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PubMed2002

The Recruit assessment Program: a program to collect comprehensive baseline health data from U.S. military personnel.

Pilot testing has begun on the Recruit Assessment Program (RAP). The RAP is a proposed Department of Defense (DoD) program for the routine collection of baseline demographic, medical, psychosocial, occupational, and health risk factor data from all U.S. military personnel at entry into the armed forces. The RAP currently uses an optically scannable paper questionnaire, which will provide data for the first building block of an electronic medical record within the DoD and the Department of Veterans Affairs. The RAP will serve several important functions, including automating enrollment into the military health care system, improving patient care and preventive medicine efforts, and providing critical data for investigations of health problems among military personnel and veterans. If the feasibility of the RAP is demonstrated and the program is fully implemented throughout the DoD, it could provide a substantial improvement in health care delivery. For the first time, DoD and Department of Veterans Affairs physicians, public health officers, and researchers will have access to comprehensive baseline health status data.

Feasibility Studies↗

PubMed2002

Pulmonary hemodynamic and tidal volume changes during exercise in heart failure.

BACKGROUND: Impairment of lung mechanics, increase of pulmonary artery pressure and limitation of exercise capacity are common findings in chronic heart failure. The objective of the present study was to evaluate whether pulmonary mechanics are correlated with pulmonary hemodynamics, whether both are correlated with the functional capacity and whether the time course of their changes during exercise correlates with the exercise capacity. METHODS: We performed a cardiopulmonary exercise test (breath by breath analysis of ventilation and gas exchange, cycloergometer, 25 W increments every 3 min) with pulmonary hemodynamic monitoring in 38 heart failure patients. The parameters were analyzed at rest, 1 min after the work rate increase and at peak exercise. RESULTS: A significant linear correlation with peak oxygen consumption was found at rest for: mean pulmonary artery pressure (mPAP, r = -0.56), right atrial pressure (RAP, r = -0.42), pulmonary wedge pressure (PWP, r = -0.53), and total pulmonary (TPR, r = -0.53) and pulmonary vascular resistances (PVR, r = -0.45); after 1 min of exercise for: cardiac index (CI, r = 0.49), mPAP (r = -0.57), RAP (r = -0.60), PWP (r = -0.45), and TPR (r = -0.67) and PVR (r = -0.38); at peak exercise for: tidal volume (r = 0.63), CI (r = 0.63), RAP (r = -0.43), TPR (r = -0.65) and PVR (r = -0.43). A significant linear correlation with peak oxygen consumption was found, for the increment between rest and 1 min of exercise, for RAP (r = -0.58) and CI (r = 0.42) and, for the increments between rest and peak exercise, for tidal volume (r = 0.79) and CI (r = 0.61) and, for the ratio between the increment between rest and 1 min of exercise/increment between rest and peak exercise, for mPAP (r = -0.42), RAP (r = 0.51) and CI (r = -0.54). The same ratio of increment of mPAP (r = 0.39) and CI (r = 0.36) correlated with that of tidal volume. CONCLUSIONS: This study provides evidence of a strong correlation between the respiratory function and pulmonary vascular pressure changes during exercise in heart failure.

Adult↗

PubMed2002

Recurrent abdominal pain in children: past, present, and future.

The management of recurrent abdominal pain (RAP) in children remains a challenge for physicians. RAP describes a diverse array of clinical presentations. These presentations usually involve abdominal pain and other nonspecific symptomatology for which no organic cause can be found. Long-term recurrence of symptoms is fairly high. RAP was once thought to be a physical manifestation of psychological stressors in children. Past research has neither confirmed nor ruled out the possibility of an organic or psychological etiology. Current theory contends that the clinical presentation of RAP represents a complex interplay between psychosocial and organic factors. New diagnostic subgroups for functional gastrointestinal diseases have been proposed. These subgroups are based on symptoms, since functional disease is often accompanied by no evidence of organic dysfunction. Future research will provide further information on the diagnostic distinctions and different indications for treatment between these subgroups that make up the broader category of RAP.

Abdominal Pain↗

PubMed1992

Influence of furosemide on hemodynamic responses during exercise in horses.

Four hours prior to exercise on a high-speed treadmill, 4 dosages of furosemide (0.25, 0.50, 1.0, and 2.0 mg/kg of body weight) and a control treatment (10 ml of 0.9% NaCl) were administered IV to 6 horses. Carotid arterial pressure (CAP), pulmonary arterial pressure (PAP), and heart rate were not different in resting horses before and 4 hours after furosemide administration. Furosemide at dosage of 2 mg/kg reduced resting right atrial pressure (RAP) 4 hours after furosemide injection. During exercise, increases in treadmill speed were associated with increases in RAP, CAP, PAP, and heart rate. Furosemide (0.25 to 2 mg/kg), administered 4 hours before exercise, reduced RAP and PAP during exercise in dose-dependent manner, but did not influence heart rate. Mean CAP was reduced by the 2-mg/kg furosemide dosage during exercise at 9 and 11 m/s, but not at 13 m/s. During recovery, only RAP was decreased by furosemide administration. Plasma lactate concentration was not significantly influenced by furosemide administration. Furosemide did not influence PCV or hemoglobin concentration at rest prior to exercise, but did increase both variables in dose-dependent manner during exercise and recovery. However, the magnitude of the changes in PCV and hemoglobin concentration were small in comparison with changes in RAP and PAP, and indicate that furosemide has other properties in addition to its diuretic activities. Furosemide may mediate some of its cardiopulmonary effects by vasodilatory activities that directly lower pulmonary arterial pressure, but also increase venous capacitance, thereby reducing venous return to the atria and cardiac filling.

Animals↗

PubMed2005

[Characterization of the interaction between low density lipoprotein receptor-related protein-associated protein 1 and the cancer and embryo expression protein 65].

OBJECTIVE: To understand the mechanism of cancer and embryo expression protein 65 (CEP65) in cancer development. METHODS: CEP65 was used as a bait protein to isolate the partners of CEP65 from a human placenta cDNA library with yeast two hybrid system. The DNA fragments from positive clone were expressed prokaryotic and mammalian cells respectively, the GST pull-down experiment was performed to ascertain the binding activity. RESULTS: After screening a human placenta cDNA library, the low density lipoprotein receptor-related protein-associated protein 1 (RAP) was isolated and shown to interact with CEP65. GST pull-down assay results indicated that His-CEP65 and GST-RAP expressed by prokaryotic system were immunoprecipitated, and so were Myc-RAP and GST-P65 expressed by mammalian cells. CONCLUSION: RAP can interact with CEP65 and RAP may be a candidate to mediate the function of CEP65.

Animals↗

PubMed2005

[Laparoscopy in chronic abdominal pain in children].

UNLABELLED: The recurrent chronic abdominal pain (RAP) is one of the most usual pathologies in pediatrics. It may appear in the form of periodical or continuous sharp crisis. In order to be accepted as chronic, the presence of this pain must last at least 3 months. In many of the reference publications, only between 5 and 1% of the cases are considered to have an organic ethiology and the rest are labelled as functional processes of psychological origin. The reason for our communication is to show our experience on 304 RAP patients from 1995 to 2001. We also want to highlight the usefulness of laparoscopy in order to diagnose and treat 14.45% (44) of cases of this group of patients. MATERIAL AND METHODOLOGY: 304 patients between 5 and 14 years old were studied from 1995 to 2001. We followed a protocol of: medical and personal medical record, specific anamnesis for RAP, detailed description of the diet and intestinal habits, physical exploration. Laboratory: 1) blood analysis, hepatic profile, glucose, cholesterol, creatinine, amylase, 2) urine sediment and may be urine culture, 3) faeces analysis and 4) vaginal flow analysis. Image diagnosis is: simple abdomen radiography, ultrasonography and intestinal Rx. Guided and specific determinations: spired urea test, gastric chemism, lactose test, gastroscopy and biopsy, colonoscopy and biopsy, laparoscopy. RESULTS: In short, we can say: 74 patients (23.4%) come with inappropiate feeding diets, 31 (10.1%) with helicobacter pilori, 20 (6.5%) with adenoids, pharynx and pharyngeal processes, the same figure from gynaecologic origin, 18 (5.9%) from psychological origin, and in 44 cases (14.45%) laparoscopy was indicated. CONCLUSIONS: The anatomopathological study in the cases in which we carried out laparoscopic appendicectomy does not allow us to accept the symptoms of chronic appendicitis. The exploratory laparoscopy and the appendectomy have meant benefits for the solution to this pathology in 14.45% of patients. It is essential to carry out a long-term follow-up, at least 12 months, to be sure RAP is cured. We must carry on looking for aetiological cause of RAP.

Abdominal Pain↗

PubMedDate not supplied

Increased atrial natriuretic factor secretion after endothelin injection in dogs.

Hemodynamic and hormonal responses to bolus intravenous injections of synthetic porcine endothelin (pET) were examined in anesthetized dogs. There were no significant changes in mean blood pressure (MBP), right atrial pressure (RAP), or plasma atrial natriuretic factor (ANF) concentration in response to 40 pmol/kg of the peptide. However, responses to 400 pmol/kg of the peptide were significant: MBP rose from 114 +/- 6 mmHg (mean +/- SE) to 139 +/- 7 mmHg (p less than 0.01), RAP rose from 5.4 +/- 0.9 mmHg to 7.8 +/- 1.1 mmHg (p less than 0.01), and ANF increased from 45 +/- 10 pg/ml to 277 +/- 33 pg/ml (p less than 0.01). Peak value of RAP was observed 2.6 +/- 0.4 min, while peak of ANF was 11.4 +/- 0.9 min after peptide injection. There was a strongly positive correlation (r = 0.93, p less than 0.01) between the increase in RAP and the increase in ANF in dogs given 400 pmol/kg of pET. These results indicate that exogenously administered pET to anesthetized dogs alters hemodynamics and induces ANP release, and are compatible with a postulate that the ANF release is caused by elevated RAP.

Animals↗

PubMed1986

Whole kidney response to reduced arterial pressure during converting enzyme inhibition in the rat.

Autoregulatory efficiency of renal blood flow (RBF) and glomerular filtration rate (GFR) was evaluated in male Sprague-Dawley rats during interference with the renin-angiotensin system by a converting enzyme inhibitor (CEI), captopril (3 mg X h-1 X kg-1 BW). RBF and GFR were approximately 25 (p less than 0.01) and 20% (p less than 0.02) higher, respectively, in rats infused with CEI than in control rats at spontaneous renal arterial pressure (RAP). A reduction of RAP to 100 mm Hg (within the autoregulatory range) resulted in effective autoregulation of GFR and RBF in control rats. In rats given CEI, however, the autoregulation of GFR was markedly impaired. GFR decreased by 35% (p less than 0.001), while RBF remained relatively unchanged. This caused the filtration fraction to decrease from 0.33 +/- 0.01 to 0.29 +/- 0.01 (p less than 0.001). RAP had a consistent effect on the urine flow rate, even though both GFR and RBF were well autoregulated in control rats. No significant decrease in electrolyte excretion was detected within the autoregulatory range in control rats, but during converting enzyme blockade this excretion decreased progressively as RAP was reduced, and the decrease correlated well to the reduction in GFR. In summary, these results suggest that the renin-angiotensin system plays an important intrarenal role in the autoregulation of GFR, probably through an efferent arteriolar mechanism. Furthermore, it is demonstrated that the contralateral kidney efficiently compensates in urinary electrolyte excretion for an acute unilateral reduction of RAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

[Recent angina pectoris: the first experience using programmed stimulation of the heart for the detection of the electrical instability of the heart ventricles].

Programmed ventricular stimulation was performed in 41 patients with recent angina pectoris (RAP, defined as less than 3 months old), 14 patients after large focal myocardial infarction (MI) and 9 patients without organic heart disease (WHD). The prevalence and number of repetitive ventricular responses (RVR) after programmed stimulation with one to three extra stimuli (2 ms, 2 MDS) from 2 right-ventricular sites at sinus rhythm and three basic pacing cycle lengths (600, 500 and 400 ms) were compared in RAP, MI and WHD patients. In 56% of WHD patients, 32% of RAP patients, and 22% of MI patients, RVRs were absent. Five or more RVR were provoked in MI patients only (43%). The incidence of ventricular fibrillation during programmed stimulation was 2.5% in RAP patients and 22% in MI patients. Differences in incidence are not significant, but show the influence of the severity or organic coronary arterial and left-ventricular damage on the prevalence of RVRs. Programmed stimulation seems to have no diagnostic value for the detection of electrical instability in RAP patients without a history of MI.

Adult↗

PubMed1983

Nuclear left ventriculography at rest and during atrial pacing in the evaluation of coronary artery disease.

This study was undertaken to examine the value of rapid atrial pacing (RAP) combined with left-ventricular nuclear (LVN) angiography in the diagnosis of ischemic heart disease. It included 32 patients: 12 normal subjects and 20 with clinical coronary artery disease (CAD) and greater than 50% narrowing of a coronary artery (significant CAD). The ECG and an LVN angiogram (LVNA) were recorded at rest and during graded RAP. In the normal subjects, left-ventricular wall motion was normal at rest and during atrial pacing, but a wall motion abnormality (WMA) appeared in one subject. Left-ventricular ejection fraction (EF) did not change significantly. In the 20 patients with significant CAD, the diagnostic sensitivity of the ECG during RAP was 100% and 90% for the nuclear angiogram (presence or appearance of WMA at rest and during RAP). The mean EF in this group decreased from 0.38 to 0.31. WMA on the LVNA was present in 79% of patients with significant left-anterior descending, in 44% of those with right, and in 33% of those with circumflex coronary artery disease. WMA (at rest or on pacing) occurred in 17% of patients with 50 to 89% narrowing of an artery, in 50% with 90 to 99% narrowing and in 68% with total obstructions. The LVNA (rest and/or RAP) identified patients with significant single-vessel disease, but underestimated the extent of double-and triple-vessel disease. The LVNA at rest and during atrial pacing was an excellent method of evaluating significant coronary artery disease.

Adult↗

PubMed1980

[Effect of intravenous nytroglicerin in hypertensive patients during and after open heart surgery (author's transl)].

The present study was performed to compare hemodynamic effect of intravenous Nitroglycerin (TNT i.v.) in 14 patients developing acute hypertension (Group I) and in 7 non hypertensives after open heart surgery (Group II). In all patients, m.a. 56.6 yrs, (10 mitral and/or aortic prosthetic valve replacements, 9 aorto-coronary bypass, 1 open mitral commissurotomy, 1 closure of atrial septal defect) TNT was infused at doses of 0.5, 1, 2 microgram X kg X min. and subsequently at 2 microgram X kg X min. after volume administration (2 + V.A.) to maintain right and left atrial pressure the same as control (P = N.S.). Mean arterial, right and left atrial pressures (MAP, RAP, LAP), cardiac frequency and index (CF, CI and systemic vascular resistance index (SVRI) were monitorized. TNT i.v. resulted in hypertensive patients (Group I) in reduction vs. control of: a) RAP (--20.17%) and LAP (--20.58%) at 0.5 microgram X kg X min. b) RAP (--26.13%), LAP (--27.50%), MAP (--19.94%) and CI (--12.98%) at 1 microgram X kg X X min. c) RAP (--22.47%), LAP (--26.89%), MAP (--24.68%), CI (--12.6%) and SVRI (--17.34%) at 2 microgram X kg X min. When RAP and LAP was maintained by volume administration TNT i.v. (2 microgram X kg X min.) resulted in an even greater increase in CI and a greater decrease in MAP and SVRI ((--22.04% and --24.88% respectively). No significant hemodynamic modification (P less than or equal to 0.05) were observed in non hypertensive patients (Group II) at all doses of TNT i.v. The results confirm a predominant venodilator effect of TNT at low doses and a good effect on arterial resistances at high doses in hypertensive patients. In view of previous reports of differing effects on ischemia TNT i.v. may be preferable to other vasodilator drugs for control of acute post-ECG hypertension, only on condition to maintain an adequate left ventricular filling pressure to prevent a fall of cardiac index. Moreover the absence of significant (P less than or equal to 0.05) hemodynamic modifications in non hypertensive patients may be a further advantage in the treatment of myocardial ischemia with i.v. TNT.

Adult↗

PubMed1994

Rapamycin selectively inhibits the growth of childhood rhabdomyosarcoma cells through inhibition of signaling via the type I insulin-like growth factor receptor.

We show that cell lines derived from childhood alveolar rhabdomyosarcoma (RMS) are very sensitive to the growth-inhibitory effects of the immunosuppressive agent rapamycin (RAP), compared to other human cell lines (50% inhibitory concentration range of 0.1-8 ng/ml, compared to 1280 to > 10,000 ng/ml). Our data suggest that the sensitivity of RMS lines is due to RAP inhibition of insulin-like growth factor 1 receptor-mediated signaling, which is essential for continued proliferation of RMS cells. The embryonal RMS line Rh1, which was resistant to RAP in serum-containing medium (50% inhibitory concentration, 4180 ng/ml), was highly sensitive under autocrine conditions of growth, indicating that resistance was due to paracrine signaling pathways insensitive to RAP action. FK506 reversed RAP action in all cell lines, indicating a dependence on complexing with the cytosolic FK506-binding protein for activity.

Carrier Proteins↗

PubMed1994

The humoral immune response to Helicobacter pylori infection in children with recurrent abdominal pain.

The systemic humoral immune response to Helicobacter pylori antigens was investigated in 36 children with recurrent abdominal pain (RAP). H. pylori was cultured and Helicobacter-like organisms (HLO) were seen in six children, three of whom had active and two inactive chronic gastritis. None of these children had endoscopic abnormalities. All sex children had increased IgG antibodies to heat-stable H. pylori antigens which were of the IgG1 and IgG3 subclasses. Using six other IgG tests, four of which were commercially available, two to five H. pylori-positive children were found seropositive. Five of six H. pylori-negative children with inactive chronic gastritis and no endoscopic abnormalities had increased IgM antibody levels in addition to increased or borderline increased IgG antibody levels to H. pylori, indicating activity in a chronic H. pylori infection. Five children without H. pylori and with no morphological changes, but with gastritis or duodenitis by endoscopy, had significantly lower IgG and IgA antibody levels compared to other groups. Six of nineteen children without H. pylori, and with no morphological or endoscopic changes had increased IgG and IgM antibody levels to H. pylori. All H. pylori-negative children were seronegative by the four commercial kits. Overall, 12 (33%) of 36 children with RAP were either H. pylori positive by culture and microscopy or had increased IgG antibody levels to H. pylori, which is significantly different from the 10-14% seropositive rate of asymptomatic children. H. pylori may therefore be a cause of RAP in one quarter to one third of the children with RAP in whom other etiologies of RAP are excluded. Further studies on a large number of children are needed for an extended evaluation of the humoral immune response to H. pylori and for further examination of commercial kits which seem to give a high number of false-negative results.

Abdominal Pain↗

PubMed1993

[The improvement of the Doppler echocardiographic method for the estimation of pulmonary systolic pressure].

The formulas currently utilized for noninvasive evaluation of right ventricular systolic pressure (RVSP) include right ventricular-right atrial pressure gradient (RV-RAG) and right atrial pressure (RAP). The former is expressed by trans-tricuspid systolic flow velocity, the latter is generally assumed. We recently observed that ultrasound estimation of RAP through inferior vena cava collapsibility index (CI) may help in the choice of the more appropriate formula for the evaluation of RVSP. However, these traditional methods (method A:RV-RAG + 10; method B:RV-RAG x 1.1 + 14) have limitations, particularly when RAP is low. The present study was undertaken to improve noninvasive estimation of RVSP through new formulas based on CI prediction of RAP. One hundred and four patients, in whom tricuspid regurgitation was adequately documented with CW-Doppler, were included in this study. They were classified into 3 groups: Group 1 with CI > 45%, Group 2 with CI < or = 35%, Group 3 with CI 35-45%. RVSP was evaluated by 3 different methods: A, B, and C. Method C was based on CI, assigning 6, 16, or 9 mmHg to RAP (respectively, the mean values in the 3 groups of our previous study). Results indicate that method C improves noninvasive estimation of RVSP in Group 1 and Group 2, with respect to other methods, with reduction of the SEE and of the mean difference of the t-test between hemodynamic and echographic values. In Group 3, Doppler estimation by method A and C, and catheter measurements are comparable, whereas method B significantly overestimates the actual value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1996

Prediction of right ventricular dysfunction after left ventricular assist device implantation.

BACKGROUND: Right ventricular dysfunction (RVD) significantly affects mortality and morbidity after left ventricular assist device (LVAD) implantation, and its occurrence often is unpredictable. The aim of the present study was to identify predictors of RVD after LVAD implantation. METHODS AND RESULTS: We studied right ventricular (RV) hemodynamics in 28 patients before and after LVAD implantation with a rapid-response thermistor pulmonary artery catheter. Measurements included mean right atrial pressure (RAP), mean pulmonary arterial pressure (PAP), cardiac index, transpulmonary gradient (TPG), pulmonary vascular resistance (PVR), RV end-diastolic and end-systolic volume indexes (EDVI and ESVI, respectively), and RV ejection fraction (RVEF). We regarded patients who had RAP > or = 15 mm Hg at LVAD explantation (n = 8) or who required an RV assist device (n = 3) as the RVD group (n = 11). The other patients were categorized as the RV nondysfunctional group (RVN, n = 17). Before LVAD implantation, the RVD group had larger RV volumes (200 +/- 107 versus 125 +/- 46 mL/m2 for EDVI; 177 +/- 109 versus 104 +/- 48 mL/m2 for ESVI) and higher preload (23 +/- 6 versus 17 +/- 6 mm Hg for RAP) and afterload (20 +/- 9 versus 13 +/- 6 mm Hg for TPG; 5.9 +/- 3.0 versus 3.8 +/- 2.0 Wood units for PVR) than the RVN group (P < .05 for all). RVEF and PAP did not differ significantly. LVAD implantation remarkably improved RV hemodynamics in both groups, decreasing RV volumes, preload, and afterload and increasing RVEF in all patients, but post-LVAD PAP tended to be higher in the RVD group. Multivariate logistic regression analysis revealed that RAP and TPG before LVAD implantation and an acute decrease (delta) in PAP by LVAD were significant predictors of RVD (P < .05). The sensitivity for predicting RVD by a combination of at least two of these three predictors (RAP > or = 20 mm Hg, TPG > or = 16 mm Hg, and delta PAP < or = 10 mm Hg) was 82%, and the specificity was 88%. CONCLUSIONS: Dilated right ventricle with increased RV preload and afterload predisposes to RVD after LVAD implantation. Not only baseline parameters but also the immediate hemodynamic response to the LVAD are predictive, and a combination of these parameters may be useful in predictions of the occurrence of RVD after LVAD implantation.

Adult↗

PubMed1998

Helicobacter pylori infection in recurrent abdominal pain.

OBJECTIVE: To study the relationship between Helicobacter pylori (Hp) infection and recurrent abdominal pain (RAP) and to evaluate various modalities to diagnose Hp infection. DESIGN: Prospective case control study. SETTING: Teaching hospital. METHODS: Children between 3-12 years of age with RAP in whom upper gastrointestinal endoscopic examination was indicated were studied. Endoscopic biopsy specimen were collected from duodenum, antrum and esophagus. Apart from histopathological examination of biopsy material, rapid urease test (RUT) of the antral biopsy specimen and blood examination to estimate specific IgG antibodies to Hp by Indirect Solid Phase Enzyme Immunoassay was performed. The results of Hp IgG antibodies was compared with age matched controls. RESULTS: Thirty one children with RAP were subjected to endoscopic examination and their anti Hp IgG antibodies status compared with 26 controls. Hp colonization was detected in 7 children (23%) with RAP; by RUT in 23% and antral biopsy in 16% of cases. Anti Hp IgG antibodies were also positive in almost equal proportion (19%) of controls (p = 0.757). Endoscopic examination revealed esophagitis in 16% of cases and none had evidence of gastric or duodenal erosion, ulcer or cobblestone appearance of antrum. A significant correlation of Hp was noticed with chronic antral gastritis (p = 0.002), chronic duodenitis (p = 0.02) and age > 10 years (p = 0.02). No significant correlation was noticed between Hp colonization and various socioeconomic risk factors. CONCLUSION: Hp does not seem to be commonly associated with RAP in our patient population as Hp colonization was detected in only 23% of cases which was not significantly higher than the seroprevalence of anti Hp IgG antibodies in the controls. However, a small sample size of our study limits drawing any firm conclusions. Antral gastritis and chronic duodenitis had a significant correlation with Hp colonization. RUT was found to be a reliable diagnostic test to detect Hp.

Abdominal Pain↗

PubMed1999

The Rap1 GTPase functions as a regulator of morphogenesis in vivo.

The Ras-related Rap GTPases are highly conserved across diverse species but their normal biological function is not well understood. Initial studies in mammalian cells suggested a role for Rap as a Ras antagonist. More recent experiments indicate functions in calcium- and cAMP-mediated signaling and it has been proposed that protein kinase A-mediated phosphorylation activates Rap in vivo. We show that Ras1-mediated signaling pathways in Drosophila are not influenced by Rap1 levels, suggesting that Ras1 and Rap1 function via distinct pathways. Moreover, a mutation that abolishes the putative cAMP-dependent kinase phosphorylation site of Drosophila Rap1 can still rescue the Rap1 mutant phenotype. Our experiments show that Rap1 is not needed for cell proliferation and cell-fate specification but demonstrate a critical function for Rap1 in regulating normal morphogenesis in the eye disk, the ovary and the embryo. Rap1 mutations also disrupt cell migrations and cause abnormalities in cell shape. These findings indicate a role for Rap proteins as regulators of morphogenesis in vivo.

Amino Acid Sequence↗

PubMed2007

Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons.

The Rap family of small GTPases is implicated in the mechanisms of synaptic plasticity, particularly synaptic depression. Here we studied the role of Rap in neuronal morphogenesis and synaptic transmission in cultured neurons. Constitutively active Rap2 expressed in hippocampal pyramidal neurons caused decreased length and complexity of both axonal and dendritic branches. In addition, Rap2 caused loss of dendritic spines and spiny synapses, and an increase in filopodia-like protrusions and shaft synapses. These Rap2 morphological effects were absent in aspiny interneurons. In contrast, constitutively active Rap1 had no significant effect on axon or dendrite morphology. Dominant-negative Rap mutants increased dendrite length, indicating that endogenous Rap restrains dendritic outgrowth. The amplitude and frequency of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-mediated miniature excitatory postsynaptic currents (mEPSCs) decreased in hippocampal neurons transfected with active Rap1 or Rap2, associated with reduced surface and total levels of AMPA receptor subunit GluR2. Finally, increasing synaptic activity with GABA(A) receptor antagonists counteracted Rap2's inhibitory effect on dendrite growth, and masked the effects of Rap1 and Rap2 on AMPA-mediated mEPSCs. Rap1 and Rap2 thus have overlapping but distinct actions that potentially link the inhibition of synaptic transmission with the retraction of axons and dendrites.

Action Potentials↗