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D Dent

Publications and source records attributed to D Dent.

At least 19 recordsLinked to original sources
PubMed2006

An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes.

BACKGROUND AND OBJECTIVES: In patients with breast cancer (BC), the sentinel node (SN) is the first node in the axillary basin that receives the primary lymphatic flow and can be used to accurately assess the axillary nodal status without removal of the axillary contents. Currently, histology and/or immunohistochemistry are the routine methods of SN analysis. The primary objective of this study was to develop a reproducible reverse transcription (RT) PCR assay, with emphasis on achieving high specificity for accurate detection of BC micrometastases in the SN. To correct for the heterogeneity of BC cells, a multimarker approach was followed, with the further aim of improving the detection rate of the assay. METHODS: In total, 73 markers were evaluated, of which 7 were breast epithelial markers and 66 were either cancer testis or tumour associated antigens. Twelve BC cell lines and 30 SNs (from 30 patients) were analysed using RT-PCR to determine the in vitro and in vivo detection rates for each of the markers. In addition, 20 axillary nodes obtained from a patient with brain death were used as controls to optimise the PCR cycle numbers for all the markers. RESULTS: Of the 30 SNs, 37% (11/30) were positive on haematoxylin and eosin analysis. Extensive immunohistochemical (IHC) analyses of the haematoxylin and eosin negative nodes confirmed the presence of very small numbers of BC cells in an additional 40% (12/30) of SNs. Molecular analysis with the hMAM-A alone identified metastases in 70% (21/30) of SNs. Using MAGE-A3 in combination with hMAM-A identified metastases in 90% (27/30) of patients. Seven SNs (23%) were negative for micrometastases (with haematoxylin and eosin and IHC) but RT-PCR positive for either hMAM-A or MAGE-A3. CONCLUSIONS: As IHC analysis resulted in a 77% detection rate compared with 37% for haematoxylin and eosin analysis, we consider that IHC is essential in order not to miss SN micrometastases. Molecular analysis with hMAM-A and MAGE-A3 allows detection of BC micrometastases with a 90% detection rate. However, the clinical value of histologically negative but RT-PCR positive SNs can only be determined with long term follow up.

Breast Neoplasms↗
PubMed2004

In vivo immunostimulatory effects of CpG oligodeoxynucleotide in cattle and sheep.

Oligodeoxynucleotides (ODN) containing cytosine-phosphate-guanosine (CpG) motifs have been shown to activate the innate immune system and protect mice and chicken from bacterial and viral infections. Unfortunately, similar studies in other veterinary species are lacking. In this study we assessed the in vivo immunostimulatory effects of CpG ODN 2007, an ODN with previously demonstrated in vitro biological activity. The in vivo effects of ODN 2007 were compared in two closely related outbred species, sheep and cattle, to determine if there were common biological responses. We demonstrated that subcutaneous (s.c.) injection of the CpG ODN induces an acute phase response in the form of a transient fever, a mild transient increase in circulating neutrophils and elevated serum haptoglobin in both sheep and cattle. Sheep injected with CpG ODN also exhibited increased serum 2'5'-oligoadenylate (2'5'-A) synthetase activity, but no increase in serum 2'5'-A synthetase was detected in cattle. The ODN-induced responses were stronger in animals injected with CpG ODN formulated in 30% emulsigen than phosphate buffer saline (PBS) alone. These in vivo data demonstrate for the first time that a CpG ODN induces acute phase immunostimulatory responses in sheep and cattle. However, CpG ODN-induced antiviral effector molecule 2'5'-A synthetase was detected only in sheep but not in cattle.

2',5'-Oligoadenylate Synthetase↗
PubMed2000

Risk of breast cancer in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen contraceptives.

Recent studies have suggested that progestogen-only contraceptives and combined estrogen/progestogen oral contraceptives (COCs) may increase the risk of breast cancer among women less than 35 years of age or among recent users. The authors conducted a case-control study, in which cases of breast cancer (n = 484) [corrected] and controls (n = 1,625) hospitalized for conditions unrelated to contraceptive use were interviewed from 1994 to 1997 in hospitals in greater Cape Town, South Africa. The women were aged 20-54 years, resided in a defined area around Cape Town, and were Black or of mixed racial descent. The relative risk for exposure to injectable progestogen contraceptives (IPCs), mostly depot medroxyprogesterone acetate, was 0.9 (95% confidence interval (CI) 0.7, 1.2). There were no consistent associations within categories of age or recency or duration of use. For exposure to COCs, the overall relative risk was 1.2 (95% CI 1.0, 1.5). Among women below age 35 years, the relative risk was 1.7 (95% CI 1.0, 3.0), and it was unrelated to the duration or recency of use. The findings suggest that IPCs do not increase the risk of breast cancer, and that COCs may increase the risk among women below age 35 years, although bias cannot be excluded.

Adult↗
PubMed1997

A case control study of breast cancer risk and exposure to injectable progestogen contraceptives. Methods and patterns of use among controls.

OBJECTIVE: To describe the patterns of use of injectable progestogen contraceptives (IPCs) among coloured and black women in the Western Cape. These data are part of an ongoing study in the Western Cape, the main aim of which is to explore the relationship between IPCs and breast cancer. DESIGN: A population-based case-control study of breast cancer risk in relation to the use of IPCs among coloured and black women. SETTING: The Western Cape, including the Cape metropole and surrounding rural areas. STUDY SUBJECTS: All coloured and black women with newly diagnosed breast cancer, resident in the study area and below age 55 years, who present at either of the two tertiary care hospitals in the Western Cape are recruited. Controls are a sample of hospitalised patients representative of the populations from which the patients are drawn. Cases are frequency-matched to controls according to cross-tabulation of age, ethnic group and residential area in a ratio of approximately 1:3. MEASUREMENTS: Questionnaires are administered by trained nurse interviewers, information is elicited on a wide range of variables, including sociodemographic variables, medical history, family history of breast disease, lifetime history of all methods of contraception and use of non-contraceptive female steroids, reproductive variables, cigarette smoking, alcohol consumption and other potentially confounding variables. RESULTS: Between January and December 1994, 122 incident cases and 389 controls were enrolled. Ever-use of IPCs among the controls was 72% (N = 280) and use for 5 years or more was 30% (N = 117). Use of IPCs in the distant past was common, with 61% (N = 232) of all controls having initiated use 10 or more years previously. Current use was also high (19%). Other contraceptive methods were used far less commonly. CONCLUSION: Coloured and black women in South Africa have been using and continue to use IPCs for more commonly and for longer periods than women anywhere else in the world. It is therefore especially important to evaluate the risk of breast cancer and other health effects of IPCs. The rates of use identified in this study ensure that there will be adequate statistical power to evaluate long-term use, use in the distant past and current use of IPCs.

Adult↗
PubMed1995

Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue.

Changes in mucosal defense have been implicated as important factors affecting infections complications in critically ill patients. To study the effects of nutrient administration on gut-associated lymphatic tissue (GALT), ICR mice were randomized to receive chow plus intravenous saline, intravenous feeding of a total parenteral nutrition (TPN) solution, or enteral feeding of the same TPN solution. In a second series of experiments, a more complex enteral diet (Nutren) was compared with chow feeding and enteral TPN. After 5 days of feeding with experimental diets, lymphocytes were harvested from the mesenteric lymph nodes (MLNs), Peyer's patches (PPs), lamina propria (LP) cells, and intraepithelial (IE) spaces of the small intestine to determine cell yields and phenotypes. Small intestinal washings, gallbladder contents, and sera were collected and analyzed for immunoglobulin A (IgA) levels. In both series of experiments, there were no significant changes within the MLNs. There were significant decreases in total cell yields from the PPs, IE spaces, and LP in animals fed with TPN solution, either enterally or parenterally, as compared with chow-fed mice. Total T cells were decreased in both TPN-fed groups in the PPs and LP, whereas total B cells were decreased in the PP, IE, and LP populations. Total cell numbers remained normal in the Nutrenfed group, except for a decrease in LP T cells. CD4+ LP cells decreased significantly with a reduction in the CD4/CD8 ratio in mice fed TPN solution either intravenously or enterally, whereas IgA recovery from small intestinal washings was significantly decreased in the same groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Assembly of recombinant rotavirus proteins into virus-like particles and assessment of vaccine potential.

Rotavirus structural proteins VP4, VP6 and VP7 from Bovine Rotavirus Strain C486 were cloned and expressed in a baculovirus expression system. Combinations of the proteins were assembled into a series of virus-like particles, and a murine model was used to determine the capacity of the recombinant proteins and particles to induce protective immunity. All of the proteins induced humoral immunity as measured by an ELISA against whole virus. However, only the antisera from animals immunized with VP4 neutralized virus and inhibited haemagglutination. Challenge of neonates born to animals immunized with VP4 protein on assembled particles or in cell lysates showed protection against challenge with both homologous (bovine C486) and heterologous (SA-11) strains of rotavirus. In contrast, the offspring of mice immunized with VP6 were only partially protected. Neonates of animals immunized with virus-like particles composed of VP7 assembled on VP6 spherical particles were protected against challenge with the homotypic virus and significantly protected from a heterotypic challenge whereas unassembled VP7 protein provided only partial protection against challenge.

Animals↗
PubMed1993

Risk of abdominal septic complications after feeding jejunostomy placement in patients undergoing splenectomy for trauma.

Compared with total parenteral nutrition, enteral feeding via jejunostomy reduces septic complications in patients with severe trauma. However, violation of the bowel with insertion of a jejunostomy tube may increase the risk of intra-abdominal abscess (IAA), particularly if no simultaneous gastrointestinal tract injury exists. The records of 123 patients requiring splenectomy for trauma at a level I trauma center during a 6-year period (1986 to 1992) were reviewed to examine the incidence of IAA in patients with and without simultaneous jejunostomy placement in the presence and absence of gastrointestinal tract injuries. Thirty patients had jejunostomies placed (J), and 93 did not (NoJ). There were no significant differences between the groups in age, Abdominal Trauma Index, Injury Severity Score, or transfusion requirements. The incidence of IAA was not significantly different between the J and NoJ groups in the presence or absence of gastrointestinal tract injuries. Thus, jejunostomy placement does not increase the incidence of IAA after splenectomy regardless of the presence of a gastrointestinal tract injury.

Abdomen↗
PubMed1990

Neuroimmunomodulation of in vivo anti-rotavirus humoral immune response.

Neuropeptides and neurohormones (neurotransmitters) have been shown to modulate immune responses in vitro and in vivo. Since reproduction and lactation are regulated by neurohormones, we investigated whether neurohormones could enhance anti-rotavirus immunity in milk. Rotavirus-free mice were immunized orally with killed bovine rotavirus (BRV) and bred 6 weeks post-immunization. Post-whelping, each group of dams (ten mice/group) was given a single injection of prolactin (PRL), estrogen, PRL and estrogen or testosterone. The effects of neuropeptides, substance P (SP) and somatostatin (SS) on serum and lactogenic anti-rotavirus humoral immune responses were also investigated. The results revealed that in the groups given PRL or estrogen, anti-rotavirus antibody titers in milk and serum were enhanced. In contrast, testosterone had a negative effect on antibody titers. The administration of neuropeptide SP resulted in some enhancement of the lactogenic anti-rotavirus antibody titer at day 9 post-whelping whereas the opposite effect was observed following administration of SS. Prolactin given at 100 micrograms/mouse, on the day after whelping, gave optimum milk and serum antibody responses. Neurotransmitters potentiated immune responses to the weaker immunogenic proteins, VP4 and VP7 as well as to the strongly immunogenic VP6. In order to verify that the enhancement of anti-rotavirus antibody production was due to PRL and not to other factor(s), bromocriptine (BCR), a selective PRL inhibitor, was used as a control. Mice given BCR exhibited a drastic reduction in anti-rotavirus antibody in serum and milk. The role of neurotransmitters in the modulation of the lactogenic immune response and its significance in protection of neonates from enteric infections is discussed.

Animals↗
PubMed1989

Development of a murine model to study the pathogenesis of rotavirus infection.

A murine model to study enteritis induced by bovine (BRV) and murine rotavirus (MRV) has been developed. The course of infection was determined by clinical symptoms of diarrhea and virus isolation as well as histopathological, immunohistochemical, and electron microscopic methods. Both isolates were able to replicate and produce clinical symptoms in neonatal mice. Rotavirus-free neonates were orally inoculated with MRV or BRV and observed over a 192-hr postinoculation (HPI) period. Following infection with 10(4) PFU of virus, diarrhea and maximal intestinal dysfunction, as measured by xylose absorption, did not occur until beyond 20 hr postinfection even though maximal virus production occurred at 10-15 HPI. Immunohistochemically and by electron microscopy we were able to demonstrate viral antigen and virus particles in the enterocytes of villous tips at 5-8 HPI. The appearance of diarrheal symptoms was dependent on the virus dose and the type of virus isolate inoculated. The disease could be induced with doses as low as 1 x 10(2) PFU/mouse of BRV and 1 x 10(1) PFU/mouse of MRV. On the basis of these results, MRV was found to be more virulent than BRV in this model. The model should prove useful for studies designed to assess rotavirus virulence genes and for vaccine protection studies. This work emphasizes the need for early sample collection for critical evaluation of any vaccine or antiviral agent using this model.

Animals↗