Disease relevance of RAPH1

• Altered expression and deletion of RMO1 in osteosarcoma [1].
• Lpd is recruited to EPEC and Vaccinia, pathogens that exploit the actin cytoskeleton for their own motility [2].
• Twelve cases of T gamma LPD (lymphoproliferative disorders of Fc gamma receptor-bearing T cells) involving an expansion of large granular lymphocyte/natural killer (LGL/NK) cells were investigated for the expression of LGL/NK-associated markers and for T beta gene rearrangement [3].
• T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena [4].
• Maternal low protein diet (LPD) fed during only the preimplantation period of development (0-4.25 days after mating), before return to control diet for the remainder of gestation, induced programming of altered birthweight, postnatal growth rate, hypertension and organ/body-weight ratios in either male or female offspring at up to 12 weeks of age [5].

Psychiatry related information on RAPH1

• Furthermore, major depression with melancholia and major depression without melancholia, both conform to the LPD profile of endogenous depression whereas other depressive syndromes do not [6].
• Social support and high self-efficacy for men and high self-efficacy for women are associated with improvement of the compliance with LPD therapy, leading to good therapeutic effects [7].

High impact information on RAPH1

• All the cases selected were classified as T gamma LPD on the basis of morphology, function, and phenotype of the circulating cells [3].
• The LPD regimen significantly reduced insulin and essential amino acid levels, and increased glucose levels within maternal serum by day 4 of development [5].
• MR-GEF and PDZ-GEF both contain a region immediately N-terminal to their catalytic domains that share sequence homology with Ras-associating or RalGDS/AF6 homology (RA) domains [8].
• Predictive saccades were also strongly hypometric in both PD groups but especially in LPD (e.g. for rightwards saccades: controls = 19 degrees, SD = 1.6; LPD = 14 degrees, SD = 2.7; RPD = 15.7 degrees, SD = 2.3) [9].
• Urinary urea appearance and plasma urea were significantly lower on LPD [10].

Chemical compound and disease context of RAPH1

• To investigate the short-term renal effects of protein restriction and unchanged salt intake in chronic renal failure (CRF), patients with moderate CRF (creatinine clearance 41 +/- 5 ml/min) and healthy controls (CON) ate a normal protein diet (NPD) for four weeks, and thereafter a low protein diet (LPD, 0.4 g/kg body wt/day) for three weeks [11].
• Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown [12].
• On LPD, protein intake (0.64 +/- 0.05 vs 1.15 +/- 0.09 g kg-1 body weight (BW) per day, P less than 0.001), plasma urea (6.6 +/- 1.3 vs 11.0 +/- 2.0 mmol l-1, P less than 0.01) and urea appearance (0.06 +/- 0.01 vs 0.16 +/- 0.03 gN kg-1 body weight per day, P less than 0.001) were lower [13].
• To test whether the combination of both may have an additive antiproteinuric effect, we studied the effects of single treatment with ACEi (10 mg enalapril o.d.), LPD (target, 50% reduction in protein intake), and the combination of both in 14 of such patients with stable proteinuria exceeding 3 g per day [14].
• When UNEx, AUTO and LPD recurrent abortion subgroups were compared with each other (Student's t-test) total thiols and erythrocyte GSH of UNEx and AUTO subgroups were diminished in comparison with LPD [15].

Biological context of RAPH1

• RMO1 is located at 2q33, a region of frequent loss of heterozygosity in cancer, and exhibited loss of heterozygosity in 6 out of 9 primary osteosarcoma tumor samples (67%) [1].
• We identified Lamellipodin (Lpd) as an Ena/VASP binding protein [2].
• These phenotypes are more severe than loss of Ena/VASP, suggesting that Lpd regulates other effectors of the actin cytoskeleton in addition to Ena/VASP [2].
• The purposes of this investigation were to evaluate the characteristics of three consecutive menstrual cycles and to determine the frequency ofluteal phase deficiency (LPD) and anovulation in a sample of sedentary and moderately exercising, regularly menstruating women [16].
• OBJECTIVE--To compare the effect of a normal protein diet (test diet) in which chicken and fish were substituted for red meat with a low-protein diet (LPD) on glomerular filtration rate (GFR) in normoalbuminuric insulin-dependent-diabetes mellitus (IDDM) patients [17].

Anatomical context of RAPH1

• Northern blot analysis indicated that RMO1 mRNA is ubiquitously expressed in tissues except for peripheral blood leukocytes [1].
• Conversely, knockdown of Lpd expression impairs lamellipodia formation, reduces velocity of residual lamellipodial protrusion, and decreases F-actin content [2].
• Lpd overexpression increases lamellipodial protrusion velocity, an effect observed when Ena/VASP proteins are overexpressed or artificially targeted to the plasma membrane [2].
• Therefore, in an effort to characterize the usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the T-cell type LGL of five patients [4].
• Highly significant changes in desmosome frequency, diameter and LPD were observed between epidermal strata and, in basal and upper horny cells, between different regions of the same cell surface [18].

Associations of RAPH1 with chemical compounds

• Lpd contains a PH domain that binds specifically to PI(3,4)P2, an asymmetrically localized signal in chemotactic cells [2].
• RESULTS: As expected, maternal protein restriction led to reduced nephron endowment in LPD offspring [19].
• This study examines the longitudinal changes in peritoneal macrophage (PMØ) function in patients dialyzed continuously with either lactate (LPD; 40 mM lactate, pH 5.2)-buffered or bicarbonate/lactate (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3)-buffered PDF [20].
• RESULTS: UAER [median CD: 269.4 (range: 111-1128) microg/min; LPD: 229.3 (76.6-999.3) microg/min; UD: 312.8 (223.7-1223.7) microg/min; P < 0.01] and mean (+/-SD) non-HDL cholesterol (CD: 3.92 +/- 0.99 mmol/L; LPD: 3.92 +/- 0.93 mmol/L; UD: 4.23 +/- 1.06 mmol/L; P = 0.042) were lower after CD and LPD than after UD [21].
• The blunted elevation in FSH during the luteal-follicular transition in exercising women with LPD may explain their lower follicular estradiol levels [16].

Other interactions of RAPH1

• Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics [2].

Analytical, diagnostic and therapeutic context of RAPH1

• None of the monkeys demonstrated significant adverse effects, and at 1 month the 2 LPD/pAAVaspa monkeys were positive for human ASPA transcript by reverse transcriptase polymerase chain reaction of brain tissue punches [22].
• Podocyte density was lowest in the LPD diabetic animals (not significant), and the area covered by each podocyte was greater in the LPD diabetic group (2.40+/-0.693 x10(-3) mm(2)) than in the LPD control group (1.68+/-0.374 x10(-3) mm(2), p<0.001) and in the NPD diabetic animals (1.71+/-0.291 x10(-3) mm(2), p<0.05) [23].
• Glomerular volume correlated inversely with glomerular number (r=-0.64, p=0.035), but total glomerular filtration surface area was reduced in the LPD animals (4,770+/-541 vs 5,779+/-1,302 mm(2), p=0.05) [23].
• Sixteen CRF patients consuming an LPD were randomly assigned to receive a supplement of a highly fermentable fiber, gum arabic (50 g/d), or a placebo (1 g pectin/d) in a prospective, single-blind, crossover design [24].
• Lipoproteins and lipoprotein-deficient plasma (LPDP) were purified and analyzed by Western blots [25].

References