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J M Cowan

Publications and source records attributed to J M Cowan.

At least 19 recordsLinked to original sources
PubMed1992

Cytogenetic evidence of the multistep origin of head and neck squamous cell carcinomas.

BACKGROUND: Head and neck squamous cell carcinomas are associated with tobacco and alcohol use; therefore, the incidence of this type of tumor is expected to rise in the future as a result of the increasing numbers of female and adolescent smokers. Previous reports of cytogenetic analysis of this type of tumor have implicated a number of chromosomal regions in recurring changes, but no clear pattern of characteristic changes has emerged. PURPOSE: We have undertaken cytogenetic analysis of 10 cell lines which were established from squamous cell carcinomas of the head and neck, to determine the possible sites of additional tumor suppressor genes and oncogenes that may contribute to malignant transformation. METHODS: Metaphases were harvested from cultures of cells in the exponential growth phase, following exposure to Colcemid (demecolcine) at a final concentration of 30 ng/mL for 5 hours. Air-dried slides were G-banded using trypsin and Giemsa. Fifteen metaphases were photographed and fully karyotyped. RESULTS: We observed that several chromosomal regions were lost at high frequency, including 18q (10 of 10 lines), 10p (eight of 10 lines), 3p (six of 10 lines), 8p (seven of 10 lines), and the short arms of the acrocentric chromosomes (seven of 10 lines). Nine of 10 lines had additional copies of 7p. We also noted clustering of breakpoints in a number of chromosome bands, including 1p22, 10q11.2, 11q13, and the short arms of the acrocentric chromosomes. CONCLUSION: The observation of loss of multiple chromosomal regions in a significant number of lines analyzed is consistent with the theory that tumorigenesis occurs as the result of the accumulation of a number of genetic alterations, as proposed for colorectal carcinoma. The high frequency with which these changes are seen suggests that genes located in these regions have a role in the etiology of this type of tumor.

Carcinoma, Squamous Cell↗
PubMed1992

Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas.

Previous studies have suggested that structural abnormalities involving the short arm of chromosome 9 are frequently associated with gliomas. The alpha-, beta-, and omega-interferon (IFNA, IFNB1, and IFNW, respectively) and the methylthioadenosine phosphorylase (MTAP) genes have been mapped to the short arm of chromosome 9, band p22. Homozygous deletions of these genes have been reported in many leukemia- and glioma-derived cell lines. In this report, we present a detailed analysis of partial and complete homozygous or hemizygous deletions of DNA sequences on 9p in human cell lines and primary tumor samples of glioma patients. Ten of 15 (67%) glioma-derived cell lines had hemizygous or homozygous deletion of IFN genes or rearrangement of sequences around these genes, while 13 of 35 (37%) primary glioma tumor samples had hemizygous (8 tumors) or homozygous (5 tumors) deletion of the IFN genes. The shortest region of overlap of these deletions maps in the interval between the centromeric end of the IFN gene cluster and the MTAP gene. In the cell lines and primary tumors examined, these gross genomic alterations were seen only in association with high grade or recurrent gliomas. Our observations confirm that loss of DNA sequences on 9p, particularly the IFN genes, occurs at a significant frequency in gliomas, and may represent an important step in the progression of these tumors. These results are consistent with a model of tumorigenesis in which the development or progression of cancer involves the loss or inactivation of a gene or several genes that normally act to suppress tumorigenesis. One such gene may be located on 9p; this gene may be closely linked to the IFN genes. Nevertheless, loss of the IFN genes, when it occurs, may play an additional role in the progression of these tumors.

Brain Neoplasms↗
PubMed1992

Differential retention of tumor- and differentiation-suppressor functions in cells derived from a human squamous cell carcinoma.

Three morphologically distinct cell lines--F.2a, V, and B.2--were isolated from a single human squamous cell carcinoma. Although all three cell lines can grow indefinitely in culture, they differ in a number of important transformation-related phenotypes. Only B.2 is strongly tumorigenic when injected into the flanks of nude mice, and only V can efficiently grow in semisolid media. The dominance of these traits was investigated by generating somatic cell hybrids among the three cell lines. F.2a was able to suppress the tumorigenicity of B.2 cells, whereas B.2 inhibited the capacity for anchorage-independent growth of V, the latter trait being a function of the ability of these epithelial cells to differentiate when deprived of support. The influence of exogenously added growth factors was also evaluated. This study indicates that the particular tumor we examined consisted of a heterogeneous population of cells with distinct growth and differentiation capacities.

Animals↗
PubMed1992

Cytogenetics in head and neck cancer.

Cytogenetic analysis of cell lines has identified a number of chromosomal regions that are likely to contain the genes important in malignant transformation in HNSCC. Further work needs to be done comparing results from cells grown in culture with tumors from which they are derived to determine the applicability of cytogenetic analysis. Preliminary results suggest that some of the chromosome changes observed may correlate with a cell's response to radiation and as such could provide a tool for evaluating a patient's response to planned therapy.

Carcinoma, Squamous Cell↗
PubMed1991

Cytogenetic analysis in melanoma and nevi.

We have presented data from the cytogenetic analysis of melanocytes derived from four dysplastic nevi and 14 melanomas. We have confirmed previous results from melanomas, including the loss of chromosome 6q and duplication of 1q and 7p. We did not observe an excess of rearrangements involving chromosomes 2 and 3, but we found frequent deletion of chromosomes 9p, 10p, 10q, and 11q. We observed the loss of chromosome 9 in 2 of 4 dysplastic nevi, and combining this observation with that from the melanomas suggests that deletion or inactivation of a gene on 9p may be a primary event in melanocyte transformation. Other tumor suppressor genes are likely to be involved in the transformation process, and these are most likely located on 10p, 10q, 11q, and 6q. We observed many rearrangement involving chromosome band 1p13 and suggest that activation of a gene in that band may also contribute to the transformation process.

Chromosome Aberrations↗
PubMed1990

Symmetrical chromosome rearrangements in cell lines established from human radiation-induced sarcomas.

We report the establishment of cell lines from six radiation-induced tumors, three osteosarcomas, and three soft tissue sarcomas. Cytogenetic analysis of the lines showed mostly balanced rearrangements in the osteosarcomas; the soft tissue sarcomas had more unstable karyotypes. The rearrangements observed were unlike those previously reported for spontaneously occurring tumors of the same histological type and were more typical of the long-term changes observed after radiation exposure.

Adolescent↗
PubMed1990

Monosomy 12p in a radiation-induced germ cell tumor.

We report results of cytogenetic analysis of a cell line established from a radiation induced germ cell tumor. Tumors of this type are rare, and there is only one other report of chromosome analyses of solid tumors induced by radiotherapy (Cowan et al., 1990). The cells were grown for over a year, and harvested at passage 13. The karyotype was pseudodiploid, with several balanced translocations. Spontaneously occurring germ cell tumors are associated with i(12p). We did not observe an i(12p), but instead found monosomy of 12p and 7q22----q32.

Cell Line↗
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

The response of the Intoxilyzer 4011AS-A to a number of possible interfering substances.

Five Intoxilyzer 4011AS-As were tested for their response to eleven chemicals and one mixture of chemicals. The air/water partition ratios were also determined for these eleven chemicals and one mixture. The chemicals tested and their approximate partition ratios were the following: acetaldehyde (190:1), acetone (341:1), acetonitrile (578:1), isoprene (1:1), isopropanol (1671:1), methanol (3229:1), methylene chloride (11:1), methyl ethyl ketone (229:1), toluene (5.5:1), 1,1,1-trichloroethane (14:1), trichloroethylene (20:1), and a 50:50 mixture of 1,1,1-trichloroethane and trichloroethylene (14:1). Of the eleven chemicals and one mixture studied during this experiment, only three, isopropanol, toluene, and methyl ethyl ketone, could reasonably interfere with the test, and then only under unusual circumstances--those circumstances being a slight additive effect to a breath ethanol concentration near the level required for prosecution. Any substantial additive effect from these three substances would illuminate the interference light which invalidates the test. The mean illumination point of the interference light was 0.0286 g/210 L for methyl ethyl ketone, 0.0294 for toluene, and between 0.0116 and 0.0292 for the apparent alcohol concentration for isopropanol, depending on the amount of isopropanol metabolized to acetone. Even with these unusual circumstances considered, the Intoxilyzer 4011AS-A must be viewed as an effective way of determining the ethanol concentration in human breath for evidential purposes.

Alcoholic Intoxication↗
PubMed1988

Cytogenetic analysis of melanocytes from premalignant nevi and melanomas.

We karyotypically analyzed cultured melanocytes from a variety of lesions, including congenital and dysplastic nevi, primary melanoma, and metastatic melanoma. The cells derived from congenital nevi had normal karyotypes, as did 22 of the 26 cultures derived from dysplastic nevi. The karyotypes of melanocytes from primary and metastatic melanomas were all abnormal. The only chromosome change in common between the nevi with abnormal karyotypes and the melanomas was the loss of one copy of chromosome 9 (two of four nevi and four of 11 melanomas, including three from the same patient) or the loss of the short arm of chromosome 9, especially of region 9pter-p22 (three of 11 melanomas). We suggest that deletion of a gene or genes on 9p, possibly interferon genes, is an initial step in the malignant transformation of melanocytes.

Adolescent↗
PubMed1988

Regional assignment of six polymorphic DNA sequences on chromosome 21 by in situ hybridization to normal and rearranged chromosomes.

We have assigned six polymorphic DNA segments to chromosomal subregions and have established the physical order of these sequences on the long arm of chromosome 21 by in situ hybridization of cloned probes to normal metaphase chromosomes and chromosomes 21 from individuals with three different structural rearrangements: an interstitial deletion, a ring chromosome, and a reciprocal translocation involving four different breakpoints in band 21q22. Segments D21S1 and D21S11 map to region 21q11.2----q21, D21S8 to 21q21.1----q22.11, and D21S54 to 21q21.3----q22.11; D21S23 and D21S25 are both in the terminal subband 21q22.3, but they are separated by a chromosomal breakpoint in a ring 21 chromosome, a finding that places D21S23 proximal to D21S25. The physical map order D21S1/D21S11-D21S8-D21S54-D21S23-D21S25 agrees with the linkage map, but genetic distances are disproportionately larger toward the distal end of 21q.

Chromosome Aberrations↗
PubMed1987

Normal murine melanocytes in culture.

A major obstacle to applying the techniques of molecular biology to the genetics and cell biology of pigmentation has been our inability to grow normal murine melanocytes in culture. We report here the establishment and characterization of continuously proliferating cultures of cutaneous pigment cells from seven strains of mice. Melanocytes were grown from the dermis of newborn mice in medium containing 12-0-tetradecanoyl-13-phorbol-acetate; a substance, such as melanotropin, that raises intracellular levels of cyclic AMP; and an extract made from human placenta.

Animals↗
PubMed1987

The interpretation of electromyographic responses to electrical stimulation of the motor cortex in diseases of the upper motor neurone.

The complexities of interpreting results of electrical stimulation of the motor cortex in pathological states are discussed and illustrated by reference to results from a variety of patients with diseases affecting the upper motor neurone (multiple sclerosis, cervical spondylosis and myelopathy, motor neurone disease, hemiparesis due to cerebral infarction, and hereditary spastic paraplegia). The abnormalities of the electromyographic (EMG) responses after anodal cortical stimulation consisted of delay in the latency to onset, dispersion or reduction in response size or even absence of EMG responses. These changes were not confined to any specific condition or pathology. Previous work has suggested that the sequence of events that follow anodal cortical stimulation involves repetitive excitatory inputs to spinal motoneurones and transmission across at least one central synapse. Accordingly, delayed latencies may not exclusively indicate slowing of motor conduction, while the absence of any response may not indicate complete failure of conduction in corticomotoneurone pathways.

Adult↗
PubMed1987

Cytogenetic and molecular genetic studies of a patient with atypical lymphoid hyperplasia.

We have karyotyped cells from a lymph node of a patient with atypical lymphoid hyperplasia. Among other clonal chromosomal abnormalities, a t(2;19) translocation was observed with breakpoints at 2p11.2 and 19q13. The genes for transforming growth factor alpha and beta have been mapped to 2p11-p13 and 19q13, respectively, but Southern blot analysis did not reveal any alteration in the structure of these genes. Similarly, the kappa immunoglobulin gene, which maps to 2p11-p12 was not rearranged. In addition, Southern blot analysis using immunoglobulin and T-cell receptor genes as probes, did not demonstrate any clonality of either B or T cells. We propose that this patient represents an early, polyclonal stage of atypical hyperplasia. The chromosome changes observed may have been one of the etiologic factors causing this disorder.

Aged↗
PubMed1987

Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma.

A translocation that involves chromosome X (band p11.2) and chromosome 18 (band q11.2) was observed in short-term in vitro cultures of cells from five synovial sarcomas and one malignant fibrous histiocytoma. In four of these tumors, the translocation t(X;18)(p11.2;q11.2) was reciprocal. The two other tumors had complex translocations: t(X;18;21)(p11.2;q11.2;p13) and t(X;15;18)(p11.2;q23;q11.2). A translocation between chromosomes X and 18 was not detected in other histological types of soft tissue sarcoma. The X;18 rearrangement appears to characterize the synovial sarcoma and is the first description of a primary, nonrandom change in the sex chromosome of a human solid tumor.

Adolescent↗
PubMed1987

Motor cortex stimulation in intact man. 1. General characteristics of EMG responses in different muscles.

This paper is the first of two papers describing our five-year experience with the technique of electrical stimulation of the human motor cortex. In this first paper we illustrate the basic distribution and behaviour of electromyographic responses in limb muscles to anodal stimulation of the motor cortex in intact, awake human subjects. These responses may be recorded at short latency, with estimates of conduction velocities from the brain to the spinal cord suggesting transmission in rapidly conducting pathways, such as the corticomotoneuronal component of the corticospinal tract. The site at which the stimulus activates these motor pathways to produce responses at such short latency is likely to be at, or adjacent to the origin of these major descending motor pathways in the cerebral cortex. The best stimulating sites for activation of arm or leg muscles corresponds to the known somatotopic arrangement of the cerebral cortex. The electromyographic response characteristics are different in the contracting, as compared with the relaxed muscle; the EMG response latency shortens, its size becomes larger and its threshold is lowered when the muscle is voluntarily made to contract. The mechanisms that are responsible for these characteristics are examined in the following paper.

Adult↗