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Biomedical subjects

J Searle

Publications and source records attributed to J Searle.

At least 37 records · Page 2Linked to original sources
PubMed1996

Intravascular fasciitis: a case report and review of the literature.

A 49 year old man presented with a mass in the inguinal region that for 3 mths had been associated with slight discomfort. Clinically the mass was thought to be an enlarged lymph node. Histology however showed nodular fasciitis. There was also an associated smaller lesion that was histologically identical and which involved the wall of a medium sized vein with protrusion into its lumen. These appearances were typical of intravascular fasciitis. Review of the Royal Brisbane Hospital Pathology files for 12 yrs from 1982, revealed no other such cases. We describe here the clinical and pathological features of this case and review the literature on this rare condition.

Fasciitis↗
PubMed1996

Nodular fasciitis and related pseudosarcomatous lesions of soft tissues.

BACKGROUND: Nodular fasciitis is characterized by a proliferation of spindle cells which may be misdiagnosed as sarcomas due to the rich cellularity, mitotic activity and variant morphologic patterns. METHODS: This report includes 42 cases of nodular fasciitis and related conditions of skin and soft tissue from the pathology files of the Royal Brisbane Hospital, Queensland, Australia. There were 33 cases of nodular fasciitis, three cases of ossifying fasciitis, three cases of proliferative fasciitis, two cases of proliferative myositis and one case of intravascular fasciitis. Two-thirds of cases were referred from outside Royal Brisbane Hospital. RESULTS: Nodular fasciitis and ossifying occurred most commonly in young adults with 16 patients (44%) between the ages of 20 and 29. However, the other variants of nodular fasciitis including proliferative myositis and intravascular fasciitis occurred in older people (six patients being older than 49 years) and more commonly occurring in men (n=5). A painless rapidly growing mass was most common. The lesions of nodular fasciitis were most often located in the upper extremity with the forearm most commonly affected. CONCLUSIONS: Nodular fasciitis and related conditions are benign. All patients are alive and well 3 months to 13 years (mean 7.2 years) after simple local resection.

Adolescent↗
PubMed1996

Fearing the worst--why do pregnant women feel 'at risk'?

Whilst pregnancy and childbirth are generally regarded as a joyful and exciting time in a woman's life they are also filled with fear, uncertainty, a feeling of being 'at risk' and anxieties about what the pregnancy and future may hold. In a society where the perinatal and maternal mortality and morbidity rates are low, where do these fears and uncertainties arise from? Why do pregnant women fear the worst? What are the implications of this? A cross-sectional and qualitative study of 376 postnatal women in a major public teaching hospital in Melbourne was undertaken in 1995 to explore women's beliefs and fears about pregnancy and birthing outcomes, through their perceptions and use of routine antenatal screening tests. Through women's perceptions about the value of, and expectations of, routine antenatal screening tests, and their fears during pregnancy, the author explores the 'notion of risk' as perceived by these women.

Adolescent↗
PubMed1995

An Alu VpA marker on chromosome I demonstrates that replication errors manifest at the adenoma-carcinoma transition in sporadic colorectal tumors.

Widespread mutations in simple tandemly repeated (STR) DNA sequences are frequently found in colorectal tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) and less frequently in sporadic colorectal cancers. This aims of this study were to determine the type of DNA sequence most commonly affected by such mutations and to examine the point in the natural history of the tumor where replication errors (RERs) appear. An unselected series of colorectal tumors (49 adenomas and 108 carcinomas) was examined with 4 different STR markers: one Alu VpA polymorphism (MYCLI), one tetranucleotide repeat (D17S846), one dinucleotide repeat (D3S1029), and one polyA repeat (AP delta 3 delta). All 3 positive adenomas and 18 of 20 positive carcinomas showed replication errors in the Alu VpA sequence at the MYCLI locus, making this marker more than twice as sensitive as the best of the other 3 markers. Importantly, all positive adenomas showed small foci of carcinoma in situ. This suggests that replication errors manifest at the adenoma/carcinoma transition in sporadic colorectal tumors.

Adenoma↗
PubMed1995

Colorectal carcinomas show frequent allelic loss on the long arm of chromosome 17 with evidence for a specific target region.

Allelic loss is a common mechanism of inactivation of tumour-suppressor genes in colorectal carcinomas. A number of known or putative tumour-suppressor genes including NF1, BRCA1, NME1, NME2 and prohibitin are present on the long arm of chromosome 17, and this region has not been extensively analysed in colorectal tumours. In this study 72 colorectal carcinomas were examined for allelic loss at eight loci on chromosome 17. Allelic loss was frequent both at the p53 locus, which is known to be important in colorectal carcinoma, and also telomeric to p53 on 17p. Allelic loss continued to be present in more than 50% of cases in the pericentromeric region and on proximal 17q to the marker LEW101 (D17S40) at 17q22-23. The most telomeric markers on 17q showed lower rates of allelic loss. Analysis of cases with partial deletions which did not include the p53 locus showed a common region of overlap of the deletions centred on D17S40. This suggests the target of allelic loss on 17q is a tumour-suppressor gene in this region.

Alleles↗
PubMed1995

Fine deletion mapping on the long arm of chromosome 9 in sporadic and familial basal cell carcinomas.

Basal cell carcinomas (BCCs) are the most common sporadic cancers worldwide. They are also a cardinal manifestation of a familial cancer predisposition syndrome, naevoid BCC syndrome (NBCCS). The gene responsible for NBCCS is likely to be a tumour suppressor gene and has been genetically mapped to a 2cM region between microsatellite markers, D9S196 and D9S180 at 9q22.3-q31. 101 BCCs (63 sporadic and 38 familial) were examined for loss of heterozygosity (LOH) in the candidate region of the NBCCS gene. Deletions were found in 46% and all LOH is consistent with genetic mapping of the NBCC locus. These findings strongly support the hypothesis that inactivation of the putative tumour suppressor, the NBCCS gene, is important in the formation of sporadic BCCs. One sporadic tumour indicates that the smallest region of overlap of these deletions is within the interval between D9S287 and D9S180. If this is confirmed in additional tumours, it would further narrow down the NBCCS region and exclude one candidate gene, that for the C complementation group of Fanconi anaemia, which maps proximally to D9S287. However, it would not exclude another candidate, the gene for the A complementation group of xeroderma pigmentosum (XPAC). Evidence of imprinting was also sought but preliminary data indicate that it is unlikely to occur at the NBCCS locus.

Adult↗
PubMed1994

Establishment of a cell line from a hepatocellular carcinoma from a patient with hemochromatosis.

We describe the establishment and characterization of a novel hepatoma cell line. This cell line, designated RBHF-1, was established from a hepatocellular carcinoma of a 67-yr-old man with a history of genetic hemochromatosis. At this writing, the cells have been maintained in RPMI-1640 tissue-culture medium and fetal calf serum without any additional supplements for 30 mo. The cells form colonies on soft agar and are not tumorigenic in nude mice. The cell line is polymorphic and displays characteristics of mature hepatocytes by synthesizing albumin, alpha 2-macroglobulin, fibronectin and alpha-fetoprotein. Cytogenetic analysis shows multiple chromosomal aberrations, with a consistent deletion in the long arm and deletions or rearrangements in the short arm of chromosome 1. There is no evidence for hepatitis B or hepatitis C virus infection of the cell line. The cells contain no detectable intracellular iron after staining with Perls' stain. Unlike other hepatoma cell lines, there is no detectable binding of epidermal growth factor to RBHF-1 cells. This is the first cell line to be established from a patient with hemochromatosis, and it provides a potentially important model for the study of hepatocyte transformation in association with iron overload.

Aged↗
PubMed1994

Loss of heterozygosity on the long arm of chromosome 11 in colorectal tumours.

We have examined a series of human colorectal adenomas, carcinomas and cell lines derived from human colorectal cancer for loss of heterozygosity (LOH) on chromosome 11q22-23 by polymerase chain reaction (PCR) amplification of a microsatellite polymorphism of the dopamine D2 receptor (DRD2) locus. LOH was demonstrated in 5/30 (16.7%) adenomas and 23/68 (33.8%) carcinomas. Only 2/20 (10%) cell lines showed homozygosity which could potentially be as a consequence of LOH. This moderate level of loss in the tumour samples was probably not an underestimation as a result of excessive stromal contamination because high rates (68-77%) have been detected in the same samples on chromosomes 17 and 18. In contrast to a previous report, LOH in carcinomas at 11q22-23 occurred at a lower frequency and was not associated with Dukes' stage, degree of differentiation, mucin production or the location of the cancer. However, a significant association was found between LOH on chromosome 11 and chromosome 14. Thus, inactivation of any putative tumour-suppressor gene at 11q22-23 by LOH is not a very common event in the development of colorectal tumours, but may be biologically significant if accompanied by chromosome 14 deletions.

Adenoma↗
PubMed1994

Cerebral metastasis of an atrial myxoma mimicking an epithelioid hemangioendothelioma.

A 60-year-old woman presenting with a 15-month history of Jacksonian seizures was found on computed tomography (CT) scan to have an enhancing subcortical lesion high in the left anterior parietal lobe. The excised tumor had light microscopic features similar to those of an epithelioid hemangioendothelioma, and immunohistochemical stains confirmed its vascular nature. At surgery, the patient had no clinical or radiological (including CT body scan) evidence of any other lesion. However, 22 months after symptoms first appeared, she presented with dyspnea and bilateral pleural effusions, and a left atrial myxoma was detected echocardiographically. The histologic features of the resected myxoma were identical to those of the previously excised cerebral lesion, and it became apparent that the intracranial tumor was a metastasis of the atrial myxoma. This case illustrates that before a diagnosis of visceral epithelioid hemangioendothelioma is rendered, the possibility of metastatic occult cardiac myxoma should be considered. Echocardiography is warranted for such patients.

Brain Neoplasms↗
PubMed1994

Association of the SS genotype of the L-myc gene and loss of 18q sequences with a worse clinical prognosis in colorectal cancers.

L-myc is a nuclear oncogene which is sometimes activated late in tumourigenesis. Digestion of DNA with EcoRI reveals a simple restriction fragment length polymorphism (RFLP) located in the second intron of L-myc, with allele sizes 10 kb (L-allele) and 6.6 kb (S-allele). Some studies have suggested that the presence of the S-allele in the constitutional DNA of a patient with cancer is associated with a higher risk of metastasis in lung, breast and renal cell carcinomas. The aims of this study were to determine if the S-allele was significantly associated with metastasis and also with inactivation of tumour suppressor genes in colorectal cancer. One hundred and twenty-four Caucasian colorectal cancer patients were studied for L-myc genotype, and a subgroup of these (108) had their tumours examined for allele loss at multiple loci on nine chromosomal arms (1p, 1q, 5q, 8p, 14q, 17p, 17q, 18q, 22q) and for mutations in the 12th codon of K-ras. The percentage of individuals with the SS genotype was 19% (4/21) Dukes Stage A, 19% (10/54) Dukes B, 25% (8/32) Dukes C and 40% (8/20) Dukes D. The trend observed here is significant (P < 0.05, Wilcoxon Rank Sum Test). Also, the SS genotype was significantly more common in individuals whose tumours showed allelic loss on 18q (P < 0.01, Fishers Exact Test). This work suggests that the S-allele of L-myc, or a gene in linkage disequilibrium with it, may modify the development of colorectal cancer.

Adult↗
PubMed1993

Genomic instability occurs in colorectal carcinomas but not in adenomas.

Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary nonpolyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4-15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas.

Adenocarcinoma↗
PubMed1993

Exclusion of APC and MCC as the gene defect in one family with familial juvenile polyposis.

BACKGROUND: In familial juvenile polyposis, multiple juvenile polyps occur throughout the colon. The genetic defect has not been characterized. The risk of colon cancer is increased, although the magnitude of the increased risk is controversial. The hypothesis of this study was that the genetic defect is within a tumor suppressor gene, possibly one already known to be inactivated in colorectal neoplasia. METHODS: Linkage analysis using the short tandem repeat polymorphism D5S346 was performed to determine if juvenile polyposis was linked to either APC (adenomatous polyposis coli) or MCC (mutated in colorectal carcinoma) genes within a single large family. RESULTS: A family in which eight subjects have been affected by juvenile polyposis over three generations is described. Six affected subjects had colectomies in childhood, but the two who have so far survived beyond 35 years of age have developed adenocarcinoma of the jejunum. Within this family, linkage analysis excluded linkage of the juvenile polyposis trait to either APC or MCC. CONCLUSIONS: In a family with juvenile polyposis with a clear predisposition to malignancy, including carcinoma of the jejunum, APC and MCC were not the defective genes causing the condition.

Adenomatous Polyposis Coli↗
PubMed1993

Preneoplastic significance of hepatic iron-free foci in genetic hemochromatosis: a study of 185 patients.

Sublobular nodules of hepatocytes free of iron or exhibiting much less iron than the surrounding parenchyma, referred to in this study as iron-free-foci, are frequently found in the livers of patients with genetic hemochromatosis complicated by hepatocellular carcinoma. To test the hypothesis that such nodules are preneoplastic lesions, iron-free foci were sought in the initial liver biopsy specimens of 185 patients with untreated and uncomplicated genetic hemochromatosis. Iron-free foci were found in 14 (7.6%) patients, all men, aged from 38 to 76 yr, with heavy iron overload and with fibrosis or cirrhosis. Twelve patients with iron-free foci were followed for 0.9 to 15 yr (7 +/- 6 yr). In six (50%), HCC developed, compared with 2 (8%) from a control group consisting of 24 patients without IFF matched according to age, sex, degree of fibrosis, liver iron amount and follow-up duration. The mean number of iron-free foci per iron-free foci-positive specimen was 3.2 +/- 2.1. Ten patients had dysplastic aspects in their iron-free foci, and four had intrahepatocytic iron-positive inclusions at the periphery of iron-free foci. Proliferative cell nuclear antigen was positive in 75% of iron-free foci and in 24% +/- 21% of hepatocyte nuclei in iron-free foci. This study clearly demonstrates that iron-free foci are proliferative lesions and strongly suggests that such nodules are preneoplastic foci. Therefore the finding of IFF in the initial liver biopsy specimen from a patient with genetic hemochromatosis should lead to regular screening for hepatocellular carcinoma.

Adult↗
PubMed1993

Frequent loss of heterozygosity on chromosome 14 occurs in advanced colorectal carcinomas.

The current model for colorectal tumorigenesis defines four specific mutations (activation of a ras proto-oncogene and inactivation of the APC, p53 and DCC tumor-suppressor genes) that accumulate in a colonic epithelial cell as it progresses towards a carcinoma. However, further mutations must be needed for progression to malignancy because advanced adenomas have been observed with all four of these mutations. Loss of heterozygosity (LOH) for 11 loci spanning the distal portion of the long arm of chromosome 14 was studied in 89 sporadic colorectal adenocarcinomas and 25 adenomas. The overall rate of LOH in carcinomas was 53% (46/86 informative carcinomas). The smallest region of overlap (SRO) of deletions includes the markers D14S19 to D14S20. No LOH was seen in the 18 informative adenomas examined. There was a significant trend towards higher levels of LOH within the SRO in advanced Dukes' stages (P = 0.016). Since frequent loss of heterozygosity in a specific region of a chromosome may reflect the inactivation of a tumor-suppressor gene located there, these data suggest that a gene involved in the progression of colonic neoplasia may reside on the distal portion of the long arm of chromosome 14, and that its inactivation may be a critical event in this process.

Adenocarcinoma↗
PubMed1992

Loss of heterozygosity at the human RAP1A/Krev-1 locus is a rare event in colorectal tumors.

Kirsten-ras-revertant-1 (Krev-1/Rap1A) is a recently identified tumor suppressor gene which induces flat revertants when introduced into a variety of ras-transformed cell lines in vitro. Since 47% of colorectal carcinomas have transforming mutations in ras protooncogenes, and since Krev-1 is expressed at high levels in normal colonic mucosa, we hypothesized that inactivation at the Krev-1 locus may be necessary for transformation of colonic cells. Loss of heterozygosity is a common method of inactivation of tumor suppressor genes in colorectal tumors. Therefore, we analyzed loss of heterozygosity in 52 patients with sporadic colorectal cancer. Because Krev-1 had no previously described polymorphisms, we first identified a BclI restriction fragment length polymorphism which showed 40% heterozygosity in 50 unrelated individuals. However, only one tumor from 18 informative patients showed allelic loss at the Krev-1 locus. This suggests that loss of heterozygosity is not a common mechanism of inactivation at the Krev-1 locus in colorectal cancer. However, the results do not exclude a role for Krev-1 in the etiology of this neoplasm because inactivation may occur by other mechanisms.

Alkaline Phosphatase↗
PubMed1991

Multiple paternity in wild common shrews (Sorex araneus) is confirmed by DNA-fingerprinting.

We have tested for the occurrence of multiple paternity in wild common shrews by karyotypic analysis and DNA-fingerprinting of five wild-caught females and their litters. Karyotypic data suggest that some litters were sired by more than one male, but provide no definitive evidence. By using DNA-fingerprinting, it was possible to establish that two males sired the litter of two females. The present report shows that multiple paternity is not a rare phenomenon in the common shrew and by using DNA-fingerprinting it is possible to assign individual offspring to different male parents even when none of the putative fathers are available for inspection.

Animals↗