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Biomedical subjects

J Freedman

Publications and source records attributed to J Freedman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Blood platelet adhesion to protein studied by on-line acoustic wave sensor.

The attachment of blood platelets to the surface of bare and protein-coated thickness-shear mode acoustic wave devices operating in a flow-through configuration has been studied. Platelets in washed from bind to the gold electrodes of such sensors, but the resulting frequency shifts are far less than predicted by the conventional mass-based model of device operation. Adherence to albumin and various types of collagen can be produced by on-line introduction of protein or by a pre-coating strategy. Differences in attachment of platelets to collagen types I and IV and the Horm variety can be detected. Platelets attached to collagen yield an interesting delayed, but reversible signal on exposure to a flowing medium of low pH. Scanning electron microscopy of sensor surfaces at various time points in this experiment reveals that originally intact platelets are eventually destroyed by the high acidity of the medium. The reversible frequency is attributed to the presence of removable platelet granular components at the sensor-liquid interface.

Albumins↗
PubMed2001

IVIg inhibits reticuloendothelial system function and ameliorates murine passive-immune thrombocytopenia independent of anti-idiotype reactivity.

Although the mechanism of action of intravenous immunoglobulin (IVIg) in treating antibody-dependent thrombocytopenia remains unclear, most studies have suggested that IVIg blocks the function of Fc receptors in the reticuloendothelial system (RES) and/or the protective effect may be due to the presence of variable region-reactive (anti-idiotype) antibodies within IVIg. We evaluated the effect of IVIg on platelet counts in a murine model of passively induced immune thrombocytopenia (PIT). Although IVIg was unable to neutralize the binding of two platelet-specific monoclonal antibodies to their target antigens either in vivo or in vitro, it was able to prevent PIT as well as ameliorate pre-established PIT mediated by these antibodies. IVIg adsorbed against the antibody used to induce thrombocytopenia or endogenous murine immunoglobulin also protected against PIT, indicating that antibodies with anti-idiotype activity present in IVIg are not necessary for its effective treatment of PIT. IVIg significantly blocked the ability of the RES to clear antibody-sensitized red blood cells. F(ab')2 fragments of IVIg, which are unable to block the RES but retain the idiotypic regions, were ineffective at protecting mice from PIT. Our data suggest that IVIg exerts its rapid effect by inhibiting RES function and that anti-idiotype interactions are not required.

Adsorption↗
PubMed2001

Association between cholecystectomy and adenocarcinoma of the esophagus.

BACKGROUND & AIMS: Barrett's esophagus, which is linked to adenocarcinoma of the esophagus, is associated with reflux of bile. Duodenogastric reflux is increased after cholecystectomy. This study aims to evaluate if cholecystectomy is associated with an increased risk of adenocarcinoma of the esophagus. METHODS: A population-based cohort study of cholecystectomized patients in Sweden between 1965 and 1997 cross-linked with the Swedish Cancer Register. RESULTS: Cholecystectomized patients had an increased risk of adenocarcinoma of the esophagus (standardized incidence ratio [SIR], 1.3; 95% confidence interval [CI], 1.0-1.8). Esophageal squamous-cell carcinoma was not found to be associated with cholecystectomy (SIR, 0.9; 95% CI, 0.7-1.1). Patients with gallstone disease on whom surgery was not performed did not have an increased risk of adenocarcinoma or squamous-cell carcinoma of the esophagus. CONCLUSIONS: Cholecystectomy is associated with a moderately increased risk of adenocarcinoma of the esophagus, possibly by the toxic effect of refluxed duodenal juice on the esophageal mucosa. Further studies are needed regarding the link between bile reflux and esophageal carcinogenesis.

Adenocarcinoma↗
PubMed2001

Outcomes of HIV/AIDS case management in New York.

The purpose of this study was to examine HIV case management (CM) outcomes in New York State. The results presented here are part of a larger study that explored: client needs identified during CM, success in arranging needs, other case managers used by the client, coordination between multiple case managers, client satisfaction with CM, and the correlation between health care costs and CM. This paper focuses on the linkage of clients with services. Twenty-eight agencies and 588 clients participated in the study. Each client's chart was reviewed; clients and case managers were interviewed. Almost 9,000 client needs were identified; 79.3% of these needs were for services. Over 72% of needed services were arranged for clients. However, of the services arranged, 12.9% were never utilized. Success in arranging services did not vary based on client demographics; client utilization of services, once arranged, varied based on only one demographic factor (clients who lived outside of New York City had higher utilization rates than those who lived in the city, p < or = 0.05). Services provided directly by the CM agency were arranged and utilized more frequently than services provided by another agency (p < or = 0.05). Medical needs were arranged and utilized at a higher rate-and legal needs at a lower rate-than other services, regardless of where the service was provided (p < or = 0.05). On average it took 2.3 months to arrange a service; however it took less time to arrange medical services and more time to arrange legal services (p < or = 0.05). Females, individuals whose mode of HIV transmission was heterosexual contact, clients whose children were living with them, the inadequately housed, and those without a high school diploma had significantly more needs than other clients (p < or = 0.05). Our study supports CM models that provide intensive services to women with children; the provision of multiple services, in addition to CM, within a single agency; and the need for case manager training on how to work with clients to increase service utilization.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Speciesism?.

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Animal Welfare↗
PubMed2000

Quantification of platelet activation status by analyzing P-selectin expression.

Platelet activation status (PAS) is used for characterizing quality and function of platelets in various experimental and clinical settings. In this study, we created a set of platelet populations differing in PAS, using stimulation of platelets with thrombin in a wide range of concentrations, and analyzed a number of flow cytometric parameters, which characterize PAS by measuring P-selectin (CD62) expression. We found that PAS of a platelet population depends significantly on the specific parameters used for detecting CD62 expression and can differ several fold. We revealed the parameters which are more sensitive for distinguishing the differences between populations with similar low and similar high PAS. Selection of valid and sensitive flow cytometric parameters for PAS evaluation and distinguishing the differences between platelet populations with similar PAS can serve for diagnosis of platelet-associated disorders and monitoring their course and therapeutic interventions.

Flow Cytometry↗
PubMed2000

Flow cytometric parameters for characterizing platelet activation by measuring P-selectin (CD62) expression: theoretical consideration and evaluation in thrombin-treated platelet populations.

Two flow cytometric parameters are generally used to quantify platelet activation as measured by P-selectin (CD62) expression: percentage and mean channel fluorescence of CD62-positive platelets (%(+) and MCF(+), respectively). We describe a method for calculation of indices of platelet activation for positive (IPA(+)) and total (IPA(Sigma)) platelets, which reflect integrated amounts of CD62 expressed in these populations; IPA(+) is calculated as the product of %(+) and MCF(+), whereas IPA(Sigma) is exclusively determined by mean fluorescence of the total platelet population (MCF(Sigma)) and does not depend on %(+). We use these parameters to characterize human platelet activation in whole blood samples treated with varying human alpha-thrombin concentrations, mimicking the variations in platelet activation in a number of clinical settings. Multiparameter analysis of CD62 expression may be useful for selective diagnosis of disorders with systemic or localized platelet activation and for monitoring the clinical course of the disease and effect of therapeutic interventions.

Blood Platelets↗
PubMed2000

Unique processing pathways within recipient antigen-presenting cells determine IgG immunity against donor platelet MHC antigens.

Recipient IgG immunity against leukoreduced donor platelets is dependent on indirect T-cell allorecognition and is suppressed in vivo by inhibitors (aminoguanidine, AMG) of inducible nitric oxide synthase (iNOS). To examine recipient processing pathways of donor platelet antigens, enriched macrophages (antigen-presenting cells [APC]) from BALB/c (H-2(d)) mice were pulsed with allogeneic C57BL/6 (H-2(b)) platelets and transfused weekly into naive BALB/c mice. Platelet-pulsed APC stimulated IgG antidonor antibody production in 45% of recipients by the second transfusion and in 100% by the sixth transfusion; this response was enhanced by pulsing in the presence of interferon-gamma. By the sixth transfusion, high-titer IgG1 (mean titer 4990) and IgG2a (1933) isotypes specific for donor major histocompatibility complex (MHC) class I antigens were detected. Platelet pulsing in the presence of AMG or colchicine significantly inhibited the ability of APC to stimulate IgG alloantibodies; only 50% (P <.005) and 20% (P <.0001) of recipients, respectively, produced antibodies by the sixth transfusion. AMG inhibition was reversed by the addition of L-arginine, the substrate for iNOS. In contrast, pulsing in the presence of chloroquine, the proteasome inhibitory peptide MG115, or Brefeldin A enhanced APC immunity (70-100% of recipients antibody positive by the second transfusion [P <.05]); these agents allowed the pulsed APC to stimulate IgG2a but inhibited IgG1 production and this correlated with a reduction in serum interleukin (IL)-4 levels. The results suggest that for donor platelet antigens to stimulate IgG alloantibodies, recipient APC use the essential generation of nitric oxide and a noncytosolic, pH-independent processing pathway, which can be exploited as an effective immunotherapy target to further inhibit alloimmunization against leukoreduced platelets. (Blood. 2000;95:1735-1742)

Ammonium Chloride↗
PubMed2000

Porcine von Willebrand factor and thrombin induce the activation of c-Jun amino-terminal kinase (JNK/SAPK) whereas only thrombin induces activation of extracellular signal-related kinase 2 (ERK2) in human platelets.

The interaction of platelets with subendothelial von Willebrand factor (VWF), especially under high shear stress, is considered to be the first activation step which primes platelets for subsequent haemostatic events. The signalling cascade which results from the interaction of VWF and its receptor GPIbIX has only been partially defined. Mitogen-activated protein kinases (MAPKs) are a family of downstream transmembrane signalling serine-threonine kinases and have been demonstrated to be present and functional in platelets; these include the extracellular signal-related kinases (ERKs), c-Jun amino-terminal kinases (JNKs) and p38 MAPK. Previously, we showed that p38 MAPK was not required in VWF-induced human platelet activation. It is not known whether VWF-dependent platelet activation involves the activation of the JNK and ERK family of signalling molecules. This report demonstrates that porcine von Willebrand factor (pVWF) induced a sustained and stable JNK activation measurable by 1 min after activation. Thrombin also induced JNK activation assessed at 1 min after activation. In contrast to thrombin, pVWF did not induce ERK2 activation at any time point tested. To ensure that ERK activation was unnecessary for pVWF-dependent platelet activation, we functionally inhibited ERK-dependent signalling with PD98059, a potent and selective inhibitor of the MAP kinase kinase (MEK-1), which is the upstream kinase of ERK1 and ERK2. Although PD98059 inhibited ERK2 activation in platelets, it had no effect on pVWF- or thrombin-induced platelet alpha or lysozomal granule release, modulation of membrane glycoprotein CD41, microparticle formation, platelet shape change or platelet agglutination. It is concluded that pVWF and thrombin induced JNK activation, but whereas thrombin induced ERK2 activation VWF did not; functional ERK2 activity was also not required for pVWF- or thrombin-dependent platelet activation.

Animals↗
PubMed2000

Monoclonal antibody-mediated inhibition of the human HLA alloimmune response to platelet transfusion is antigen specific and independent of Fcgamma receptor-mediated immune suppression.

Presensitization of donor platelets with allo-specific immunoglobulin (Ig)G results in a diminished immune response against subsequent transfusions of platelets. To understand better the mechanism of how alloantibody presensitization results in a decreased alloimmune response, we have used murine monoclonal antibodies directed to polymorphic and non-polymorphic regions of human leucocyte antigen (HLA) as well as platelet-specific molecules. Here, we demonstrated that presensitization with anti-human HLA class I antibodies, as well as beta2-microglobulin-specific antibody, protected against alloantibody production to five subsequent untreated platelet challenges. Use of complement fixing, non-fixing or F(ab')2 fragments of HLA-specific antibody also resulted in complete inhibition of alloantibody production. This protection was not seen when the platelets were presensitized with monoclonal antibodies to CD42a (GPIX), CD32 (low-affinity IgG/Fcgamma receptor) or murine IgG and was thus independent of B-cell FcgammaRII-mediated immune suppression. The inhibition observed was independent of HLA alloantigenic specificity as antibodies directed at the beta2-microglobulin portion of HLA class I were as effective as antibodies against any of the HLA-alpha regions (either polymorphic or non-polymorphic) of class I. This work demonstrates that monoclonal antibody-mediated suppression of the human HLA alloimmune response to platelet transfusion is antigen specific and is independent of FcgammaRII-mediated immune regulation, complement fixing or HLA alloantigenic specificity.

Animals↗
PubMed2000

Cholecystectomy, peptic ulcer disease and the risk of adenocarcinoma of the oesophagus and gastric cardia.

BACKGROUND: Gastro-oesophageal reflux is a strong risk factor for oesophageal adenocarcinoma. Bile and pancreatic enzymes may be particularly carcinogenic. Cholecystectomy causes an increased gastric level of these constituents. A decreased risk of oesophageal adenocarcinoma has been observed in persons infected with cagA-positive Helicobacter pylori. There is a strong correlation between ulcer disease and Helicobacter pylori infection. The aim of this study was to determine whether previous cholecystectomy or peptic ulcer disease affects the risk of oesophageal carcinoma. METHODS: Data were collected as a nationwide population-based case-control study in Sweden between 1995 and 1997. Multivariate adjusted odds ratios (ORs) were calculated with logistic regression. RESULTS: There was no statistically significant association between cholecystectomy and the risk of oesophageal carcinoma. Among persons with previous peptic ulcer, the adjusted OR for oesophageal adenocarcinoma was below unity (OR = 0.6, 95 per cent confidence interval 0.3-1.1). The relative risk estimates for cardia adenocarcinoma and oesophageal squamous cell carcinoma were close to unity. CONCLUSION: Cholecystectomy, despite its effect on the composition of gastric juice, does not appear to increase the risk of adenocarcinoma of the oesophagus or gastric cardia. While the data do not contradict a protective effect of H. pylori, the results are also consistent with absence of such an effect.

Adenocarcinoma↗
PubMed2000

Effect of premedication guidelines and leukoreduction on the rate of febrile nonhaemolytic platelet transfusion reactions.

Platelet transfusion reactions were prospectively studied in haematology/oncology patients at five university teaching hospitals over three consecutive summers. The initial summer study provided baseline information on the use of premedications and the rate of platelet transfusion reactions (fever, chills, rigors and hives). Most (73%) platelet recipients were premedicated and 30% (95% CI 28-33%) of transfusions were complicated by reactions. The second study followed implementation of guidelines for premedicating platelet transfusions. Despite a marked reduction in premedication (50%), there was little change in the platelet transfusion reaction rate, 26% (95% CI 24-29%), or the type of reactions. The third study followed implementation of prestorage platelet leukoreduction while maintaining the premedication guidelines. The reaction rate decreased to 19% (95% CI 17-22%). For nonleukoreduced platelets, there was a statistically significant association between the platelet age and reaction rate (P = 0.04). For leukoreduced platelets, there was no statistically significant association between platelet age and reaction rate (P = 0.5). Plasma reduction of nonleukoreduced platelet products also reduced the reaction rate. These prospective studies document a high rate of platelet transfusion reactions in haematology/oncology patients and indicate premedication use can be reduced without increasing the reaction rate. Prestorage leukoreduction and/or plasma reduction of platelet products reduces but does not eliminate febrile nonhemolytic platelet transfusion reactions.

Blood Preservation↗
PubMed2000

Relationship of myoma cell size and menopausal status in small uterine leiomyomas.

CONTEXT: Although myomas shrink after menopause, the cellular mechanism for this phenomenon has received little attention. It was recently demonstrated that fibrous degeneration is significantly associated with postmenopausal status in both small and large myomas. OBJECTIVE: The purpose of the present study was to evaluate whether reduction in myoma cell size is also associated with postmenopausal status in small myomas. DESIGN: Tumor size and patient age have also been related to fibrous degeneration in small (<1 cm) myomas. Therefore, in the present study, 10 pairs of premenopausal and postmenopausal small myomas were matched within 3 years for patient age, within 1 mm for size, and within 1 grade for degree of fibrous degeneration. Most of the women were in their 50s, the decade during which postmenopausal fibrous degeneration in small myomas is most prevalent. Myoma cell size was derived by morphometric evaluation of relative myoma cell area (correcting for percentage of stroma, as measured by point counting) and by direct counting of the number of myoma cells per unit area in trichrome-stained sections. RESULTS: Small myomas from postmenopausal women had significantly (P <.05) smaller cell sizes than did size-matched myomas from age-matched premenopausal women. Myoma cell sizes and nucleus-cell (N/C) ratios were highly variable, especially in premenopausal myomas. CONCLUSIONS: Reduction in myoma cell size is significantly associated with postmenopausal status in small uterine leiomyomas and may be an important mechanism for postmenopausal shrinkage of myomas. In addition, the high variability of myoma cell size and N/C ratio may further support the somatic mutation theory (ie, the theory that diverse mutations may account not only for variations in the growth potential of uterine myomas, but also for variations in their cellular details).

Cell Size↗
PubMed2000

Physician unions: organizing women in the year 2000.

Interest in physician unions is growing, but surprisingly little has been written about whether union membership addresses the particular needs and interests of women physicians. We begin by looking at the history of physician unions in the United States and then examine physician unions today, and how labor laws influence union membership of physicians. The third section looks at why women join unions, whether these reasons hold true for women physicians, and what role women are playing in physician unions. Finally, we give examples of union responses to gender discrimination and such issues as maternity leave, salary inequities, sexual harassment, and promotions. Since women are prominent as leaders in physician unions, these unions seem to be responsive to the needs of their women members.

Female↗