Biomedical subjects

Paul S Thorner

Publications and source records attributed to Paul S Thorner.

22 records · Page 2Linked to original sources

PubMed2002

Significance of p53 expression in immature teratomas.

Twenty-nine pediatric immature teratomas were reviewed to determine the frequency and clinical significance of p53 expression. Tumors were stained for p53 expression by immunohistochemistry and results were correlated with the presence of other germ cell tumor elements and with outcome. Sequencing of p53 for mutations was performed on positive cases. Eighteen cases showed widespread positive p53 staining of the immature teratoma elements, 9 showed staining only in very occasional cells, and 2 cases showed no staining. Of the 18 positive cases, 5 recurred. All five were pure immature teratomas at diagnosis. Four recurred as immature or mature teratoma and one as a sarcoma; all except one showed frequent cells positive for p53 in the recurrent tumor. Another 5 of the 18 diffusely positive cases contained immature teratoma as well as other malignant germ cell elements at diagnosis; none of these recurred. None of the remaining eight cases with frequent positive cells, the nine cases with occasionally positive p53 staining, or the two cases with no staining recurred or demonstrated other germ cell tumor elements. We conclude that p53 expression is not unusual in immature teratoma and diffuse p53 immunopositivity is associated with recurrence or the presence of malignant elements in approximately 50% of cases. In only 1 of 29 cases tested was p53 immunopositivity associated with mutations in the p53 gene; hence, overexpression in the majority of cases is presumed to reflect increased half-life of the protein from undetermined stabilizing factors. Expression of p21, a p53 target gene, was only focal, suggesting impaired transcriptional activation by p53. The finding of frequent p53-positive cells in immature teratoma should prompt a search for malignant elements within the tumor and affected patients should be followed closely for evidence of recurrence.

Adolescent↗

PubMed2002

Identification of a novel gene NCRMS on chromosome 12q21 with differential expression between rhabdomyosarcoma subtypes.

Rhabdomyosarcoma (RMS) is a malignant soft tissue tumor showing varying degrees of skeletal muscle differentiation. Two major histologic subtypes exist, alveolar and embryonal, each with associated molecular genetic changes. We have used Representational Difference Analysis (RDA) to compare gene expression between the two RMS subtypes and have identified the novel gene NCRMS (non-coding RNA in RMS) that has increased expression in the alveolar subtype relative to the embryonal subtype. Multiple alternatively spliced forms of NCRMS were identified through library screening, RACE, and comparison to human expressed sequence tags (ESTs). Northern blot analysis indicated the transcript size to be 1.25 kb in alveolar RMS. There was no sequence homology to any of the known genes in GenBank, but extensive homology to ESTs from various species. Comparison to human genomic sequences identified at least 11 exons mapping to chromosomal region 12q21. Differential expression of NCRMS was noted between various tumor types. Since NCRMS RNA possesses limited potential for protein coding, yet with conserved sequences between different species, it is likely that NCRMS is a functional non-coding RNA. Known genes in its proximity include myogenic regulators Myf5 and Myf6, growth factor Igf1, and another potential differentially expressed gene (ATP2B1) in RMS isolated by RDA.

Alanine Racemase↗

PubMed2002

Angiostrongylus cantonensis infection mimicking a spinal cord tumor.

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis and meningoencephalitis. Almost all cases are self-limiting and are diagnosed by cerebrospinal fluid eosinophilia and enzyme-linked immunosorbent assay; pathology reports are restricted to postmortem samples from lethal cases. We report on what we believe is the first case of A. cantonensis infection diagnosed by biopsy in a living patient. The spinal cord was biopsied because of the unusual clinical presentation of a myelopathy without meningeal symptoms, together with a mass lesion that was clinically and radiologically diagnosed as a spinal cord tumor.

Adult↗

PubMed2001

Abnormal glomerular basement membrane laminins in murine, canine, and human Alport syndrome: aberrant laminin alpha2 deposition is species independent.

Kidneys from mice, dogs, and humans with X-linked and autosomal-recessive forms of Alport syndrome were examined by immunofluorescence for expression of laminin alpha, beta, and gamma chains using monospecific antibodies. Laminin alpha2 chain was absent from glomerular basement membranes (GBM) in normal human, murine, and canine kidneys but was abnormally deposited in Alport GBM, regardless of species or inheritance pattern. In murine and canine Alport kidneys, laminin alpha2 seems to be deposited as part of both laminin-2 (alpha2beta1gamma1) and laminin-4 (alpha2beta2gamma1) but as part of only laminin-4 in human Alport kidneys. GBM laminin alpha2 chain deposition was not observed in a variety of non-Alport human glomerulopathies. This finding adds to the list of proteins that are aberrantly deposited in Alport GBM as a consequence of the absence of the alpha3, alpha4, and alpha5 chains of type IV collagen: (1) type IV collagen alpha1 and alpha2 chains, (2) type V collagen, (3) type VI collagen, and most recently (4) the laminin alpha2 chain and (5) the laminin alpha1 and beta1 chains in mice and dogs. These findings emphasize further the critical role played by the alpha3, alpha4, and alpha5 chains of type IV collagen in establishing and maintaining the composition, structure, and function of mature GBM.

Animals↗