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Biomedical subjects

E Cahill

Publications and source records attributed to E Cahill.

13 recordsLinked to original sources
PubMed2001

Diaminoindanes as microsomal triglyceride transfer protein inhibitors.

The synthesis and biological activities of biarylamide-substituted diaminoindanes as microsomal triglyceride transfer protein (MTP) inhibitors are described. One of the more potent compounds, 8aR, inhibited both the secretion of apoB from Hep G2 cells and the MTP-mediated transfer of triglycerides between synthetic acceptor and donor liposomes with IC(50) values of 0.7 and 70 nM, respectively. In normolipidemic rats and dogs, oral administration of 8aR dose-dependently reduced both plasma triglycerides and total cholesterol. Moreover, in rats and dogs, 8aR also prevented the postprandial rise in plasma triglycerides following a bolus administration of a fat load. Because MTP inhibitors decrease very low density lipoprotein assembly in the liver, the potential for hepatic lipid accumulation was evaluated. In normolipidemic rats, hepatic cholesterol and triglyceride contents were dose-dependently increased by 8aR. However, hepatic lipid accumulation resulted in negligible change in total liver weight and was reversible after withdrawal of the compound.

Animals↗
PubMed1999

T-cell and antibody response characterisation of a new recombinant pre-S1, pre-S2 and SHBs antigen-containing hepatitis B vaccine; demonstration of superior anti-SHBs antibody induction in responder mice.

The incidence of non-responders to hepatitis B (HB) virus SHBs antigen (Ag) vaccines has prompted the development of pre-S containing vaccines. The aim of this study was to characterise the murine immune response to a novel recombinant particle (Hepagene) (Medeva plc) containing pre-S1, pre-S2 and SHBsAg components. Hepagene induced potent in vitro spleen T-cell proliferative responses in both BALB/c (maximum stimulation index (SI) = 38) and SWR/J (maximum SI = 43) strains of mouse, following immunisation. High concentrations of interferon-gamma and low concentrations of interleukin-10 were detected in the media of spleen cells stimulated with Hepagene. The anti-Hepagene antibody response was higher in SWR/J mice and alhydrogel adjuvant significantly improved the titres. Anti-pre-S1 antibody was detected in both strains of mouse, whereas antipre-S2 antibody was only detected in SWR/J mice. IgG subclass analysis of the anti-Hepagene response revealed a Th2-type response in BALB/c mice and a mixed Th1/Th2 response in SWR/J mice. Hepagene induced higher anti-SHBs antibody responses than Engerix-B (11097 and 1276 IU/ml, respectively) in BALB/c mice. Hepagene therefore, stimulates strong cellular and humoral immune responses in murine models. The high anti-SHBs antibody response suggests that Hepagene is an improved hepatitis B virus vaccine.

Amino Acid Sequence↗
PubMed1998

Characterization of the T- and B-cell immune response to a new recombinant pre-S1, pre-S2 and SHBs antigen containing hepatitis B vaccine (Hepagene); evidence for superior anti-SHBs antibody induction in responder mice.

Hepagene is a novel recombinant particle consisting of the pre-S1, pre-S2 and small surface (SHBs) antigens (Ag) of the hepatitis B virus (HBV) and is adjuvanted with alhydrogel in the final formulation. It has been primarily developed to enhance anti-SHBs antibody titres in inadequate responders, to conventional SHBsAg vaccines. Since non-compliance is also a problem with existing HBV vaccine schedules, the ability to accelerate current immunization regimens to provide more rapid protection has also been an important objective. Here we describe the T- and B-cell responses to Hepagene in two strains of responder mouse (BALB/c and SWR/J). Hepagene induced high in vitro spleen T-cell proliferative responses in both strains (max. Stimulation Index = 43), following intraperitoneal immunization. High concentrations of interferon-gamma (max. = 5000 pg/mL) were detected in the media of spleen cells cultured with non-adjuvanted Hepagene particles. SWR/J mice showed the highest serum antibody (Ab) titres to non-adjuvanted Hepagene. The presence of alhydrogel adjuvant in the vaccine formulation significantly improved the titres. Anti-pre-S1 Ab was detected in both strains of mouse but anti-pre-S2 Ab was only detected in the SWR/J strain. In BALB/c mice, the anti-Hepagene (non-adjuvanted) IgG1 Ab subclass was predominant but in SWR/J mice IgG1, IgG2a and IgG2b subclasses were of a similar magnitude. In BALB/c mice, Hepagene induced higher anti-SHBs Ab responses than Engerix-B (11097 IU/mL and 1276 IU/mL, respectively), following two doses of vaccine (10 micrograms/mouse). The vaccine therefore, induces strong cellular and humoral immune responses and these data suggest that Hepagene is an improved hepatitis B vaccine.

Animals↗
PubMed1998

The effects of fasting and refeeding healthy volunteers on serum folate levels.

Fasting serum folate levels are commonly used in assessing folate status and also in estimating the bioavailability of synthetic folic acid and food folate. Previous work has shown that serum folate more than doubles in concentration during a 48 hour fast. Following a 24-hour standardisation procedure, serum and urinary folate levels were measured in nine healthy female volunteers fasting for 36 hours and in the first 6 hours during refeeding. Serum folate concentration increased from a mean of 14.8 ng/ml to 29.3 ng/ml during the 36 hour fast and fell to 22.1 ng/ml during the 6 hour refeeding period. The rise in serum folate concentration during the fast was negatively related to serum folate concentration at 0 hours fasting. It is hypothesised that the enterohepatic recirculation of folate plays an important role in the underlying physiological mechanism. These findings highlight the need to standardise energy intake to control for hepatic influences on folate metabolism in future studies assessing the bioavailability of folate in food.

Adolescent↗
PubMed1990

Parathyromatosis in hyperparathyroidism.

Recurrent hyperparathyroidism after parathyroidectomy may present a difficult diagnostic problem. A rare etiology is parathyromatosis (multiple nodules of hyperfunctioning parathyroid tissue scattered through the neck and mediastinum) due to spillage of otherwise benign parathyroid tissue during surgery. We present a case of recurrent hyperparathyroidism and parathyromatosis due to tissue spillage during surgical removal of probable double adenomas, a rare cause of primary hyperparathyroidism. Thus, parathyromatosis must be included in the differential diagnosis of recurrent or persistent hyperparathyroidism, distinguished from parathyroid carcinoma by histologic criteria. The surgeon must be careful of parathyroid spillage during surgery, even of benign tumors of the parathyroids.

Adenoma↗
PubMed1981

Investigation of the requirements for O-glycosylation by bovine submaxillary gland UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosamine transferase using synthetic peptide substrates.

Peptides containing a triprolyl sequence carboxyl to a threonine residue can be O-glycosylated by a crude Triton x-100 extract of porcine submaxillary glands (Young, J. D., Tsuchiya, D., Sandlin, D. E., and Holroyde, M. J. (1979) Biochemistry 18, 4444-4448). In the present paper, we have studied the characteristics of the O-glycosylating enzyme, UDP-N-acetylgalactosamine: polypeptide N-acetylgalactosamine transferase, from a membrane extract of bovine submaxillary glands using 11 synthetic peptide substrates in which the Thr-Pro-Pro-Pro was varied. The effect of these changes was measured by determining the apparent Km and Vmax values of the substrates. The studies thus far reveal: threonine cannot be glycosylated without a carboxyl triprolyl sequence; the alpha amino acid group of the threonine must be blocked; the nature of the group NH2-terminal to the threonine affects the kinetics of the reaction; and one residue can be between the threonyl and the triprolyl sequence. The triprolyl sequence in a protein may be an important signal for O-glycosylation.

Animals↗