Evaluation of disease activity in rheumatic patients by leucocyte adhesiveness/aggregation.

Previous work has shown that leucocyte adhesiveness/aggregation (LAA), as measured by the leukergy test, correlates well with disease severity in rheumatic patients. As LAA is probably a manifestation of the acute phase reaction various components of the acute phase reaction were measured in order to identify the best marker of disease activity. In addition to LAA, the following variables were measured in 79 patients with various rheumatic diseases and in 10 controls: white blood cell and platelet counts, erythrocyte sedimentation rate, haptoglobin, fibrinogen, C reactive protein, albumin, globulin, caeruloplasmin, alpha 1, alpha 2, beta, and gamma globulin, and haemoglobin concentrations. Patients were graded according to the state of their disease as mild, moderate, or severe. The extent of leucocyte adhesiveness/aggregation in peripheral blood proved to be the best laboratory variable for the grading of disease activity. Correct grading was obtained in 63% of the patients by means of the LAA, compared with 48% with C reactive protein, 41% with caeruloplasmin, 40% with haptoglobin, and 32% with haemoglobin. It is suggested that LAA of the peripheral blood during inflammation may be used as a reliable marker of disease severity.     

Fear and C-reactive protein cosynergize annual pulse increases in healthy adults

Recent international terror outbreaks notably involve long-term mental health risks to the exposed population, but whether physical health risks are also anticipated has remained unknown. Here, we report fear of terror-induced annual increases in resting heart rate (pulse), a notable risk factor of all-cause mortality. Partial least squares analysis based on 325 measured parameters successfully predicted annual pulse increases, inverse to the expected age-related pulse decline, in approximately 4.1% of a cohort of 17,380 apparently healthy active Israeli adults. Nonbiased hierarchical regression analysis among 27 of those parameters identified pertinent fear of terror combined with the inflammatory biomarker C-reactive protein as prominent coregulators of the observed annual pulse increases. In comparison, basal pulse primarily depended on general physiological parameters and reduced cholinergic control over anxiety and inflammation, together indicating that consistent exposure to terror threats ignites fear-induced exacerbation of preexisting neuro-immune risks of all-cause mortality.Recent international terror outbreaks involve mass psychological trauma, leading to long-term mental health risks in the exposed population (1, 2). Fear-induced reactions involve cortical and limbic brain regions that together enhance threat-predictive sensory stimuli (3) by interacting with cholinergic signaling pathways (4) in the hippocampus (5), the central amygdala (6), and the prefrontal cortex, especially in adults (7). Imminent fear may even cause immediate cardiac death [e.g., after an earthquake (8)]. However, whether fear exposure elevates cardiac risks of death to otherwise healthy civilians, and if so, what are the causes of such risks, remains unknown.Pulse is a promising modifiable predictor of cardiovascular and all-cause mortality. Elevated pulse associates with increased systemic inflammation and endothelial dysfunction in older adults (9) and predicts increased risk of death from ischemic heart disease (10). Changes in basal pulse and pulse variability are tightly associated with sudden cardiac death and all-cause mortality, also in asymptomatic men (11). Pulse reflects a complex trait, determined by multiple genetic, environmental, and other endogenous factors that play a substantial role in population variation (12). These include excessive inflammation, shown to associate with pulse increases (13), to be controlled by cholinergic imbalance (decreased vagal tone or increased sympathetic activity) (14), and to increase mortality (15). However, whether specific psychological factors determine the basal pulse and annual pulse changes in active adults is still unknown, perhaps because the intensity of psychological phenomena largely depends on external sources and is highly variable.Although fear of terror (FOT) is universal, Israel has been exposed to the repeated stress of multiple wars and terror attacks for more than 60 y, with a major impact on the entire society (16). To approach the health risks involved in FOT, we therefore explored the parameters determining resting heart rate (pulse) and its annual change in the Israeli population.     

Giant Cavernous Hemangioma of the Liver Complicated by Abscess and Thrombosis

A case of giant cavernous hemangioma of the liver complicated by abscess formation and thrombosis is presented. To our knowledge, complication of hepatic hemangioma by an abscess has not been previously reported. The clinical and radiographic features, as well as the management of giant hepatic cavernous hemangiomas is discussed.     

The concomitant appearance of aggregated erythrocytes, leukocytes and platelets in the peripheral blood of patients with risk factors for atherothrombosis

Risk factors for atherothrombosis including increased leukocyte count, hyperlipidemia, diabetes mellitus, hypertension as well as smoldering inflammation and hyperfibrinogenemia might affect the aggregability of peripheral blood erythrocytes, leukocytes as well as platelets. We have used a simple slide test and image analysis to reveal the presence of these aggregabilities obtained in one single drop of peripheral venous citrated blood in 48 individuals with risk factors for atherothrombosis. A significant correlation was noted between the state of adhesiveness/aggregation of all the above mentioned three cellular elements and the concentrations of total and LDL cholesterol. The correlation with triglycerides concentrations was more modest. A significant reduction of adhesiveness/aggregation was noted in 18 individuals following an intervention to reduce the concentration of cholesterol and triglycerides. This reduction might have a favorable hemorheologic effect. Our results are significant in that they show that it is possible to detect the above mentioned changes in whole blood, following a single step and minimal manipulations, at real time and low cost.     

Isolation of the regulatory domain of scallop myosin: role of the essential light chain in calcium binding.

The regulatory domain of scallop myosin, consisting of a regulatory light chain (R-LC), an essential light chain (E-LC), and a portion of heavy chain, occupies the neck region of myosin. This domain is directly involved in the regulation of molluscan muscle contraction, which is triggered by direct Ca2+ binding to myosin. We have isolated a soluble functional complex (regulatory complex) comprised of R-LC, E-LC, and a 10-kDa heavy chain fragment in a 1:1:1 stoichiometry by clostripain digestion of the myosin head (papain subfragment 1). N termini of the heavy chain fragments were either leucine-812 or valine-817. The isolated complex retained the specific Ca2(+)-binding site and bound Ca2+ with a similar affinity and selectivity as myosin. The individual components of the regulatory complex were isolated after complete denaturation with guanidine hydrochloride. The regulatory complex was reconstituted from isolated light chains and the heavy chain fragment. The renatured complex regained Ca2+ binding quantitatively. To elucidate the function of the E-LC in Ca2+ binding, we constructed hybrid regulatory complexes. The hybrid complexes reconstituted with molluscan E-LC and R-LC regained the specific Ca2(+)-binding site, whereas the hybrid complex formed with rabbit skeletal E-LC [alkali LC 2 (A2-LC)] and scallop R-LC did not. The results demonstrate that E-LCs from myosins regulated by direct Ca2+ binding are required for the specific Ca2+ binding in the molluscan muscle.     

The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with respiratory tract infections

The state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood has been employed as a marker of inflammation. In the present study we examined patients with varying intensities of inflammation caused by respiratory tract infections to further investigate the reliability of the state of LAA for the detection and assessment of the severity of disease activity. The study includes 140 controls, 46 patients with upper respiratory tract infection, 30 with bronchitis, 27 with suspicion of pulmonary infiltrate, and 39 with small and 18 with large pulmonary infiltrate. Assessment was based on assuming an increasing severity of inflammation from the 1st to the 6th diagnostic category and by making use of discriminant analysis. It was found that the state of LAA proved to be the best variable to classify the patients into their diagnostic category (F to enter 27), followed by erythrocyte sedimentation rate at the 1st h (F to enter 20.8) and total white blood cell count (F to enter 8.3). These studies were followed by animal experimentation. A highly significant correlation (p = 0.005) was found between the state of LAA in the peripheral blood and the degree of pulmonary leukostasis in a model of endotoxemia in rabbits. These results suggest that the state of LAA is not an epiphenomenon and represents the tendency of the white blood cells to stick to the endothelium which facilitates their migration into the tissues.