PubMed Health⌕ Search

Biomedical subjects

S L Cohn

Publications and source records attributed to S L Cohn.

At least 73 records · Page 4Linked to original sources
PubMed1993

Preferential amplification of the paternal allele of the N-myc gene in human neuroblastomas.

Genomic imprinting plays a role in influencing the parental origin of genes involved in cancer-specific rearrangements. We have analysed 22 neuroblastomas with N-myc amplification to determine the parental origin of the amplified N-myc allele and the allele that is deleted from chromosome 1p. We analysed DNA from neuroblastoma patients and their parents, using four polymorphisms for 1p and three for the N-myc amplicon. We determined that the paternal allele of N-myc was preferentially amplified (12 out of 13 cases; P = 0.002). However, the paternal allele was lost from 1p in six out of ten cases, consistent with a random distribution (P > 0.2). These results suggest that parental imprinting influences which N-myc allele is amplified in neuroblastomas, but it does not appear to affect the 1p allele that is deleted in the cases that we have examined.

Adrenal Gland Neoplasms↗
PubMed1993

Hox gene expression in differentiating human neuroblastoma cells.

Neuroblastoma, a malignancy of early childhood arises in the embryonal neural crest. Neuroblastoma cells are in a state of arrested differentiation; however, they can be induced to differentiate in vitro by retinoic acid. As a first step toward understanding the molecular mechanisms of neuroblastoma differentiation we analyzed the expression pattern of the developmentally important Homeobox genes in cells treated with retinoic acid. The strategy employed involved rapid screening of a cDNA library prepared from retinoic acid treated human LA-N-5 neuroblastoma cells for Homeobox genes by the polymerase chain reaction. Multiple Homeobox genes were amplified from recombinant phage DNA using degenerate primers directed against the conserved homeobox. To date 6 Homeobox genes (HoxC6, HoxC8, HoxD1, HoxD4, HoxD8, and HoxD9) have been identified in the cDNA library prepared from LA-N-5 cells treated with retinoic acid. HoxD1 and HoxC8 are being reported for the first time to be expressed in neuroblastoma cells. Preliminary studies indicate that there is an induction of Homeobox gene expression in differentiating LA-N-5 neuroblastoma cells.

Amino Acid Sequence↗
PubMed1992

RNA expression of the WT1 gene in Wilms' tumors in relation to histology.

BACKGROUND: On the basis of accumulating data, the recently isolated WT1 gene is a Wilms' tumor gene and a putative tumor suppressor gene. These findings include expression in developing fetal kidney, intragenic deletions in tumors, and germline mutations in predisposed individuals. Wilms' tumors, which exhibit a broad range of differentiation, are composed of three cell types: blastema, epithelium, and stroma. PURPOSE: The purpose of this study was to investigate the relationship between WT1 gene expression and histologic composition in Wilms' tumors in an effort to elucidate how the WT1 gene functions in proliferation of these histologic components. METHODS: We used Northern blot hybridization to study WT1 gene expression by messenger RNA (mRNA) accumulation in 20 tumors of varying histology and in adjacent uninvolved kidney tissue. In two patients, tumors were also compared before and after therapy. RESULTS: Tumors that were predominantly blastemal expressed high amounts of WT1 mRNA, whereas predominantly stromal tumors expressed either low or undetectable amounts. Blastemal tumors that were predominantly poorly differentiated expressed WT1 mRNA at higher levels than those that were more well differentiated. Although we expected that a putative tumor suppressor gene like WT1 would generally be expressed at lower levels in tumor than in normal kidney, this was true only in predominantly stromal cells. One of the two patients studied before and after therapy had a dramatic response to therapy accompanied by a decline in WT1 gene expression and disappearance of blastemal and epithelial elements. CONCLUSIONS: A correlation was observed between WT1 gene expression and histology of the tumors. Level of expression was inversely related to the degree of differentiation in blastemal tumors and in the patient with a dramatic response to therapy. These results, in conjunction with the observation that WT1 mRNA is abundant in normal fetal kidney, suggest that WT1 gene expression is related to kidney development, especially in differentiation of blastemal components. IMPLICATIONS: Further studies to search for alterations of the WT1 gene in tumors and to identify regulatory factors in gene expression will increase understanding of the role of this gene in normal development and tumorigenesis.

Gene Expression Regulation, Neoplastic↗
PubMed1991

Differential expression of N-myc in phenotypically distinct subclones of a human neuroblastoma cell line.

Neuroblastomas are malignant childhood neoplasms that arise from derivatives of the neural crest. We report the characterization of a new neuroblastoma cell line, designated NBL-W, derived from the primary tumor of a patient with stage IVS disease (S. L. Cohn, C. V. Herst, H. S. Maurer, and S. T. Rosen, J. Clin. Oncol., 5: 1441-1444, 1987) according to the criteria of Evans [A. E. Evans, G. J. D'Angio, and J. Randolf, Cancer (Phila.), 27: 374-378, 1971]. Neurite-bearing (N) and substrate-adherent (S) cell lines have been subcloned from the parent line. N and S cells can interconvert, and both cell types label with the neural crest cell surface marker antibody, HNK-1. Cells in the subcloned lines and in the parent line have been shown by Southern blot analysis to contain approximately 100 copies of the N-myc gene. Cytogenetic analysis shows a homogeneously staining region present on chromosome 19. Although these subclones are of identical genotype, the S cells express lower amounts of N-myc mRNA and protein as compared to the N cells. N cells express several neuronal proteins including the neurotransmitter-processing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase, the neuronal intermediate filament proteins peripherin and NF66/alpha-internexin, and the neural cell adhesion molecule. S cells generally lack neuronal markers but express the mesenchymal intermediate filament protein vimentin, and a small subset of the S cells express glial fibrillary acidic protein. Some S cells were labeled weakly with neural cell adhesion molecule antibody; others were negative. S cells did not express the glial marker S-100 or a melanocyte marker, tyrosinase. Thus, S cells express the neural crest marker HNK-1 but do not express a set of antigens characteristic of any known cell type derived from the neural crest. These results are consistent with the suggestion that differential N-myc expression may be involved in the interconversion of N and S cells but indicate that the S cell phenotype need not represent a highly differentiated neural crest derivative.

Cell Differentiation↗
PubMed1990

Vascular problems of the lower extremity in athletes.

The vascular anatomy of the lower extremity predisposes the popliteal area to traumatic injury owing to tethering at the adductor hiatus and the soleus arch. Knee dislocations should be followed with arteriography or exploration of the vessels. Epiphyseal separations of the proximal tibia and distal femur, as well as fractures about the knee, should be observed closely for 24 to 48 hours to ensure that the vascular status is intact. Traumatic pseudoaneurysms may arise from seemingly minor trauma and are treated surgically. The etiology of nonspecific claudication in the athletic population requires a careful history and physical examination and may require vascular studies in order to determine if the etiology is one of popliteal artery entrapment syndrome, adventitial cystic disease of the popliteal artery, or adductor canal outlet syndrome. Buerger's disease may be seen more frequently as the use of smokeless tobacco increases in the athletic population and may be distinguished from these other claudication-causing entities by its distribution to the upper and lower extremities in a distal fashion. A sense of alertness to these vascular entities will add to the quality of care of athletes.

Athletic Injuries↗
PubMed1990

Prolonged N-myc protein half-life in a neuroblastoma cell line lacking N-myc amplification.

Genomic amplification of the oncogene N-myc is associated with rapid tumor progression and poor prognosis in patients with neuroblastoma (NB). However, 40% of NBs which lack N-myc amplification are also clinically aggressive. Factors other than N-myc copy number must therefore play a role in determining tumor progression in these NBs. We have established an unusual human NB cell line (NBL-S) from the primary tumor of a patient with rapidly progressive disease which lacks N-myc amplification. The doubling time in vitro (48 h) and the time from injection of 2 x 10(7) cells to detectable tumors in nude mice (46 days) in similar to NB cell lines with amplified N-myc. However, karyotype analysis reveals no evidence of double minutes (DMs), homogeneously staining regions (HSRs), or chromosome 1p deletions, features commonly seen in NB cell lines. The cells have the cell surface phenotype typical of N-myc amplified NB (HLA-A,B,C negative and HSAN 1.2 positive), and similar to other NB cell lines, N-myc RNA and protein are expressed. Interestingly, the half-life of the N-myc protein in NBL-S is prolonged (approximately 100 min) compared to the short N-myc protein half-life previously described in N-myc amplified NB cell lines (approximately 30 min). Because N-myc protein is thought to have a regulatory role, prolongation of the half-life of this protein may be an important factor in the regulation of growth in NBs which lack N-myc amplification and rapidly progress.

Animals↗
PubMed1990

Analysis of DNA ploidy and proliferative activity in relation to histology and N-myc amplification in neuroblastoma.

Diploid DNA content, advanced stage, unfavorable histology, and N-myc amplification are all associated with aggressive disease and poor prognosis in childhood neuroblastoma. DNA diploidy is associated with advanced stage and unfavorable histology, but the relationships among ploidy, N-myc amplification, and proliferative activity are not known. To determine if DNA diploidy is associated with N-myc amplification, we studied 29 neuroblastomas with flow cytometric analysis and Southern blot analysis. Clinical and histologic features were also evaluated. Sixty percent of the N-myc-amplified tumors were diploid, compared to 26% of the neuroblastomas, which lacked N-myc amplification (P = 0.11). In our analysis of proliferative activity and N-myc amplification, a higher mean percentage of cells in S phase was seen in the N-myc-amplified tumors (13.4%) than in the unamplified tumors (10%), but again the result was not statistically significant (P = 0.14). Significant associations were seen between unfavorable histology and DNA diploidy (P = 0.05), and between unfavorable histology and high proliferative activity (P = 0.007). Our data suggest that biologic factors other than N-myc amplification play a role in determining the aggressiveness of at least some diploid neuroblastomas.

Blotting, Southern↗
PubMed1990

Fractures about the knee in sports.

In a review of fractures about the knee in sports, we have emphasized that these are uncommon but not unseen injuries. Within the spectrum of each fracture type, and excluding motor vehicle injuries, the fractures are usually of the more benign type. The athlete can anticipate participating at his or her desired level of play after appropriate treatment and rehabilitation in most instances. As in any fracture treatment, rehabilitation of the athlete is extremely important and enhanced, when feasible, by early motion. As the AO Group espouses "life is movement, movement is life."

Athletic Injuries↗
PubMed1988

Single copies of the N-myc oncogene in neuroblastomas from children presenting with the syndrome of opsoclonus-myoclonus.

Patients with neuroblastoma who present with the syndrome of opsoclonus and myoclonus enjoy a remarkably good prognosis independent of their stage of disease or their age at diagnosis. The presence of N-myc amplification also has been found to be an independent prognostic factor in neuroblastoma. Patients with multicopy N-myc tumors have rapid tumor progression whereas those with single-copy tumors have a significantly better progression-free survival. The authors examined four primary, untreated neuroblastomas for the N-myc copy number from patients who presented with opsoclonus and myoclonus. All four tumors had single copies of N-myc, and all four patients are alive with no evidence of recurrent disease with 6+ to 54+ months' follow-up. This appears to be the only report of N-myc analysis in this group of children. It would be interesting to analyze more neuroblastomas from patients who present with opsoclonus and myoclonus to determine how many of these patients have single N-myc copy tumors.

Child, Preschool↗
PubMed1987

The spectrum of metabolic bone disease in lymphoblastic leukemia.

Eight patients with childhood acute lymphoblastic leukemia (ALL) and hypercalcemia, osteopenia, or vertebral compression fractures seen at our institution during the last 12 years were evaluated for biochemical evidence of bone disease. Five patients were hypercalcemic, three had abnormal phosphorous levels, and four had elevated alkaline phosphatase values. Parathyroid hormone (PTH) was measured by a polyvalent radioimmunoassay in five patients and these levels were abnormally high in three patients. Four of these five patients also had PTH measured by a midregion-specific radioimmunoassay. One patient had a high PTH value. Two patients had low levels and one patient had a normal PTH level. Although these studies suggest diverse biochemical mechanisms may be contributing to the bone changes and hypercalcemia seen in childhood ALL, ectopic PTH production as well as ectopically produced fragments of PTH may have a role in mediating bone resorption and hypercalcemia.

Adolescent↗