Biomedical subjects

J Squire

Publications and source records attributed to J Squire.

83 records · Page 5Linked to original sources

PubMedDate not supplied

Expression of WT1 in pediatric small cell tumors: report of two cases with a possible mesothelial origin.

The WT1 gene is normally expressed in fetal kidney and mesothelium, and its expression has been suggested as a marker for Wilms tumor and mesothelioma. We examined WT1 expression levels by reverse-transcriptase polymerase chain reaction (RT-PCR) in 38 childhood small-cell tumors including Wilms tumor, embryonal and alveolar rhabdomyosarcoma, Ewing sarcoma, lymphoma, desmoplastic small round-cell tumor (DSRCT), synovial sarcoma, extrarenal rhabdoid tumor, and two tumors that were atypical for this group of tumors. WT1 expression was only detected in Wilms tumor, rhabdoid tumor, and in these two cases of uncertain histogenesis. Both arose in the peritoneal cavity and by immunohistochemistry were diffusely positive for vimentin, keratin, and desmin. Tonofilaments were identified by electron microscopy in one of the cases. RT-PCR failed to detect the t(11;22) translocation associated with DSRCT in either case. Our results suggest that WT1 expression is an unusual feature of childhood non-Wilms tumors and, in the right setting, it may indicate a mesothelial origin. The expression of WT1 may play a role in mesodermal cells acquiring epithelial characteristics, a concept supported by the mixed epithelial and mesenchymal phenotype of these two cases.

Biomarkers, Tumor↗

PubMedDate not supplied

Variant EWS-WT1 chimeric product in the desmoplastic small round cell tumor.

Chromosome translocations found in neoplasms often result in the creation of hybrid genes encoding chimeric proteins. Desmoplastic small round cell tumor (DSRCT) is a recently described aggressive malignancy associated with a unique chromosomal translocation t(11;22)(p13;q12). This translocation has recently been characterized, revealing the rearrangement and fusion of the WT1 gene on chromosome 11 to the EWS gene on chromosome 22. Fusion of these two genes results in the production of a putative oncogenic protein composed of the zinc finger DNA-binding domains of WT1 linked to the potential transcriptional regulatory domains of EWS. The typical chimeric transcript consists of the first 7 exons of EWS and the last 3 exons of WT1. We report here the first case of DSRCT with a variant EWS-WT1 chimeric product that includes 9 exons of EWS and 3 exons of WT1.

Adolescent↗

PubMedDate not supplied

Is nurse-supervised exercise stress testing safe practice?

OBJECTIVE: Nurses have been performing exercise stress tests (EST) without medical supervision since 1978 in our hospital-based cardiac rehabilitation unit. This study was conducted to examine the incidence of cardiovascular complications and to describe the competency-based training program for the nurses performing the EST. DESIGN: Descriptive, retrospective audit of prospective data. SETTING: Single comprehensive cardiac rehabilitation center in a large tertiary referral hospital in western Sydney, Australia. SUBJECTS: Seventeen thousand, four hundred and sixty-seven patients were included in this study over a 12-year period. METHOD: Data were collected on all ESTs performed by the cardiac rehabilitation nurses from January 1986 to December 1997 in relation to serious cardiovascular complications and other EST parameters. RESULTS: In this study, 17,467 ESTs were performed on 5054 patients who had 6273 separate presentations. The most common entry diagnosis was after an acute myocardial infarction (50%). The mean age was 58 +/- 10.5 years (range 15 to 87 years; 80% male). The left ventricular ejection fraction (n = 2822) was 49% +/- 14%. In a subgroup analysis of 14,454 patients, 14% had a positive EST (ST segment >1.9 mm depression). There were no deaths associated with the EST, and there were 13 major complications in 12 patients. This figure included no cardiac arrests, 11 episodes of conscious sustained ventricular tachycardia, 1 reinfarction, and 1 mitral valve rupture, representing a 0% mortality rate and a 0.075% major morbidity rate. CONCLUSION: This study shows that nurse-supervised EST of higher risk patients in the hospital-based cardiac rehabilitation setting has been a safe practice from a mortality and morbidity rate perspective. This finding may be accounted for by the high training standard and reaccreditation of the nurses on the advanced practice of performing EST.

Adolescent↗

PubMedDate not supplied

Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma.

Through family studies and analysis of patients with congenital chromosome abnormalities, the germ-line mutation responsible for the hereditary form of the eye tumour, retinoblastoma, has been assigned to the q14 region on chromosome 13 and closely linked to an enzyme called esterase D (ESD). Knudson has proposed that as few as one somatic event in addition to the germ-line mutation is required to induce tumours in patients with the hereditary form of retinoblastoma; the non-hereditary form requires two somatic events to occur in the same cell. The somatic event(s) may involve either mutation of the remaining normal gene at 13q14 or mutation of a gene at another site in the genome. Here we have examined six retinoblastoma patients who are heterozygous for electrophoretic variants of ESD. Although the normal cells of all six patients expressed both variants, the tumour cells of four patients expressed enzyme from only one of the two ESD alleles. We tentatively conclude that induction of a retinoblastoma tumour requires the somatic inactivation of genes near the ESD locus including the remaining normal gene at the retinoblastoma (RB) locus.

Cell Line↗

PubMedDate not supplied

Tumour induction by the retinoblastoma mutation is independent of N-myc expression.

Retinoblastoma (RB) tumours form in the eyes of young children when homozygosity for a mutation at the Rb-1 locus develops in a somatic retinal cell. A similar shift to homozygosity for the RB mutation has been observed in osteogenic sarcoma (OS) tumours that commonly arise as second tumours in children who survive RB. This observation suggests that the Rb-1 locus controls the expression of genes with oncogenic potential; a possible target is the oncogene N-myc, which is sometimes amplified and over-expressed in the neuroectodermal tumours neuroblastoma and RB. However, N-myc is developmentally regulated in normal murine embryogenesis, and an alternative possibility is that the expression of the gene in tumour cells reflects their embryonic origin and is unrelated to the RB mutation. We have therefore examined N-myc expression in various fetal, adult and tumour tissues, and report here that the gene is expressed in fetal but not in adult brain and retina and in near-diploid RB tumour samples at levels similar to those observed in normal fetal retina. Only RB tumours with genomic amplification of the N-myc gene exhibited increased levels of expression; and no N-myc transcripts were detected in osteogenic sarcomas initiated by mutations at the Rb-1 locus. We therefore conclude that the expression of N-myc in RB tumours probably reflects the origin of the tumour from an embryonic tissue normally expressing the gene and is not directly associated with the mutation at the RB locus.

Animals↗

PubMedDate not supplied

Familial Evans syndrome: a report of an affected sibship.

PURPOSE: This report describes the clinical course of three siblings, all of whom had Evans syndrome in childhood. PATIENTS: The coexistence of autoimmune hemolytic anemia and thrombocytopenia, in the absence of a known underlying cause, led to the diagnosis of Evans syndrome in a 4-month-old girl and subsequently in her two brothers when they were 4 and 13 years old. RESULTS: The 4-month-old girl had a life-threatening relapsing course unresponsive to corticosteroids, intravenous gamma-globulin, thymectomy, and cyclophosphamide. She eventually responded to splenectomy. Her two brothers had milder disease that responded to corticosteroids. Cytogenetic analyses revealed the presence of a familial Y;15 translocation in all three children and their father. CONCLUSION: There are few reported cases of familial Evans syndrome, and they are usually associated with an inherited congenital abnormality. We report the unusual finding of three siblings with the disease and no known congenital abnormality.

Adolescent↗

PubMedDate not supplied

Astroblastoma: report of a case with ultrastructural, cell kinetic, and cytogenetic analysis.

Astroblastomas are rare tumors of cerebral hemispheres of young adults. We report an astroblastoma in a 15-year-old girl and present the first descriptions of cytogenetic abnormalities in this tumor. The tumor was relatively well demarcated from the brain and revealed prominent perivascular rosettes as well as intervascular clear cells that contained abundant glycogen. Cytogenetic analysis revealed an abnormal hypodiploid karyotype with 45 chromosomes and monosomies of chromosomes 10, 21, and 22 and two marker chromosomes in all cells examined. The tumor had a Ki-67 labelling index of 4.7% and assessment of ploidy by flow cytometry revealed 96% of cells in the G0G1 phase and 4% of cells in the G2M phase. Assessment of proliferation and ploidy indices in further cases may provide important prognostic data for this poorly understood entity. Further cytogenetic studies will also help to identify if there are consistent karyotypic abnormalities in these enigmatic tumors.

Adolescent↗

PubMedDate not supplied

Assessment of MYCN amplification in neuroblastoma biopsies by differential polymerase chain reaction.

Amplification of the oncogene MYCN is a genetic change frequently observed in neuroblastoma and is an indicator of poor prognosis. MYCN copy number is currently determined by Southern blot hybridization. This technique takes 2 to 3 weeks, is labor-intensive, is sensitive to DNA degradation, and requires large quantities of DNA. We have evaluated a new, semiquantitative method of estimating gene copy number that uses differential polymerase chain reaction (PCR). The procedure can be performed in 1 day, is highly reproducible, and requires only nanogram quantities of DNA. It employs a semiquantitative, nonisotopic PCR technique based on differential competition for PCR substrates. MYCN gene primers are amplified together with primers from a single-copy internal control gene. Following electrophoretic separation, the ratio of the two PCR products is determined visually and by densitometric analysis of ethidium bromide-stained agarose gels. This differential ratio is then compared to a series of ratios generated from standards of known MYCN gene copy number. We compared the results obtained by this differential PCR method with those obtained by conventional Southern blotting in 16 cases of primary neuroblastoma. All amplified tumors were detected by differential PCR, and no false positives were observed. We confirmed that differential PCR is a rapid and reliable alternative to Southern blotting for MYCN copy number assessment and is highly suited to the analysis of DNA derived from needle biopsies.

Base Sequence↗

PubMedDate not supplied

Molecular and cytogenetic analysis of a cerebellar primitive neuroectodermal tumor with prominent neuronal differentiation: detection of MYCN amplification by differential polymerase chain reaction and Southern blot analysis.

Oncogene amplification is uncommon in cerebellar primitive neuroectodermal tumor (medulloblastoma) and its frequency and diversity are greater in medulloblastoma cell lines. We describe a medulloblastoma in a 10-year-old-girl with striking neuronal differentiation evident in the islands of ganglion cells intermixed with more primitive undifferentiated cells. The islands of ganglion cells showed prominent synaptophysin positivity. Karyotypic analysis revealed hypo- and hyperdiploidy with multiple random rearrangements and double minute chromosomes. Differential polymerase chain reaction and Southern blot analysis revealed up to 25-fold MYCN amplification.

Base Sequence↗

PubMedDate not supplied

Implantable defibrillator recipients' responses to device implantation and design.

The implantable cardioverter defibrillator (ICD) is a surgically inserted device that follows a well-established pattern of technology innovation and rapid adoption without extensive clinical trials. Few devices are as obviously life-saving in potentially fatal situations and deliver such sudden and sometimes painful therapy. Although patients' quality of life and adjustment to the device both physically and psychologically are relatively well-documented, few studies have explored recipients' responses to the device itself or elicited their thoughts on the technological design. The findings presented here are from a prospective Australian study that surveyed 110 ICD recipients pre-insertion and at 3, 12, and 18 months post-insertion. Recipients' responses to the device and their thoughts on design were sought. Respondents were overwhelmingly willing to: 1) accept the ICD, 2) recommend it to others, and 3) welcome such innovations as warning tones, device-controlled drug delivery, and telephone interrogation of the device.

Adolescent↗

PubMedDate not supplied

Heterogeneity of MYCN amplification in a child with stroma-rich neuroblastoma (ganglioneuroblastoma).

Amplification of MYCN portends rapid tumor progression and poor prognosis in neuroblastoma. MYCN copy number has been described as homogeneous within a tumor and congruent in primary tumor and metastasis. We report a child with stage III favorable histology stroma-rich neuroblastoma (ganglioneuroblastoma) and a poor outcome with an apparent change in MYCN gene amplification by Southern blot. Initial biopsy revealed a ganglioneuroblastoma with predominance of differentiating cells designated as neuroblastoma, stroma-rich, intermixed (Shimada). Southern blot failed to demonstrate MYCN gene amplification. After front-line chemotherapy failed, a total resection was performed. In this specimen, Southern blot demonstrated MYCN amplification (15-20 copies) in the undifferentiated component and no amplification in the differentiated. Fluorescence in situ hybridization (FISH) analysis performed retrospectively on both tumor biopsies demonstrated MYCN amplification in the undifferentiated sections of both tumor specimens but not in the differentiated ones. This is the first well-documented case report of heterogeneous MYCN amplification in a child with neuroblastoma. Because key therapeutic decisions are based on the presence of MYCN amplification, physicians diagnosing and treating children with neuroblastoma need to be aware of the possibility that MYCN amplification may be heterogeneous within a tumor and may be missed using techniques based on pooled DNA such as Southern blotting. FISH may be a preferable method for determining MYCN amplification.

Blotting, Southern↗