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Biomedical subjects

M McMenamin

Publications and source records attributed to M McMenamin.

At least 19 recordsLinked to original sources
PubMed1999

Absence of Epstein-Barr virus encoded RNA and latent membrane protein (LMP1) in salivary gland neoplasms.

A series of 55 (42 benign and 13 malignant) salivary gland tumours were investigated by immunohistochemistry, to detect Epstein-Barr virus (EBV) latent membrane protein (LMP1) and by in situ hybridization for EBV-encoded RNA. Non-neoplastic gland from all the patients with tumours and 15 control glands were also examined. All cases, both neoplastic and non-neoplastic were negative for LMP1 and failed to show any positive signal by in situ hybridization for EBV RNA. One undifferentiated carcinoma from a European patient was included in the group. These results confirm previous reports of an ethnic association between EBV and undifferentiated carcinomas of the salivary gland. They do not support an aetiological role for EBV in other salivary gland tumours.

Adenoma↗
PubMed1997

Cavernous hemangioma in the submandibular gland masquerading as sialadenitis: case report.

This report describes a case of cavernous hemangioma in the submandibular gland of a 37-year-old Irish woman. The lesion clinically and radiologically (as shown both by plain radiographs and computed tomography imaging) resembled salivary calculous disease. Numerous phleboliths were present in the hemangioma. The rarity of a cavernous hemangioma in such a location and its simulation of salivary calculous disease stimulated us to report the case.

Adult↗
PubMed1995

Phospholipase A2 is activated by tumor necrosis factor-alpha in primary hepatocytes stimulated by a deleted form of hepatocyte growth factor.

Several factors are released in the liver microenvironment immediately after injury. Among these factors TNF alpha is implicated as a regulator of hepatocyte proliferation. Hepatocytes in the intact liver are mostly in the G0 phase of the cell cycle and after injury (including collagenase perfusion) display a constitutive expression of the growth-regulated c-myc oncogene. TNF alpha co-added with dHGF in hepatocyte cultures, superinduced the DNA synthetic response observed at all time points. In parallel, TNF alpha/dHGF-treated hepatocytes have shown increased expression of the c-myc oncogene at times corresponding to the in vitro G1 phase of the cell cycle. TNF alpha activated PLA2 in hepatocytes and it is believed that the subsequent production of PGE2 plays a role in the "priming" process in these cells and at the same time amplifies the proliferating signals induced by hepatocyte-specific growth factors.

Animals↗
PubMed1992

Transforming growth factor-alpha-induced DNA synthesis and c-myc expression in primary rat hepatocyte cultures is modulated by indomethacin.

Primary hepatocytes stimulated with epidermal growth factor (EGF) secrete prostaglandins into the culture medium as soon as 1 h after the addition of the EGF. Transforming growth factor-alpha (TGF alpha), a potent hepatocyte mitogen, shares the same receptor with EGF, and its expression is increased after partial hepatectomy. TGF alpha is also secreted in culture. We have observed that TGF alpha induced hepatocyte DNA synthesis (30 h after addition) and at the same time stimulated the production of prostaglandins E2 and F2 alpha by the cultured hepatocytes. Indomethacin at 20-100 microM inhibited the TGF alpha-induced hepatocyte DNA synthesis, and this effect was specifically due to the inhibition of prostaglandin formation. Indomethacin also inhibited a TGF-alpha-induced increase in hepatocyte c-myc expression, indicating that prostaglandins mediate this increase, as previously shown for EGF. TGF alpha increased the expression of the EGF receptor gene, and this was prevented by the presence of an antibody against TGF alpha in the culture medium. We therefore suggest that TGF alpha induces hepatocyte proliferation either through coupling with its receptor (i.e. the EGF receptor) or by subsequent phosphorylation of lipocortin I. This leads to activation of phospholipase. A2, which seems to regulate the metabolism of arachidonic acid and the formation of prostaglandins. Thus hepatocyte proliferation in vitro appears to be controlled by a self-regulatory autocrine pathway involving activation of phospholipase A2 and secretion of prostaglandins and TGF alpha.

Animals↗
PubMed1991

[Plasmid analysis of antibiotic resistant Shigella isolates].

A correlation between the multiple drug resistance patterns and the plasmid profiles given by 70 clinical isolates of Shigella sonnei and Shigella flexneri was investigated in this study. The most common plasmids were purified from different isolates by electroelution and characterized via restriction endonuclease digestions.

Anti-Bacterial Agents↗
PubMed1991

Role of oncogenes and tumour suppressor genes in human lung carcinogenesis.

Six families of activated protooncogenes, ras, raf, fur, neu, jun and myc have so far been associated with human lung cancer. Human bronchial epithelial cells in vitro are being used to investigate the functional role of these specific oncogenes and growth regulatory genes in carcinogenesis and tumour progression. When transferred into normal human bronchial epithelial cells by the highly efficient protoplast fusion method, the v-Ha-ras oncogene initiates a cascade of events leading to decreased responsiveness of these cells to inducers of squamous differentiation, aneuploidy and, less frequently, 'immortality' and tumorigenicity with metastasis in athymic nude mice. Transfection of the SV40 T antigen gene results in nontumorigenic cell lines that have a nearly normal pathway of terminal squamous differentiation and can be transformed into malignant cells by transfected Ha-ras, N-ras or Ki-ras. The combination of transfected c-myc and c-raf-1 also transforms human bronchial epithelial cells into neoplastic cells that exhibit some phenotypic traits found in small-cell carcinomas. These and other results indicate that proto-oncogenes dysregulate the pathways of growth and differentiation of human bronchial epithelial cells and play an important role in human carcinogenesis. Analyses of allelic deletion and somatic cell hybrids are being used to identify the chromosomal localization of tumour suppressor genes. We have examined 54 non-small-cell bronchogenic carcinomas with 13 polymorphic markers. Loss of heterozygosity was more frequent than among 23 squamous-cell carcinomas than among 23 adenocarcinomas or eight large-cell carcinomas. Loss of heterozygosity for chromosome 17p was found in 89% of cases of squamous-cell carcinoma and 18% of adenocarcinomas. Analysis of chromosome 11 for allelic deletions revealed two commonly deleted regions (11p13 and 11p15.5). Somatic cell hybrids between normal human bronchial epithelial cells and Hut292DM, a lung carcinoma cell line, had a finite lifespan in vitro and were nontumorigenic in athymic nude mice. Tumour suppressive effects of individual or combinations of specific human chromosomes on Hut292DM are being examined by formation of microcell-cell hybrids. Chromosome 11 has tumour suppressor activity in these hybrids. Both of these studies suggest that tumour suppressor genes play a dominant role in lung carcinogenesis and provide in-vitro model systems for isolating these genes by subtraction library and insertional mutagenesis techniques.

Bronchi↗
PubMed1988

A new experimental metastasis model in athymic nude mice, the human malignant melanoma LOX.

The human tumor line LOX was established as an s.c. xenograft in nude mice from a lymph-node metastasis of a patient with malignant melanoma. I.v. injection into adult nude mice of single-cell suspensions prepared from xenografts resulted in progressively growing lung tumor colonies that killed the animals. No difference in colony formation was seen between cells taken from lung colonies and s.c. xenografts. An in vitro cell line, LOX-L, was established from lung colonies, and the monolayer cells, detached with EDTA, retained the same ability to form experimental lung metastases. In a total of 14 experiments, 82 of 89 mice receiving 1 X 10(6) viable tumor cells died with a mean survival time of 34.1 +/- 4.8 days. Long-term passaging in vivo and in vitro did not result in any alteration of the lung-colonizing potential of the LOX cells, whereas trypsinization of the cells before i.v. injection reduced lung colony formation. The life span was inversely related to the number of LOX cells injected, permitting estimation of the cell kill caused by chemotherapy. Mice injected i.v. with the LOX cells showed the same relative response to cis-diamminedichloroplatinum (CDDP) and mitozolomide (MZA) as did animals carrying s.c. xenografts. The LOX cells have shown a remarkable stability and similarity to the cells of the patient's tumor with respect to morphology, karyotype and chemosensitivity. The LOX model may be useful for testing effects of therapy on lung micro- and macrometastases, and the activity of antimetastatic agents, as well as for studying mechanisms involved in the metastatic process.

Animals↗
PubMed1988

Human bronchial epithelial cells with integrated SV40 virus T antigen genes retain the ability to undergo squamous differentiation.

Human bronchial epithelial cells transformed by either DNA virus infection (SV40 or Adenovirus 12-SV40 hybrid virus) or transfection with the SV40 large T antigen gene were studied for their ability to undergo squamous differentiation when exposed to 12-O-tetradecanoylphorbol-13 acetate (TPA), transforming growth factor-beta 1 (TGF-beta 1), or fetal bovine serum (FBS), agents that induce the squamous differentiation of normal human bronchial epithelial cells. Squamous differentiation occurred in all ten T-antigen-positive cell cultures when they were exposed to either FBS or TGF-beta 1, but none differentiated when exposed to TPA. From one cell line, designated BEAS-2B, two subclones were isolated, one of which was induced to undergo squamous differentiation by FBS, and a second that failed to undergo squamous differentiation and was mitogenically stimulated when exposed to serum. These phenotypically different subclones provide a new in vitro cellular system for delineating the mechanism(s) of human bronchial epithelial cell squamous differentiation in response to FBS or TGF-beta 1.

Antigens, Viral↗
PubMed1988

Uncontrolled nuclear division in normal x transformed somatic cell hybrids.

Uncontrolled nuclear division (UND), as indicated by progressive multinucleation when cell division is inhibited by cytochalasin B, is a very characteristic property of transformed cells growing in vitro. In an attempt to determine the genetic basis for this transformation phenotype we have produced a series of somatic cell hybrids between different transformed and normal cells. In all hybrids there was suppression of UND but in some this was only transient. In hybrids between transformed human cells and mouse 3T3 cells, UND was only re-expressed when the human parental cell line had been transformed by SV40 virus. The results lend tentative support to the suggestion that cellular mechanisms involved in the induction and suppression of UND may not be the same in all cell lines.

Animals↗
PubMed1985

Effect of cytochalasin B on somatic cell hybrids between normal and transformed cells.

Cytochalasin B (CB) prevents cytokinesis in animal cells. In normal cells nuclear division and DNA synthesis are also blocked and the cells, held in the G1 phase of the cell cycle, remain either mononucleate or binucleate. In transformed cell lines DNA synthesis and nuclear division continue and the cells become multinucleate. We have examined the response to CB in two sets of somatic cell hybrids made between cells that display multinucleation after CB treatment and cells that do not. In a cross between transformed mouse LMTK cells and normal rat embryo lung cells, very little multinucleation was observed after treatment with CB for 7 days. The ability of the LMTK cells to form clones in soft agar was also significantly reduced in these hybrids. Segregant sub-clones that re-expressed both of these transformation phenotypes were isolated. These had reduced chromosome numbers. A second cross was made between two variants of the BHK cell line, one of which displayed a high level of multinucleation in CB while the other did not. Again the hybrids showed a response similar to that of the non-multinucleating parent. From the results obtained with these two hybrids we conclude that the multinucleation induced in transformed cells by CB behaves as a recessive character in crosses with normal cells.

Animals↗
PubMed1984

Synthesis of alpha (immediate-early) proteins in Vero cells infected with pseudorabies virus.

The synthesis of alpha (immediate-early) polypeptides in Vero cells infected with pseudorabies virus was studied. Cycloheximide was added at the beginning of infection and removed several hours later. The accumulated alpha mRNA was translated either in vivo in the presence of actinomycin D to prevent further mRNA synthesis, or in vitro. In intact cells three electrophoretically distinct virus-specific proteins were synthesized, with apparent molecular weights of approximately 180 000 (A), 190 000 (B) and 200 000 (C). The accumulation of B and C was prevented by the proline analogue azetidine. Only protein A was detected in vitro. Proteins B and C were not detected in normally infected cells. All three were associated with the nuclear fraction of cell homogenates and A and B were phosphorylated. The radioactivity of B and C declined during a chase period while that of A increased. This change was prevented by adding cycloheximide during the chase. The pattern of chymotrypsin digestion products suggested that A and B at least were similar proteins. It is presumed that protein A is the single immediate-early protein previously described and analogous to ICP 4 of herpes simplex virus. The significance and function, if any, of proteins B and C is not known but it is possible that they represent stages in the formation or transport of A within the cell and that the progression depends on an unstable protein which is depleted in cells treated with cycloheximide.

Animals↗