Fibronectin concentrations in plasma in peripheral vascular disease

Fibronectin (Fn) concentrations were measured immunoturbidimetrically in plasma of normal subjects and patients with peripheral vascular disease (PVD) before and after venous compression, which caused Fn concentrations to increase in both normal subjects and PVD patients. Basal Fn concentrations and those after 10-min compression were not significantly different in normal subjects and PVD patients. Five minutes after the release of compression, Fn had consistently declined in normal subjects and reverted to baseline values; in contrast, in PVD patients values either increased further or decreased inconsistently. Thus the Fn concentration at 15 min was significantly (P less than 0.001) greater in PVD patients than in normal subjects. Plasma albumin concentrations, measured in parallel to ensure that changes in Fn concentrations were not nonspecific, increased to a greater extent in normal subjects than in PVD patients and reverted to normal after the removal of compression. The Fn/albumin ratio remained unchanged in normal subjects after venous compression, whereas that in PVD patients increased and remained higher, even after decompression. The sustained increase in plasma Fn concentrations and in the Fn/albumin ratio in PVD patients after venous compression may indicate endothelial injury.     

Effect of titanium surface texture on the cell-biomaterial interface.

To improve the in vivo performance of engineered implants, this study examines the independent effects of surface chemistry and topography on fibroblast morphology and density in vitro. Titanium (Ti) was sputter-coated onto smooth and microtextured polyethylene terephthalate (PET). Test specimens were evaluated in 24-h, fibroblast cultures and assessed with scanning electron microscopy (SEM) for cellular morphology and density. Fibroblast density increased, as the Ti film thickness increased. The fibroblasts exhibited contact guidance on the textured test specimens. The greatest cellular density was found on the Ti-coated, textured test specimens. In conclusion, Ti and surface texture appeared to strongly influence fibroblast density and morphology as compared to PET and smooth surfaces.     

Stimulatory effect of immunoglobulins and Fc fragments on glucose oxidation and glucose transport by adipocytes

Following our demonstration that human IgG, its Fc fragments and IgM stimulate lipogenesis in adipocytes, we embarked on a study to investigate whether these proteins stimulate the oxidation and transport of glucose by adipocytes, and whether such a stimulation is mediated through the insulin receptor. Using a simplified method for the measurement of [14C]-carbon dioxide produced from [U-14C]-glucose by rat adipocytes, we demonstrated that both IgG, Fc fragments and IgM produced a dose-dependent stimulation of oxidation of glucose by adipocytes. These proteins also produced a stimulation of 3-o-methylglucose uptake by adipocytes. IgG, Fc Fragments and IgM did not, however, alter specific binding of insulin to adipocytes. These data provide further evidence that human IgG and IgM may have a role in regulating metabolic activity of adipose tissue. These effects are exerted independently of the insulin receptor and are probably mediated through the interaction of its Fc fraction with putative Fc receptors on the adipocyte membrane. A similar interaction may be important in the regulation of metabolic activity of other cells with Fc receptors.     

The effect of tiaprofenic acid and indomethacin administration of human platelet function

The present study compares the effects of two non-steroidal anti-inflammatory drugs (NSAIDs) on platelet function. Tiaprofenic acid (300 mg twice daily) and indomethacin (25 mg thrice daily) were administered to healthy volunteers for 6 days. Platelet aggregation and thromboxane A₂ (TXA₂) release (assessed as TXB₂, the stable, spontaneous breakdown product of TXA₂) were assessed before the adminstration of NSAIDs; on day 6 (2–3 h after the last dose of NSAID); and on days 7 and 8 (24 h and 48 h after the last dose of NSAID). Both tiaprofenic acid and indomethacin significantly inhibited platelet aggregation and TXA₂ release. The extent and duration of inhibition was similar for both drugs, and the inhibition tended to reverse within 24–48 h of cessation of medication. The time required for reversal of the inhbitiory effect of NSAIDs on platelets may be of relevance in patients who are bleeding (e.g. from gastric erosions caused by NSAIDs). Tiaprofenic acid in the present study and in previous work has not been shown to be a selective inhibitor of prostanoid synthesis, as was originally claimed.     

Inflammation: the link between insulin resistance, obesity and diabetes

Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.     

Multiple Copies of the Upstream Regulatory Region of the Major Capsid Protein Gene of Bacteriophage MB78 Inhibit Phage Morphogenesis

The 2.311 kb EcoRI F fragment of bacteriophage MB78 has been cloned in multicopy vectors pUC19 and pCR90. Salmonella typhimurium strains carrying such plasmids cannot support development of phage MB78 while other Salmonella phages like P22 and 9NA grow normally. Most of the phage MB78 induced functions are normal in such transformed hosts but proper maturation of the phage particles does not take place. Deletion of 138 bp from the 3 end of the cloned fragment reverses the inhibitory effect. Analysis of nucleotide and the deduced amino acid sequence of a 1.2 kb HindIII-SalI fragment of the phage genome which overlaps the 138 bp confirms that this part contains the upstream regulatory region of the major structural protein gene. It seems that in presence of multiple copies of the upstream regulatory region (which includes a number of promoter like sequence) of the coat protein gene, the maturase gene is down regulated and this is effective only in cis, a situation quite similar to that of Q RNA phages.     

Identification of a Strong Promoter of Bacteriophage MB78 that Lacks Consensus Sequence Around Minus 35 Region and Interacts with Phage Specific Factor

A strong promoter of bacteriophage MB78 does not have minus 35 consensus sequence although it has a TGn motif immediately upstream of minus 10 sequence as well as the AT rich UP element. It is efficiently recognised by the sigma 70 RNA polymerase, however, a phage-specific factor competes with sigma 70 RNA polymerase for binding to this region, the binding of the factor being stronger than that of the polymerase. Contrary to the reports in the literature the polymerase appears not to bind to the UP element whereas the phage-specific factor does. The latter seems to be involved in the regulation of the promoter activity. This revised version was published online in July 2006 with corrections to the Cover Date.     

Exocrine pancreatic function (serum immunoreactive trypsin, fecal chymotrypsin, and pancreatic isoamylase) in Indian diabetics

Forty-nine patients with tropical calcific pancreatitis (TCP), 51 insulin-dependent diabetics (IDDMs), 87 non-insulin-dependent diabetics (NID-DMs), and 66 nondiabetic controls were studied to evaluate their exocrine pancreatic function by measurement of serum immunoreactive trypsin (IRT, normal for white caucasians from the U.K. of 140-414 micrograms/L), pancreatic isoamylase (PIA, normal of 35-125 U/L), and fecal chymotrypsin (FCT, normal of greater than 6.6 u/g). The majority of patients were studied within 1 year of diagnosis. TCP subjects included 7 nondiabetics, 6 with impaired glucose tolerance (IGT-TCP), and 36 diabetics [fibrocalculous pancreatic diabetes (FCPD)]. There was evidence of active pancreatitis (IRT greater than 800 micrograms/L) and partial preservation of function in nondiabetic TCP subjects [median IRT of 220 micrograms/L (range of 102-1,360 micrograms/L), FCT of 2.2 u/g (range 0.7-12.8 u/g)] and also in IGT-TCP subjects [IRT of 370 micrograms/L (range of 30-1,360 micrograms/L), FCT of 4.2 u/g (range of 1-38 u/g)]. FCPDs showed severely diminished exocrine function [IRT of 50 micrograms/L (range of 0-184 micrograms/L), FCT of 0.23 u/g (range of 0-10.4 u/g)]; none showed IRT greater than 800 micrograms/L. IDDMs and NIDDMs also showed diminished exocrine pancreatic function in approximately 30 and approximately 10%, respectively. Controls showed a wide range of IRT and FCT concentrations; IRT concentrations tended to be higher than those reported in white Caucasians from the U.K. Three controls, one IDDM, and two NIDDMs showed "pancreatic" IRT concentrations in the absence of symptoms. PIA concentrations were diminished in FCPD but were similar in IDDM and NIDDM subjects compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)