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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 343 records · Page 19Linked to original sources
PubMed1991

Multiple recurrent giant cell lesions associated with high circulating levels of parathyroid hormone-related peptide in a young adult.

Parathyroid hormone-related peptide (PTHrP, PLP) has previously been identified and assays are now available which can be used in clinical situations. A case is reported of a normocalcaemic young adult female in whom multifocal recurrent giant cell osteolytic lesions in the maxilla and elsewhere were associated with a raised plasma level of parathyroid hormone-related peptide. The lesions were histologically identical to reparative giant cell granuloma of the jaws and to osteitis fibrosa cystica associated with hyperparathyroidism.

Adult↗
PubMed1991

Retroconversion of immature teratoma of the ovary: CT appearances.

We have studied seven patients presenting to the Royal Marsden Hospital between 1983 and 1989 with metastatic immature teratoma of the ovary. All patients underwent initial surgery followed by combination chemotherapy and a second laparotomy. Serial CT scans were performed at 2-3 monthly intervals from diagnosis until the second laparotomy, and the results of this were correlated with the CT appearances. In six of the seven patients CT scanning demonstrated 'retroconversion' of immature malignant tumour masses to benign mature disease during treatment. CT features of maturation included increased density of mass lesions, whose margins became better circumscribed in relation to adjacent tissues, and the onset of internal calcification, with fatty areas and cystic change. These changes on CT correlated exactly with normalization of an initially raised serum tumour marker, alpha feto-protein (AFP) in all six patients. The second laparotomy revealed only mature teratoma in all patients following chemotherapy. In three patients show continued growth of the mature deposits necessitated further surgery for local pressure symptoms, but overall, none has shown malignant relapse, and all are currently well between 1 and 6 years after diagnosis. This is the first report of the CT appearances of retroconversion of immature ovarian teratoma in a series of patients, which is an important radiological diagnosis to make in order to avoid confusion with advancing malignancy. A review of the literature is presented.

Adolescent↗
PubMed1991

Expression of members of the myf gene family in human rhabdomyosarcomas.

Northern analysis of tumour RNA has been used to examine the expression of members of the myf family of muscle determining genes (myf3, myf4, myf5 and myf6) in a series of 20 rhabdomyosarcomas. A 2.0 kb myf3 transcript was observed in 85% of tumours, a 1.8 kb myf4 transcript was detected in 70% of tumours and a 1.7 kb myf5 transcript was observed in 55% of tumours. Transcription of myf6 occurred in 28% of tumours, but there were several transcript sizes (1.2, 1.5, 2.0 and 3.5 kb) and in some individual tumours two or more transcripts were observed. Only two rhabdomyosarcomas, one classified as embryonal and one as pleomorphic, failed to exhibit transcription of members of the myf gene family. We were unable to detect transcription of myf genes in neuroblastomas, Wilms' tumours, hepatoblastomas, paediatric non-Hodgkin's lymphoma and leiomyosarcomas. When considered together these observations suggest that expression of myf genes could provide an extremely useful marker in the diagnosis of rhabdomyosarcoma.

Adolescent↗
PubMed1991

Heteroduplex DNA formation is associated with replication and recombination in poxvirus-infected cells.

Poxviruses are large DNA viruses that replicate in the cytoplasm of infected cells and recombine at high frequencies. Calcium phosphate precipitates were used to cotransfect Shope fibroma virus-infected cells with different DNA substrates and the recombinant products assayed by genetic and biochemical methods. We have shown previously that bacteriophage lambda DNAs can be used as substrates in these experiments and recombinants assayed on Escherichia coli following DNA recovery and in vitro packaging. Using this assay it was observed that 2-3% of the phage recovered from crosses between point mutants retained heteroduplex at at least one of the mutant sites. The reliability of this genetic analysis was confirmed using DNA substrates that permitted the direct detection of heteroduplex molecules by denaturant gel electrophoresis and Southern blotting. It was further noted that heteroduplex formation coincided with the onset of both replication and recombination suggesting that poxviruses, like certain bacteriophage, make no clear biochemical distinction between these three processes. The fraction of heteroduplex molecules peaked about 12-hr postinfection then declined later in the infection. This decline was probably due to DNA replication rather than mismatch repair because, while high levels of induced DNA polymerase persisted beyond the time of maximal heteroduplex recovery, we were unable to detect any type of mismatch repair activity in cytoplasmic extracts. These results suggest that, although heteroduplex molecules are formed during the progress of poxviral infection, gene conversion through mismatch repair probably does not produce most of the recombinants. The significance of these observations are discussed considering some of the unique properties of poxviral biology.

Bacteriophage lambda↗
PubMed1991

The relationship between plasma psoralen concentration and psoralen-UVA erythema.

The plasma 8-methoxypsoralen (8-MOP) concentration was measured in 60 patients commencing psoralen photochemotherapy (PUVA). At the time of blood sampling each patient was phototested using a series of 10 exposures to UVA. The resulting erythema was measured objectively 72 h after irradiation and dose-response curves for psoralen-UVA erythema were constructed. Although the dose of 8-MOP was calculated according to body weight, patients receiving 30 mg of 8-MOP had a significantly lower mean plasma concentration than those receiving higher doses. There was no significant correlation between plasma 8-MOP concentration and minimal phototoxic dose, either estimated visually or calculated from the dose-response curves. However the slope of the dose-response curve showed significant correlation with plasma 8-MOP concentration. The variation between patients in the rate of increase of the erythemal response, but not the variation in threshold sensitivity, can be explained by difference in plasma psoralen concentration.

Adolescent↗
PubMed1991

In-situ hybridization using digoxigenin-labelled probes in human skin.

This study demonstrated that in-situ hybridization using digoxigenin-labelled oligonucleotide poly-T probes and digoxigenin-labelled riboprobes for keratin 14 is possible on routinely fixed paraffin-embedded sections. The resolution and time course of the detection system compared favourably with isotopically labelled probes. Major differences were shown in keratinocyte messenger RNA content with differentiating cells expressing high levels when compared with the basal layers. Previous work on the distribution of keratin 14 messenger RNA was confirmed and we were able to show that using non-isotopic in-situ hybridization, sensitive and accurate cellular localization was feasible in skin sections.

Digoxigenin↗
PubMed1991

A comparative study of proliferation indices and ploidy in dysplastic naevi and malignant melanomas using flow cytometry.

Cell proliferation indices and DNA content have been determined in 18 intradermal naevi, 40 dysplastic naevi and 16 superficial malignant melanomas (less than 0.76 mm depth of invasion) using flow cytometry. In this study, proliferation indices of intradermal naevi and dysplastic naevi were not significantly different from each other. Abnormalities of DNA ploidy were not identified in the intradermal naevi or dysplastic naevi; whereas three of the malignant melanomas were aneuploid. In addition, cellular proliferation was increased within the group of malignant melanomas, in comparison with the naevi. This study has found no evidence to indicate that sporadic dysplastic naevi were more likely than intradermal naevi to transform to malignant melanoma, when objective criteria were employed. However, dysplastic naevi could be distinguished from some early malignant melanomas by absence of aneuploidy and by low cell proliferation indices.

Adolescent↗
PubMed1991

Modulation of immortalizing properties of human papillomavirus type 16 E7 by p53 expression.

The E7 protein is one of the principle transforming proteins encoded by human papillomavirus type 16 (HPV16), a virus strongly associated with the development of cervical carcinoma. In the present study we show that cotransfection of wild-type human or murine p53 sequences with E7 and ras markedly reduces transformation in baby rat kidney cells, although no effect of p53 is seen on the ability of E7 to transform an established mouse line to anchorage independence. In contrast, expression of mutant p53 strongly potentiates the transforming function of E7 and confers marked growth factor independence to cells cotransformed by E7 and ras. These data suggest that E7 and p53 function in separate yet complementary biochemical pathways.

Animals↗
PubMed1991

Patterns of epithelial expression of Fos protein suggest important role in the transition from viable to cornified cell during keratinization.

An antibody directed against the DNA-binding region of c-fos was used to localize the distribution of cells positive for Fos protein in epithelial tissues. The antibody consistently bound to the nuclei of epithelial cells in the late stages of differentiation, just prior to cornification. The epidermis, palate, buccal mucosa, gingiva, tongue, forestomach and vagina in estrus all produced this type of labelling, suggesting a burst of expression immediately before cell death and cornification. The differentiating cells of the hair follicle, including the hair and inner root sheath, were also labelled. Non-keratinized tissues including junctional epithelium, embryonic epidermis and diestrus vaginal epithelium showed little or no Fos labelling. With the onset of keratinization at 18 days gestation or with induction of estrus in ovariectomized mice with estradiol benzoate, the epidermis and vagina expressed Fos protein in the manner typical for keratinized tissues. The Er/Er mutant epidermis, a tissue that is blocked in its ability to keratinize, overexpresses Fos with Fos-positive cells appearing in virtually every cell layer. Gel shift analysis demonstrates the presence of a functional AP-1 complex in epidermal extracts that is recognized by our antibody. Our data suggest that the expression of Fos is intricately related to epithelial cell differentiation, specifically in relation to the process of cornification and cell death.

Animals↗
PubMed1991

Focal myositis, a benign inflammatory pseudotumour: CT appearances.

Focal myositis is a rare benign pseudotumour of skeletal muscle, of unknown cause. Clinically it presents as an enlarging mass within muscle, usually of an extremity, and is often mistaken for a soft tissue neoplasm. The diagnosis is made by biopsy which reveals characteristic histological changes of inflammation, focal degeneration and regeneration, and some evidence of denervation. The CT findings include irregularity and enlargement of the muscles involved, with diffuse, poorly defined fatty infiltration of the muscle planes, but no evidence of an associated mass. We present two cases of focal myositis of the calf, both of which mimicked a soft tissue neoplasm, and in which CT was helpful in determining the nature and extent of the abnormality, for needle biopsy, and follow-up.

Adult↗
PubMed1991

The role of bone scintigraphy in the evaluation of talar dome fractures.

We undertook a retrospective study of 122 patients with ankle pain to determine the accuracy of bone scintigraphy using 99mTc-methylene diphosphonate (MDP) for detection of osteochondral talar dome fractures (OCTDF). Plain radiographs, which were available in 97 patients, had not revealed any abnormality in the talar dome. Bone scintigraphy was followed by CT, which was considered to be the reference test in diagnosing OCTDF. Analysis of our data showed that when the bone scan findings in the two highest confidence categories (high and moderate probability) were accepted as abnormal, the sensitivity and the specificity of the test were 0.94 and 0.76, respectively. Although CT is mandatory to establish the stage of OCTDF, it cannot be used routinely due to its high cost. Bone scintigraphy appears to be a good screening procedure that will identify patients who are likely to benefit from further radiographic studies such as CT. These findings are subject to further confirmation in a prospective study.

Adolescent↗
PubMed1991

Detection of transforming genes by transfection of DNA from primary soft-tissue tumours.

A series of adult soft-tissue tumours were screened for the presence of activated oncogenes by transfecting tumour DNA into NIH3T3 mouse fibroblasts. In these studies an activated K-ras gene that contained a mutation at the second position of codon 12 (GGT----GAT) was found in a leiomyosarcoma. In addition, following transfection of DNA from a liposarcoma, we identified an activated gene that failed to hybridize to probes prepared from 10 known human oncogenes (K-ras, H-ras, N-ras, ret, met, trk, mas, dbl, raf and hst) that have previously been detected in DNA transfection experiments. BamHI-BamHI fragments of this activated gene of 3.5 and 8.5 kb were cloned from NIH3T3 secondary transfectants using a probe that detects the human alu family of highly repetitive DNA sequences. Repeat-free subclones of these BamHI fragments were used to map this gene to human chromosome 19 (p13.2-q13.3). Our studies also demonstrate that a subclone from one of the BamHI fragments detects a 3.0 kb transcript in primary and secondary transfectants.

3T3 Cells↗
PubMed1991

Treatment of metastatic para-aortic paraganglioma by surgery, radiotherapy and I-131 mIBG.

A patient with a malignant, functioning, aortico-sympathetic paraganglioma and a solitary bone metastasis causing paraplegia was treated by spinal decompression, irradiation of the metastasis, surgical excision of the primary tumour and systemic I-131 meta-iodobenzyl-guanidine (mIBG). Sixteen months after treatment there was no clinical, radiological or biochemical evidence of residual disease and neurological function was restored. The case supports the use of combined treatment incorporating mIBG in patients with metastatic neuroendocrine tumours which demonstrate mIBG uptake.

3-Iodobenzylguanidine↗
PubMed1990

Serial cytogenetic studies showing persistence of original clone in Hodgkin's disease.

A case of Hodgkin's disease is described in which cytogenetic studies were performed at intervals for 5 years. Clonally related chromosomally rearranged cells persisted during that time, with emergence of more complex karyotypes in the terminal phase of the disease. The chromosome findings are discussed in relation to the limited data available on banded karyotypes in Hodgkin's disease.

Bone Marrow Cells↗
PubMed1990

The influence of local recurrence of extremity soft tissue sarcoma on metastasis and survival.

One hundred seventy-five consecutive patients with soft tissue sarcoma of the limb and limb girdle were studied using univariate and multivariate analysis. The most important factor determining risk of local recurrence was the quality of treatment of the primary tumor, with wide or radical surgery plus radical radiotherapy obtaining the best local control. Tumor size, site, and histologic grade were not predictive of local recurrence. The important tumor variables predicting survival were tumor size at first presentation and histologic grade. Tumors with greater than 10 cm greatest diameter and high-grade tumors carried a poor prognosis. Local recurrence was significantly associated with reduced survival, but only when (correctly) considered as a time-dependent variable in multivariate analysis. Irradiation was also significantly associated with poor survival. Review of the literature indicates that local recurrence is believed to have little influence on survival. Since the relevant randomized controlled trials have been small, the evidence is inconclusive.

Adolescent↗