Search PubMed⌕ Search

Biomedical subjects

J A Colwell

Publications and source records attributed to J A Colwell.

At least 73 records · Page 4Linked to original sources
PubMed1983

New concepts about the pathogenesis of atherosclerosis in diabetes mellitus.

New concepts about the pathogenesis of atherosclerosis in diabetes mellitus are presented. Emphasis is given to alterations of endothelial function, as indicated by von Willebrand factor activity, prostacyclin release, and fibrinolytic activity in diabetes mellitus. Previous work on platelet aggregation and arachidonic acid metabolism is updated and recent findings are emphasized. The atherogenic mix of elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol levels in uncontrolled diabetes mellitus is noted. The lipid hypothesis is extended by consideration of very low-density lipoprotein and intermediate-density lipoprotein metabolism in diabetes. Lipoprotein-cell interactions that may contribute to atherosclerosis are reviewed and suggestions are made for future research in order to clarify the pathogenesis of atherosclerosis in diabetes mellitus.

Animals↗
PubMed1983

In vitro culture of cells exfoliated in the urine by patients with diabetes mellitus.

As an approach to facilitate the understanding of the progression of diabetic renal disease, we assessed the urine of diabetic patients and normal volunteers for the presence of cells that could be cultured in vitro. The results suggest that both normal control subjects and diabetic patients, without clinically detectable microangiopathy, exfoliate few culturable cells into the urine. In contrast, diabetics with documented retinopathy but without nephropathy exfoliate substantially higher numbers of culturable cells (5.2 cells/100 ml urine), whereas diabetics with both retinopathy and advanced nephropathy exfoliate even greater numbers of culturable cells (50.8 cells/100 ml urine). The cells that are exfoliated and culturable can be divided into five distinct cell types based on morphology at the light microscope level. The exfoliated cells proliferate at clonal density after isolation from urine and are epithelial in appearance. These data suggest that the culture of cells from urine might have diagnostic value as an early indicator of diabetic renal disease and provide a convenient, noninvasive new source of human kidney epithelial cells.

Cells, Cultured↗
PubMed1983

Predicting insulin requirements for a portable insulin pump using the Biostator. Evidence for reversible insulin resistance in poorly controlled type I diabetics.

Glycemic control was achieved in 14 patients with insulin-dependent diabetes mellitus (IDDM) by 36-48-h treatment with a recently marketed clinical model, Biostator glucose controller (Life Science Instruments, Miles Laboratories, Elkhart, Indiana). Control was maintained by continuous subcutaneous insulin infusion with a portable pump, programmed using infusion profiles from the Biostator. Control of glycemic excursion with the Biostator was variable among patients. This control, reflected by the M-value or a blood glucose index (mean of pre-, peak, and 2-h postmeal levels for four meals) of each patient, correlated directly with their prior glycemic control, as assessed by hemoglobin A1c (HbA1c) level (r = 0.66, P less than 0.01 and r = 0.82, P less than 0.005, for M-value and blood glucose index, respectively). Total insulin infused by the Biostator/24 h overpredicted the subcutaneous infusion dose required on day 2 of pump treatment (183 +/- 11%, P less 0.001). Therefore, these data were not used to program the portable pump. Instead, total insulin dose was estimated using a dietary glucose/insulin (G/I) ratio. This ratio, derived from dietary total available glucose, urine glucose, and insulin dose/24 h during depot insulin treatment, accurately estimated total insulin for pump infusion (97 +/- 4%). The basal infusion rate of the Biostator between 2400 and 0600 h also exceeded the subcutaneous infusion requirement and was reduced to 40% for the initial pump basal rate. The remainder of the insulin (total minus basal) was distributed as premeal boluses according to the Biostator infusion profile for meals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Do platelets have anything to do with diabetic microvascular disease?

It has been postulated that abnormal platelet and endothelial function may contribute to microangiopathy in diabetes mellitus. If this proposal is correct, alterations in platelet and endothelial function should be found before the appearance of vascular disease in insulin-dependent patients and in animal models of diabetes mellitus. This appears to be the case for the following: platelet aggregation, increased platelet production of the proaggregatory prostaglandin metabolite thromboxane, decreased endothelial production of the antiaggregatory prostaglandin prostacyclin, and decreased platelet survival. Insulin therapy will return some of these findings to normal. Platelet-plasma interactions that promote platelet aggregation and increased plasma levels of the platelet-specific protein beta-thromboglobulin have been reported in insulin-dependent diabetic patients who have not manifested vascular complications as well as in those with vascular complications. It has now been demonstrated in animal models that platelet microthrombi are found in small retinal vessels after months of experimental diabetes. Collectively, these findings demonstrate that alterations in platelet and endothelial function that favor thrombosis occur early in the diabetic state and may contribute to microvascular disease. There are several ongoing studies of antiplatelet agents in diabetic vascular disease that will provide clinical evidence bearing on the major postulate. Until these and other studies are completed, the platelet-endothelial story remains an attractive hypothesis in the genesis of diabetic microvascular disease.

Animals↗
PubMed1983

Elevated glucose concentrations increase factor VIIIR:Ag levels in human umbilical vein endothelial cells.

To determine if endothelial cell metabolism is affected by the elevated glucose concentrations known to occur in diabetes mellitus, we measured cellular Factor VIIIR:Ag in endothelial cells grown under conditions of increased glucose concentration. The results of this study illustrate that, under cell culture conditions, an increase in glucose concentration results in increased cellular levels of Factor VIIIR:Ag. Specifically, a glucose concentration of 300 mg/dl resulted in a 23% increase in Factor VIIIR:Ag levels while a glucose concentration of 600 mg/dl resulted in a 54% increase in Factor VIIIR:Ag levels. These in vitro findings may relate to the increase in plasma Factor VIIIR:Ag levels known to occur in diabetic patients.

Antigens↗
PubMed1983

Time course of changes in in vitro platelet function and plasma von willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag) in the diabetic rat.

The relationship between platelet abnormalities and vessel wall changes in diabetes is not known. We have examined the time course of alterations in in vitro platelet function and endothelial damage, as assessed by measurement of plasma levels of von Willebrand factor (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag), in streptozotocin-induced diabetic rats. Platelet aggregation and the platelet release reaction in response to ADP, thrombin, and collagen were measured in suspensions of washed platelets prepared from rats 3, 7, 14, or 28 days after induction of diabetes and in control animals. Platelets from diabetic animals showed enhanced aggregation response to ADP as early as 3 days after induction of diabetes and became hyperresponsive to thrombin after 7 days, compared to control platelets. Thrombin-induced release of serotonin was greater in platelets from diabetic animals at 14 days. Collagen-induced responses were not different at any time studied. VIIIR:WF was determined by ristocetin-induced platelet agglutination time in gel-filtered platelets, and VIIIR:Ag was determined by immunoelectrophoretic technique. VIIIR:WF and VIIIR:Ag were significantly enhanced in plasma from rats at 28 days after induction of diabetes and VIIIR:Ag was enhanced in plasma from rats at 14 days after induction of diabetes, but at the earlier times studied, neither were different from values in plasma from control-treated rats. Changes in VIIIR:WF and VIIIR:Ag therefore occurred later than the changes in platelet function. Plasma cholesterol concentrations were not significantly different at any of the times studied, but plasma triglyceride concentrations were significantly increased at 3 days and remained increased with further durations of diabetes. This may have contributed to the observed platelet and vessel wall changes. If these in vitro alterations reflect in vivo behavior, then platelet alterations occur before vessel wall changes and therefore do not appear to be a consequence of such changes in experimental diabetes mellitus.

Adenosine Diphosphate↗
PubMed1983

Release of PAF by human polymorphonuclear leucocytes stimulated by immune complexes bound to Sepharose particles and human erythrocytes.

Human polymorphonuclear leucocytes (PMN) incubated with surface-bound immune complexes (IC) release a substance that induces platelet aggregation and serotonin-release. This substance was identified as platelet-activating factor (PAF) on the basis of its sensitivity to phospholipase A2 and of its purification by thin-layer chromatography in identical conditions to those used to purify zymosan-induced PAF. We used two types of substrates to absorb our IC:Sepharose particles to which we coupled human serum albumin, and which were later incubated with specific rabbit antiserum to form surface-bound immune complexes, and human erythrocytes, to which soluble IC can be passively adsorbed. Both types of surface-bound IC were found to stimulate the release of PAF by human PMN in the absence of complement. These results suggest that PMN may play a central role in the early stages of IC-induced inflammation: they recognize IC adsorbed to red cells or to any other cell able to adsorb IC, and they induce the activation of platelets and release of vasoactive amines, which leads to the increase of vascular permeability believed to be essential for extravascular IC deposition.

Animals↗
PubMed1982

Surface binding, internalization and degradation by cultured human fibroblasts of low density lipoproteins isolated from type 1 (insulin-dependent) diabetic patients: changes with metabolic control.

A previous study of low density lipoprotein metabolism by cultured cells focused on the metabolism of normal lipoproteins in vitro by fibroblasts isolated from diabetic patients. No abnormalities were found. We have followed the opposite approach. Using normal human fibroblasts as test cells we compared the metabolism in vitro of low density lipoproteins isolated from diabetic patients before and after metabolic control. We found a significant decrease (p less than 0.02) in internalization and degradation of low density lipoproteins isolated from diabetic patients before metabolic control when compared with those isolated from normal control subjects or from the same patients after metabolic control. The observed changes were mainly apparent in intracellular degradation. To evaluate whether the observed differences in low density lipoprotein behaviour were correlated with lipid or apolipoprotein composition, we measured cholesterol, triglyceride, apolipoprotein B and total protein levels in the low density lipoproteins tested. A significant decrease (p less than 0.05) of the triglyceride/protein ratio was found in post-control low density lipoproteins suggesting that a high triglyceride content may interfere with low density lipoprotein metabolism. The present study represents the first observation that metabolic control in diabetes mellitus can alter low density lipoprotein-cell interaction and suggests a possible mechanism for the enhanced incidence of atherosclerosis in diabetic patients.

Adolescent↗
PubMed1982

Polymorphonuclear leucocytes release a factor(s) that induces platelet aggregation and ATP release after interaction with insoluble and surface-fixed immune complexes.

We have found that human polymorphonuclear leucocytes (PMN) can be stimulated by large aggregates (heat-aggregated IgG, chemically polymerized IgG, heavily aggregated human immune complexes) and by surface-bound immune complexes (IC) to release enzymes (lysozyme, beta glucuronidase) and a factor(s) able to induce platelet aggregation and ATP release from the platelets. Surface-bound IC were most effective in stimulating the release of this factor(s). We used several substrates for their preparation: plastic-adsorbed antigen. Sepharose-coupled antigen and polymerized antigen. The platelet-aggregating factor(s) released by IC-stimulated PMN and zymosan-stimulated PMN were compared for their susceptibility to inhibition by indomethacin. Both induced a first phase of platelet aggregation that was resistant to indomethacin, but the second phase of aggregation and the release of platelet ATP were inhibited to a variable degree, more pronounced in the case of the factor(s) released after PMN-IC interaction. The lack of inhibition of the early phases of aggregation induced by our factor(s) when platelets were simultaneously exposed to indomethacin suggests that the classical, phospholipid PAF is released under these experimental conditions. Although, further experiments will be necessary to fully characterize the factor(s) involved, our observations suggest a complex interrelationship between human PMN and platelet activation, which may play an important role in the sequence of events that mediate the tissue deposition of IC and appearance of inflammatory changes.

Adenosine Triphosphate↗
PubMed1981

Increased platelet arachidonic acid metabolism in diabetes mellitus.

Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine if platelet obtained from insulin-dependent diabetic subjects synthesize increased quantities of the labile aggregating substance, thromboxane A2 (TXA2), and if it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (P less than 0.01, N = 12) in platelet-rich plasma obtained from diabetics compared with matched controls. Arachidonic acid-stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, P less than 0.02, N = 15). Platelet aggregation induced by arachidonic acid (0.4-0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (P less than 0.04, N = 14), a competitive antagonist of the actions of prostaglandin H2 or TXA2 on platelets, compared with matched controls. The results support the notion that platelets obtained from some insulin-dependent diabetic subjects manifest increased synthesis of TXA2, which may contribute to the enhanced platelet aggregation.

Arachidonic Acid↗
PubMed1981

Plasma factors and platelet aggregation in diabetes mellitus.

Plasma fron some diabetic patients, particularly those with advanced retinopathy and nephropathy, will potentiate ADP-induced platelet aggregation. Partial purification of plasma from a diabetic patient with nephropathy has yielded a fraction with this activity. A linea dose response curve relating plasma factor (6.25-50 ng protein) and platelet aggregation or ATP release at 4 minutes after adding ADP has been found. The effect is blocked by exposure of platelets to aspirin, prostaglandin or eicosapentaenoic acid. Soluble immune complexes are found in many diabetics and are known to be platelet-active. We have isolated immune complexes from sera of six diabetics and have shown enhancement of the second phase of platelet aggregation and of ATP release by these immune complexes from platelets sensitized to ADP. We conclude that plasma proteins from diabetics may accentuate ADP-induced platelet aggregation and ATP release, possibly by acting through prostaglandin pathways. Immune complexes appear to be one group of plasma proteins with such platelet active behavior. Further studies are indicated to characterize these plasma factors and to assess their in vivo significance regarding platelet function and vascular disease in diabetes mellitus.

Antigen-Antibody Complex↗
PubMed1981

Increased platelet prostaglandin and thromboxane synthesis in diabetes mellitus.

Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. These studies were designed to determine if platelets obtained from diabetic subjects manifest increased metabolism of arachidonic acid to labile aggregating substances, such as thromboxane A2 (TXA2), and if they play a role in the enhanced platelet aggregation. Arachidonic acid stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (p less than 0.01, n = 12) in platelet-rich plasma obtained from diabetic compared to matched controls. Arachidonic acid stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, p less than 0.02, n = 15). Platelet aggregation induced by arachidonic acid (0.4-0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (p less than 0.04, n = 14), an antagonist of the actions of prostaglandin H2 or TXA2 on platelets, compared to matched controls. We conclude that platelets obtained from some diabetic subjects manifest increased metabolism of arachidonic acid to labile aggregating substances which may contribute to the enhanced platelet aggregation.

Arachidonic Acids↗
PubMed1981

Increased platelet thromboxane synthesis in diabetes mellitus.

Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine whether platelets obtained from diabetic subjects synthesize increased quantities of the labile aggregating substance. TXA2, and whether it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (p < 0.01, n = 12) in platelet-rich plasma obtained from diabetic patients than in matched controls. Arachidonic acid-stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, p < 0.02, n = 15). Platelet aggregation induced by arachidonic acid (0.4 to 0.8 mM) was inhibited significantly less than in matched controls by imidazole, a thromboxane synthetase inhibitor (p < 0.01, n = 11), and 13-azaprostanoic acid, an antagonist of the actions of PGH2 or TXA2 on platelets (p < 0.04, n = 14). We conclude that platelets obtained from some diabetic subjects manifest increased synthesis of TXA2, which may contribute to the enhanced platelet aggregation.

Adult↗