Plasmodium falciparum AMA-1 erythrocyte binding peptides implicate AMA-1 as erythrocyte binding protein

The role of AMA-1 during merozoite invasion has not yet been determined. However, reported experimental evidence suggests that this protein can be used, in particular as erythrocyte-binding protein, since, Fab fragments against this protein are able to block merozoite invasion. Using a previously described methodology, eight peptides with high binding activity to human erythrocyte, scattered along the different domains and having around 130 nM affinity constants, were identified in the Plasmodium falciparum AMA-1 protein. Their binding activity was sialic acid independent. Some of these peptides showed homology with the erythrocyte binding domains of one of the apical organelle protein family, MAEBL, identified in rodent malarial parasites. One of these peptides shares amino acid sequence with a previously reported B-cell epitope which induces antibodies to block parasite growth. The critical residues were identified for erythrocyte binding conserved peptides 4313 (DAEVAGTQYRLPSGKCPVFG), 4321 (VVDNWEKVCPRKNLQNAKFG), 4325 (MIKSAFLPTGAFKADRYKSH) and 4337 (WGEEKRASHTTPVLMEKPYY). All conserved peptides were able to block merozoite invasion of new RBC and development, suggesting that these peptides are involved in P. falciparum invasion.     

Using multiple cutpoints for the free-to-total prostate specific antigen ratio improves the accuracy of prostate cancer detection

BACKGROUND: Using a single cutpoint for the free-to-total (F/T) prostate specific antigen (PSA) ratio loses important diagnostic information. We evaluated the performance of multiple F/T PSA cutpoints in detecting prostate cancer in men with nonspecific PSA values. METHODS: We extracted sensitivity and specificity data from 12 studies reporting on >or=30 cancer patients with PSA values between 2.0 and 10.0 ng/mL. We calculated stratum-specific likelihood ratios (LR) and areas under the receiver operating characteristic (ROC) curves. RESULTS: Multiple cutpoints for the F/T PSA ratio significantly increased the area under the ROC (0.70) compared with the single investigator-selected cutpoint (0.62), P < 0.004. The LR for the most positive cutpoint stratum (2.62) was significantly higher than the LR for a positive test from the single cutpoint (1.36), P < 0.004. CONCLUSIONS: Using multiple cutpoints increased the discriminating power of the F/T PSA ratio and led to greater probability revisions in the most positive test-result strata.     

Renal diseases in children in Venezuela,South America

The present study reports epidemiological data on renal disorders in children in Venezuela. Information was obtained from 14 centers for the period January through December 1998. A total of 3,624 patients were evaluated as either a first outpatient consultation or as a first hospital admission. Nearly 70% of the patients could be grouped in one of the following categories: (1) urinary tract infections (32%), with detection of abnormalities of the urinary tract in 25%, (2) metabolic disorders (28%), mainly idiopathic hypercalciuria and hyperuricosuria, (3) glomerulonephritis (9.5%). The other 30% corresponded to urolithiasis 7%; renal tubular acidosis 5.6%; nephrotic syndrome 4.5%; primary hematuria 4.2%; acute renal failure 2.8% (43% were secondary to acute dehydration, 15% to birth asphyxia, 14% to septicemia, and 23% to multiple factors); chronic renal failure 1.6% (secondary to glomerulopathies, predominantly focal glomerulosclerosis, structural abnormalities of the urinary tract, hereditary disorders, and renal hypoplasia/dysplasia); miscellaneous diseases 4.8%. Hence, the spectrum of renal disorders in Venezuela is wide, sharing similarities with countries of both the developed and developing world. These data will hopefully contribute to the development of national healthcare policies appropriate to the epidemiology of the country.     

2001 National MCH Epidemiology Awards: Recognizing Excellence

Maternal and Child Health Journal -     

Identification of the key amino acids of gliai cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

Glial cell line-derived neurotrophic factor （GDNF） plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha 1 （GFR alpha 1）, and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFR alpha 1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFR alpha 1 mutations was made, and PC12 cell lines stably expressing different GFR alpha 1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF- GFR alpha 1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFR alpha 1 central region were found to be critical for GFR alpha 1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFR alpha 1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/ S318A mutation in the GFR alpha 1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFR alpha 1 may be involved in binding to GDNF and Ret.     

Reversible findings of restricted diffusion in 5‐flourouracil neurotoxicity

A 35‐year‐old woman presented with neurotoxicity correlated to an i.v. regimen of 5‐fluorouracil as episodes of acute confusional state and abnormalities of symmetrically restricted diffusion in the periventricular white matter and corpus callosum. On discontinuing the medication, the areas of severely restricted diffusion had entirely resolved, with minimal residual T2 signal abnormality. In this case, immediate discontinuation of the chemotherapeutic agent apparently reversed the patient's symptoms and findings on MRI. The scant information available in the published literature regarding this phenomenon is reviewed with regard to 5‐fluorouracil.