Lipoproteins and the haemostatic system in atherothrombotic disorders

The early belief that the haemostatic system has no active role in the formation of the atheromatous plaque is no longer tenable. Rather, the association between hypercholesterolaemia and atherosclerosis appears to arise in part because of various effects of high concentrations of LDL and VLDL particles on the cellular and humoral components of the system, thereby promoting plaque growth and thrombosis. These may be summarized as follows: 1. High concentrations of native LDL have been reported to promote the adhesion of monocytes to the endothelial cell, suggesting that the latter undergoes a form of activation upon such exposure. Oxidized LDL is more potent in this respect, and persistent exposure of endothelium to such particles can eventually lead to cell injury. 2. Activated endothelial cells acquire characteristics on their luminal surface conducive to thrombin generation and fibrin production. Thrombin has several actions on the endothelial cell, monocyte, smooth muscle cell and platelet which in the presence of hypercholesterolaemia will promote the formation of atheroma. 3. Oxidatively modified LDL can activate circulating monocytes, when they also acquire procoagulant properties which favour thrombin production. 4. Platelets show an increased tendency to aggregate when exposed to hypercholesterolaemic plasma. This effect may arise in part because the platelet of the hypercholesterolaemic patient expresses an increased number of fibrinogen binding sites on its surface following activation by agonists such as ADP. These hyperaggregable platelets adhere to activated endothelial cells which express von Willebrand factor on their surface, and to subendothelial proteins exposed in the gaps that open between injured endothelial cells. Platelets exposed to raised LDL levels also show a reduced sensitivity to prostacyclin, an antiaggregatory agent. Oxidatively modified LDL has been reported to stimulate aggregation of platelets in the absence of other agonists such as ADP or thrombin (spontaneous aggregation). 5. Platelet aggregation and fibrin deposition at sites of endothelial injury will create microthrombi which become incorporated into the lesion by organization, thereby increasing the fibrous and cellular content of the atheromatous plaque. 6. Lipolysis of triglyceride-rich lipoproteins at the endothelial cell surface leads to transient activation of the coagulation mechanism with activation of factor VII. Activated factor VII is a potent procoagulant when it forms a complex with tissue factor in the atheromatous lesion. Persistent hypertriglyceridaemia is accompanied by raised concentrations of factor X, factor IX, factor VII and prothrombin. 7. Hypertriglyceridaemia is associated with an increased plasma concentration of PAI-1 and a reduction in plasma fibrinolytic activity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Tissue hypercarbic acidosis as a marker of acute circulatory failure (shock)

Measurement of pH of the stomach wall (gastric intramural pH) by the tonometric method has been utilized both experimentally and clinically as an indicator of the capability of the stomach to extract and utilize oxygen. As such, it serves as a metabolic marker of acute perfusion failure (circulatory shock). More recently, researchers have found that increases in the PCO2 accounted for the decline in pH; this was documented in tissues other than the stomach wall, including the esophageal and sublingual mucosa. In this review, tissue PCO2 is identified as a universal indicator of impaired perfusion and contrasted with conventional hemodynamic and metabolic markers of perfusion failure.     

Role of specific instances in controlling a dynamic system.

This article examines the claim that the learning of a dynamic control task is mediated by a lookup table consisting of previously successful trials on the task. Consistent with the predictions of a lookup table, in 2 experiments participants tended to give the same response to situations in which they had previously been successful rather than unsuccessful. Further, in both experiments, participants' knowledge did not generalize to new dissimilar situations, unless the dynamic control task was governed by a highly salient rule. A version of G. Logan's (1988) instance theory, which assumes that participants store each successful response as a separate instance linking the situation to the response, was able to quantitatively match a range of measures of participants' performance with 1 free parameter, except in the case in which the control task was governed by a salient rule. In a complementary way, an alternative rule-based model could only match participants' performance when the control task was governed by a highly salient rule. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The adaptational system as a dynamical feedback system

Growth hormone receptor is a cytokine-type receptor which is required for normal somatic growth and for numerous metabolic processes. Its complementary DNA (cDNA) has been isolated in various species leading to intensive studies to elucidate the mechanism of action of the growth hormone. However, serious difficulties have been reported in cloning in Escherichia coli, an intact full-length human cDNA. In this study, the cDNA is shown to contain a cryptic bacterial promoter driving inappropriate expression of a part of human growth hormone (hGH) receptor which is toxic for E. coli growth. Identification of this promoter and its inactivation by changing only one nucleotide led us to obtain stable bacterial clones containing a high copy number of full-length coding sequences. This molecular clone was used in a baculovirus/insect cell system to produce large amounts of glycosylated recombinant receptor. Binding studies with 125I-labelled hGH revealed an affinity constant of 2.8 x 10(9) M(-1), similar to that reported for the native liver receptor. This report described a general method of cloning which could be applied to similar unclonable cDNA fragments.     

The influence of trazodone on the circulatory system in patients with endogenous depression. I. Basic circulatory parameters

In patients with endogenous depression in remission, decline of systolic blood pressure and a statistically significant shortening of pulse time were found.     

Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor

NLS proteins are transported into the nucleus by the importin alpha/beta heterodimer. Importin alpha binds the NLS, while importin beta mediates translocation through the nuclear pore complex. After translocation, RanGTP, whose predicted concentration is high in the nucleus and low in the cytoplasm, binds importin beta and displaces importin alpha. Importin alpha must then be returned to the cytoplasm, leaving the NLS protein behind. Here, we report that the previously identified CAS protein mediates importin alpha re-export. CAS binds strongly to importin alpha only in the presence of RanGTP, forming an importin alpha/CAS/RanGTP complex. Importin alpha is released from this complex in the cytoplasm by the combined action of RanBP1 and RanGAP1. CAS binds preferentially to NLS-free importin alpha, explaining why import substrates stay in the nucleus.     

Magnesium and the transport system

For the purpose of studying the sex differences of the human face we collected five separate images, which consist of several parts of the face, from frontal view photographs of 48 male and 52 female college students. We traced outlines of their faces with simple lines (traced items), and made reproductions of the photographs of their eyes, mouth and nose by using a copying machine (reproduced items). The test subjects were 16 males and 8 females. They looked at parts of the face shown in each image, and categorized them individually by judging on their sex. Then, we calculated the percentages of correct judgments (percentage correct) for each image. By comparing the percentage correct between male and female we concluded that the sex of the subjects did not affect the results of their judgments. In the traced items the percentage correct for the face as a whole, which contained the outlines of the eyes, mouth, nose and the lower jaw, was 69%, but it decreased to 61% when the outline of the lower jaw was removed. Hence, the outline of the lower jaw apparently has a characteristic shape easily noticed by males. In the reproduced items the percentage correct was 65% for the eyes, 68% for the mouth and 58% for the nose. The mouth, therefore, has more distinguishing characteristics than the eyes or nose, especially with females. On the other hand, there is no correlation between the percentage correct for the eye, mouth and nose items. Hence, we concluded that the sexual specificity for the shape of the young Japanese face appears on their parts independently.     

Development of a sensitive and specific assay system for cholecystokinin tetrapeptide

Cholecystokinin is a gastrointestinal and neuropeptide which has been implicated in a wide range of physiological and behavioral processes. We have developed a sensitive and specific assay system to measure the various forms of cholecystokinin (CCK) in human plasma. This 3-step system involves i) extraction of CCK fragments from plasma using reverse phase chromatography; ii) separation of peptides by high performance liquid chromatography; and iii) detection and quantification of peptides with a double-antibody radioimmunoassay, using an antibody raised against cholecystokinin tetrapeptide (CCK-4) coupled to thyroglobulin and 125I Bolton-Hunter CCK-4 as tracer. The antibody detects CCK-4, sulfated CCK-8 (CCK-8S) and nonsulfated CCK-8 (CCK-8ns) with equal affinity. The lower limit of detection is 2.7 fmol, with an ED50 of 10.6 +/- 2.2 fmol. Mean CCK-like immunoreactivity (CCK-LI) in the plasma of 12 healthy subjects was determined to be 12.9 +/- 2.1 pM CCK-4 equivalents. Concentrations of each individual peptide in plasma were determined to be 1.0 +/- 0.2 pM, 3.4 +/- 0.8 pM and 1.9 +/- 0.4 pM for CCK-4, CCK-8s and CCK-8ns respectively.     

Degassing metal in a circulatory vacuum-treatment unit

High efficiency has been achieved in degassing steel at OAO Oskol’skii Elektrometallurgicheskii Kombinat, thanks to the introduction of circulatory vacuum-treatment units.     

Work attitudes as predictors of attendance on a specific day.

Examined the relationship between the work attitudes and work attendance of 3,010 managerial employees on a specific day in a natural field setting. Job satisfaction data were obtained from the Index of Organizational Reactions (IOR). Since occasional absenteeism at the managerial level is not subject to financial penalty and is relatively free of social and work-group pressures, it represents behavior that is generally under the control of the individual employee. Moreover, because the particular day investigated in the present study followed a crippling snowstorm, attendance on that day involved considerable effort. Results show significant relationships between work-related attitudes and attendance on the specific day studied and generally support J. B. Herman's (1973) point of view that work attitudes do predict work-related behavior when such behavior is under the control of the S. (PsycINFO Database Record (c) 2010 APA, all rights reserved)