Expression of ICAM-1, LFA-3, VLA-2 and HLA-ABC molecules was associated with the epithelial cell type represented by the SH-EP variant. In contrast, low expression of these molecules and high expression of N-CAM was associated with the neuronal SH-SY5Y cells. Exposure of the NB cells to differentiation inducers (retinoic acid, 5'-bromodeoxyuridine and phorbol esters) and cytokines (tau-interferon, alpha-tumor necrosis factor) resulted in a variable up-regulation of the expression of all CAMs, except N-CAM, regardless of the type of differentiation induced. In an attempt to establish a link between the pattern of expression of CAM on NB cells and their susceptibility to natural killer (NK) or lymphokine-activated killer (LAK) cell lysis, the analysis revealed that NB cells expressing CAM and a differentiated phenotype were less susceptible to NK lysis, but no difference in the sensitivity of the NB cell types to LAK effectors was observed. Treatment of NB target cells with cytokines or PMA decreased their susceptibility to NK and LAK lysis, while induction of differentiation with RA or BUdR resulted in no changes in the sensitivity to NK and LAK lysis. In conclusion, expression of HLA-ABC and several co-regulated CAMs was shown to be associated with a differentiated phenotype in NB, with an overall decreased sensitivity to NK/LAK effector cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Energy demands for walking in dysvascular amputees as related to the level of amputation.

Cardiac function and oxygen consumption were measured in 25 patients who underwent amputation for peripheral vascular disease (PVD), and in five similarly aged control patients with PVD. Five patients at each of the midfoot, Syme's, below-, through-, and above-knee amputation levels and the five controls were measured at rest, normal walking speed, and maximum walking speed on a treadmill. At normal walking speed, all of the patients functioned at approximately 80% of their cardiac capacity. Normal walking speed and cadence decreased and oxygen consumption per meter walked increased with more proximal amputation. The ratio of cardiac function and oxygen consumption at normal walking speed as compared with at rest increased with more proximal amputation, and the capacity to increase walking speed and oxygen consumption lessened. Our results suggest that peripheral vascular insufficiency amputees function at a level approaching their maximum functional capacity. At more proximal amputation levels, the capacity to walk short or long distances is greatly impaired.

Amputation, Surgical↗
PubMed1990

In vitro modulation and relationship between N-myc and HLA class I RNA steady-state levels in human neuroblastoma cells.

Neuroblastoma cell lines and tumors are characterized by low HLA class I expression. The majority of neuroblastoma cell lines and a high percentage of disseminated tumors display amplification of the nuclear protooncogene N-myc. An inverse correlation between HLA class I expression and N-myc amplification and overexpression has been recently described in neuroblastomas (NBs). In this study we have shown that cytokines (recombinant gamma-interferon, recombinant alpha-tumor necrosis factor), differentiation agents (dibutyryl cyclic AMP, phorbol myristate acetate) and growth factors (nerve growth factor, epithelial growth factor) were able to influence the growth rate and surface expression of HLA class I molecules as well as of a tumor-associated antigen on 2 representative NB cell lines. Induced decreased growth rate in NB cells was not always related to decreased N-myc expression. Analysis at the mRNA level revealed that both N-myc and HLA class I RNA steady-state levels could be modulated by several substances, including recombinant gamma-interferon, phorbol myristate acetate, dibutyryl cyclic AMP, and epithelial growth factor and were not necessarily linked. An inverse correlation between N-myc and HLA mRNA levels was observed only after exposure of NB cells to recombinant alpha-tumor necrosis factor. We conclude that N-myc and HLA class I RNA steady-state levels can be modulated independently and suggest that they are not necessarily inversely regulated.

Blotting, Northern↗
PubMed1989

Epidermal growth factor responsiveness of a new human neuroblastoma cell line.

A human neuroblastoma cell line, CA-2E, has been established from a bone-marrow aspirate of a 16-month-old boy with progressive disease. The karyotype and antigen phenotype of the cells correspond to those of a neuroblastoma. This cell line grows well in liquid cultures supplemented with 5% fetal calf serum; conversely, colony formation in semi-solid medium by cells from early passages is dependent upon exogenous EGF. With time in continuous culture, the cloning efficiency in the absence of EGF increases, but the line remains sensitive to EGF, as evidenced by an enhancement of the number and size of colonies. A relative dependence upon EGF in liquid cultures has also been clearly demonstrated by limiting the concentration of serum. Long-term (over 2 weeks) treatment with EGF results in a decreased rate of proliferation, a decreased proportion of clonogenic cells, and the appearance of flat, epithelial-type cells. In some experiments, EGF also has a remarkable effect in inducing neurite outgrowth and process branching. Our results suggest that EGF may have both proliferation- and differentiation-inducing effects on this neuroblastoma cell line. We have also shown that EGF induces increased proliferation in 7 out of 8 other human neuroblastoma cell lines. Functional response of neuroblastoma cells to EGF appears to be a general phenomenon which may be related to a block in the normal maturation pathway of the neural crest cells from which this tumor originates.

Animals↗
PubMed1989

New anti-GD2 monoclonal antibodies produced from gamma-interferon-treated neuroblastoma cells.

Three monoclonal antibodies (IgG2) have been produced from hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice hyperimmunized with gamma-interferon-treated neuroblastoma cells. The 3 MAbs, 7A4, 2A6 and IG8, detected an antigen present on neuroblastoma tumors and cell lines, but also on some neuro-ectoderm-derived tissues and cells. All 3 clones were shown to react with an epitope of the di-sialo-ganglioside GD2 molecules highly expressed by some neuro-ectoderm-derived tumors, mainly neuroblastoma. Whereas MAb IG8 specificity was restricted to GD2 and its o-acylated form, MAb 2A6 and 7A4 were also able to detect GD3 at high concentration of antibody as shown by TLC analysis and immunodetection. The 3 MAbs were able to lyse 100% neuroblastoma cells in the presence of rabbit or human complement. Direct binding assays with 125I-labelled MAbs showed that MAb 7A4 might be a good candidate for in vivo immunolocalization experiments. The high proportion of anti-GD2 MAbs obtained by our fusion and the increased binding of anti-GD2 MAbs on gamma-IFN-treated neuroblastoma cells suggests a modulation of the exposure and an increase in the immunogenicity of GD2 induced by gamma-IFN.

Animals↗
PubMed1989

Regression of herniated nucleus pulposus: two patients with lumbar radiculopathy.

Thirty percent to 95% of patients with lumbar radiculopathy secondary to a bulging or herniated disc improve to a pain-free and functional level with nonsurgical treatment. What happens to the herniated disc material as this improvement occurs is unclear. We present two patients with lumbar radiculopathy documented by physical examination and electrodiagnostic testing. Both patients had herniated disc material at the L5 to S1 level on computed tomography (CT) scans corresponding to the side and level of their lesion on physical examination and electrodiagnostic testing. In both instances, the radiculopathy resolved with conservative treatment. CT scans were repeated in three months on one patient and four months on the other. The scans showed major resolution of the herniated disc material in both patients. These two cases demonstrate that in some patients with proven radiculopathy secondary to herniated nucleus pulposus, the herniated disc material will no longer be visible on CT scan and is presumed to resorb as the symptoms abate.

Adult↗
PubMed1988

Immunocytochemical detection of neuroblastoma cells infiltrating clinical bone marrow samples.

To evaluate the feasibility and clinical usefulness of immunocytochemical detection of bone marrow metastases in neuroblastoma, we studied bone marrow samples from patients undergoing intensive therapy, followed in the majority of cases by autologous bone marrow rescue. Two monoclonal antibodies were used in an indirect immunoenzymatic assay to test 384 samples collected from multiple bone marrow sites during 79 staging procedures in 48 patients. Of 578 immunocytochemical tests, 59 (10%) yielded non-evaluable results. Analysis by individual bone marrow sites showed an agreement between cytological and immunocytochemical examinations in 276 of 309 (89%) evaluable tests with 5 A7 and in 179 of 210 (85%) with UJ 13 A. Infiltration by neuroblastoma cells was reported in 9% of samples by cytology, in 6% by immunochemistry with 5 A7 and in 16% with 13 A. Analysis of results by staging demonstrated agreement between cytological examination and immunocytochemical detection with both monoclonal antibodies in 60 of 75 (80%) evaluable stagings. Bone marrow metastasis was detected by cytology in 22% of stagings, by immunochemistry with 5 A7 in 23%, with UJ 13 A in 25%. Detailed analysis of discordant results revealed that they were related partly to bone marrow sampling variability associated with focal and minimal metastasis of neuroblastoma cells. These data suggest the clinical usefulness of immunocytochemical detection as a complementary test to cytological examination for accurate evaluation of bone marrow infiltration in patients with disseminated neuroblastoma.

Antibodies, Monoclonal↗
PubMed1987

In vitro antigenic modulation of human neuroblastoma cells induced by IFN-gamma, retinoic acid and dibutyryl cyclic AMP.

Testing with a panel of 26 monoclonal antibodies (MAbs) showed the antigenic profile of 13 human neuroblastoma cell lines to be characterized by a generally poor antigenic expression; therefore, Interferon-gamma (IFN-gamma), dibutyryl cyclic-AMP and retinoic acid were used to analyse the modulation of surface antigenic expression during differentiation. Treatment of neuroblastoma cell lines with IFN-gamma resulted mainly in induction or increase of class-I MHC antigenic expression. Induction of class-II MHC antigens was obtained on only one neuroblastoma cell line out of 13, thus representing an exceptional event. An increase in some other antigens expressed by neuroblastoma cell lines was also observed. In contrast, and in addition to morphological maturation, treatment of these cell lines with the differentiation inducer dibutyryl-cyclic-AMP (dbc-AMP), resulted in general down-modulation of antigenic expression, particularly of neuroblastoma-associated 5A7 or Leu7 antigens. Retinoic acid treatment had no significant effect on MHC antigens, but it decreased expression of 5A7 and Leu7 antigens, and markedly increased the expression of the melanoma-associated antigen Me14-D12. The similarity between the antigenic profile of in vitro differentiated neuroblastoma cells and that of mature ganglioneuroma cells suggests that compounds like cyclic-AMP or retinoic acid are excellent tools for further investigations of the mechanisms of neuroblastoma differentiation and might have important clinical applications.

Antigens, Neoplasm↗
PubMed1987

Temperature effect on antidromic and orthodromic sensory nerve action potential latency and amplitude.

The measurement of sensory nerve action potential (SNAP) latency and amplitude is often necessary to accurately diagnose disorders of peripheral nerves. The sensory evoked response can be obtained using either the antidromic (AD) or orthodromic (OD) technique. In a previous study we demonstrated that in healthy subjects the AD SNAP distal latency of median and ulnar nerves at 14 cm distance is approximately 0.2 msec slower than the OD SNAP distal latency at 32C. The AD SNAP amplitude was also two times greater than the OD SNAP amplitude. In this study we observed that these differences between the AD and OD SNAP latency and amplitude varied significantly as temperature changed. The AD median nerve SNAP distal latency was delayed by .06 msec/degree with cooling. The OD median nerve SNAP distal latency was delayed by .03 msec/degree with cooling. These values represent less of a slowing per degree centigrade cooling than has been previously noted in the literature. The median nerve SNAP amplitude was found to increase with upper extremity cooling with the AD and OD technique by 3.5 microV and 0.5 microV per degree, respectively. For accurate interpretation of SNAP latency and amplitude, the electromyographer must be familiar with the technique used and the differing effect of the temperature with each technique.

Adult↗
PubMed1986

Highly selective recognition of human neuroblastoma cells by mouse monoclonal antibody to a cytoplasmic antigen.

Immunization of a BALB/c mouse with cells from the human neuroblastoma line LAN-1 and fusion of the spleen cells with mouse myeloma cells, NS-1, led to the production of a monoclonal antibody (Mab) with a rather unique reactivity for neuroblastoma. This Mab, named 5 A7, detects an antigen of an apparent molecular weight of 65,000-67,000, localized mainly in the cytoplasm and released into culture medium, as revealed by immunoprecipitation and immunoblotting experiments. By immunoperoxidase staining using a biotin-avidin technique, Mab 5 A7 demonstrates a restrictive staining for neuroblastoma cell lines. Following extensive testing on freshly frozen specimens of neuroblastoma and other tumors, Mab 5 A7 shows a highly selective reactivity for neuroblastomas (13 of 14) and some cells of one primitive neuroectodermal tumor (ependymoblastoma). No reactivity could be detected with Mab 5 A7 on the 57 other tumor tissues tested. Among the normal fetal or adult tissue specimens tested, positive staining is found only on adult brain, colonic crypts, some renal tubules, and fetal medulla of the adrenal gland. Among bone marrow specimens tested, only those infiltrated by neuroblastoma cells gave a positive staining. Normal or malignant hematopoietic cells showed no reactivity with Mab 5 A7. Our results with Mab 5 A7 suggest that this reagent not only provides a valuable probe for the immunohistological diagnosis of neuroblastoma on fresh tumor specimens but also allows the detection of bone marrow infiltration by neuroblastoma cells.

Animals↗
PubMed1982

Demonstration at the single-cell level of the existence of distinct clusters of epitopes in two predefined human Ia molecular subsets.

The expression at the cell surface level of two previously defined human Ia antigen subsets, NG1 and NG2, was studied. Two monoclonal hybridoma antibodies, D1-12 (anti-NG1) and D4-22 (anti-NG2), labeled with distinct fluorochromes, were used as probes. The results indicate that NG1 and NG2 molecules are simultaneously expressed on the same cell, and moreover, that they are identifiable as spatially separate structures. In addition, when a series of 6 other anti-Ia monoclonal antibodies previously described were analyzed in a checkerboard test of binding inhibition at the cell surface level, they were found to closely mimic the reactivity pattern of either D1-12 or D4-22 antibody, suggesting that NG1 and NG2 Ia subsets express independent clusters of highly immunogenic epitopes.

Antibodies, Monoclonal↗
PubMed1978

Rabbit antiserum against Daudi-cell membrane fractions detects cell surface antigens present on subpopulations of human lymphocytes.

An antiserum was produced by immunization of rabbits with membrane preparations of a human lymphoblastoid B cell line, Daudi. After absorption with a human endometrial carcinoma cell line, this antiserum appeared to be specific for antigen(s) present on adult and fetal thymocytes as well as on tonsillar lymphocytes but absent, or present in very small amounts, on normal or phytohemagglutinin- (PHA) stimulated peripheral blood lymphocytes (PBL). When T and B cell-enriched fractions from tonsillar lymphocytes were tested with the anti-Daudi serum, the reactivity was equally distributed in each population. Among 13 human lymphoblastoid cell lines tested, reactivity was demonstrated on three out of four T cell lines, and on four out of nine B cell lines. The positive reacting B cell lines were derived from two African and two American Burkitt lymphomas. The antigen(s) described does not seem to be related either to human Ia-type antigens or to Epstein-Barr virus-associated antigens because these antigens are not present on fetal or adult thymocytes. Reciprocal absorption experiments indicate that this anti-Daudi serum detects the same antigenic structures present on certain subpopulations of T and B lymphocytes.

Absorption↗
PubMed1978

Rabbit antiserum to human thymocyte membranes: specificity for normal and malignant T-lymphocytes.

An antiserum was obtained by immunization of rabbits with human thymocyte membrane fractions. After appropriate absorptions, the antiserum was shown to detect specifically a population of T-cells. When tested by complement-mediated cytotoxicity the antiserum lysed 95% of thymocytes, 65% of normal PBL and 45% of tonsillar lymphocytes. It was also cytotoxic for three different T-cell lines (MOLT-4, CCRF-CEM and CCRF-HSB-2). When peripheral or tonsillar lymphocytes were separated into populations enriched in B- and T-cells, the percentage of cells lysed by the antiserum correlated well with the proportion of E-rosetting cells. Treatment of PBL with the antiserum and complement resulted in an increase of SmIg-positive B-cells in the residual cell fraction, which could no longer form E-rosettes. Treatment of PBL with the antiserum alone completely inhibited the E-rosette formation. The cytotoxic index on PBL from patients with various lymphoid disorders always correlated with the proportion of T-cells as assessed by E-rosette formation. Finally, the absorptive capacity of thymocytes for the antiserum was ten times higher as compared to that of PBL or tonsil cells.

Animals↗
PubMed1977

Genetic effects of photoadducts and photocross-links in the DNA of phage lambda exposed to 360 nm light and tri-methylpsoralen or khellin.

The furocoumarin, 4,5',8-trimethylpsoralen, sensitizes cells and viruses to 360 nm light, producing cross-links and monoadducts in their DNA. The furanochromone khellin is a less effective sensitizing agent than psoralen, but has been found to induce cross-links and adducts in DNA also. The number of cross-links increases as the square of the time of exposure to light. We found that greater fluences were required for khellin than for psoralen, possibly because of the less favorable angle of the distal unsaturated bonds for corss-linking pyrimidines in adjacent base pairs. By adjusting the time of exposure to 360 nm light, lambda phages were damaged with [3H]psoralen and [3H]khellin so as to produce equal numbers of cross-links. These exposures were found to produce 8-times more [3H]khellin than [3H]psoralen adducts in the DNA of the phages. Similar exposures were made with nonradioactive photosensitizers to determine the effectiveness of lambda phages carrying cross-links and monoadducts in producing genetic recombinants. Lambda phage-prophage genetic corsses were performed with psoralen and khellin-damaged phages under repressed conditions in which replication of the damaged DNA was blocked. It was estimated from the results that cross-links were about 20-times more effective than monoadducts for inducing recombination under repressed conditions. In tests on the survival of plaque forming ability on wild type bacteria, it was estimated that cross-links were about 15-times more effective than the adducts. The results support the conclusion that, in homoimmune crosses with psoralen-damaged lambda phages infecting wild type lysogens, more than three-quarters of the induced recombination can be attributed to cross-links rather than to monoadducts.

Binding Sites↗