Stuart E. Lind

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.

Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation.

We determined the plasma kinetics of both actin and complexes of actin with the two high affinity actin-binding proteins of plasma, gelsolin, and vitamin D-binding protein (DBP). Actin is cleared rapidly from the plasma by the liver (half-disappearance time, 0.5 h). Using radiolabeled actin-binding proteins, we found that actin accelerated the clearance of both plasma gelsolin and the vitamin D-binding protein. In separate experiments we found that DBP-actin complexes were cleared more quickly than gelsolin-actin complexes, at a rate comparable to the clearance of actin from the blood. A low affinity interaction (dissociation constant, 2.9 X 10(-4) M) between actin and fibronectin was found, suggesting that little actin will bind to fibronectin in plasma. We conclude that while plasma gelsolin and DBP may both clear actin from the circulation, DBP appears to play a more important role. By so doing, DBP may conserve the filament-severing activity of plasma gelsolin.

Human platelets contain gelsolin. A regulator of actin filament length.

Morphologic and biochemical studies suggest that actin in human platelets polymerizes in response to various stimuli and that shortening of actin filaments can be regulated by calcium. We report that human platelets contain gelsolin, a protein of Mr 91,000 that binds reversibly to actin in the presence of calcium. Platelet gelsolin exhibits immunologic crossreactivity with rabbit macrophage gelsolin and shortens actin filaments as demonstrated by viscosity measurements and gel point determinations. Gelsolin is active in micromolar calcium concentrations and its effects upon actin filaments are reversible. Gelsolin may be a dynamic regulator of actin filament length in the human platelet.

Sequential binding of actin monomers to plasma gelsolin and its inhibition by vitamin D-binding protein.

Functional studies that distinguish free from actin-bound gelsolin based on the ability of the former to sever actin filaments reveal that the binding of actin monomers to gelsolin is highly cooperative and can be prevented by prior incubation of actin with vitamin D-binding protein (DBP), even though the apparent affinity of gelsolin for actin is 50-fold greater than that of DBP. Measurements of actin binding by immunoprecipitation and pyrene-actin fluorescence establish that DBP-actin complexes do not bind to gelsolin and that DBP removes one of the actin monomers in a 2:1 actin-gelsolin complex. These studies may explain why DBP-actin complexes exist in blood plasma in vivo in the presence of free gelsolin and suggest that the interaction of gelsolin with actin in cells and plasma may be regulated in part by actin monomer binding proteins.

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 of 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 physicians behavior. Patient preferences may change if increasing numbers of women are told their results by the radiologist.

Effects of semi-dilute actin solutions on the mobility of fibrin protofibrils during clot formation

Low concentrations of actin filaments (F-actin) inhibit the rate and extent of turbidity developed during polymerization of purified fibrinogen by thrombin. Actin incorporates into the fibrin clot in a concentration-dependent manner that does not reach saturation, indicating nonspecific trapping of actin filaments in the fibrin network. Actin does not retard activation of fibrinogen by thrombin, but rather the alignment of fibrin protofibrils into bundles which constitute the coarse clot. In contrast, equivalent F-actin concentrations have little or no effect on the turbidity of plasma clots. The difference is attributed to the presence of a plasma protein, gelsolin, that severs actin filaments. Purified gelsolin greatly reduces the effect of F-actin on the turbidity of a pure fibrin clot and decreases the fraction of actin incorporated by the clot. A calculation of the extent to which the gelsolin concentrations used in these experiments reduce the fraction of actin filaments which are long enough to impede each others rotational diffusion indicates that it is the overlapping actin filaments which retard the association of fibrin protofibrils. The findings suggest that one role for the F-actin depolymerizing and particularly actin severing activities in blood is to prevent actin filaments released by tissue injury from interfering with the formation of coarse fibrin clots.

Cortical Actin Structures and Their Relationship to Mammalian Cell Movements

Cytoplasmic filaments effect cell movement, organize the cytoplasm, and support the cell membrane. Three filament systems are currently recognized: actin filaments, intermediate filaments, and microtubules. In this chapter we describe the role of actin filaments in the structure and movement of metazoan cytoplasm.

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.

Zymosan activated plasma infusion in sheep: Effects of ethanol administration

Abstract Zymosan activated plasma infusion induces pulmonary sequestration of neutrophils and the release of TXA 2 into the pulmonary vascular bed causing profound and transient pulmonary hypertension. Since ethanol (ETOH) inhibits several inflammatory functions of neutrophils, including adherence and aggregation, we examined the ability of anesthetic doses of ETOH to alter the hemodynamic and cellular response to the infusion of zymosan activated plasma (ZAP) in vivo. Twenty five ml of autologous ZAP was intravenously infused into five control and seven (ETOH-treated sheep during mechanical ventillation. In control sheep the mean pulmonary artery pressure (PAP) transiently increased from 14.7±1.4 mm Hg (mean±SEM) to a pead of 38+8 mm Hg by three minutes after beginning the infusion of ZAP. Blood leukocyte concentration transiently decreased 19% below the baseline value due to pulmonary sequestration of polymorphonuclear leukocytes (PMN). Plasma TXB 2 levels measured by radioimmunoassay (RIA) increased from 0.2 to 5.4 ng/ml six minutes after the initiation of ZAP infusion. In five sheep, intravenous infusion of 200 ml of 96% ETOH yielded very high plasma concentrations (882±101 mg%) and completely inhibited both the rise of PAP and the increase of plasma TXB 2 levels after ZAP infusion. However, blood leukocytes transiently decreased 58% below the baseline value. Lower plasma levels of ETOH (200 and 400 mg%) did not prevent either the increase of PAP or the elevation of plasma TXB 2 after ZAP infusion.