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Biomedical subjects

S E Lind

Publications and source records attributed to S E Lind.

At least 19 recordsLinked to original sources
PubMed1992

Effects of actin filaments on fibrin clot structure and lysis.

The muscle and cytoskeletal protein actin is released from cells as a consequence of cell death and interacts with components of the hemostatic and fibrinolytic systems, including platelets, plasmin, and fibrin. We report here that incorporation of actin filaments into fibrin clots changes their viscoelastic properties by increasing their shear modulus at low deforming stresses and by nearly eliminating their tendency to become more rigid with increasing deformation (ie, exhibit strain-hardening). The viscoelastic effects depended on the length of the actin filaments as shown by the effects of the plasma filament-severing protein, gelsolin. Binding of actin to fibrin clots also varied with actin filament length. The plasma actin-binding proteins gelsolin and vitamin D-binding protein reduced, but did not eliminate, the incorporation of actin in the clot. Fluorescence microscopy showed a direct association of rhodamine-labeled actin filaments with the fibrin network. Incubation of clots containing long actin filaments in solutions containing physiologic concentrations of gelsolin (2 mumol/L) released 60% of the actin trapped in the clot. Reduction of the actin content of a fibrin clot by incubation in a gelsolin-containing solution resulted in an increased rate of clot lysis. The ability of plasma gelsolin to shorten actin filaments may therefore be of physiologic and potentially of therapeutic importance insofar as gelsolin-mediated diffusion of actin from the clot may restore the clot's rheologic properties and render it more sensitive to the lytic action of plasmin.

Actins↗
PubMed1992

Patients' preferences for learning the results of mammographic examinations.

The communication of diagnostic test results is an important aspect of the interaction between doctors and patients. Communication of mammogram results is of particular interest because the test is used to detect a common and potentially dangerous malignancy and because patients in the United States are able in some locations to obtain mammography at their own request, rather than being referred by a physician. We conducted a survey to learn about the preferences of a group of women at a traditional mammography center for learning the results of this commonly performed test. We asked women undergoing mammography to respond to questionnaires designed to learn: 1) How they felt about different methods of telling patients the results of mammograms; 2) How they were informed of the results of previous mammograms; 3) How they were told the results of the current mammograms. Patients indicated that if no abnormality is detected, they prefer to have their doctor call with the result, but if the study is 'abnormal' they wish to be told by their own physician in the office. Failing to notify the patient if the study is normal was the least preferred outcome. This group of patients did not express an interest in the most immediate form of notification (i.e. learning the result from the radiologist performing the test). Analysis of how patients felt about ways in which they were previously informed of the results of mammograms suggests that their reactions are influenced to a large extent by their clinical status. Patients undergoing mammography for diagnostic purposes, for example, were less pleased by a 'preferred' method (i.e. being told by their physician) than were those undergoing screening mammography. While patients have opinions about how they would prefer to be told their mammogram results, they are accepting a variety of methods of telling, if they are receiving good news. If abnormalities are found, patients prefer to be told in person by their own physician. Interpretations of surveys of patient satisfaction should be tempered by the finding that the clinical status of the patient alters their perceptions of satisfaction with this aspect of their physician's behavior. Patient preferences may change if increasing numbers of women are told their results by the radiologist.

Adult↗
PubMed1992

Histamine, actin-gelsolin binding, and polyphosphoinositides in human umbilical vein endothelial cells.

Histamine activates inositol phospholipid metabolism, increases calcium, and causes a change in shape of human umbilical vein endothelial (HUVE) cells. Changes in endothelial cell shape are determined, in part, by changes in the actin cytoskeleton. Gelsolin is an actin-binding protein with the potential to alter the actin cytoskeleton in response to changes in cell calcium and/or changes in polyphosphoinositides. Therefore, we examined the interactions of actin and gelsolin in HUVE cells in which inositol phospholipid metabolism was activated with histamine. In HUVE cells exposed to histamine we estimated actin-gelsolin binding by quantitating actin and gelsolin, immunoprecipitated with anti-gelsolin Sepharose. We estimated the relative amount of filamentous actin in the histamine-exposed HUVE cells by quantitating the amount of actin that was Triton soluble. We also measured the amount of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) in the HUVE cells before and after exposure to histamine. We found that histamine decreased the amount of actin that was immunoprecipitated with gelsolin, decreased the fraction of cell actin that was Triton soluble, and increased PIP and PIP2. These results demonstrate that histamine promotes actin filament formation in HUVE cells and that histamine-mediated changes in actin-gelsolin binding in these cells are better predicted by changes in polyphosphoinositides than by increases in cell calcium.

Actins↗
PubMed1991

Actin accelerates plasmin generation by tissue plasminogen activator.

Actin has been found to bind to plasmin's kringle regions, thereby inhibiting its enzymatic activity in a noncompetitive manner. We, therefore, examined its effect upon the conversion of plasminogen to plasmin by tissue plasminogen activator. Actin stimulated plasmin generation from both Glu- and Lys-plasminogen, lowering the Km for activation of Glu-plasminogen into the low micromolar range. Accelerated plasmin generation did not occur in the presence of epsilon-amino caproic acid or if actin was exposed to acetic anhydride, an agent known to acetylate lysine residues. Actin binds to tissue plasminogen activator (t-Pa) (Kd = 0.55 microM), at least partially via lysine-binding sites. Actin's stimulation of plasmin generation from Glu-plasminogen was inhibited by the addition of aprotinin and was restored by the substitution of plasmin-treated actin, indicating the operation of a plasmin-dependent positive feedback mechanism. Native actin binds to Lys-plasminogen, and promotes its conversion to plasmin even in the presence of aprotinin, indicating that plasmin's cleavage of either actin or plasminogen leads to further plasmin generation. Plasmin-treated actin binds Glu-plasminogen and t-PA simultaneously, thereby raising the local concentration of t-PA and plasminogen. Together, but not separately, actin and t-PA prolong the thrombin time of plasma through the generation of plasmin and fibrinogen degradation products. Actin-stimulated plasmin generation may be responsible for some of the changes found in peripheral blood following tissue injury and sepsis.

Actins↗
PubMed1991

Actin is a noncompetitive plasmin inhibitor.

Actin, one of the most abundant cellular proteins, circulates at micromolar concentrations in peripheral blood. Because actin released from dying cells may be trapped in fibrin clots that form at sites of tissue injury, we examined the effects of actin upon lysis of fibrin clots in vitro. Incorporation of native rabbit skeletal muscle actin into fibrin clots slowed their rates of lysis for periods of up to 24 h, an effect not seen when comparable concentrations of human IgG or bovine serum albumin were added instead. Actins isolated from a variety of sources inhibited plasmin's hydrolysis of the synthetic substrate S-2251 in a noncompetitive manner, with a Ki of a 0.6-3.1 microM. Inhibition was rapid, but covalent actin-plasmin complexes were not formed. Both epsilon-aminocaproic acid and tranexamic acid prevented actin's inhibition of plasmin, suggesting that accessible lysine residues of actin interact with the kringle (lysine-binding) regions of plasmin. Neither of the high-affinity actin-binding proteins of plasma (plasma gelsolin and vitamin D-binding protein) prevented actin from inhibiting plasmin. These findings suggest that actin released into the extracellular space following cell death may modulate plasmin action, and hence a number of plasmin-dependent biological responses, at sites of inflammation and tissue injury.

Actins↗
PubMed1991

Oncologists vary in their willingness to undertake anti-cancer therapies.

Previous studies have shown that groups of cancer sub-specialists differ in their stated willingness to undergo treatment for diseases lying within their area of expertise. In order to learn whether oncologists feel similarly about other forms of cancer, medical, radiation, and surgical oncologists were asked to fill out a questionnaire indicating whether they would be willing to undergo either chemotherapy or radiation therapy for a variety of common malignancies, or recommend them to a spouse or sibling. Subjects were also asked whether they would undertake an experimental therapy (interleukin-2) for any of three malignancies, or recommend such treatment to a spouse or relative. Fifty-one oncologists (14 radiation oncologists, 14 surgical oncologists, and 23 medical oncologists) were recruited from the staff of four university teaching hospitals. Although they agreed about accepting or declining therapy for some examples, there was considerable heterogeneity in their responses. In only 37% of the 30 cases involving standard therapies did greater than or equal to 85% of the oncologists agree that they would accept or refuse therapy. Only some of the variation of the responses could be attributed to the sub-specialty orientation of the oncologists. Physicians were as willing to recommend standard therapies for themselves as a spouse or sibling. Physicians were also divided in their opinion about whether they would accept a particular experimental therapy if diagnosed with one of three neoplasms. They were significantly more likely, however, to recommend it for a spouse or sibling than to accept it for themselves. Variation in the proportion of patients who receive anti-cancer therapies may relate, in part, to differences in opinion concerning the worth of such therapies among oncologists or primary physicians. This study shows that oncologists are quite heterogeneous with regard to their personal preferences for anti-cancer treatments for a variety of malignancies. Further studies are required to learn if such attitudes (among oncologists or primary physicians) directly affect the administration of such therapies.

Adult↗
PubMed1990

American oncology and the discourse on hope.

From the perspective of medical anthropology and comparative research, American oncology appears as a unique variant of international biomedical culture, particularly when contrasted with oncological practice in societies such as Japan and Italy. Based on interviews with 51 oncologists in Harvard teaching hospitals, this paper argues that American oncological practice draws on distinctive cultural meanings associated with "hope" and is infused with popular notions about the relationship between psyche and soma, the progressive efficacy of biotechnical interventions, truth-telling, and the nature of the physician-patient relationship.

Adult↗
PubMed1989

Apparent response of refractory post-transfusion purpura to splenectomy.

Post transfusion purpura (PTP) is a rare disorder characterized by the abrupt onset of severe thrombocytopenia following transfusion. A patient with PTP and massive bleeding was refractory to corticosteroids, gamma globulin, and plasma exchange but developed an immediate and sustained rise in platelet count following splenectomy. Splenectomy may be a useful therapeutic modality in patients with refractory PTP.

Aged↗
PubMed1989

Telling the diagnosis of cancer.

Although a concensus has emerged in this country that patients should be told when cancer is discovered, no data is available to indicate how and where patients are currently told that they have cancer. Fifty-five patients undergoing anticancer therapy were therefore interviewed to learn how this process occurs. The majority of patients were told by surgeons (74%) and only a minority by primary care physicians (11%). Most were told in a traditional medical setting (42% in the doctor's office, 17% in a hospital room), but 23% were told over the telephone and 19% in the recovery room. Two indicators of patient satisfaction with the telling process suggested that different sites of telling were not equivalent. Patients told over the telephone or in the recovery room were more likely to describe the telling in negative terms and less likely to describe their doctors as being helpful in understanding their illness than those told in a doctor's office or in their hospital bed. This pilot study indicates considerable variation in this aspect of patient care and suggests directions for future research. To determine whether interviews that explore these issues with cancer patients are unpleasant or stressful, patients' reactions to being subjects in this study were sought. Patients asked directly at the completion of the interview or surveyed 2 to 4 months later said the interview had been helpful and/or a positive experience. None expressed negative feelings about participating. Concerns about the psychological harm resulting from such study of this patient group do not appear to be warranted and should not impede future research.

Female↗
PubMed1988

Depression of gelsolin levels and detection of gelsolin-actin complexes in plasma of patients with acute lung injury.

Actin is the major protein of muscle and nonmuscle cells and is one of the most abundant body proteins. Physiologic or pathologic cell death may therefore result in the liberation of large amounts of this fibrous protein into the extravascular space. The potential for long actin filaments to increase plasma viscosity and change the rheology of the microvasculature are potentially obviated by the presence of 2 recently recognized plasma actin-binding proteins, vitamin-D-binding protein, and plasma gelsolin. As part of our initial evaluation of this newly recognized physiologic system in humans, we measured levels of gelsolin in plasma samples from patients with extensive lung injury. Gelsolin levels were depressed in 25 of 25 patients with the adult respiratory distress syndrome (ARDS), a disease characterized by massive cellular injury, as determined by either of 2 functional assays for gelsolin. Mean total gelsolin concentration of 20 patients with ARDS was 89.2 +/- 33 micrograms/ml (normal levels, approximately 240 micrograms/ml; p less than 0.001) and the mean free gelsolin concentration 69.6 +/- 29 micrograms/ml (normal levels, approximately 240 micrograms/ml; p less than 0.001). Gelsolin concentrations of 6 patients with bacterial pneumonias were also depressed, but to a lesser degree (mean total level, 117 +/- 21 micrograms/ml). Direct demonstration of the presence of actin in these plasmas (but not in normal plasmas) was performed by precipitating actin directly with DNase-Sepharose beads, or indirectly with antigelsolin-Sepharose beads, as confirmed with immunoblotting. Actin was found in 18 of 19 patients using DNase beads and in 7 of 19 using antigelsolin beads.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1988

Circulating actin-gelsolin complexes following oleic acid-induced lung injury.

Plasma gelsolin is one of two extracellular proteins that bind actin, a major body protein, with high affinity. The authors performed a series of experiments to determine whether tissue injury leads to actin release and the formation of circulating actin-gelsolin complexes. Two functions of plasma gelsolin, filament-nucleating and filament-severing activity, were used to measure total and free gelsolin concentrations, respectively. Both gelsolin and gelsolin-actin complexes nucleate actin assembly, whereas only free gelsolin severs actin filaments. Therefore, nucleation reflects the total gelsolin concentration, severing, the free gelsolin concentration, and the difference, gelsolin-actin complexes. Injection of F-actin in the rat caused a reduction in the free, but not total, gelsolin levels, consistent with the formation of circulating actin-gelsolin complexes. Oleic acid (50 mg/kg) administered intravenously in rats, a treatment that causes acute hemorrhagic pulmonary necrosis, caused the free gelsolin concentration to fall to a greater extent than the total gelsolin concentration, which indicated the presence of circulating actin-gelsolin complexes. Lower doses (9-27 mg/kg) in rabbits caused a qualitatively similar but smaller change in the free gelsolin level. Plasma gelsolin was immunoprecipitated at times when actin-gelsolin complexes were present, as determined functionally, and bound actin was demonstrated by immunoblotting with an anti-actin antiserum. These studies show that considerable amounts of actin are released into the extracellular space during acute lung injury and that circulating actin-gelsolin complexes can be detected in the peripheral blood.

Actins↗
PubMed1988

Decreased plasma gelsolin levels in patients with Plasmodium falciparum malaria: a consequence of hemolysis?

Mammalian plasma contains a high-affinity actin-binding protein, plasma gelsolin, that severs actin filaments. Destruction of erythrocytes could result in the release of erythrocyte cytoskeletal actin into the plasma where it could bind to gelsolin. If the clearance of actin-gelsolin complexes exceeds its synthesis, lowering of the plasma gelsolin concentration might follow. To test this hypothesis, we measured plasma gelsolin levels in patients with falciparum malaria, a disease where at least part of the hemolysis takes place in the intravascular space and that is usually not accompanied by dysfunction of other organs. Two functional gelsolin assays showed that the mean plasma gelsolin concentration of 18 Nigerian children with Plasmodium falciparum malaria was less than 50% (P less than .001) of healthy Nigerian control subjects tested at the same time. Patients with pneumonia and febrile seizures also had depressed gelsolin levels, which indicates that factors other than hemolysis can lower gelsolin concentrations. Gelsolin levels were measured in 11 patients from The Gambia with P falciparum malaria before and approximately 3 weeks after treatment. In all cases the gelsolin level increased after treatment. To confirm the hypothesis that hemolysis can result in a lowering of plasma gelsolin levels, hemolysis was induced in rabbits, either acutely (by the injection of human serum) or subacutely (by the administration of phenylhydrazine). A fall in plasma gelsolin levels was seen, the rate of fall differing with the extent of hemolysis. Affinity adsorption of plasma from animals undergoing acute hemolysis with Sepharose beads coupled to the actin-binding protein DNase I, followed by immunoblotting of adherent proteins with antiactin antiserum demonstrated the presence of actin in circulating rabbit plasma. These studies suggest that under some conditions components of the red cell cytoskeleton are exposed to plasma proteins and that accelerated clearance of actin-gelsolin complexes may explain in part the depressed plasma gelsolin levels seen in patients with falciparum malaria.

Actins↗
PubMed1988

Resolution of malignant ascites after intraperitoneal chemotherapy in women with carcinoma of the ovary.

The treatment of malignant ascites is a difficult task that faces the physician who is treating patients with advanced carcinoma. We describe the clinical course of three patients with malignant ascites caused by advanced carcinoma of the ovary who were treated with cisplatin-based intraperitoneal chemotherapy. In all three patients, there was resolution of the ascites with relief of symptoms caused by abdominal distention. Although one patient had a fall in the serum level of CA 125 (the antigen marker of carcinoma of the ovary) with repeated courses of intraperitoneal therapy, there was little reduction in the bulky abdominal tumors. Even though intraperitoneal chemotherapy, as currently administered, does not appear to effect a significant reduction in tumor in women with bulky carcinoma of the ovary, it may be of benefit in improving the quality of life. Larger numbers of patients should be studied to better assess the role of this method of treatment in the palliative cure of patients with symptomatic malignant ascites.

Aged↗
PubMed1987

Reversible binding of actin to gelsolin and profilin in human platelet extracts.

This paper documents the reversible appearance of high-affinity complexes of profilin and gelsolin with actin in extracts of platelets undergoing activation and actin assembly. Sepharose beads coupled to either monoclonal anti-gelsolin antibodies or to polyproline were used to extract gelsolin and profilin, respectively, from EGTA-containing platelet extracts and determine the proportion of these molecules bound to actin with sufficient affinity to withstand dilution (high-affinity complexes). Resting platelets (incubated for 30 min at 37 degrees C after gel filtration) contained nearly no high-affinity actin/gelsolin or actin/profilin complexes. Thrombin, within seconds, caused quantitative conversion of platelet profilin and gelsolin to high-affinity complexes with actin, but these complexes were not present 5 min after stimulation. The calcium-dependent actin filament-severing activity of platelet extracts, a function of free gelsolin, fell in concert with the formation of EGTA-stable actin/gelsolin complexes, and rose when the adsorption experiments indicated that free gelsolin was restored. The dissociation of high-affinity complexes was temporally correlated with the accumulation of actin in the Triton-insoluble cytoskeleton.

Actins↗