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M Talbot

Publications and source records attributed to M Talbot.

At least 55 records · Page 3Linked to original sources
PubMed1996

Thyroid pathologies in transgenic mice expressing a human activated Ras gene driven by a thyroglobulin promoter.

Four transgenic mice carrying the human activated c-Ha-Ras gene, the expression of which was driven into the thyroid gland by a bovine thyroglobulin promoter, have been produced. The M1 and M2 mice developed papillary thyroid carcinomas and the M2 mouse also developed a lung carcinoma, however none of them transmitted the transgene. Both the M3 and the M4 mice gave rise to transgenic lines. M3 progeny mice develop a goitre with morphological aspects of hyperplasia as well as a thymus hyperplasia. M4 developed a papillary thyroid carcinoma and a lung carcinoma. Lung tumors but not thyroid tumors were observed in M4 adult transgenic progeny. In this M4 line, thyroid dysgenesis leading to growth retardation and premature death was observed upon serial backcross that enhanced the DBA/2J genetic background. The development of thyroid tumors in M1, M2, M4 transgenic mice demonstrates the oncogenic potential of activated Ras gene in the thyroid gland. The M4 line raises interesting questions relative to the interference between the Ras-mediated signal transduction pathway and thyroid morphogenesis.

Animals↗
PubMed1995

Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma.

The risk of cancer of the cervix is linked with sexual behaviour. Although infectious agents such as human papillomaviruses (HPVs) are implicated, these alone may be insufficient to induce the disease. We have investigated the potential role of oxidation products of the polyamines spermine and spermidine and the diamine putrescine in seminal plasma (SP) as co-factors in the development of cervical cancer. These amines are oxidised by polyamine oxidase (PAO) and diamine oxidase (DAO) to generate oxygen radicals and hydrogen peroxide, reactive aldehydes and acrolein, which are likely to exert local mutagenic, cytotoxic and immunosuppressive effects in vivo. Using a chemiluminescence assay, we determined the levels of these amines in 187 samples of SP. Spermine plus spermidine, as substrates for PAO, were present in a range equivalent to 0-4.8 mg ml-1 spermine. Putrescine, as a substrate for DAO, was detectable in only 4 of 40 samples assayed (range 0-168 micrograms ml-1) and constitutes a minor component of the oxidisable content of SP. Cervical mucus (126 samples) was assayed for the presence of PAO and DAO. Both enzymes were present in 14.3% of the samples, PAO only in 21.4%, DAO only in 15.1% and neither enzyme in 49.2%. PAO levels ranged from 0 to 0.828 pmol peroxide generated min-1 mg-1 mucus and DAO levels ranged from 0 to 7.0 pmol peroxide generated min-1 mg-1 mucus. These results suggest that sexual activity in the absence of physical barrier contraception may lead to the generation of mutagenic and immunosuppressive polyamine oxidation products within the female genital tract. We thus propose that women with high levels of PAO and/or DAO in their cervical mucus may be at increased risk of cervical cancer, especially if the male partner's SP shows high polyamine levels. HPV infection may synergise with the effects of polyamine oxidation by suppressing apoptosis in keratinocytes carrying potentially oncogenic mutations, leading to the survival and proliferation of transformed cells in the cervix.

Adolescent↗
PubMed1994

Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice.

Transgenic mice have been used to address the issue of the oncogenic potential of mutant guanine nucleotide stimulatory factor (Gs) alpha subunit in the thyroid gland. The expression of the mutant Arg-201-->His Gs alpha subunit transgene has been directed to murine thyroid epithelial cells by bovine thyroglobulin promoter. The transgenic animals develop hyperfunctioning thyroid adenomas with increased intracellular cAMP levels and high uptake of [125I]iodine and produced elevated levels of circulating triiodothyronine and thyroxine. These animals demonstrate that the mutant form of Gs alpha subunit carries an oncogenic activity, thus supporting the model that deregulation of cAMP level alters growth control in thyroid epithelium. These animals represent models for humans with autonomously functioning thyroid nodules.

Animals↗
PubMed1994

Correlation between p53 gene expression and tumor-cell proliferation in oropharyngeal cancer.

The aim of our study was to analyze the correlation between tumor-cell kinetics measured in vivo and p53 gene expression in a series of 49 oropharyngeal cancers. The duration of the S phase (TS), the labelling index (LI) and the potential doubling time (Tpot) were obtained by flow-cytometry measurements of a tumor biopsy obtained after i.v. injection of 200 mg bromodeoxyuridine into patients. An adjacent section of the same samples was studied by immunohistochemistry for the detection of p53 protein. Over-expression of the p53 protein, as defined by strong p53 immunostaining of tumor nuclei, was found in 23/49 of the samples. Aneuploid tumors showed a higher LI, a shorter Tpot and a higher proportion of p53 gene over-expression. A significant correlation was seen between p53 over-expression and short Tpots. Indeed 87.5% of the tumors with a very short Tpot (< or = 3 days) had p53 over-expression, as compared with 27% of tumors with a longer Tpot (> 3 days). Our data strongly suggest that over-expression of the p53 gene is associated with rapid tumor-cell proliferation in this type of cancer.

Aged↗
PubMed1993

Immunohistochemical study of adrenocortical carcinoma. Predictive value of the D11 monoclonal antibody.

BACKGROUND: The diagnosis of adrenocortical carcinoma (ACC) may be difficult with conventional light microscopy, especially when the tumor is nonfunctioning. Until now, no specific adrenocortical tumor marker was available. The current study was undertaken to investigate the interest of the D11 MoAb for the diagnosis and prognosis of ACC. METHODS: Eighteen adrenocortical carcinomas, 10 primary adrenomedullary tumors, 20 primary hepatocellular carcinomas, 50 primary renal cell carcinomas, 5 primary lung carcinomas, and 18 intraadrenal metastases were analyzed immunohistochemically with the D11 monoclonal antibody. ACC were also evaluated for the expression of other tumor markers, including neuron-specific enolase, chromogranin A, S-100, Leu-7, vimentin, KL1, AE1AE3, and epithelial membrane antigen. Relationships between clinical features and results of immunohistochemistry were also sought. RESULTS: Nuclear D11 staining appears to be highly specific for normal adrenocortical cells and related tumors. Nuclear D11 positivity was demonstrated in 44% of ACC and was restricted to well-differentiated tumors. No cytoplasmic or nuclear D11 staining was observed in adrenomedullary tumors. D11 reactivity confined to the cytoplasm was found in 5 of 18 adrenal metastases, in all 20 hepatocellular carcinomas tested, in 3 of 5 lung carcinomas, and in 1 of 50 primary renal cell carcinomas. Patients with nuclear D11 immunostaining were initially seen with metastases less often and survived longer than those with no nuclear D11 immunostaining (P < 0.05). CONCLUSIONS: Nuclear D11 immunoreactivity may help to differentiate ACC from intraadrenal metastases and adrenomedullary tumors. This also selects a group of ACC patients with a more favorable outcome.

Adolescent↗
PubMed1993

The role of sulfhydryl groups and calcium in the mercuric chloride-induced inhibition of glutamate uptake in rat primary astrocyte cultures.

Inhibition by mercuric chloride (MC) of the astrocytic uptake of the excitotoxic neurotransmitter L-glutamate (L-GLU) has been postulated to contribute to MC neurotoxicity. In the present study, we analyzed the ability of two sulfhydryl (SH)-protecting agents: a cell membrane non-penetrating compound-reduced glutathione (GSH), and the membrane permeable dithiothreitol (DTT), to reverse the inhibitory action of MC on the initial rate of uptake of radiolabelled GLU (100 microM) in primary cultures of rat astrocytes. MC at 5 microM concentration reduced the uptake to 46% of control when present in the incubation medium during the 5 min of actual uptake, and to 27% of control when astrocytes were preincubated for 30 min in HEPES buffer containing MC prior to GLU uptake measurements. GLU uptake inhibition caused by 30 min preincubation with MC was partly relieved by the addition of 1 mM DTT during the actual 5 min uptake period. However, this inhibition could not be reversed by 1 mM GSH. Accordingly, it is postulated that the inhibitory effect exerted by MC on GLU uptake is associated with vulnerable SH groups located within, but not on the surface of the cell membrane. Neither 5 microM N-ethylmaleimide (NEM) nor 5 microM or 25 microM iodoacetate (IA) affected GLU uptake, indicating steric hindrance of the access of these two sulfhydryl reagents to the SH groups critical for the uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Identification of a subset of normal B cells with a Burkitt's lymphoma (BL)-like phenotype.

Fresh biopsy cells from cases of Burkitt's lymphoma (BL) display a homogeneous cell surface phenotype. The cells were found to be reactive with the pan B cell marker B1, and consistently co-expressed the BL-associated glycolipid antigen, BLA, and the common acute lymphoblastic leukemia antigen, CALLA, but lacked the B cell "activation" antigens characteristically expressed on EB virus-transformed normal B cells. Microscopic and cell sorter analysis of cells isolated from a series of fresh normal tonsils have identified a subpopulation of normal B cells carrying the same cell surface markers. That BLA and CALLA could be co-expressed on individual B cells was demonstrated by two-color immunofluorescence (IF) of tonsils in suspension, and immunoperoxidase (IP) staining of serial tonsil sections. These BLA+, CALLA+, "activation" antigen- cells were further characterized as B1+, sIgM+, sIgD-, C3d/EB virus receptor+ and were susceptible to virus-induced transformation in vitro. IF studies on Percoll-fractionated tonsillar cell populations and direct examination of IP-stained tonsil semi-thin sections indicated that the BLA+, CALLA+ cells were localized in germinal centers. Their morphological characteristics matched those of BL cells, and their location within germinal centers was consistent both with the known phenotype of germinal center tonsillar B cells and with the description of BL as a proliferation of centroblasts. We suggest that this population of tonsillar germinal center B cells provides the normal counterpart of BL tumor cells.

Antibodies, Monoclonal↗
PubMed1987

Acid secretory capacity and plasma gastrin concentration after administration of omeprazole to normal subjects.

In a randomized double-blind study, two groups of eight healthy volunteers received either placebo or omeprazole 40 mg o.m. for 14 days. Fasting plasma gastrin concentration and peak acid output in response to a maximal intravenous dose of pentagastrin were measured before, during and after the 14 days of treatment. Omeprazole caused a 68% (mean) decrease in the peak acid output when measured 24 hours after the last dose, with a simultaneous increase in the fasting plasma gastrin concentration. When measured 1, 2, 3 and 8 weeks after cessation of treatment, there was no significant difference in the peak acid output between the two groups. The study demonstrates that there is no increase in the acid production capacity after 2 weeks of treatment with omeprazole. Thus it would appear that the rise in the plasma gastrin concentration during short-term treatment with omeprazole does not induce parietal cell hypertrophy or hyperplasia.

Adult↗
PubMed1984

[Value of immunohistochemistry in the study of medullary cancer of the thyroid. Implications of the results for the concept of the APUD system and of apudomas].

Immunohistochemical studies in medullary thyroid carcinoma demonstrate the presence of C cells secreting calcitonin but also of other cells secreting other peptides or proteins. These different cells exist in the tumor as well as in metastases. These results and other reported in the literature suggest a common ultimobranchial and endodermal origin for these cells.

APUD Cells↗
PubMed1984

[Immunohistochemical and ultrastructural studies of thyroid cancer].

The results of immunohistochemical and ultrastructural studies have improved our understanding and provide a better method of classifying thyroid carcinoma. These techniques have also enabled identification of tumours with composite cell populations. These tumours pose clinical, diagnostic and therapeutic problems, and pose fundamental questions such as the relationship between vesicular and C cells. In addition, these techniques are the only available method of determining in situ within the tumour tissue the exact location of different antigens. This information may contribute to the study of the function of the molecules in question and of their accessibility to antibodies in vitro or in vivo.

Fluorescent Antibody Technique↗
PubMed1983

[Collagen gel culture of human thyroid cancers].

When seeded on collagen gel surface, human thyroid cells from normal tissue or carcinoma form a monolayer. When the isolated cells are embedded inside the collagen gel, they reorganize into three-dimensional structures. The cells isolated from normal tissue, adenoma, or well-differentiated follicular carcinoma show the typical arrangement of follicular thyroid cells: the apical poles, characterized by microvilli, are oriented towards the follicular lumen; intercellular junctions are present. In contrast, in the papillary and moderately-differentiated follicular carcinomas, the cells are hardly ever associated, and ultrastructural nuclear anomalies are often observed.

Adenoma↗