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K J Sweeney

Publications and source records attributed to K J Sweeney.

26 records · Page 2Linked to original sources
PubMed1993

Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression.

Cyclins and proto-oncogenes including c-myc have been implicated in eukaryotic cell cycle control. The role of cyclins in steroidal regulation of cell proliferation is unknown, but a role for c-myc has been suggested. This study investigated the relationship between regulation of T-47D breast cancer cell cycle progression, particularly by steroids and their antagonists, and changes in the levels of expression of these genes. Sequential induction of cyclins D1 (early G1 phase), D3, E, A (late G1-early S phase), and B1 (G2 phase) was observed following insulin stimulation of cell cycle progression in serum-free medium. Transient acceleration of G1-phase cells by progestin was also accompanied by rapid induction of cyclin D1, apparent within 2 h. This early induction of cyclin D1 and the ability of delayed administration of antiprogestin to antagonize progestin-induced increases in both cyclin D1 mRNA and the proportion of cells in S phase support a central role for cyclin D1 in mediating the mitogenic response in T-47D cells. Compatible with this hypothesis, antiestrogen treatment reduced the expression of cyclin D1 approximately 8 h before changes in cell cycle phase distribution accompanying growth inhibition. In the absence of progestin, antiprogestin treatment inhibited T-47D cell cycle progression but in contrast did not decrease cyclin D1 expression. Thus, changes in cyclin D1 gene expression are often, but not invariably, associated with changes in the rate of T-47D breast cancer cell cycle progression. However, both antiestrogen and antiprogestin depleted c-myc mRNA by > 80% within 2 h. These data suggest the involvement of both cyclin D1 and c-myc in the steroidal control of breast cancer cell cycle progression.

Breast Neoplasms↗
PubMed1993

Organophosphorous insecticide susceptibility of mosquitoes in Maryland, 1985-89.

From 1985 to 1989, the susceptibility of the 9 major culicine mosquito species in Maryland to the larvicide temephos or the adulticide malathion was studied. The susceptibility of Culex spp. to temephos has declined in most areas of Maryland since 1967; however, only one strain of Culex pipiens was found to be temephos resistant in this study. Aedes sollicitans, Ae. albopictus and Ae. taeniorhynchus were temephos susceptible. All mosquitoes tested in the adult stage were susceptible to malathion.

Aedes↗
PubMed1993

Expression and amplification of cyclin genes in human breast cancer.

Cyclins, the regulatory subunits of cyclin-dependent kinases, play an important role in the control of cellular proliferation. Since dysregulated expression of these genes may contribute to the malignant phenotype the expression and amplification of cyclin A, B1, C, D1, D2, D3 and E genes were studied in 20 breast cancer cell lines. Increased expression of one or more of the cyclin A, B1, D1 or E genes was found in seven cell lines (35%); of these five (25%) showed increased expression of cyclin D1. Overexpression occurred in both the presence and absence of gene amplification. Conversely, amplification did not invariably lead to overexpression. Cyclin D2 expression was lower in breast cancer cell lines than in cultured normal breast epithelial cells. Cyclin D1 expression was further investigated in breast tumour biopsies: 56 of 124 specimens (45%) expressed higher levels of cyclin D1 mRNA than normal breast tissue. These data implicate dysregulated expression of several cyclin genes, particularly cyclin D1, as a potential factor in the pathogenesis of breast cancer.

Base Sequence↗
PubMed1992

Hyaluronic acid in progeria and the aged phenotype?

Hyaluronic acid (HA) is implicated in functions such as vascularity, morphogenesis, repair, and the general integrity of the extracellular matrix. Hence, it is considered possible that HA is involved in the most conspicuous features of the progeroid phenotype. However, it is not known whether the increase in HA excretion seen in progeria patients is due to a primary genetic defect or is a secondary effect due to some deeper problem. The phenomenon of 'normal' aging is suggested to have a more complex etiology and phenotype than progeria and the role of HA levels is less well-defined.

Aging↗
PubMed1987

Salmonella typhimurium aroA mutants as carriers of the Escherichia coli heat-labile enterotoxin B subunit to the murine secretory and systemic immune systems.

We investigated the ability of Salmonella typhimurium vaccines to deliver heterologous antigens to the systemic and secretory immune systems of the mouse, while retaining their immunogenicity against salmonellosis. S. typhimurium SL3261, an avirulent aroA mutant, or SL3261 carrying plasmid pBRD026, a pBR322 derivative encoding the gene for Escherichia coli LT-B were used to immunize BALB/c mice orally. Both immunizing strains invaded the mononuclear phagocyte system of the mice, grew slowly until approximately day 14 post-infection, and then were rapidly cleared. No salmonellae were detected in livers, spleens, mesenteric lymph nodes or Peyer's patches by day 42. Mice immunized with either strain and challenged orally with the virulent parent strain, SL1344, several weeks after clearing the immunizing organism, were protected against the lethal S. typhimurium infection. Mice infected with SL3261 (pBRD026) developed substantial levels of IgG and IgA anti-LT-B antibodies 14 days post-infection in both serum and gut samples. The sera neutralized the effects of LT in an in vitro Vero cell assay. Thus, aroA mutants of S. typhimurium can deliver a heterologous antigen from a different enteric pathogen to the murine systemic and secretory immune systems without altering their efficacy against salmonellosis.

Animals↗
PubMedDate not supplied

D2 lymphadenectomy in the management of gastric cancer.

BACKGROUND: Gastric carcinoma is a significant cause of death in Ireland. Surgery offers the best option of cure, but the five-year survival following resection remains dismal at 10-15%. Experience from Japan and from some Western units suggest that an extended (D2) lymphadenectomy in association with gastrectomy increases the prospect of cure, but concern about the morbidity and mortality of this operation and lack of evidence from randomised studies has limited its acceptance. AIMS: This study reports the experience of a specialist upper gastrointestinal unit with D2 gastrectomy in a four-year audit. METHODS: Sixty-two resections were performed for gastric cancer. RESULTS: Nineteen patients were deemed unsuitable for the D2 procedure and underwent a more limited lymphadenectomy (D0 or D1). Forty-three patients underwent D2 resection, 12 with an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total distal resection. Eight patients undergoing D2 resection had extended resections, five with splenectomy and three with a distal pancreatectomy. Post-operative complications occurred in 31% of patients. Thirty-day and 90-day mortality were zero. Median survival was 822 days in the D2 group (range 120-1,320). CONCLUSIONS: These results show that a D2 gastrectomy can be performed with a low morbidity and mortality and a median survival of greater than two years.

Adenocarcinoma↗
PubMedDate not supplied

Surgical management of perforated peptic ulcer disease.

BACKGROUND: Surgery for perforated peptic ulcer disease is one of the most common emergency procedures carried out in the western world. The role of postoperative empiric Helicobacter Pylori eradication therapy is controversial. METHODS: The clinical, operative and postoperative surveillance details of 84 consecutive patients who underwent surgery for perforated peptic ulcer were reviewed. RESULTS: All patients underwent omentopexy +/- simple closure followed by proton pump therapy. Patients were followed-up for an average of 44 +/- 19 months. Females were older than male patients (59 +/- 20 vs. 46 + 17 years; p<0.05), presented with symptoms of a longer duration (17.9 +/- 16 vs. 8.9 +/- 9 hours; p=0.045) and had a higher mortality rate (18% vs 3%; p<0.05). Seventy-nine per cent of patients received postoperative empiric Helicobacter Pylori eradication therapy. CONCLUSIONS: Surgery for perforated peptic ulcer is associated with a significant perioperative mortality rate. Elderly female patients are particularly at risk.

Aged↗