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Background: Although major advances have been made in the treatment of HER2+ metastatic breast cancer (MBC), the goal of care remains largely palliative, therefore better treatments are needed. Given encouraging preclinical and clinical data, the combination of cyclin dependent 4/6 kinase inhibitors and HER2-directed therapy is further being evaluated in this trial. Trial Design: In this phase I/II multicenter trial, we will determine the maximum tolerated dose (MTD) of abemaciclib (Abem) combined with T-DM1. Three Abem dose levels will be examined, 50 mg, 100 mg and 150 mg. The phase 2 portion of this trial will examine whether PFS is increased with addition of Abem to T-DM1 in two pt cohorts - those with ER+ HER2+ MBC and those with ER-HER2+ MBC. For phase 2, a pre-registration biopsy is required to confirm ER and HER2-status and to determine levels of tumor infiltrating lymphocytes; vimentin (an epithelial-mesenchymal transition marker); and CD8 and FOXP3 expression. Blood samples will be collected pretreatment , at 6 weeks, and at progression for all pts. Eligibility Criteria: Phase I&II: All pts must have HER2+ MBC per ASCO-CAP guidelines and prior treatment with a taxane, trastuzumab and pertuzumab. For the phase Iportion, pts can have measurable or non-measurable disease with no restriction on the number of prior lines of therapy. In the phase II portion, pts must have measurable disease with ≤1-2 prior lines of chemotherapy alone, ≤1 HER2-directed therapy alone, and/or chemotherapy with HER2-directed therapies. There is no limit on prior endocrine therapy. Specific Aims: The primary objective of the phase II trial is to assess whether addition of Abem to T-DM1 increases PFS in one or both patient cohorts. Secondary objectives include an assessment of toxicity, objective response rates and overall survival. Correlative studies will assess the association between baseline TIL levels, vimentin expression, and CD8/FOXP3 expression with PFS. Changes in peripheral blood mononuclear cells, CTCs, ctDNA and serum thymidine kinase 1 during the course of treatment will be examined to determine if there is a link with PFS outcomes overall and separately for each cohort. Pharmacogenomic studies will determine if pts with the FCGR3A-158 polymorphism derive less benefit from T-DM1 and have inferior PFS outcomes compared with pts who do not have this polymorphism. Statistical Methods:Phase I: Standard 3+3 design, with dose limiting toxicities as per protocol. Phase II: For each pt cohort, a stratified randomization scheme will be used to assign pts to treatment with liver mets as a stratification factor. For each pt cohort, a stratified log rank test will be used to assess whether PFS is increased with the addition of Abem to T-DM1. A non-binding futility analysis will be applied in each cohort after 58 events in the ER+ HER2+ MBC study cohort and 48 events in the ER- HER2+ MBC study cohort. Present Accrual: 0; target accrual: minimal 120 pts., maximal 140 pts CohortOne-sidedalphaPowerAccrual Period (accrual rate)Follow-up after close of enrollmentPFS with T-DM1PFS with abema and T-DM1Number of eligible patientsER+/HER2+0.100.912 months (5-6 pts per month)12 months12 weeks24 weeks64 (32 per arm)ER-/HER2+0.100.8512 months (3-4 pts per month)12 months6 weeks12 weeks50 (25 pts per arm) Citation Format: Ciara C O Sullivan, Jun He, Vera J Suman, Krishna R Kalari, Roberto A Leon-Ferre, Jose C Villasboas-Bisneto, Pratima Chalasani, Demet Gokalp Yasar, Daniel M Anderson, Philip J Stella, Anthony J Jaslowski, Susan H Tannenbaum, Angela Saverimuthu, Donald Northfelt, Alvaro Moreno-Aspitia, Jodi M Carter, Minetta C Liu, Liewei Wang, Zhenkun Lou, Matthew P Goetz. A phase I/II trial of abemaciclib and T-DM1 in women and men with HER2-positive advanced or metastatic breast cancer that has progressed on treatment with a taxane, trastuzumab and pertuzumab (THP) (ACCRU-BR-1801) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-19-05.

A substantial portion of breast cancer survivors are active in the workforce, yet factors that allow survivors to balance work with cancer management and to return to work are poorly understood. We examined breast cancer survivors' most valued/desired types of support in early survivorship.Seventy-six employed breast cancer survivors answered an open-ended survey question assessing the most valued/desired support to receive from healthcare providers during early survivorship to manage work and health. Cutrona's (Journal of Social and Clinical Psychology 9:3-14, 1990) optimal matching theory and House's (1981) conceptualization of social support types informed our analyses. Data were content-analyzed to identify themes related to support, whether needed support was received or not, and the types of healthcare providers who provided support.We identified six themes related to types of support. Informational support was valued and mostly received by survivors, but they expected more guidance related to work. Emotional support was valued but lacking, attributed mainly to providers' lack of personal connection and mental health support. Instrumental (practical) support was valued but received by a small number of participants. Quality of life support to promote well-being and functionality was valued and often received. Other themes included non-specific support and non-support.This study expands our understanding of how breast cancer survivors perceive work-related support from healthcare professionals. Findings will inform targeted interventions designed to improve the support provided by healthcare professionals.Breast cancer survivors managing work and health challenges may benefit by having their unmet support needs fulfilled.

Contains fulltext : 70343.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA. METHODS: A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks. RESULTS: There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient's assessment of pain, and patient's and physician's global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible. CONCLUSIONS: The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.

A report is presented on two patients who received surgery on a disc prolapse between the lumbar vertebrae 4 and 5 as treatment for compression of the fifth lumbar root, but in whom the clinically relevant disc prolapse was located higher (lumbar vertebrae 1/2 or thoracic vertebra 12/lumbar vertebra 1). Magnetic resonance tomography made a major contribution to the later diagnosis of the high disc prolapses. Besides precise localization of the lesion, MRT made it easier to understand why such a high disc prolapse can cause a compression syndrome of the fifth lumbar root.

Hemophagocytic lymphohistio-cytosis (HLH) is a rare but serious medical condition with variable clinical outcome. HLH presents real diagnostic and therapeutic challenges to the treating physician despite the major advances in molecular laboratory testing and the immune-chemotherapeutic interventions. Here we present a unique case ofHLH in the setting of hemoglobin H disease provoked by disseminated Yersinia enterocolitica infection. The hemoglobinopathy led to an iron overload state, which provided an optimal milieu for the siderophilic bacterium, Y. enterocolitica, to disseminate. This over whelming infection triggered an uncontrolled and dysregulated inflammatory cytokine cascade with resulting clinical sequelae. The patient was treated conservatively without immunosuppressive therapy and recovered quickly. The long-term outcome of such cases needs further definition.

SummaryRegional limb perfusion with antineoplastic agents stresses the local vasculature in a variety of ways. However, by monitoring the perfusates from limbs treated with melphalan alone or with melphalan plus tumor necrosis factor (TNF) and interferon-γ (IFN-γ), we were able to distinguish the effect of the cytokines on the observed coagulant and fibrinolytic responses. We collected samples of effluent from a series of lower extremities that were perfused with the cytokines and/or melphalan as treatment for localized melanoma. Both regimens produced statistically significant evidence of coagulant and fibrinolytic activation. However, limbs receiving cytokines in addition to the melphalan responded with a sharper rise in tissue plasminogen activator (tPA) and plasmin (plasmin-antiplasmin complexes [PAP]) than limbs treated with melphalan alone. Evidence of thrombin formation (prothrombin fragment 1+2 [FI+2], thrombin-antithrombin complexes [TAT]) was also greater when the cytokines were included, although the response was delayed and less consistent than the fibrinolytic activation.

Operations on lumbar disc prolapses are the most frequent operations in German neurosurgery divisions. After such operations, spondylodiscitis is a dreaded complication which is sometimes difficult to diagnose. Treatment of spondylodiscitis is always protracted and a burden for doctors and patients. Hence, it appears worthwhile to present a further report on discitis and spondylodiscitis, infections of the intervertebral space and the surrounding tissues after disk operations. Various clinical pictures are described: septic progress forms with neurological disorders and the necessity of open wound treatment as well as clinical pictures without septic signs with good recovery after immobilisation and antibiotic treatment. In two cases, CT-guided puncture of purulent suppuration with identification of the causative organisms and specific antibiotic treatment was possible. All patients had a relatively good result: pareses and/or bladder/rectal disorders disappeared completely in every case. The causes of discitis are discussed. The condition arises when nosocomial microorganisms, or very frequently even harmless skin bacteria, enter the wound. A large number of operations are carried out under pressure of time and under hectic conditions, as well as in a confined space in operation theatres which are too warm; these factors increase the susceptibility to infection. However, the resistance of the patient to infection is also weakened after longterm prior antiinflammatory treatment and a stay in hospital before the operation. Besides appropria to treatment of the infection (immobilisation, wound treatment, antibiotic therapy), psychological management of the patient is an important component of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

When planning treatment of tumours in the sella region it is of the utmost importance to obtain precise information about the localization, spread, and (if possible) the type of alteration. Aside from the classic radiographic methods of native diagnosis, angiography, and CT, MRI has been available for some years now. This is a method whereby images can be gained from the various stages of an energetic reaction in the biological substrate: tomograms are possible for any desired plane--those routinely needed for cerebral diagnosis from the horizontal, coronary, and sagittal planes and, given a further improvement of this technology, from special oblique planes which can be matched to the direction of a probable surgical approach. A number of examples demonstrate the significance of this new method, which is a valuable addition to the procedures used up to now: indeed, in some cases it is superior to them. It has been shown that most of the neighbouring structures which border on or have been pushed aside by the tumour in the sella region (blood vessels, brain, optic chiasma, subarachnoid spaces, and occasionally even bone structures) can be identified better than with the procedures used up to now. MRI has thus proved to be valuable, and occasionally indispensable, for the correct choice when considering the many therapeutic methods available for tumours in the sella region.

Endothelial cells (EC) synthesize and secrete von Willebrand factor (vWF), a multimeric glycoprotein required for normal hemostasis. Within human endothelial cells, vWF multimers of extremely high molecular weight are stored in rod-shaped organelles known as Weibel-Palade bodies. Inflammatory mediators, such as interleukin-1, induce in vitro a variety of procoagulant responses by EC, including the secretion of stored vWF. We postulated that other inflammatory mediators might act to balance this procoagulant reaction, thereby assisting in the maintenance of blood fluidity during immune activation. Both gamma- interferon (gamma-IFN) and tumor necrosis factor (TNF) were found to act independently and cooperatively to depress the stimulated release of vWF from EC. Analysis of stored vWF in either gamma-IFN and/or TNF- treated EC demonstrated a loss of high molecular weight multimers while immunofluorescent studies documented a loss of visible Weibel-Palade bodies. This suggests that gamma-IFN and TNF interfere with normal vWF storage. gamma-IFN acted in a dose-, time-, and RNA-dependent fashion, and its inhibition of vWF release was reversible with time. No effect of gamma-IFN on EC was noted when anti-serum to gamma-IFN was added. Unlike gamma-IFN, alpha-interferon did not effect EC vWF. Therefore, gamma-IFN and TNF may be important in decreasing vWF release during inflammatory or immunologic episodes.

The need for effective science and technology advice continues to increase while the infrastructure for providing such help is in a state of crisis. The President and the Congress are constantly confronted with decisions about new medical technologies, advanced weapon systems, wireless communication regulation, and other matters that hinge on technical facts. While technical analysis is almost never sufficient to make wise choices, absent competent, timely, targeted scientific and technical analysis, these decisions will depend on unchallenged assertions by special interests and ideologues. Programs are likely to be poorly designed and subject to costly mistakes. Even worse, lacking competent advice, the nation may fail to act on problems until they are costly and difficult to solve or fail to seize important opportunities to achieve public objectives in security, education, health care, the environment, or other critical areas. This report develops options for improving the fundamental structures of science and technology advice based on examination of two cases where science and technology advice did not serve the nation well, interviews with many of the key figures in science and technology advice for Congress and the administration, and a review of recent literature.

The Second Canadian Consensus Conference was convened to discuss the latest developments in the management of osteoarthritis (OA) and rheumatoid arthritis (RA), and to make evidence-based recommendations, specifically regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for these indications in primary care practice. The recent availability of cyclo-oxygenase-2-specific inhibitors has raised questions as to their role in the pharmacological management of OA and RA, particularly in relation to conventional treatments such as acetaminophen and nonspecific NSAIDs (with or without misoprostol or proton pump inhibitors). The recommendations in this document, which were arrived at through critical review of data from published randomized, clinical trials, deal with treatments of choice, information to discuss with patients, use of NSAIDs in patients at risk for serious upper gastrointestinal complications, renal or hepatic impairment or congestive heart failure, appropriate follow-up, and the use of NSAIDs with anti- hypertensives, warfarin, low dose acetylsalicylic acid and other medications. The goal of these recommendations is to improve patient outcomes in the primary care setting by maximizing treatment efficacy and minimizing rates of adverse events.

Regional limb perfusion with antineoplastic agents stresses the local vasculature in a variety of ways. However, by monitoring the perfusates from limbs treated with melphalan alone or with melphalan plus tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma), we were able to distinguish the effect of the cytokines on the observed coagulant and fibrinolytic responses. We collected samples of effluent from a series of lower extremities that were perfused with the cytokines and/or melphalan as treatment for localized melanoma. Both regimens produced statistically significant evidence of coagulant and fibrinolytic activation. However, limbs receiving cytokines in addition to the melphalan responded with a sharper rise in tissue plasminogen activator (tPA) and plasmin (plasmin-antiplasmin complexes [PAP]) than limbs treated with melphalan alone. Evidence of thrombin formation (prothrombin fragment 1 + 2 [F1 + 2], thrombin-antithrombin complexes [TAT]) was also greater when the cytokines were included, although the response was delayed and less consistent than the fibrinolytic activation.

OBJECTIVE. To make recommendations for the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) in primary care practice, particularly for patients at high risk for NSAID-induced complications. OPTIONS. The use of misoprostol to prevent gastrointestinal ulceration and other unwanted NSAIDs effects was considered. The role of cyclooxygenase-2 (COX-2) versus COX-1 inhibiting agents was also examined. OUTCOMES. Reduction of complications associated with long-term use of NSAIDs. EVIDENCE. Evidence was gathered in late 1995 from published research studies and reviews. Position papers were prepared by faculty and advisory board members and discussed at the Canadian NSAID Consensus Symposium in Cambridge, Ont., Jan. 26 and 27, 1996. VALUES. Recommendations were based on randomized, placebo-controlled clinical trials (level I evidence) and case-control studies (level II evidence) involving NSAID use when such evidence was available. When the scientific literature was incomplete or inconsistent in a particular area, recommendations reflect the consensus of the participants at the symposium (level III evidence). Physicians were recruited from across Canada for their expertise in rheumatology, gastroenterology, epidemiology, gerontology, family practice, and clinical and basic scientific research. BENEFITS, HARMS AND COSTS. Although a reduction in complications due to inappropriate NSAID use should reduce costs of additional investigations, admissions to hospital and time lost from work, definitive cost analysis studies are not yet available. RECOMMENDATIONS. Currently, no NSAID is available that lacks potential for serious toxicity; therefore, long-term use of NSAIDs should be avoided whenever possible, particularly in high-risk patients (e.g., those who are elderly, suffer from hypertension, congestive heart failure, renal or hepatic impairment or volume depletion, take certain concomitant medications or have a history of peptic ulcer disease) (level I evidence). If NSAIDs are to be used in patients with gastric or nephrotoxic risk factors, the lowest effective dose of NSAID should be used (level III evidence); NSAIDs that are weak COX-1 inhibitors may be preferred (level II evidence). In addition, concomitant administration of misoprostol is recommended in patients at increased risk for upper gastrointestinal complications (level I evidence). However, the clinical judgement of the practising clinician must always be part of any therapeutic decision. VALIDATION. These recommendations are based on the consensus of Canadian experts in rheumatology, gastroenterology and epidemiology, and have been subjected to external peer review.

Von Willebrand factor (vWf), a multimeric adhesive glycoprotein synthesized, stored, and secreted in megakaryocytes and endothelial cells, is normally found in plasma, platelets and subendothelium. While many substances mediate the release of vWf from endothelial cells, factors that enhance vWf synthesis and partitioning to its regulated pathway are currently unknown. We studied the effect of pharmacologic doses of heparin on the vWf content of endothelial cells. After a lag of 8 h and in the presence of crude or purified growth factor, heparin at doses between 0.25 and 2 U (1.4-11 micrograms)/ml, increased the content of high molecular weight vWf. The increased amounts of vWf were localized to Weibel-Palade bodies and extracellular matrix. Lower molecular weight highly sulfated heparin or heparin-like compounds were most active in growth factor dependent endothelial cell vWf expression. There was no clear importance of polysaccharide sequence or protein core.

Operations on lumbar disc prolapses are the most frequent operations in German neurosurgery divisions. After such operations, spondylodiscitis is a dreaded complication which is sometimes difficult to diagnose. Treatment of spondylodiscitis is always protracted and a burden for doctors and patients. Hence, it appears worthwhile to present a further report on discitis and spondylodiscitis, infections of the intervertebral space and the surrounding tissues after disk operations. Various clinical pictures are described: septic progress forms with neurological disorders and the necessity of open wound treatment as well as clinical pictures without septic signs with good recovery after immobilisation and antibiotic treatment. In two cases, CT-guided puncture of purulent suppuration with identification of the causative organisms and specific antibiotic treatment was possible. All patients had a relatively good result: pareses and/or bladder/rectal disorders disappeared completely in every case. The causes of discitis are discussed. The condition arises when nosocomial microorganisms, or very frequently even harmless skin bacteria, enter the wound. A large number of operations are carried out under pressure of time and under hectic conditions, as well as in a confined space in operation theatres which are too warm; these factors increase the susceptibility to infection. However, the resistance of the patient to infection is also weakened after longterm prior antiinflammatory treatment and a stay in hospital before the operation. Besides appropria to treatment of the infection (immobilisation, wound treatment, antibiotic therapy), psychological management of the patient is an important component of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Tenoxicam 20 mg OD was compared with piroxicam 20 mg OD for patients with rheumatoid arthritis (RA). One hundred and two patients from 5 centers were enrolled: 51 in the tenoxicam group and 51 in the piroxicam group. Evaluation of the primary efficacy variables demonstrated no difference in efficacy between treatment groups. The overall incidence of adverse clinical/laboratory experiences was similar between treatment groups. Six patients discontinued the study because of gastrointestinal intolerance, 3 from each treatment group. Our study demonstrates that tenoxicam 20 mg OD and piroxicam 20 mg OD have similar efficacy and safety in patients with active RA.

When planning treatment of tumours in the sella region it is of the utmost importance to obtain precise information about the localization, spread, and (if possible) the type of alteration. Aside from the classic radiographic methods of native diagnosis, angiography, and CT, MRI has been available for some years now. This is a method whereby images can be gained from the various stages of an energetic reaction in the biological substrate: tomograms are possible for any desired plane--those routinely needed for cerebral diagnosis from the horizontal, coronary, and sagittal planes and, given a further improvement of this technology, from special oblique planes which can be matched to the direction of a probable surgical approach. A number of examples demonstrate the significance of this new method, which is a valuable addition to the procedures used up to now: indeed, in some cases it is superior to them. It has been shown that most of the neighbouring structures which border on or have been pushed aside by the tumour in the sella region (blood vessels, brain, optic chiasma, subarachnoid spaces, and occasionally even bone structures) can be identified better than with the procedures used up to now. MRI has thus proved to be valuable, and occasionally indispensable, for the correct choice when considering the many therapeutic methods available for tumours in the sella region.

A report is presented on two patients who received surgery on a disc prolapse between the lumbar vertebrae 4 and 5 as treatment for compression of the fifth lumbar root, but in whom the clinically relevant disc prolapse was located higher (lumbar vertebrae 1/2 or thoracic vertebra 12/lumbar vertebra 1). Magnetic resonance tomography made a major contribution to the later diagnosis of the high disc prolapses. Besides precise localization of the lesion, MRT made it easier to understand why such a high disc prolapse can cause a compression syndrome of the fifth lumbar root.

Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease.

This study identifies two forms of evaluative bias toward political objects — positivity and negativity — in addition to the familiar one of partisanship. Bias is measured, predominantly, using open-ended responses to questions on political parties in the NES studies. The incidence of varieties of evaluative orientation toward the parties over time, beginning in 1952, is reported; so also are demographic and cognitive correlates of evaluative bias. Finally, hypotheses on differential assimilation and contrast effects in candidate perception are tested.

Human hybridomas have been produced by fusing peripheral blood lymphocytes from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with the GM 4672 human cell line. 262 hybridoma clones from the fusions of four RA and five SLE patients were screened for binding to denatured DNA (dDNA), native DNA, and the Fc fragment of human IgG (HIgG). Of the 17 hybridoma antibodies (nine RA, eight SLE) selected for strong binding to denatured DNA, Fc, or both, five reacted with dDNA only, one with Fc only, and eight with both dDNA and Fc. Hybridoma supernatants exhibiting dual reactivity were absorbed over HIgG and bovine serum albumin (BSA)-Sepharose immunoabsorbent columns. The reactivities to both DNA and HIgG were completely removed by the HIgG column but unaffected by passage over the BSA column, and both DNA binding and rheumatoid factor activities were recovered in the acid eluates from the Sepharose-IgG column. The binding of dual reactive hybridoma autoantibodies to the Fc fragment of HIgG was specifically competed by dDNA and HIgG, providing additional evidence that one antibody may be capable of reacting both as a rheumatoid factor and as an anti-DNA antibody.

The idiotype determinants found on hybridoma anti-DNA autoantibodies produced from the fusion of peripheral blood lymphocytes from 13 systemic lupus erythematosus (SLE) and five rheumatoid arthritis (RA) patients with the GM 4672 human lymphoblastoid line were analyzed. A total of 47 SLE and 21 RA hybridomas were studied, of which 26 SLE and 10 RA produced anti-DNA autoantibodies. Rabbit antisera, raised to six of the SLE hybridoma anti-DNA IgM antibodies, were rendered idiotype specific by multiple absorptions on human IgM and IgG immunoabsorbent columns. In direct binding radioimmunoassays, all six anti-idiotype antisera reacted specifically with the anti-DNA antibody used as immunogen. In competition studies, five anti-idiotype antisera were able to inhibit the binding of their homologous idiotype to DNA-coated tubes. In addition, DNA and polynucleotides inhibited the binding of the five idiotypes to anti-idiotype-coated tubes, suggesting that these anti-idiotypes react with idiotype determinants located within the antigen-combining sites of the anti-DNA antibody molecules. Shared idiotypes were detected among the 68 hybridoma antibodies by direct binding studies on anti-idiotype-coated tubes. Our results revealed that 58% (21/36) of the anti-DNA antibodies and 16% (5/32) of the non-DNA-binding antibodies reacted with at least one anti-idiotype serum. Five anti-idiotype antisera reacted only with hybridoma anti-DNA antibodies from SLE patients. The other anti-idiotype antiserum reacted with both SLE- and RA-derived hybridoma anti-DNA and non-DNA-binding antibodies. These studies indicate that some anti-idiotype antisera may detect specific idiotypes found only on SLE-derived anti-DNA auto-antibodies, whereas other antisera detect shared idiotypes found on both RA and SLE DNA-binding and non-DNA-binding antibodies.

The clinical association of lupus anticoagulant antibodies with thrombocytopenia and thrombosis was the rationale for investigating the in vitro reactivity of these human hybridoma lupus anticoagulant antibodies with platelets. Fifty human hybridoma antibodies from 13 patients with systemic lupus erythematosus, 2 women with multiple spontaneous abortions, and 4 normal individuals were analyzed for lupus anticoagulant, antiplatelet, anti-DNA, and antiphospholipid reactivities. Of the hybridoma antibodies studied, 25 had lupus anticoagulant activity, 21 had antiplatelet reactivity, and 7 of these antibodies had both lupus anticoagulant and antiplatelet properties. No correlation was found between lupus anticoagulant antibody activity and antiplatelet, anti-denatured DNA, anticardiolipin, anti-egg phosphatidylethanolamine, antiphosphatidylserine, antiphosphatidylinositol, and antiphosphatidylcholine reactions. In contrast, antiplatelet activity was strongly correlated with antiphosphatidylethanolamine (rho = 0.761, p less than 0.001), anticardiolipin (rho = 0.748, p less than 0.001), and anti-dDNA (rho = 0.745, p less than 0.001) reactivities. Pretreatment of platelets with deoxyribonuclease, ribonuclease, trypsin, or phospholipases A2 and C resulted in different effects on the binding of individual hybridoma antibodies to platelets, suggesting that antiplatelet antibodies may recognize different epitopes on the platelet membrane. Our data demonstrate that most hybridoma lupus anticoagulant antibodies did not bind directly to platelets in vitro. This suggests that additional serum factors may be required in vivo to explain the association of these antibodies with thrombocytopenia and thrombosis.

Patients with systemic lupus erythematosus (SLE) have an increased incidence of arterial and venous thromboses. The mechanism by which thromboses develop in these patients is unknown. We had previously observed that the sera of patients with SLE contain antibodies and immune complexes that can bind to endothelial cells. Because endothelial cells can synthesize tissue factor, a potent activator of coagulation, we studied the effect of IgG complexes and sera from patients with SLE on the production of tissue factor by these cells. Human umbilical venous endothelial cells incubated with heat-aggregated IgG (HA-IgG) (0.5 to 4.0 mg) elaborate procoagulant activity in a dose-dependent manner. All procoagulant activity was found in the particulate cell fraction, and none was secreted into the medium. Maximum expression of procoagulant activity required 6 to 8 hr, and its production was totally inhibited by the addition of cyclohexamide or actinomycin D. The presence of gel-filtered platelets augmented production of procoagulant activity by endothelial cells stimulated by HA-IgG. Endothelial cell procoagulant activity was not inactivated by diisofluoropropylphosphate, required the presence of Factor VII for its expression, and was neutralized by a specific anti-tissue factor antibody. Endothelial cells incubated with sera from 14 of 16 patients with SLE produced increased amounts of tissue factor compared with 21 normal sera (p less than 0.025). Fractions of two SLE sera containing monomeric IgG, IgA, or IgM, as well as fractions containing IgG complexes, each stimulated endothelial cells to produce more tissue factor than similar fractions prepared from two normal sera. These studies demonstrate that endothelial cells will produce the procoagulant tissue factor after exposure to anti-endothelial cell antibodies or IgG-containing immune complexes. The production of tissue factor by endothelial cells at sites of immune vascular injury may play a role in the development of thromboses in patients with SLE.

Hybridoma anti-DNA antibodies have been generated from the fusion of the GM 4672 lymphoblastoid line with peripheral blood lymphocytes from four normal subjects, nine patients with rheumatoid arthritis (RA), and 13 patients with systemic lupus erythematosus (SLE). A total of 441 hybridoma clones were obtained, of which 37 secreted anti-DNA autoantibodies. The nucleic acid binding characteristics of the anti-DNA antibodies produced by two hybridomas from normal subjects, nine hybridomas from RA patients, and 18 hybridomas from SLE patients are reported. The hybridoma anti-DNA antibodies from all three groups showed similar antigen-binding characteristics for denatured DNA (dDNA), native DNA (nDNA), poly(I), poly(dT), and cardiolipin, by both direct binding and competitive binding analyses. One difference noted between normal-derived anti-DNA antibodies and autoimmune-derived antibodies was the inability of the former to react with z-DNA. However, this requires further substantiation with larger numbers of normal-derived clones. The broad overlap of reactivity to nucleic acid antigens among individual anti-DNA autoantibodies found in two clinically different autoimmune diseases, namely RA and SLE, suggests that the pathogenicity of anti-DNA autoantibodies may bear no relationship to their nucleic acid antigen-binding characteristics.

What happens when a writer is given information which attacks his beliefs and thus puts him under stress? This research study shows it takes him longer to write his message, he makes more grammatical and spelling errors, he performs more editing, and the message is less readable.

The effects of referential experience upon encoder-decoder agreement were studied by presenting decoders with stimuli (abstract paintings) originally used to elicit the messages. Agreement was assessed in terms of two measures of word predictability—verbatim replacement and replacement of words of the same grammatical form classes as the deleted items. Results indicated that referential experience enhanced verbatim replacement and more for lexical type words than for members of grammatical function classes. There were no such effects upon grammatical replacement Further, there were no differences according to whether the messages had been encoded as objective descriptions or as subjective interpretations of the stimuli.

Intercorrelations among various hesitation phenomena, production variables, and message characteristics found in spoken responses were factor analysed in an attempt to establish a parsimonious description of basic attributes underlying encoding behaviour. For comparative purposes, a similar analysis was conducted on measures obtained from typewritten messages. The four factors found in the spoken messages were interpreted as : time spent in cognitive decision making, the amount of message produced, disruptions due to stress in the encoding situation, and degree of syntactic elaboration of sentences. Factors found in the analysis of typewritten messages only roughly approximated those found for speech. A subsequent analysis of part of speech frequencies in the two message types revealed additional syntactic distinctions between the two modes, distinctions which were attributed to the differential feedback conditions usually available in the different encoding situations.

In one of the few experimental studies dealing with a bona fide telecast, changes in information and meanings were investigated in connection with the televising of a congressional sub-committee hearing. The author is research assistant professor in the Institute of Communications Research at Illinois

This experimental study focused on the encoding behavior of news photographers. Significant agreement was found on such stylistic elements as number of lights, light contrast, print density, background tone and camera angle.

An earlier study by the senior author showed that headlines have a significant effect upon the interpretation of newspaper stories. An experiment with newscast “leads” produced similar results. Dr. Tannenbaum is director of research in television at Michigan State; Mrs. Kerrick is a research assistant at Illinois.

The purpose of this investigation was to determine whether providing a respondent with the designation of the grammatical form class of words deleted from prose contexts would affect his performance in a word prediction task. Word replacements were obtained under conditions where such designations were or were not provided. The results were analyzed in terms of whether response words corresponded in grammatical form class with deleted items (FC-score), as well as in terms of verbatim replacement of items (V-score). As anticipated, grammatical information did result in a greater FC-score as compared with the absence of such information, although this was greater for function-type words (articles, prepositions, auxiliaries, etc.) than for semantic-types (nouns, verbs, adjectives). As for verbatim replacement, grammatical information led to increased V-score only in the case of function-type words, as compared with the alternative condition of no information. These results were thought to be compatible with expectations based upon differences in the numbers of words belonging to the various form classes, as well as expectations regarding the effect of grammatical information upon contextual constraint.

Definitions and analyses of what is sensational have varied markedly. Using an empirical approach, the authors (1) identified dimensions of the judgment of “sensationalism” and (2) developed a semantic differential index of the sensationalism of messages. They describe their “Sendex” technique and its use.

In an experimental study calling upon three groups of subjects with differing knowledge of typography to rate sets of typefaces, the authors find proof that typography can communicate connotative variations.

It was reasoned that placing the conceptual focus on either the actor subject or on the acted-upon object of a simple situation would differentially affect the readiness to describe the situation in active or passive sentence forms. Conceptual focus was manipulated by use of a preamble which centered upon the subject or the object, with a control condition which focused upon neither. A secondary variable was whether the preamble remarks themselves were in the active or passive voice. Encoding readiness was assessed by the latency in generating prescribed sentence forms. Results supported the predictions, with the difference in latency between active and passive sentence generation increasing (from the baseline neutral focus condition) when the focus was on the actor subject, but decreasing markedly when the focus was on the acted-upon object. The preamble voice difference had little consequence as a main effect, but showed some tendency, not significant statistically, to interact with the conceptual-focus treatment.

A AMONG THE various kinds of communication content, dramaboth in the form of the legiti ate theater and as presented through the mass media of radio, television, and motion pictureshas probably been the least studied by researchers. This is particularly true with respect to experimental research, involving the controlled observation of the variables involved in dramatic presentation and their respective independent and interactive effects. By far the bulk of research activity in this area belongs in the content analysis category, and even this has not been particularly extensive.

What do sports writers mean when they say one team “gouged,” “whumped” or “whipped‘ another? Do certain verbs indicate the amount of point-spread between two teams? The authors found sports writers communicate fairly accurately with each other and with regular sports readers, but not strangers.

This study was conducted as part of the research program of the Mass Communications Research Center at the University of Wisconsin. Dr. Tannenbaum is director of MCRC; Mr. Fosdick is lecturer in journalism and a doctoral candidate in mass communications. For their help in conducting the projects, the authors are grateful to Gerald Cashman and Bradley Greenberg, graduate students in mass communications at the time the study was conducted.

In an experimental study, it is demonstrated that the relative position of an item within the radio newscast has a significant effect on its probability of recall. Dr. Tannenbaum is Director of Research in TV and Communications at Michigan State College. This study was done while he was located at Illinois.