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PubMed1994

Orally administered immunosuppressants modify intestinal uptake of nutrients in rabbits.

The effect on intestinal nutrient transport of the immunosuppressive drugs cyclosporin A (CsA), cyclosporin G (CsG), and rapamycin (RAP) was determined in New Zealand white rabbits. Rabbits received oral doses of CsA (20 mg/kg/day), CsG (10 mg/kg/day), or RAP (1 mg/kg/day) for 10 days. Animals receiving RAP had decreased food intake and weight gain compared with controls. This correlated with a decrease in both total ileal weight and corresponding mucosal weight. CsA and CsG administration had no effect on food intake, total weight gain, or intestinal weight. Villus surface area was significantly decreased in all groups as compared with controls. Jejunal uptake of D-glucose as well as 1 medium and 4 long chain fatty acids was not affected by drug administration, while both mucosal-to-serosal and net 3-0-methylglucose fluxes were increased (P < 0.05) in the jejunum by all 3 drugs. In the ileum, the rates of uptake of D-glucose as well as stearic and linoleic acids were increased in animals treated with RAP compared with controls. There was an increase in the ileal values of the maximal transport rate (Vmax) and apparent Michaelis constant (Km*) in RAP, and a fall in the Vmax and Km* in CsG. CsG administration resulted in a decreased cholesterol uptake in both jejunum and ileum, and a decreased D-glucose uptake in the ileum compared with controls. These differences in glucose uptake among groups could not be attributed to variations in body, intestinal, or mucosal weights. It is unlikely that the changes observed in CsA- and CsG-treated animals would have nutritional importance, as these animals gained weight normally. In addition, in these animals the changes mainly occurred in the ileum, not in the jejunum, where most glucose is absorbed, and the associated alterations in the values of the Vmax and Km* would lead to reciprocal changes in the rates of uptake of varying luminal concentrations of glucose. In contrast, these changes are likely to be of more importance in RAP-treated animals, since they failed to gain weight normally. The significance of these findings needs to be established in chronically treated animals.

Administration, Oral↗

PubMed1996

Decreased expression of both the low-density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor and its receptor-associated protein in late stages of cutaneous melanocytic tumor progression.

We recently found that the proteins of the proteolytic system of plasminogen activation emerge in late stages of melanocytic tumor progression. A large body of evidence suggests a role for two proteins, the low-density lipoprotein receptor-related protein (LRP)/alpha(2)-macroglobulin receptor and its receptor-associated protein (RAP), in the internalization of components of the plasminogen activation system. Here, we present data on the presence of these two proteins in human melanoma cell lines which differ in metastatic capacity, their corresponding xenografts, and in cutaneous melanocytic lesions. With flow cytometry, we found surface expression of LRP to be restricted to urokinase plasminogen activator, producing highly metastatic cell lines. These cell lines also produce higher levels of LRP mRNA, whereas RAP mRNA and protein are expressed at equal levels in all cell lines and not expressed at the cell surface. Xenografts of cell lines producing high levels of LRP remarkably contain only a small fraction of LRP-positive tumor cells. Using immunohistochemistry on frozen sections of 107 human melanocytic lesions comprising the various stages of melanocytic tumor progression, we found that expression of both LRP and RAP decreased in tumor progression. Furthermore, we noted that LRP and RAP are coexpressed within the same lesion. Using immunofluorescence double staining, we found that LRP and RAP colocalize in the same cells in the lesions studied and in the same cell structures in the cell lines studied. In conclusion, our results indicate that LRP and RAP are coordinately expressed in a decreased fashion in melanocytic tumor progression. Based on the staining results in xenografts and in human melanocytic lesions, we conclude that a strong correlation between expression of LRP and urokinase-type plasminogen activator seems not to exist in in vivo melanomas.

Animals↗

PubMedDate not supplied

The impact of managed care on the physician marketplace.

OBJECTIVE: To examine the impact of managed care on the employment and compensation of primary care and specialty physicians, as measured by changes in income, physician-to-population ratios, and specialty choices. METHODS: The authors used data from the American Medical Association's Socioeconomic Monitoring System survey, a nationally representative 1% random survey of post-residency patient-care physicians, and location data from the AMA Masterfile to evaluate the relationship between the growth in managed care from 1985 to 1993 and (a) inflation-adjusted physician incomes and (b) physician-to-population ratios for primary care physicians and specialists. They also used data from the National Residency Matching Program for 1989 through 1995 to look at trends in available positions and specialty choices. RESULTS: Primary care incomes grew 4.78% annually ($33,526 cumulatively) in states with the highest managed care growth, compared to 1.20% ($7448 cumulatively) in the lowest quartile of managed care growth. The difference in income growth for medical and surgical subspecialists between the highest and lowest quartiles was not statistically significant. The incomes of radiologists, anesthesiologists, and pathologists (RAPs) rose 0.14%, or $1700, in the highest quartile versus 4.14% ($58,558) in the lowest. Subspecialists per capita did not differ by quartile of managed care growth; but RAPs per capita increased fastest in states in the lowest quartile. Between 1989 and 1995, the number of family practice and pediatric residency positions that were filled rose 32%, while the number filled remained stable for medical and surgical subspecialists and the number of RAP positions filled fell 14%. CONCLUSIONS: The growth in managed care has been associated with significant changes in physician incomes and practice locations. Between 1985 and 1993, states with the fastest growth in managed care penetration saw the highest rate of growth in primary care physicians' income and the slowest rate of growth in RAP physicians' income. At the same time, the number of RAP physicians grew most rapidly in those states with the lowest rate of managed care growth. Finally, between 1989 and 1995, there was a dramatic increase in the number of primary care residency positions filled and a marked decrease in the number of RAP residency positions filled across the country.

Economics, Medical↗

PubMedDate not supplied

Immunohistochemical localization of alpha-2 macroglobulin receptor/low-density lipoprotein receptor-related protein, receptor-associated protein, and Gp330 in the human endometrium.

OBJECTIVE: We investigated the expression of alpha-2 macroglobulin receptor/low-density lipoprotein receptor-related protein (LRP), an analogous receptor Gp330, and the 39-kd receptor-associated protein (RAP) in the human endometrium. METHODS: Specific polyclonal and monoclonal antibodies against LRP, Gp330, and RAP were used in standard immunohistochemical analyses of normal secretory and proliferative archival endometrial tissue. RESULTS: There was prominent and uniform stromal staining for LRP in secretory and proliferative endometrium. In both phases, 10-25% of glands stained positive for Gp330, with no appreciable stromal staining for Gp330. Also in both phases, 15-30% of glands stained positive for RAP, with apical staining in proliferative glands and uniform staining in secretory glands. Stromal staining for RAP was patchy and appeared to be more intense in the secretory samples than in the proliferative ones. CONCLUSIONS: The human endometrium expresses LRP, RAP, and Gp330. These receptor proteins are known to be involved in endocytosis of multiple ligands. Some of these ligands, such as proteases, plasminogen activators, and cytokines, are produced by the endometrium and play a role in endometrial remodeling and receptivity to implantation. By virtue of their in vitro properties, it is conceivable that endometrial LRP, Gp330, and RAP are involved in endometrial physiology.

Antibodies↗

PubMed1998

Construct validity of Minimum Data Set items within the context of the Braden Conceptual Schema.

The Minimum Data Set Plus (MDS+) is used by all federally-funded long-term care facilities to assess residents and plan their care. Eighteen conditions, known as Resident Assessment Protocols (RAPs) including a pressure ulcer RAP, require a written care plan by staff. Consequently, it is important to determine if the operational definitions from the MDS+ are consistent with theoretical constructs from a conceptual schema representative of pressure ulcer risk. Examination of construct validity shows that not all of the variables in the Braden Conceptual Schema are adequately operationalized by the MDS+ or the pressure ulcer RAP. Physiologic markers of nutritional status and friction/shear are not included in the MDS+. Sensory perception is included in the MDS+ but not the pressure ulcer RAP. If the MDS+ pressure ulcer RAP is to be used to plan care and assess risk, then all items should be included. The purpose of this article is to examine the construct validity between the operational definitions of risk factors from the MDS+ and pressure ulcer RAP with theoretical constructs from the Braden Conceptual Schema.

Databases, Factual↗

PubMed1990

Rap1-B is phosphorylated by protein kinase A in intact human platelets.

Agonists that increase cAMP levels in platelets promote the phosphorylation of a 24 kDa GTP-binding protein that is immunoreactive with a monoclonal antibody (M90) to the H-ras p21 protein. Evidence is presented which indicates that this protein is rap-1b, not rap1-a as previously suggested (Ohmori, T., Kikuchi, A., Yamamoto, K., Kawata, M., Kondo, J. and Takai, Y. (1988) Biochem. Biophys. Res. Commun. 157, 670-676). The amino acid sequence of labeled peptides obtained by proteolytic cleavage of the purified phosphorylated protein was identical with that of rap-1b. Furthermore, a comparison of the kinetics of phosphorylation of synthetic peptides corresponding to the C-terminal region of rap-1a and rap-1b proteins indicated that rap-1b is the preferred substrate for phosphorylation by cAMP-dependent protein kinase.

Amino Acid Sequence↗

PubMed2003

Methodological challenges to treatment trials for recurrent abdominal pain in children.

BACKGROUND: Studies evaluating the efficacy of treatments for recurrent abdominal pain (RAP) in children have used a wide range of methods, causing difficulty in the comparison of results. An expert panel on functional gastrointestinal disorders recently made recommendations regarding the standardization of study methods for childhood RAP, but many of their recommendations remain untested or lack supportive evidence. METHODS: During completion of a pilot study and randomized controlled trial for childhood RAP, baseline data were collected regarding the child and parent reports of abdominal pain frequency and intensity, type of abdominal pain, missed activities due to abdominal pain, psychological factors for the parent and child, parenting styles, and referral source (pediatric gastroenterologist vs general pediatrician). RESULTS: Children and parent pain reports showed good agreement in children younger than 13 years (weighted kappa, 0.77; 95% confidence interval [CI], 0.71-0.84), but only marginal agreement in children 13 years or older (weighted kappa, 0.37; 95% CI, 0.30-0.45). We found no significant differences in pain characteristics or psychological factors between children referred by pediatric gastroenterologists in a tertiary care center and those referred by community-based primary care pediatricians. However, children with symptoms consistent with nonspecific functional abdominal pain were reported by their parents to have less frequent pain (P=.003) and fewer missed activities (P=.003) than children with symptoms of irritable bowel syndrome or functional dyspepsia. CONCLUSIONS: Subjects referred by gastroenterologists and general pediatricians were similar, but the subtype of functional gastrointestinal disorder might be an important baseline characteristic of subjects in future RAP studies. We suggest that future interventional studies of childhood RAP measure 2 outcomes with pain reports obtained directly from children. Any child with fewer days of pain and missed activities due to pain after therapy would be considered improved, and those with no missed activities and 4 or fewer days of pain per month at follow-up would be considered healed.

Abdominal Pain↗

PubMed1985

The use of dietary fiber in the management of simple, childhood, idiopathic, recurrent, abdominal pain. Results in a prospective, double-blind, randomized, controlled trial.

Recurrent abdominal pain (RAP) affects 10% to 18% of school-age children and is caused by obvious organic pathology in fewer than 10% of cases. Two recent studies do not support previous beliefs that most RAP is psychogenic. Studies have shown disorders of bowel motility in children with RAP similar to those of adult irritable bowel syndrome (IBS); controlled trials of additional dietary fiber in adult IBS have shown beneficial results. We did a randomized, double-blind, placebo-controlled study in 52 children with RAP and demonstrated a clinically and statistically significant decrease in pain attacks (at least 50% fewer) in almost twice as many children who were given additional fiber as placebo. Compliance was excellent in both groups and side effects were few. Although the cause of RAP is poorly understood, it is hypothesized that the beneficial effect of added fiber is due to its effect on shortening transit time, as in IBS.

Abdomen↗

PubMed1990

An immunohistochemical analysis of ras oncogene expression in epithelial neoplasms of the colon.

Colonic epithelial tumors (101) including villoglandular adenomas, carcinomas in situ, adenocarcinomas, and neuroendocrine (NE) carcinomas were studied immunohistochemically with monoclonal antibodies (MoAb) RAP-5 and RAS-10 recognizing altered and unaltered ras oncogene products. In addition, 20 samples from multiple polyposis including adenomas with and without dysplasia, carcinomas in situ, and invasive carcinomas were studied. Using immunostaining techniques, normal mucosa was weakly stained, whereas the mucosa in the vicinity of tumors or inflammation showed enhanced staining. More tumors stained intensely with MoAb RAP-5 than with MoAb RAS-10. With MoAb RAP-5, most benign and malignant tumors showed enhanced staining. No significant differences in staining were noted in relation to superficial versus deeply invasive carcinomas or clinical staging. Immunostaining was also noted in some metastases. No significant differences in enhanced staining were found in carcinomas. Interestingly, the most extensive and enhanced immunostaining was noted in the villoglandular adenomas, dysplastic adenomas, and carcinomas in situ. The authors conclude that (1) ras protein expression is detectable in most benign, borderline, and malignant epithelial tumors of the colon as determined with MoAb RAP-5 and RAS-10, whereas enhanced expression is more often detected with RAP-5; (2) enhanced ras product expression in colon carcinomas does not seem to correlate with advanced tumor stages or with exocrine, NE, or phenotypically mixed tumors; and (3) the finding of the most intensely enhanced ras products expression in villoglandular polyps and carcinomas in situ suggests a possibly significant role for the oncogene in the early phases of transformation.

Adenocarcinoma↗

PubMed1987

Preservation of the entire anal canal in conservative proctocolectomy for ulcerative colitis: a pilot study comparing end-to-end ileo-anal anastomosis without mucosal resection with mucosal proctectomy and endo-anal anastomosis.

Mucosal proctectomy with endo-anal pull-through anastomosis (MP + PTA) for ulcerative colitis reduces resting anal pressure and low RAP has been found to correlate with minor leakage of faeces or mucus. Our hypothesis was that conservative proctocolectomy with an end-to-end ileo-anal anastomosis (EEA) would result in higher anal pressure and less leakage. Twelve patients were studied after EEA and 24 after MP + PTA: each was in good health several months after operation. After EEA, maximal RAP decreased from a median 90 cmH2O (60-116 cmH2O) to 70 cmH2O (25-104 cmH2O, P less than 0.01), whereas after MP + PTA maximal RAP decreased from 85 cmH2O (70-125 cmH2O) to 40 cmH2O (22-80 cmH2O, P less than 0.003). RAP after EEA was significantly greater than RAP after MP + PTA (P less than 0.001). The pressure profile of the anal sphincter in the EEA group did not differ significantly from that of the pre-operative group at any point from 6 to 1 cm from the anal verge, and the sphincteric high pressure zone averaged 4 cm in length both before and after operation. After MP + PTA, resting anal pressure at stations 1 to 4 cm from the anal verge was significantly less than pre-operative pressure (P less than 0.001) and the sphincteric high pressure zone was only 3 cm in length compared with 4 cm before operation. Anal squeeze pressures were similar in the two groups of patients. After EEA 11 of 12 patients achieved perfect continence, day and night, whereas after MP + PTA 58 per cent of patients experienced minor faecal leakage (P less than 0.01). These findings suggest that the entire anal canal should be kept intact in the course of conservative proctocolectomy for ulcerative colitis.

Adolescent↗

PubMed1997

High-rate cardiac pacing increases blood pressure and decreases right atrial pressure in patients with hemodynamic significant acute right ventricular myocardial infarction and bradyarrhythmia.

BACKGROUND: In an 84-year-old patient with acute right ventricular myocardial infarction (RVI), complete heart block, and low cardiac output, a significant increase in blood pressure (BP) and decrease in right atrial pressure (RAP) were accidentally observed during the performance of high-rate ventricular pacing. METHODS: Based on that observation, the acute effects of high-rate cardiac pacing (VVI or AAI) on BP and RAP were studied in 15 consecutive patients (67.4 +/- 7.7 years), with hemodynamically significant RVI. Ten had advanced heart block and five had sinus bradycardia. Cardiac pacing with simultaneous recording of BP and RAP at intrinsic rhythm and at heart rates of 70, 90, 110, 130 beats/min was performed. RESULTS: Systolic BP (SBP) increased significantly from 94.6 +/- 15 mmHg during intrinsic rhythm to 101.9 +/- 13.8 mmHg-127 +/- 12.2 mmHg at heart rates 70-130 beats/min (p < 0.0001). Diastolic BP (DBP) also increased from 48.2 +/- 8.7 to 53.9 +/- 3.7-69.1 +/- 3 mmHg at heart rates 70-130 beats/min, (p < 0.014-0.0001). Mean RAP decreased from 14.5 +/- 5 to 14.1 +/- 5 mmHg-11.1 +/- 4.1 mmHg at heart rates 70-130 beats/min (p = 0.16-0.0001). Significant elevation of SBP (p < 0.007), DBP (p < 0.0075), and decrease of RAP (p < 0.038) were also detected by comparing the usual pacing rate at 70 beats/min with pacing rates at 90-130 beats/min. CONCLUSIONS: These findings, if demonstrated over a prolonged period during the acute state of RVI, may influence the management of patients with RVI to include high-rate cardiac pacing, probably in the range of 80-110 beats/min.

Aged↗

PubMed2001

Improvement of RNA fingerprinting efficiency for the analysis of differential gene expression in human cardiac macro- and microvascular endothelial cells.

RNA fingerprinting by arbitrarily primed PCR (RAP-PCR) is a powerful tool to screen differential gene expression. However, PCR-based screening techniques show a high incidence of false positive results (40-90%). In order to increase the efficiency and feasibility of RAP-PCR, the original protocol was modified and applied to analyse differential gene expression in human coronary macro- (HCEC) and microvascular (HCMEC) endothelial cells. The major modifications introduced were: (i) the use of two primers for PCR amplification, instead of reverse-transcription primer alone; (ii) the use of three cycles at low stringency followed by further amplification at high stringency; (iii) optimization of amplification cycle number, template amount, and concentration of primers, dNTP, Mg(2+); (iv) detection of fingerprints by silver staining; and (v) direct sequencing using RAP-PCR primers. Analysis of untreated and TNF alpha -stimulated (100 U ml(-1)for 1, 4, and 24 h) HCEC and HCMEC displayed 11 differentially expressed products by 18 primer combinations. Confirmation of results by RT-PCR showed that the rate of false positives attributable to our screening method was less than 20%. Among detected RAP-PCR products, the expression of Mn-superoxide dismutase, A20 zinc finger protein, and three novel genes (A/a, 4/d, 7/c) was more strongly modulated by TNF in HCEC than HCMEC. A further novel gene (B/e) was strongly expressed in HCMEC while only barely detectable in HCEC. In conclusion, modification of RAP-PCR strongly reduced the incidence of false positives, eliminated a radioactive requirement, and allowed sequencing without prior cloning, supplying an improved technology able to identify new differentially expressed genes between macro- and microvascular endothelial cells.

Cells, Cultured↗

PubMed1992

The prevalence of Helicobacter pylori serum antibodies in children with recurrent abdominal pain.

As part of a large, prospective study we investigated the prevalence Helicobacter pylori serum antibodies in children with recurrent abdominal pain (RAP). All patients suffered from recurrent bouts of abdominal pain for at least 6 months and ranged in age from 6 to 12 years. H. pylori antibodies were detected using an enzyme-linked immunosorbent assay. The prevalence of H. pylori antibodies in the RAP group was compared to that of a control group which consisted predominantly of pre-operative children. None of the control group suffered or had suffered from RAP. Antibodies to H. pylori were found in 7 of 82 (8.5%) RAP patients and in 2 of 39 (5.1%) control children. The latter difference is not significant and suggests that RAP is only rarely caused in children by H. pylori infection.

Abdominal Pain↗

PubMed2004

Electrical remodeling of the canine superior vena cava after chronic rapid atrial pacing.

BACKGROUND: The superior vena cava (SVC) might serve as the trigger and/or substrate for paroxysmal atrial fibrillation (AF). However, the electrophysiological properties of the SVC with chronic AF are unknown. The purposes of this study were to investigate the electrophysiological properties of the SVC and the electropharmacological effects of intravenous dl-sotalol on the canine SVC after chronic rapid atrial pacing (RAP). METHODS AND RESULTS: In the control group, the effective refractory period (ERP), conduction velocity, and AF inducibility of the SVC were assessed in 6 normal dogs before and after an infusion of dl-sotalol. In the experimental group, the ERP, conduction velocity, and AF inducibility of the SVC were assessed before and after dl-sotalol administration in 10 dogs after 8 weeks of RAP. The SVC showed a shorter ERP, decreased slope of rate-adaptation of the ERP, increased ERP dispersion, a decreased conduction velocity, and increased inducibility and duration of AF initiated from the SVC in the RAP dogs. In the RAP dogs, intravenous dl-sotalol significantly increased the ERP, but dl-sotalol did not change the slope of rate-adaptation of the ERP, dispersion of the ERP, conduction velocity, inducibility, or duration of AF initiated from the SVC. CONCLUSIONS: The present study demonstrates that the canine SVC shows significant electrical remodeling and increased AF vulnerability after chronic RAP. Intravenous dl-sotalol was unable to decrease the inducibility or duration of AF initiated from the SVC.

Animals↗

PubMed2004

Surgical excision of neovascularization in retinal angiomatous proliferation.

BACKGROUND: We report the postoperative outcomes of surgical neovascularization excision in patients with retinal angiomatous proliferation (RAP). METHODS: Nine eyes of eight patients with RAP who underwent surgical excision of neovascularization were studied. Surgical indications were as follows: RAP diagnosed by fluorescein and indocyanine green angiography, foveal or perifoveal neovascularization, preoperative visual acuity of 0.1 or less, Yannuzzi's stage II with detachment of retinal pigment epithelium (RPE) or stage III, and leakage on late-phase fluorescein angiography. After cataract surgery, vitreous surgery and neovascularization excision were conducted, followed by fluid-air or fluid-gas exchange. RESULTS: Visual acuity was 0.02-0.1 before surgery and 0.03-0.2 after surgery. Macular hole formation was seen in one eye but did not lead to retinal detachment. In two eyes, subretinal bleeding occurred during excision leading to vitreous bleeding after surgery. Although defects of the RPE and choriocapillaries were observed after surgery, the exudation and bleeding were absorbed. CONCLUSIONS: In stage II RAP cases with RPE detachment, surgical excision maintains constant postoperative visual acuity but results in defects of RPE and choriocapillaris; therefore, other treatment options should be examined. Surgical excision of stage III RAP seems to be promising, as postoperative visual acuity remains stable after neovascularization removal in those advanced pathologic situations.

Aged↗

PubMed2004

A comparative study between radiofrequency ablation with plication and Milligan-Morgan hemorrhoidectomy for grade III hemorrhoids.

BACKGROUND: Milligan-Morgan (MM) hemorrhoidectomy is the most favored treatment for prolapsed hemorrhoids. However, it may be associated with severe postoperative pain, long periods of convalescence and other complications. In alternative, I use a procedure of radiofrequency ablation and plication (RAP) of hemorrhoids. The present study compared the two procedures in terms of surgical parameters, postoperative pain and complications. PATIENTS AND METHODS: A total of 60 patients with grade III hemorrhoids were randomized to undergo radiofrequency ablation and plication (31 patients) or MM hemorrhoidectomy (29 patients). The patients were followed up to 2 years. RESULTS: Duration of surgery was significantly longer in the MM group as was postoperative hospitalization (p<0.05). Post-defecation pain and pain at rest were much less in the RAP group (p<0.05). Wound healing period (17 vs. 38 days) and time to return to work (7 vs. 17 days) were the other significant findings favoring RAP procedure. Early complications occurred more frequently in MM group, but late complications like external skin tags (4 vs. 2 patients) were more common in RAP group. One asymptomatic recurrence was noted in RAP group. CONCLUSIONS: Radiofrequency ablation and plication of hemorrhoids is associated with significantly less postoperative pain, shorter hospital stay and earlier return to normal activity. It can be considered as an alternative to the Milligan-Morgan hemorrhoidectomy.

Catheter Ablation↗

PubMed1995

Removal of lactoferrin from plasma is mediated by binding to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor and transport to endosomes.

LDL receptor related protein (LRP) is a ubiquitously expressed cell surface receptor that binds, at least in vitro, a plethora of ligands among them alpha 2-macroglobulin and lactoferrin (Lf). The function of LRP in internalisation and distribution of ligands within cellular metabolism is still unclear. We here investigated by combined ligand- and immunoblotting the participation of LRP/alpha 2MR and its associated protein (RAP) in receptor mediated endocytosis of Lf into rat liver. We found LRP highly enriched in sucrose density gradient fractions around density 1.10 g/ml, previously characterised as endosomal fractions. RAP was concentrated in distinct fractions around density 1.14 g/ml. This separation of RAP from LRP/alpha 2MR is physiologically meaningful as RAP avidly binds to LRP/alpha 2MR and by that shuts off all ligand binding function. In endosomal fractions we found one single binding protein for 125I-labelled Lf. With a specific anti LRP/alpha 2MR antibody and ligand blotting with 125I-labelled RAP this endosomal Lf binding site was verified to be LRP/alpha 2MR. Endosomes did not bind labelled Lf when prepared from rats that received an intravenous injection of Lf (20 mg per animal) 20 min prior to preparation. Surprisingly we immunodetected Lf in these endosomes at a position around 600 kDa, comigrating with LRP/alpha 2MR. We determined Lf binding to be optimal at pH 5.8, what led us to suggest the existence of a very stable LF-LRP/alpha 2MR complex in endosomes. These data support the idea of effective binding of Lf at pH as found in inflamed tissue environment where Lf is reported to be involved in leukocyte mediated inflammation regulation.

Animals↗

PubMed1984

Life events occurring in families of children with recurrent abdominal pain.

Thirty children with recurrent abdominal pain (RAP) were compared to 67 behaviorally disordered (BD) children and 42 healthy children on number of life events experienced within the last 12 months and on amount of readjustment necessitated by these life events. The parents of these children were also compared on these variables as well as on a subjective rating of stress which they assigned to the life events. The results revealed that the children in the RAP and BD groups had significantly more life events and more stress associated with them than did the healthy children. However, the children in the RAP and BD groups differed in type of life events, with the RAP group more likely to have experienced life events related to illness, hospitalization, and death. There were no significant differences between the parents in the RAP group and the parents of the two comparison groups. Due to methodological limitations of the study, caution should be exercised in drawing conclusions from these findings until such time that future research provides confirmatory data.

Abdomen↗