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Right atrial pressure and ANP release during prolonged exercise in a hot environment.

To investigate the relationship between right atrial pressure (RAP) and atrial natriuretic peptide (ANP) release during prolonged exercise in a hot environment (30 degrees C, 20% relative humidity), we studied with a Swan-Ganz catheter five male volunteers exercising on a cycle ergometer at 60% of peak aerobic power for 50 min. The ANP level increased from 14 +/- 3 (SE) to 69 +/- 10 pg/ml (P < 0.001) during the first 10 min of exercise as RAP rose from 4.3 +/- 0.8 to 6.9 +/- 1.1 mmHg (P < 0.001). The 10-min ANP level was significantly correlated with RAP (r = 0.88, P < 0.05) but not with heart rate, pulmonary arterial blood temperature, plasma norepinephrine, or plasma epinephrine. The 10-min RAP value was inversely correlated with blood volume (r = -0.98, P < 0.01) and also with stroke volume (r = -0.96, P < 0.01). In the next 20 min of exercise, ANP continued to increase to 101 +/- 12 pg/ml (P < 0.02 vs. 10 min) and remained at this level until 50 min of exercise, whereas RAP decreased and reached a level not significantly different from baseline at 50 min (5.7 +/- 1.0 mmHg; P < 0.01 vs. 10 min). This dissociation of ANP and RAP may have been related to the significant increases from the 10-min values of heart rate, blood temperature, norepinephrine (all P < 0.01), and epinephrine (P < 0.02) during the same period. These results suggest that ANP release is primarily controlled by atrial distension at the onset of exercise but that other stimulators may be involved thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sensitivity and specificity of hemodynamic criteria in the diagnosis of acute right ventricular infarction.

To test the sensitivity and specificity of hemodynamic criteria for acute right ventricular infarction (RVI), two groups of patients with anatomically proved acute myocardial infarction and hemodynamic monitoring were studied. Group A included 22 patients acute RVI and group B, 38 with infarction confined to the left ventricle. In both groups, the closest relation between right atrial and pulmonary capillary pressures (RAP and PCP), as well as the presence of a severe noncompliant pattern (SNCP), were studied. A SNCP was defined as a y descent deeper than the x descent in RAP. RAP was equal to or higher than PCP in 10 patients from group A and in none from group B. In group B, a significant relation was found between RAP and PCP (r = 0.777, y = 0.43x + 0.18) (p less than 0.05), and the 95% confidence limits could be calculated. Above these limits, a closer relation between RAP and PCP was only found in patients with RVI. However, six patients with RVI showed an RAP/PCP relation within 95% confidence limits of group B (sensitivity 72.7%, specificity 100%). A SNCP was present in 12 patients with RVI and only in one without RVI (p less than 0.01) (sensitivity 54.5% and specificity 97.4%). When either criterion is present (close relation between RAP and PCP or SNCP), a high sensitivity (81.8%) and specificity (97.4%) can be achieved in the diagnosis of acute RVI.

Acute Disease↗

Responses to acute changes in arterial pressure on renal medullary nitric oxide activity in dogs.

A direct relationship between renal arterial pressure (RAP) and cortical tissue nitric oxide (NO) activity in the canine kidney was reported earlier. We have conducted further experiments to evaluate medullary NO responses to alterations in RAP with the use of a NO-selective microelectrode inserted into the renal medulla of 6 anesthetized, sodium-replete dogs. Graded reductions in RAP (from 140 to 80 mm Hg) elicited decreases in medullary tissue NO concentration, with a slope of 10.2+/-4.5 nmol x L(-1) x mm Hg(-1). These changes in NO levels were associated with decreases in urinary excretion rate of nitrate and nitrite (U(NOx)V; control value, 1.7+/-0.03 nmol x min(-1) x g(-1); slope, 0.02+/-0.004 nmol x min(-1) x g(-1) x mm Hg(-1)) and sodium excretion (U(Na)V; control, 3.2+/-0.7 micromol x min(-1) x g(-1); slope, 0.06+/-0.02 micromol x min(-1) x g(-1) x mm Hg(-1)) without changes in glomerular filtration rate control (0.84+/-0.06 mL x min(-1) x g(-1)). Intra-arterial administration of the NO synthase inhibitor N(omega)-nitro-L-arginine (NLA; 50 microg x kg(-1) x min(-1)) decreased medullary NO concentration by 218+/-55 nmol x L(-1) (n=5) and attenuated the relationship between RAP and NO concentration (slope, 2.7+/-2.2 nmol x L(-1) x mm Hg(-1)). NLA infusion decreased U(NOx)V (0.8+/-0.06 nmol x min(-1) x g(-1)) and U(Na)V (1.1+/-0.2 micromol x min(-1) x g(-1)) without changes in glomerular filtration rate and attenuated RAP versus U(Nox)V and U(Na)V relationships. Total and regional blood flows, as measured by electromagnetic and laser Doppler needle flow probes, respectively, remained autoregulated both before and during NLA infusion. These data support the hypothesis that acute changes in RAP elicit changes in intrarenal NO production, which may participate in the mediation of pressure natriuresis.

Animals↗

Illusory motion from change over time in the response to contrast and luminance.

A striking illusion of motion is generated by static repeated asymmetric patterns (RAPs) such as Kitaoka's (2003) "Rotating Snakes" and Fraser and Wilcox's (1979) peripheral drift illusion. How do RAPs generate spurious motion signals, and what critical difference between RAPs and natural static scenes prevents the latter from appearing to move? Small involuntary eye movements during fixation have been suspected to play a critical role in these illusions, but here we give an account that does not depend on fixation jitter. We propose that these illusions result primarily from fast and slow changes over time in the neuronal representation of contrast ("contrast-driven RAPs") or luminance ("luminance-driven RAPs"). We show that temporal phase advance in the neural response at high contrast can account for the early, fast motion in contrast-driven RAPs (such as "Rotating Snakes") after each fixation change. An essential part of this explanation is that motion detectors fail to compensate for the dynamics of neuronal encoding. We argue that static natural patterns also generate local gain changes, but that these signals do not often trigger illusory motion because they are not usually aligned to drive global motion detectors. Movies in which real luminance changes over time, to mimic the proposed neuronal adaptations to contrast and luminance, evoke qualitatively similar percepts of motion. Experimental data are consistent with the explanation. Color and overall contrast both enhance the illusion.

Contrast Sensitivity↗

Babesia bigemina: sporozoite isolation from Boophilus microplus nymphs and initial immunomolecular characterization.

It has been hypothesized that babesial sporozoites express specific antigens that induce protective immunologic responses in cattle. However, they remain uncharacterized, partly for lack of research on the sporozoite stage of Babesia spp. This field suffers from complete knowledge of parasite development in the tick salivary gland; limited amounts of sporozoites from ticks, and a lack of protocols for induction and purification of sporozoites. In this work, Boophilus microplus larvae infected with B. bigemina were fed on susceptible cattle. Nymphs were collected and macerates were separated by a Percoll density gradient. Microscopic analysis of Giemsa-stained smears showed a larger number of sporozoites from nymphs fed for 9 days. Percoll-purified sporozoites were observed in large numbers in groups or individually and free of tick cells. RT-PCR analysis of total RNA extracted from purified sporozoites indicated transcription of the rhoptry associate protein 1 (rap-1) genes: rap-1a, rap-b, rap-1c, as well as the heat shock protein 20 (hsp-20) gene. Purified sporozoites were cultured in vitro analyzed for RAP-1a expression using an immunocytochemistry assay. Erythrocyte-attached sporozoites reacted with a specific RAP-1a monoclonal antibody. This is the first report of Babesia bigemina sporozoite antigens. Moreover, purified sporozoites will allow the characterization of stage-specific antigens involved in immunologic protection.

Animals↗

Proteinase-activated receptor-2: expression by human neutrophils.

Neutrophils were shown to express the proteinase-activated receptor-2 (PAR-2), a seven transmembrane domain receptor, which is activated by cleavage by trypsin. Granulocytes from 14 donors stained positively for PAR-2 with affinity-purified rabbit antibodies raised against a peptide corresponding to the trypsin cleavage site of human PAR-2. Neutrophil activation in response to a receptor activating peptide (RAP) varied between donors. RAP (Ser-Leu-Ile-Gly-Lys-Val-NH2) alone induced an increase in the forward and side light scatter after 5-10 minutes and a small increase in the expression of the activation molecule CD11b. The increased expression of CD11b induced by RAP was markedly enhanced by priming the neutrophils with a low concentration (1 nM) of formyl-Leu-Met-Phe. Trypsin and RAP also induced an increase in intracellular calcium, but there were large variations in the magnitude of responses between donors also in this assay. The effects of RAP in the different assays were specific; acetylated RAP was completely without activity.

Adult↗

Functional domains of the very low density lipoprotein receptor: molecular analysis of ligand binding and acid-dependent ligand dissociation mechanisms.

The very low density lipoprotein (VLDL) receptor is closely related in structure to the low density lipoprotein receptor. The ectodomain of these endocytic receptors is composed of modules which include clusters of cysteine-rich class A repeats, epidermal growth factor (EGF)-like repeats, tyrosine-tryptophan-threonine-aspartic acid (YWTD) repeats and an O-linked sugar domain. To identify important functional regions within the ectodomain of the VLDL receptor, we produced a mutant receptor in which the EGF, YWTD and O-linked sugar domains were deleted. Cells transfected with the mutant receptor were able to bind and internalize (125)I-labeled receptor associated protein (RAP). In contrast to the wild-type receptor, however, RAP did not dissociate from the mutant receptor and consequently was not degraded. Immunofluoresence data indicated that once bound to the mutant receptor, fluorescent-labeled RAP co-localized with markers of the endosomal pathway, whereas, in cells expressing the wild-type receptor, RAP fluorescence co-localized with lysosomal markers. Thus this deleted region is responsible for ligand uncoupling within the endosomes. To identify regions responsible for ligand recognition, soluble receptor fragments containing the eight cysteine-rich class A repeats were produced. (125)I-RAP and (125)I-labeled urokinase-type plasminogen activator:plasminogen activator inhibitor type I (uPA:PAI-1) complexes bound to the soluble fragment with K(D, app) values of 0.3 and 14 nM, respectively. Deletion analysis demonstrate that high affinity RAP binding requires the first four cysteine-rich class A repeats (L1-4) in the VLDL receptor while the second repeat (L2) appears responsible for binding uPA:PAI-1 complexes. Together, these results confirm that ligand uncoupling occurs via an allosteric-type mechanism in which pH induced changes in the EGF and/or YWTD repeats alter the ligand binding properties at the amino-terminal portion of the molecule.

Acids↗

Activation of protease-activated receptor-2 leads to inhibition of osteoclast differentiation.

UNLABELLED: PAR-2 is expressed by osteoblasts and activated by proteases present during inflammation. PAR-2 activation inhibited osteoclast differentiation induced by hormones and cytokines in mouse bone marrow cultures and may protect bone from uncontrolled resorption. INTRODUCTION: Protease-activated receptor-2 (PAR-2), which is expressed by osteoblasts, is activated specifically by a small number of proteases, including mast cell tryptase and factor Xa. PAR-2 is also activated by a peptide (RAP) that corresponds to the "tethered ligand" created by cleavage of the receptor's extracellular domain. The effect of activating PAR-2 on osteoclast differentiation was investigated. MATERIALS AND METHODS: Mouse bone marrow cultures have been used to investigate the effect of PAR-2 activation on osteoclast differentiation induced by parathyroid hormone (PTH), 1,25 dihydroxyvitamin D3 [1,25(OH)2D3], and interleukin-11 (IL-11). Expression of PAR-2 by mouse bone marrow, mouse bone marrow stromal cell-enriched cultures, and the RAW264.7 osteoclastogenic cell line was demonstrated by RT-PCR. RESULTS: RAP was shown to inhibit osteoclast differentiation induced by PTH, 1,25(OH)2D3, or IL-11. Semiquantitative RT-PCR was used to investigate expression of mediators of osteoclast differentiation induced by PTH, 1,25(OH)2D3, or IL-11 in mouse bone marrow cultures and primary calvarial osteoblast cultures treated simultaneously with RAP. In bone marrow and osteoblast cultures treated with PTH, 1,25(OH)2D3, or IL-11, RAP inhibited expression of RANKL and significantly suppressed the ratio of RANKL:osteoprotegerin expression. Activation of PAR-2 led to reduced expression of prostaglandin G/H synthase-2 in bone marrow cultures treated with PTH, 1,25(OH)2D3, or IL-11. RAP inhibited PTH- or 1,25(OH)2D3-induced expression of IL-6 in bone marrow cultures. RAP had no effect on osteoclast differentiation in RANKL-treated RAW264.7 cells. CONCLUSION: These observations indicate that PAR-2 activation inhibits osteoclast differentiation by acting on cells of the osteoblast lineage to modulate multiple mediators of the effects of PTH, 1,25(OH)2D3, and IL-11. Therefore, the role of PAR-2 in bone may be to protect it from uncontrolled resorption by limiting levels of osteoclast differentiation.

Animals↗

Validation of RNA arbitrarily primed PCR probes hybridized to glass cDNA microarrays: application to the analysis of limited samples.

BACKGROUND: The applicability of microarray-based transcriptome massive analysis is often limited by the need for large amounts of high-quality RNA. RNA arbitrarily primed PCR (RAP-PCR) is an unbiased fingerprinting PCR technique that reduces both the amount of initial material needed and the complexity of the transcriptome. The aim of this study was to evaluate the feasibility of using hybridization of RAP-PCR products as transcriptome representations to analyze differential gene expression in a microarray platform. METHODS: RAP-PCR products obtained from samples with limited availability of biological material, such as experimental metastases, were hybridized to conventional cDNA microarrays. We performed replicates of self-self hybridizations of RAP-PCR products and mathematical modeling to assess reproducibility and sources of variation. RESULTS: Gene/slide interaction (47.3%) and the PCR reaction (33.8%) accounted for the majority of the variability. From these observations, we designed a protocol using two pools of three independent RAP-PCR reactions coming from two independent reverse transcription reactions hybridized in duplicate and evaluated them in the analyses of paired xenograft-metastases samples. Using this approach, we found that HER2 and MMP7 may be down-regulated during distal dissemination of colorectal tumors. CONCLUSION: RAP-PCR glass array hybridization can be used for transcriptome analysis of small samples.

Acetyltransferases↗

Adult outcomes of pediatric recurrent abdominal pain: do they just grow out of it?

OBJECTIVE: To determine whether medically unexplained recurrent abdominal pain (RAP) in childhood predicts abdominal pain, irritable bowel syndrome (IBS), other somatic complaints, and psychiatric symptoms and disorders in young adulthood. METHODS: A sample of 28 young adults evaluated for RAP between the ages of 6 and 17 years were compared with 28 individually matched former childhood participants in a study of tonsillectomy and adenoidectomy. RAP caseness was established by structured retrospective chart review requiring agreement by 2 independent reviewers. Standardized assessments of abdominal pain, IBS, other somatic symptoms, psychopathology, perceived health, and history of maltreatment were performed an average of 11.1 years after the index visit. RESULTS: Former RAP patients were significantly more likely than controls to endorse anxiety symptoms and disorders, hypochondriacal beliefs, greater perceived susceptibility to physical impairment, poorer social functioning, current treatment with psychoactive medication, and generalized anxiety in first degree relatives. There were trends suggesting associations between childhood RAP and lifetime psychiatric disorder, depression, migraine, and family history of depression, but group differences on abdominal pain, IBS, other somatic symptoms, and history of maltreatment were not statistically significant. CONCLUSIONS: There is a strong and relatively specific association between childhood RAP and anxiety in young adulthood. Affected children may be at special risk to perceive physical symptoms as threatening, and should be evaluated for psychiatric disorder on initial presentation.

Abdominal Pain↗

Systematic review of treatments for recurrent abdominal pain.

OBJECTIVE: To conduct a systematic review of evaluated treatments for recurrent abdominal pain (RAP) in children. METHODS: Online bibliographic databases were searched for the terms "recurrent abdominal pain," "functional abdominal pain," "children," or "alternative therapies" in articles classified as randomized controlled trials. The abstracts or full text of 57 relevant articles were examined; 10 of these met inclusion criteria. Inclusion criteria required that the study involve children aged 5 to 18 years, subjects have a diagnosis of RAP, and that subjects were allocated randomly to treatment or control groups. The methodology and findings of these articles were evaluated critically, and data were extracted from each article regarding study methods, specific interventions, outcomes measured, and results. RESULTS: Studies that evaluated famotidine, pizotifen, cognitive-behavioral therapy, biofeedback, and peppermint oil enteric-coated capsules showed a decrease in measured pain outcomes for those who received the interventions when compared with others in control groups. The studies that evaluated dietary interventions had conflicting results, in the case of fiber, or showed no efficacy, in the case of lactose avoidance. CONCLUSIONS: Evidence for efficacy of treatment of RAP in children was found for therapies that used famotidine, pizotifen, cognitive-behavioral therapy, biofeedback, and peppermint oil enteric-coated capsules. The effects of dietary fiber were less conclusive, and the use of a lactose-free diet showed no improvement. There seemed to be greater improvement when therapy (famotidine, pizotifen, peppermint oil) was targeted to the specific functional gastrointestinal disorder (dyspepsia, abdominal migraine, irritable bowel syndrome). The behavioral interventions seemed to have a general positive effect on children with nonspecific RAP. Many of these therapies have not been used widely as standard treatment for children with RAP. Although the mechanism of action for each effective therapy is not fully understood, each is believed to be safe for use in RAP.

Abdominal Pain↗

Contribution of angiotensin II to renal hemodynamic and excretory responses to nitric oxide synthesis inhibition in the rat.

This study was performed to evaluate the contribution of angiotensin II to the effects of nitric oxide (NO) synthesis inhibition on renal hemodynamics and excretory function in rats. Intravenous infusion of N omega-nitro-L-arginine (NLA; 20 micrograms/100 g.min) increased renal arterial pressure (RAP) from 128 +/- 2 to 143 +/- 3 mm Hg (P < 0.05; N = 6) and decreased RBF by 64 +/- 3% (P < 0.01) and GFR by 41 +/- 5% (P < 0.05). In response to reduction of RAP to control levels (127 +/- 2 mm Hg) by means of an adjustable clamp (CL) placed on the suprarenal aorta, RBF and GFR exhibited efficient autoregulation and were not altered. In rats (N = 6) pretreated with the AT1 angiotensin II receptor antagonist losartan (10 mg/kg iv), the infusion of NLA increased RAP (from 114 +/- 1 to 135 +/- 2 mm Hg; P < 0.05) and decreased RBF by 42 +/- 3% (P < 0.05). However, NLA did not decrease GFR in the losartan-treated rats. As in the control rats, the reduction of RAP to 113 +/- 1 mm Hg elicited autoregulatory responses that maintained RBF and GFR. In the untreated rats, at similar RAP (128 +/- 2 (control) versus 127 +/- 2 mm Hg (NLA+CL)). NO synthesis inhibition decreased urine flow and sodium excretion (P < 0.05, in both cases). However, during blockade of AT1 receptors, NLA infusion failed to decrease urine flow and sodium excretion, even when RAP was controlled (114 +/- 1 (control) versus 113 +/- 1 mm Hg (NLA+CL)).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

The acute effects of induced tachycardia on coronary sinus and arterial plasma levels of atrial natriuretic peptide and on arterial catecholamines.

Atrial natriuretic peptide (ANP) was measured in coronary sinus (CS) plasma in seven patients with induced tachycardia. Right atrial pressure (RAP) and femoral artery (FA) levels of ANP, noradrenaline (NA) and adrenaline (A) were measured before and after 5 min with tachycardia. During tachycardia, ANP in CS plasma increased from 381 +/- 273 (mean +/- SD) to 1376 +/- 1191 pmol l-1 (p < 0.0001), and ANP levels in FA plasma from 89 +/- 48 to 231 +/- 151 pmol l-1 (p < 0.005). A significant increase was observed for peak RAP, whereas mean RAP remained unaltered. While no correlation existed between the increase in CS plasma ANP level and RAP, significant correlations were found between the changes in FA plasma ANP and RAP, and between FA plasma levels of ANP and NA. Following tachycardia, significant correlations were found both between ANP in CS and FA plasma and between the changes in these plasma levels. Whereas the changes in FA plasma levels of ANP during tachycardia seems dependent of RAP and arterial plasma levels of NA, the CS plasma ANP level appears to be independent of the two factors, probably because CS plasma ANP are drained mainly from the left side of the heart.

Adult↗

Sleep patterns in children and adolescents with functional recurrent abdominal pain: objective versus subjective assessment.

AIM: To document objective sleep patterns of children and adolescents with functional recurrent abdominal pain (RAP), and to compare them with subjective sleep assessments and sleep patterns of healthy controls. METHODS: Subjective sleep reports and sleep habit assessments were obtained from 25 adolescents with functional RAP and from 15 age- and gender-matched healthy volunteers, and were compared with continuous movement monitoring using the Actigraph for 7 consecutive days. RESULTS: Abdominal pain before falling asleep was a unanimous complaint in the RAP group, with 29% reporting awakening from sleep by the pain. Only 25% of RAP patients assessed their sleep quality as good, compared with 87% of the control group. Objective sleep patterns measurements of the RAP patients were similar to those of the control group as well as to measurements observed in a large population of school-aged children and adolescents. CONCLUSION: This study of a small group of children and adolescents with functional RAP provides objective evidence that their sleep patterns do not differ from those of normal peers, despite their subjective complaints.

Abdominal Pain↗

Postoperative reintubation after planned extubation in Thai Anesthesia Incidents Study (THAI Study).

OBJECTIVE: To analyze precipitating causes, outcomes and corrective strategies especially anesthetic related factors associated with reintubation after planned extubation in anesthetic technique of general anesthesia with endotracheal intubation. DESIGN: Prospective observational study. MATERIAL AND METHOD: Incidents of reintubation after planned extubation were extracted from the Thai Anesthesia Incidents Study (THAI Study) database conducted between February 1, 2003, and January 31, 2004, and analyzed using descriptive statistics. RESULTS: The total of two hundred and thirty four patients of reintubation after planned extubation (RAP) at the end of general anesthesia was reviewed in this study. The incidence of RAP was 27:10,000 and the incidence in the university hospital was similar to the tertiary and secondary care hospital. The incidence was increased in extreme age group (age < 1 and > 70 year). One hundred and fifty eight cases of RAP (67.5%) occurred in operating theater and recovery room which included 83 cases occurring within 10 minutes after extubation. The two most common primary diagnoses were upper airway obstruction and hypoventilation. Three main precipitating factors were residual effect of neuromuscular blocking and anesthetic agents (53-57%), upper airway obstruction (31%) and unstable hemodynamics (26.3%). Nearly half of RAP incidents occurring in the operating theater and recovery room were successful reextubation within six hours and 58-72 % of these two subgroups were complete recovery. The chance for prevention was more than 80% by additional training and supervision. CONCLUSION: More than 90% of RAP occurred in operating theater and recovery room were completely or partially related to anesthetic process. Incidence of RAP could be decreased by quality assurance process of recording, reporting and modeling care process together with increase individual experience.

Adolescent↗

The effect of thioguanine on a combination of daunorubicine, cytarabine and prednisone in the treatment of acute leukaemia in adults. The Finnish Leukaemia Group.

194 adults with acute leukaemia were randomly allocated to be treated with a combination of daunorubicine, cytarabine and prednisone either with (RAP + T) or without (RAP) thioguanine. A remission was achieved in 37% of 101 patients treated with RAP and in 35% of 93 patients treated with RAP + T. The survival and length of remission were similar in both groups. Neither regimen was superior to the other in any type of leukaemia nor in any age group of patients. In 9 of the patients failing to remit with RAP treatment a remission was obtained with other chemotherapy, while none of the patients not responding to RAP + T achieved a remission with further chemotherapy.

Acute Disease↗

Exogenous receptor-associated protein binds to two distinct sites on human fibroblasts but does not bind to the glycosaminoglycan residues of heparan sulfate proteoglycans.

We have investigated the proposal that the receptor-associated protein (RAP) of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds to heparan sulfate proteoglycans (HSP). 125I-RAP binds to two sites on the surface of fibroblasts as follows: a high affinity site with a Kd of 1.4 nM and a low affinity site (Kd = 188 nM) with a capacity of more than 1000-fold the maximum amount of lipoprotein receptor-related protein/alpha 2-macroglobulin receptor on the cell surface. 125I-RAP binding to the low affinity site was abolished by heparin or Suramin. However, maximal digestion of the glycosaminoglycan chains of HSP with heparinase or culturing the cells in chlorate, an inhibitor of proteoglycan sulfation, did not affect the binding of 125I-RAP or of 125I-labeled, methylamine-activated alpha 2-macroglobulin. Comparison of 125I-RAP degradation at two different concentrations suggests that the low affinity, high capacity site on the surface of human fibroblasts participates in the endocytosis of 125I-RAP. The nature of the low affinity site remains to be elucidated, but we can exclude the glycosaminoglycan chains of HSP.

Binding Sites↗

Right atrial pacing for risk stratification in patients with angina pectoris.

Right atrial pacing (RAP) has been used to assess the physiologic impact of coronary artery disease (CAD). Several variables have served as markers of pacing-induced myocardial ischemia or for predicting disease severity, but their clinical implications remain uncertain. Therefore, three-stage RAP was performed to evaluate whether this strategy could predict the disease severity of CAD and foretell subsequent major cardiac events in 49 patients with typical chest pain. RAP was considered positive if 1 mm or more of horizontal or downward ST depression developed. Of the 49 cases, 28 had positive RAP (group A), and the remaining 21 had negative RAP (group B). For hemodynamic data, early positive RAP had the highest post-pacing left ventricular end-diastolic pressure (LVEDP). The LVEDP increased significantly in Group A (p < 0.05), whereas there was no apparent change in group B. Furthermore, group A (36%) tended to develop typical chest pain more easily than group B (14%), but this was statistically insignificant. Group A had a higher incidence of multivessel disease than that of group B (p < 0.001), whereas group A had a lower incidence of non-significant CAD than that of group B (p < 0.001). During the mean two-year follow-up period, there were 23 major cardiac events (MCE) in group A in contrast to two episodes in group B (p < 0.005). The early positive subset had 18 episodes, whereas the late positive subset had only five episodes (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗