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Biomedical subjects

W F Ferris

Publications and source records attributed to W F Ferris.

10 recordsLinked to original sources
PubMed2006

Nitric oxide stimulates insulin gene transcription in pancreatic beta-cells.

Recent studies have identified a positive role for nitric oxide (NO) in the regulation of pancreatic beta-cell function. The aim of this study was to determine the effects of short-term exposure to NO on beta-cell gene expression and the activity of the transcription factor PDX-1. NO stimulated the activity of the insulin gene promoter in Min6 beta-cells and endogenous insulin mRNA levels in both Min6 and isolated islets of Langerhans. Addition of wortmannin prior to NO stimulation blocked the observed increases in insulin gene promoter activity. Although NO addition stimulated the phosphorylation of p38, inhibition by SB203580 did not block the effect of NO on the insulin gene promoter. NO addition also stimulated both the nuclear accumulation and the DNA binding activity of PDX-1. This study has shown that over 24h, NO stimulates insulin gene expression, PI-3-kinase activity and the activity of the critical beta-cell transcription factor PDX-1.

Androstadienes↗
PubMed2006

The effect of abdominal obesity on insulin sensitivity and serum lipid and cytokine concentrations in African women.

OBJECTIVES: Studies have shown clear associations of abdominal obesity with lipid and glucose metabolism and cytokine levels in a number of different population groups. However, no such studies have been performed in an African population in which visceral adipose tissue levels have been shown to be lower than in European subjects. DESIGN AND PATIENTS: Cross-sectional analysis in 124 African women. MEASUREMENTS: Fasting serum samples were taken from all subjects and anthropometric measurements obtained. Blood levels of glucose, insulin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglyceride, interleukin (IL)-6, IL-8 and IL-18 were measured. Subjects were separated into normal and abnormal glucose tolerant groups and into tertiles according to waist circumference (WC). Insulin resistance was assessed using the homeostasis model assessment (HOMA). RESULTS: Abnormal glucose-tolerant subjects had higher WC, glucose and HOMA levels than the normal glucose-tolerant group. Increased WC was associated with higher triglyceride, insulin and HOMA levels and lower HDL levels. Multiple regression analyses showed that WC associated positively with HOMA and serum triglyceride levels and negatively with HDL levels. IL18 was a positive but weak determinant of the HOMA level and BMI correlated positively with serum IL-6 concentrations. CONCLUSIONS: Although previous studies have shown that African subjects have a lower visceral adipose depot size than European subjects, abdominal obesity is still associated with insulin resistance and dyslipidaemia. The association between abdominal obesity and metabolic dysfunction within this population is not dependent upon IL-6, IL-8 or IL-18.

Abdominal Fat↗
PubMed2005

The relationship between insulin sensitivity and serum adiponectin levels in three population groups.

Reduced plasma adiponectin levels are associated with insulin resistance. Black South Africans, like African Americans, are more insulin-resistant than BMI-matched white subjects, as are Asian Indians. We investigated whether this interethnic variation in insulin resistance is due to differences in plasma adiponectin levels. Blood and anthropometric measurements were taken from black, white and Asian-Indian subjects. Serum adiponectin, lipids, glucose and insulin were measured; insulin sensitivity was calculated using HOMA. Black (HOMA = 2.62 +/- 0.99) and Asian-Indian subjects (HOMA = 3.41 +/- 2.85) were more insulin-resistant than BMI-matched white (HOMA = 1.76 +/- 0.63) subjects (p = 0.0001). Furthermore, the white subjects had higher adiponectin levels (8.11 +/- 4.39 microg/ml) compared to black (5.71 +/- 2.50 microg/ml) and Asian Indian (5.86 +/- 2.50 microg/ml) subjects (p = 0.003). When all ethnic groups were combined, multiple regression analysis demonstrated that serum adiponectin levels corrected for BMI and ethnicity did not correlate with HOMA, but did explain 10.0 % of the variance in HDL-cholesterol levels. Within each ethnic group, adiponectin only correlated inversely with HOMA in white subjects. Adiponectin may play a role in determining serum HDL-cholesterol levels, but ethnic variation in insulin sensitivity is not dependent on serum levels of this adipokine. The relationship between adiponectin and insulin resistance varies across ethnic groups.

Adiponectin↗
PubMed2001

Brief occlusion of the main pancreatic duct rapidly initiates signals which lead to increased duct cell proliferation in the rat.

In the course of investigating the signals associated with pancreas regeneration, we have developed a method to initiate pancreatic duct cell proliferation by brief occlusion of the main pancreatic duct. The resulting duct cell proliferation, induced by temporary partial main duct occlusion, was compared to that induced by firmly tying a cellophane strip around the head of the pancreas for longer periods of time. Both methods stimulated a biphasic increase in duct cell proliferation, with proliferation maxima at 3 and 14 days post operation. The short duration of temporary main duct occlusion (60 s) that was needed to stimulate duct cell proliferation, and the similar duct cell proliferation profiles that were observed after both the temporary and the longer term main duct occlusion, led us to conclude that the signals which initiate proliferation occur rapidly at the beginning of each procedure.

Amylases↗
PubMed2001

Major histocompatibility complex class II invariant chain expression in non-antigen-presenting cells.

In contrast to the generally accepted belief, the major histocompatibility complex (MHC) class II invariant chain (Ii) is commonly expressed intracellularly in cells that do not present exogenous antigens. Such cells include resting peripheral blood T cells and natural killer (NK) cells. In T cells, the Ii is associated with a 77 000 molecular-weight molecule (p77) that has yet to be identified. This molecule is co-precipitated with the anti-Ii monoclonal antibody (mAb) VCD-1, but not with mAb BU-45. This suggests that in the p77-Ii complex, the extracellular epitope of Ii recognized by BU-45 is hidden, whereas the Ii epitope for VCD-1 remains exposed. In antigen-presenting cells (APCs), p77 association with the Ii was minimal, if detectable. The p77-Ii association in non-professional APCs suggests that the Ii may have another, more general, function other than the one accepted in antigen presentation.

Antibodies, Monoclonal↗
PubMed2001

Determination of the tyrosine phosphorylation sites in the T cell transmembrane glycoprotein CD5.

Studies of CD5-deficient mice indicate that the transmembrane glycoprotein CD5 negatively regulates antigen receptor-mediated signals in thymocytes, lymph node T cells and B1a cells. CD5 contains four tyrosine residues in its cytoplasmic domain and is phosphorylated on tyrosine residues following antigen receptor ligation. Recently it has been proposed that CD5 function is dependent on the recruitment of the tyrosine phosphatase SHP-1 to tyrosine-phosphorylated CD5 and subsequent dephosphorylation of signaling molecules. In this study we investigated the requirements for, and sites of, CD5 tyrosine phosphorylation. Using a T cell line deficient in the tyrosine kinase p56(lck) and the same cell line reconstituted with this kinase, we show that p56(lck) expression is required for efficient CD5 tyrosine phosphorylation. Using tyrosine-phosphorylated peptides corresponding to CD5 cytoplasmic sequences we also show that the Src homology 2 (SH2) domain of p56(lck) binds prominently to pY429SQP, with 30-fold less affinity to pY463DLQ and not to pY441PAL. A number of murine CD5 Y --> F and deletion mutants were expressed in Jurkat T cells. The Y441F mutant was tyrosine phosphorylated at levels comparable to wild-type, but the Y429F and Y463F mutants were phosphorylated at lower levels. Two deletion mutants, which contain only one tyrosine residue (Y378) located at the interface of the transmembrane and cytoplasmic domains, were not tyrosine phosphorylated, suggesting that Y378 is not readily available for phosphorylation. Taken together these results suggest that both Y429 and Y463 can recruit p56(lck), and that these residues are the only prominent sites for CD5 tyrosine phosphorylation.

Amino Acid Sequence↗
PubMed1998

Thymocyte activation induces the association of the proto-oncoprotein c-cbl and ras GTPase-activating protein with CD5.

Studies of knockout mice indicate that the glycoprotein CD5, which is expressed on Tcells, most thymocytes and a subset of B cells, down-regulates TCR- and B cell receptor (BCR)-mediated signaling. CD5 is associated with the TCR and BCR, and is phosphorylated on cytoplasmic tyrosine residues following antigen receptor ligation. Cross-linking of CD5 or pervanadate stimulation of thymocytes induces the association of a 120-kDa tyrosine-phosphorylated protein with CD5. The proto-oncoprotein c-cbl associates with CD5 in pervanadate-stimulated thymocytes, and reprecipitation analysis demonstrates that the major proportion of CD5-associated pp120 is c-cbl. The GTPase-activating protein for ras (ras GAP), which is not tyrosine phosphorylated following CD5 cross-linking, associates with CD5 in pervanadate-stimulated thymocytes. Using tyrosine-phosphorylated peptides we show that ras GAP interacts in an SH2-mediated manner with the phosphorylated Y429SQP sequence of CD5. Both c-cbl and ras GAP have been proposed to suppress receptor-mediated signaling, and may contribute to CD5-mediated suppression of TCR or BCR signaling.

Amino Acid Sequence↗
PubMed1996

Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis.

Liver fibrosis results from a relative imbalance between synthesis and degradation of matrix proteins. We have previously described release of the protein collagenase inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by culture-activated human hepatic stellate cells (HSCs). In this study, we have investigated the relative expression of TIMP-1 and interstitial collagenase in culture-activated rat HSCs and rat models of liver injury and fibrosis. The complementary DNA (cDNA) for rat TIMP-1 was obtained by homology polymerase chain reaction (PCR) and sequenced. By Northern analysis using this probe, TIMP-1 messenger RNA (mRNA) expression was up-regulated with HSC activation by culture on plastic as defined by cellular expression of procollagen-1. Interstitial collagenase mRNA was expressed in early 1. Interstitial collagenase mRNA was expressed in early culture (<4 days) but became undetectable in more activated cells (7-21 days). By activity assay of serum-free cell-conditioned media, TIMP-1 was found to be released in increasingly concentrations with duration of culture on plastic. Expression of TIMP-1 interstitial collagenase, and procollagen-1 mRNAs were studied in rat models of biliary and parenchymal injury (bile duct ligation and CC14 administration) by ribonuclease protein assay. TIMP-1 mRNA expression was increased at 6, 24 hours, and 3 days after bile duct ligation and was also shown to rise in acute CC14 liver injury and remain elevated as the liver became fibrotic. TIMP-1 expression preceded procollagen-1 expression in both models. In contrasts, interstitial collagenase mRNA levels remained similar to control values throughout both models of liver injury. Total cellular RNA from hepatocytes, HSCs, and kupffer cells freshly isolated from livers after acute CC14 injury was subjected to Northern analysis. TIMP-1 transcripts were observed in nonparenchymal cells only. We suggest that increased expression of TIMP-1 relative to interstitial collagenase by HSCs may promote progression of liver fibrosis in these rat models by preventing degradation of secreted collagens.

Amino Acid Sequence↗
PubMed1992

pH-sensitive interactions between IgG and a mutated IgG-binding protein based upon two B domains of protein A from Staphylococcus aureus.

A fusion protein, consisting of the N-terminal 81 amino acids from an inactive bovine DNase I (Q38,E39-E38,Q39) and two sequential synthetic IgG-binding domains based upon domain B of Protein A from Staphylococcus aureus has been shown to bind to porcine IgG with a similar affinity and pH profile to Protein A. The same residue in each B domain (Tyr111 and Tyr169) has been mutated by cassette mutagenesis to Ser, Glu, His, Lys or Arg and the effect of the mutation on binding interactions with porcine IgG investigated. The evidence presented suggests that the interactions at the B domain are highly sensitive to the presence of a charged residue.

Amino Acid Sequence↗