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T Shepherd

Publications and source records attributed to T Shepherd.

7 recordsLinked to original sources
PubMed2001

Role of Ets transcription factors in mammary gland development and oncogenesis.

PEA3 is the founding member of a subfamily of closely related ets genes that includes ER81 and ERM. PEA3 is expressed in the epithelial cells of mammary buds at the time that these first appear during mouse embryogenesis, and it is differentially expressed during postnatal mammary gland development. PEA3 expression is highest at the onset of puberty and during early pregnancy, times of extensive epithelial outgrowth and branching. PEA3 is expressed in undifferentiated epithelial cap cells of terminal end buds, and in differentiated myoepithelial cells of ducts and alveoli. Loss-of-function mutations in the PEA3 gene compromise mammary ductal branching at the onset of puberty and early during pregnancy. PEA3 is overexpressed in the vast majority of human breast tumors and in nearly all of the HER2-positive subclass of such tumors. PEA3 is similarly overexpressed in transgenic mouse models of this malignancy. Expression of dominant-negative PEA3 in the mouse mammary gland of MMTV-HER2 transgenic mice dramatically delays the onset and reduces the incidence of mammary tumors. Hence PEA3 and/or its close relatives play key regulatory roles in both mammary gland development and oncogenesis.

Animals↗
PubMed2000

Alterations in exon 4 of the p53 gene in gastric carcinoma.

BACKGROUND & AIMS: Our long-term goal was to evaluate the role of p53 in the prognosis of gastric cancer. We previously showed a discrepancy between p53 expression and the presence of mutations when only exons 5-9 were examined. We then evaluated exon 4. METHODS: DNA was sequenced from 217 gastric cancers to detect exon 4 alterations. Codon 72 was examined by restriction enzyme digestion. RESULTS: Mutations were present in 3.2% of tumors. In addition, 2 polymorphic sites were found at codons 36 and 72. Polymorphisms at codon 36 were only found in 2 patients. In contrast, the codon 72 polymorphism was very frequent. The genotype frequency was arg/arg (54%), arg/pro (33%), and pro/pro (14%). The genotype of the polymorphic site varied with race (P = 0.001): 64% of whites had the arg/arg genotype, compared with 24% of blacks. The difference in genotype by site, sex, or histological tumor type was not statistically significant (P = 0.067). CONCLUSIONS: There are several exon 4 alterations in gastric cancers. These include the rare mutations and the very rare codon 36 polymorphism. The most common change is the codon 72 polymorphism, the genotype of which differs significantly with race. The more common arg/arg genotype in whites may explain why whites are more prone to develop cardiac cancer, whereas the more common proline allele in blacks may explain why they are more prone to develop antral cancers. Further studies are required to determine whether the codon 72 polymorphism affects patient predisposition to gastric cancer.

Adenocarcinoma, Mucinous↗
PubMed2000

A comparison of the composition of epicuticular wax from red raspberry (Rubus idaeus L.) and hawthorn (Crataegus monogyna Jacq.) flowers.

Epicuticular waxes have been characterised from the flowers of raspberry and hawthorn, on both of which adult raspberry beetles (Byturus tomentosus) can feed. The flower wax from both species had similar alkane profiles and also contained long-chain alcohols, aldehydes and fatty acids. The range of the carbon numbers detected for these classes of compounds was broadly similar in both but the relative amounts of each differed between species. Raspberry flower wax also contained fatty acid methyl esters, a group of compounds that has rarely been detected in plant epicuticular waxes, however, these were not observed in hawthorn flower wax. Long-chain alcohol-fatty acid esters with carbon numbers ranging from C36 to C48 were also detected in both plant species. However, an examination of their constituent acids indicated that in hawthorn the esters based on the C16 fatty acid predominated, whilst in raspberry flower wax, esters based on the C20 fatty acid were most abundant. Both species also contained pentacyclic triterpenoids, which accounted for, on average, over 16 and 48% of the total wax extracted from raspberry and hawthorn flowers respectively. In the former, ursolic and oleanolic acids accounted for over 90% of the pentacyclic triterpenes, whilst hawthorn flower wax, in addition to containing these acids, also contained high relative concentrations of both free and esterified alpha- and beta-amyrins.

Alcohols↗
PubMed1998

SV40 Tag transformation of the normal invasive trophoblast results in a premalignant phenotype. I. Mechanisms responsible for hyperinvasiveness and resistance to anti-invasive action of TGFbeta.

Invasion of the uterus by first trimester human placental extravillous trophoblast (EVT) cells depends on mechanisms shared by malignant cells. However, unlike tumor invasion, trophoblast invasion of the uterus is stringently controlled in situ by local molecules such as transforming growth factor (TGF)beta. Since EVT cells possess active invasion-associated genes but are nontumorigenic, our objective was to induce premalignant and then malignant phenotype into a normal EVT cell line in order to identify the molecular basis of tumor progression. Simian virus 40 large T antigen (SV40 Tag) was introduced into a normal human first trimester invasive EVT cell line, HTR8, established in our laboratory. Since the HTR8 line has a limited in vitro lifespan of 12-15 passages, SV40 Tag-transformed cells were selected on the basis of extended lifespan. A long-lived line, RSVT-2, was produced and an immortalized subclone, RSVT2/C, was further derived under a forced crisis regimen. We examined transformation-induced alterations in proliferative and invasive abilities, responses to the invasion and proliferation-regulating growth factor TGFbeta and changes in gene expression for invasion-associated enzymes or enzyme inhibitors. RSVT-2 and RSVT2/C cell lines were hyperproliferative and hyperinvasive when compared with the parental HTR8 cell line. They were also variably resistant to the anti-proliferative and anti-invasive signals from TGFbeta. Since both cell lines remained non-tumorigenic in nude mice, these properties indicate that they attained a premalignant phenotype. Both cell lines showed reduced expression of tissue inhibitor of metalloproteases (TIMP)-1, while TIMP-2 and plasminogen activator inhibitor (PAI)-I expression was was also reduced in RSVT2/C cells, thus contributing to their hyperinvasiveness. Their resistance to the anti-invasive action of TGFbeta was explained by the failure of TGFbeta to upregulate TIMPs and PAI-I, in contrast to the TGFbeta-induced upregulation noted in parental HTR8 cells.

Animals↗
PubMed1993

Acute purulent pericarditis in children caused by haemophilus influenzae.

Acute purulent pericarditis caused by Haemophilus influenzae is an unusual condition, especially in childhood. In most cases, respiratory symptoms are the presenting features, and children aged less than 4 years are most often affected. A high index of suspicion and aggressive microbiological and cardiological evaluation are often warranted to make an early diagnosis. We herein report two cases of pericarditis caused by H. influenzae in children aged less than two years. Pericardiocentesis was performed in each case. Early recognition, rapid diagnosis and aggressive medical and surgical therapy are paramount in the successful treatment of this condition.

Acute Disease↗