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Biomedical subjects

J M Cowan

Publications and source records attributed to J M Cowan.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1987

Motor cortex stimulation in intact man. 2. Multiple descending volleys.

Using an isometric strain gauge, we measured the twitch force produced in the first dorsal interosseous (FDI) muscle by a single anodal shock to the contralateral scalp. At high intensities of stimulation this twitch can greatly exceed the force produced by supramaximal stimulation of peripheral nerve. This indicates that a single cortical shock can cause repetitive firing of some or all FDI motoneurons. Such repetitive firing was demonstrated using a collision technique in which a supramaximal ulnar nerve stimulus was given at the wrist shortly after a cortical shock. The antidromic volley from the peripheral nerve stimulation failed to obliterate completely the response to cortical stimulation. Additional EMG activity was visible in the normally silent period between ulnar M and F waves. This activity must have been due to the presence of repetitive volleys of activity set up in spinal motoneurons by the cortical shock. Such activity summates with the twitch produced by the ulnar M wave to produce a very large force twitch of the muscle. Multiple firing of some motoneurons can be observed in some individuals at cortical stimulation intensities below that necessary to evoke activity in all the motoneurons in the FDI pool. Multiple firing probably was caused by repetitive excitatory inputs impinging on spinal motoneurons. These could be demonstrated using poststimulus time histogram techniques on single motor units. Low intensities of cortical stimulation produced a single short duration (mean 1.8 ms) peak of increased motor unit firing 20 to 30 ms after the shock. At high intensities, this was followed by extra peaks some 4 to 5 ms later. H reflex testing showed that the threshold of the initial descending volley, produced by the cortical stimulus was uninfluenced by a voluntary contraction. These results are discussed with reference to the D and I waves recorded from pyramidal tract after anodal stimulation of the exposed cortex in animals.

Biomechanical Phenomena↗
PubMed1987

Congenital adrenal hypoplasia, myopathy, and glycerol kinase deficiency: molecular genetic evidence for deletions.

Glycerol kinase deficiency (GKD) is an X-linked recessive trait that occurs in association with congenital adrenal hypoplasia (AH) and developmental delay with or without congenital dystrophic myopathy. Several such patients have recently been reported to have cytological deletions of chromosome region Xp21 and/or of DNA markers that map near the locus for Duchenne muscular dystrophy (DMD) in band Xp21. We have examined the initial family reported in the literature and, using prometaphase chromosome studies and Southern blot analysis with 13 different DNA probes derived from band Xp21, have found no deletions within this region of the X chromosome. When DNA samples from six other unrelated affected males were analyzed, four of them were found to have different-size deletions within Xp21. Thus, the form of GKD associated with AH and dystrophic myopathy exhibits significant genetic heterogeneity at the DNA level. No deletions were detected in two patients with isolated GK deficiency. Comparison of our molecular studies of unrelated patients with deletions of DNA segments allows us to define the region of Xp21 (between probes J-Bir and L1.4) that most likely contains the genes for GKD and AH. This location is distal to the DMD locus. The patients with progressive muscular dystrophy tended to have larger deletions that include markers known to derive from the DMD locus, while GKD/AH/dystrophic-myopathy patients without current evidence of deletion seemed to have a milder, nonprogressive form of congenital myopathy.

Abnormalities, Multiple↗
PubMed1986

The involvement of 6p in melanoma.

Karyotype analysis of first passage cells from a melanoma, occurring in a patient with a giant congenital nevus, revealed monosomy of chromosomes #6 and #11, and trisomy of chromosomes #8 and #22. Five marker chromosomes were present, including two ring chromosomes. The origin of three of the marker chromosomes was determined, and all were found to contain the region 6p21.1-6p23. The ring chromosomes were also thought to contain this region, to which the major histocompatibility locus has been mapped. The significance of these findings is discussed in the light of recent reports of chromosome studies of melanoma cells.

Child, Preschool↗
PubMed1986

SC phocomelia syndrome, premature centromere separation, and congenital cranial nerve paralysis in two sisters, one with malignant melanoma.

Two middle age sisters had most manifestations of the SC phocomelia syndrome including postnatal growth retardation, symmetric limb deficiencies with radial aplasia and absent thumbs, facial anomalies with microcephaly, microphthalmia, hypoplastic nasal alae, and borderline to mild mental retardation. Unusual findings included congenital paralysis of some cranial nerves in both patients and malignant melanoma in the proposita. Cultured lymphocytes from both patients, and skin fibroblasts, Epstein Barr virus-transformed lymphocytes, and tumor cells from the proposita demonstrated premature separation of centromeric heterochromatin (PCS) of many chromosomes, a finding noted previously in the SC phocomelia syndrome and the similar but more severe Roberts syndrome. Extensive overlap of the phenotypes of the sisters and 15 other patients with either syndrome and PCS confirms that these are either allelic conditions or the same disease--designated Roberts-SC phocomelia syndrome. The role of PCS in the syndrome(s) remains uncertain since some patients with the characteristic clinical phenotypes are reported to lack it.

Adult↗