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Biomedical subjects

C D Austin

Publications and source records attributed to C D Austin.

8 recordsLinked to original sources
PubMed1992

Have we oversold case management as a "quick fix" for our long-term-care system?

Case management has become a core component in almost every community-based, long-term-care program. Yet it is, at best, a piecemeal response to an enormous health and social services problem. Fragmented funding, ill-considered public health policy, and short-range planning assure that no single system, even one as ubiquitous as case management, will eliminate the serious problems plaguing our health care system.

Continuity of Patient Care↗
PubMed1991

Evidence that agonist-induced activation of calpain causes the shedding of procoagulant-containing microvesicles from the membrane of aggregating platelets.

One of the responses of platelets to stimulation is activation of intracellular calpain (the Ca(2+)-dependent protease). Previously, we have shown that activation of calpain in platelets is involved in the generation of platelet procoagulant activity. Because procoagulant activity is present on the microvesicles that are shed from activated platelets, in this study we examined whether calpain is involved in the shedding of microvesicles. Platelets were incubated with the physiological agonists collagen or thrombin. The extent of activation of calpain correlated positively with the amount of procoagulant-containing microvesicles that formed, and the shedding of procoagulant-containing microvesicles was inhibited by calpeptin, MDL, and EST (E-64-d), three membrane-penetrating inhibitors of calpain. The protein composition of the microvesicles shed from aggregating platelets was similar to that of microvesicles shed by platelets in which the association of the membrane skeleton with the plasma membrane had been disrupted by incubation of platelets with dibucaine or ionophore A23187. Furthermore, like microvesicles shed from dibucaine- or ionophore A23187-treated platelets, those shed from the aggregating platelets possessed procoagulant activity. These results are consistent with the possibility that activation of calpain in aggregating platelets causes the shedding of procoagulant-containing microvesicles. We suggest that the shedding of microvesicles results from the calpain-induced hydrolysis of the platelet membrane skeleton.

Blood Coagulation Factors↗
PubMed1990

The role of calpain in stimulus-response coupling: evidence that calpain mediates agonist-induced expression of procoagulant activity in platelets.

Although calpain (the Ca2(+)-dependent protease) is widely distributed, its function is poorly understood. One cell in which it becomes activated as a consequence of activation of the cell is the blood platelet. The aim of the present study was to determine whether activation of calpain was responsible for any of the responses of platelets to stimulation. Platelets were incubated with calpeptin, a membrane-penetrating inhibitor of calpain, before being exposed to an agonist. Concentrations of calpeptin that totally inhibited the agonist-induced hydrolysis of actin-binding protein (ABP) by calpain had no effect on many other responses associated with platelet activation: phosphorylation of myosin light chain, phosphorylation of P47, platelet shape change, aggregation of platelets, secretion of granule contents, or retraction of fibrin clots. However, these concentrations of inhibitor decreased the agonist-induced generation of procoagulant activity (assayed as the ability of platelets to catalyze the conversion of prothrombin to thrombin in the presence of factor Va and factor Xa). When thrombin was the agonist, the amount of ABP that was hydrolyzed was small; only a small component of the total agonist-induced procoagulant activity was inhibited by calpeptin. When collagen was the agonist, more ABP was hydrolyzed and the amount of procoagulant activity generated was greater; calpeptin decreased the collagen-induced procoagulant activity to levels comparable with those induced by thrombin in the presence of the inhibitor. We suggest that there are at least two mechanisms by which procoagulant activity is generated on activated platelets and that the agonist-induced activation of calpain mediates one of these mechanisms. These results show that activation of calpain is a component of the stimulus-response pathway in platelets.

Blood Coagulation↗
PubMed1990

Role of the membrane skeleton in preventing the shedding of procoagulant-rich microvesicles from the platelet plasma membrane.

The platelet plasma membrane is lined by a membrane skeleton that appears to contain short actin filaments cross-linked by actin-binding protein. Actin-binding protein is in turn associated with specific plasma membrane glycoproteins. The aim of this study was to determine whether the membrane skeleton regulates properties of the plasma membrane. Platelets were incubated with agents that disrupted the association of the membrane skeleton with membrane glycoproteins. The consequences of this change on plasma membrane properties were examined. The agents that were used were ionophore A23187 and dibucaine. Both agents activated calpain (the Ca2(+)-dependent protease), resulting in the hydrolysis of actin-binding protein and decreased association of actin with membrane glycoproteins. Disruption of actin-membrane interactions was accompanied by the shedding of procoagulant-rich microvesicles from the plasma membrane. The shedding of microvesicles correlated with the hydrolysis of actin-binding protein and the disruption of actin-membrane interactions. When the calpain-induced disruption of actin-membrane interactions was inhibited, the shedding of microvesicles was inhibited. These data are consistent with the hypothesis that association of the membrane skeleton with the plasma membrane maintains the integrity of the plasma membrane, preventing the shedding of procoagulant-rich microvesicles from the membrane of unstimulated platelets. They raise the possibility that the procoagulant-rich microvesicles that are released under a variety of physiological and pathological conditions may result from the dissociation of the platelet membrane skeleton from its membrane attachment sites.

Actins↗
PubMed1988

Phosphorus and proton magnetic resonance spectroscopic studies on the relationship between transparency and glucose metabolism in the rabbit lens.

We report the results of a series of nuclear magnetic resonance (NMR) experiments designed to investigate the relationship between particular aspects of glucose metabolism and cataract formation in the rabbit lens. The glucose metabolism of the rabbit lens incubated in TC-199 medium containing 5.5 mM glucose, in glucose-deficient medium, and in modified Earle's medium containing 5.5 mM glucose devoid of NaCl, is examined in conjunction with the assessment of lens transparency. Significant age-dependent differences in the phosphorus metabolite profile and in hexosemonophosphate shunt flux, as measured by NMR, were observed in lenses incubated in TC-199 medium containing 5.5 mM glucose. Incubation in glucose-deficient medium for 8 hr results in significant increases in the levels of inorganic phosphate and phosphomonoesters, and decreases in ATP and L-alpha-glycerolphosphate. These levels regain near-normal values after 24 hr incubation in control medium containing 5.5 mM glucose. By contrast, shunt flux is three times the basal level during the recovery period. Lens clarity, as assessed by slit lamp micrography, was maintained throughout the duration of the experiment. Incubation of adult and juvenile lenses for 18 hr in Earle's medium (pH 7.4 or 9.2) containing 5.5 mM glucose, and no NaCl, results in uniform lenticular opacification within 18 hr and changes in ultrastructure of the epithelial and cortical lens fiber cells. No statistically significant change in the NMR visible phosphorus metabolite profile or intralenticular pH is observed for the adult rabbit lens relative to a lens incubated under control conditions. For the juvenile rabbit lens, small, but statistically significant differences in the levels of dinucleotide and uridinediphosphoglucose were observed. Shunt flux, in contrast, is increased two-fold. These results demonstrate that the NMR visible phosphorus metabolite profile of the lens does not necessarily correlate with transparency, and that hexosemonophosphate shunt activity provides a sensitive measure of prior or current lenticular stress.

Age Factors↗
PubMed1986

The Veterans Administration Northwest Regional Health Services Research and Development Field Program: organization, activities, and early outcomes.

In 1982, the Veterans Administration established Health Services Research field programs in each of the six VA regions. Herein, we describe the historical origins, organization, responsibilities, activities, and early accomplishments of one of these programs--the Northwest Regional HSR&D field program. Special reference is made to this program's commitment to health services research relevant to geriatrics and gerontology, including the development of a system-wide agenda for research, information syntheses in geriatrics-relevant health services research topics, and the conduct of funded projects pertinent to care of the elderly. The importance of a medical center location for the field programs is discussed, and early indications of institutional impact are described.

Aged↗