Cellular immune responses of patients with juvenile chronic arthritis to retinal antigens and their synthetic peptides

The objective of this study was to determine the proliferative responses of peripheral blood lymphocytes of ocular antigens like retinal S-antigen, peptides M and G of S-antigen, yeast histone H3 peptide 106–121 homologous to peptide M and peptide R16 of interphotoreceptor retinoid binding protein (IRBP) in children with juvenile chronic arthritis (JCA). We have studied the in vitro proliferative response of peripheral blood lymphocytes from 41 patients with JCA (10 with and 31 without uveitis) and 23 healthy controls against the above antigens. The responders were retested after 1 or 6 months. Fifty (5/10) and 9.7% (3/31) of JCA patients with and without uveitis, respectively, responded (stimulation index >3) to S-antigen or one of its peptide listed above or yeast histone H3 peptide or R16 of IRBP. None of the healthy controls responded to any of these antigens. The difference in the frequency of responders (SI>3) between JCA associated with uveitis and healthy controls was statistically significant (p=0.001). Similarly, the difference between JCA with and without uveitis was also significant (p=0.013). Our findings suggest that these antigens may have a role in the pathogenesis of uveitis in a subset of patients with JCA.     

An assessment of gene prediction accuracy in large DNA sequences

One of the first useful products from the human genome will be a set of predicted genes. Besides its intrinsic scientific interest, the accuracy and completeness of this data set is of considerable importance for human health and medicine. Though progress has been made on computational gene identification in terms of both methods and accuracy evaluation measures, most of the sequence sets in which the programs are tested are short genomic sequences, and there is concern that these accuracy measures may not extrapolate well to larger, more challenging data sets. Given the absence of experimentally verified large genomic data sets, we constructed a semiartificial test set comprising a number of short single-gene genomic sequences with randomly generated intergenic regions. This test set, which should still present an easier problem than real human genomic sequence, mimics the approximately 200kb long BACs being sequenced. In our experiments with these longer genomic sequences, the accuracy of GENSCAN, one of the most accurate ab initio gene prediction programs, dropped significantly, although its sensitivity remained high. Conversely, the accuracy of similarity-based programs, such as GENEWISE, PROCRUSTES, and BLASTX was not affected significantly by the presence of random intergenic sequence, but depended on the strength of the similarity to the protein homolog. As expected, the accuracy dropped if the models were built using more distant homologs, and we were able to quantitatively estimate this decline. However, the specificities of these techniques are still rather good even when the similarity is weak, which is a desirable characteristic for driving expensive follow-up experiments. Our experiments suggest that though gene prediction will improve with every new protein that is discovered and through improvements in the current set of tools, we still have a long way to go before we can decipher the precise exonic structure of every gene in the human genome using purely computational methodology.     

Water-clear cell adenoma of the parathyroid gland: a rare entity

Water-clear cell hyperplasia is a rare but well-documented cause of primary hyperparathyroidism. Parathyroid adenomas of water-clear cell type are exceptionally rare, and only five case reports are available at present in the medical literature. We report an additional case of water-clear cell adenoma of the parathyroid gland, and the differential diagnoses are discussed.     

Heterogeneity in synaptic transmission along a Drosophila larval motor axon

At the Drosophila melanogaster larval neuromuscular junction (NMJ), a motor neuron releases glutamate from 30-100 boutons onto the muscle it innervates. How transmission strength is distributed among the boutons of the NMJ is unknown. To address this, we created synapcam, a version of the Ca2+ reporter Cameleon. Synapcam localizes to the postsynaptic terminal and selectively reports Ca2+ influx through glutamate receptors (GluRs) with single-impulse and single-bouton resolution. GluR-based Ca2+ signals were uniform within a given connection (that is, a given bouton/postsynaptic terminal pair) but differed considerably among connections of an NMJ. A steep gradient of transmission strength was observed along axonal branches, from weak proximal connections to strong distal ones. Presynaptic imaging showed a matching axonal gradient, with higher Ca2+ influx and exocytosis at distal boutons. The results suggest that transmission strength is mainly determined presynaptically at the level of individual boutons, possibly by one or more factors existing in a gradient.     

Mortality trends in falciparum malaria--effect of gender difference and pregnancy

Falciparum malaria in pregnancy is a significant health problem in India. Pregnant women constitute an important high risk group for malaria infection which may cause abortions, stillbirths, intra-uterine growth retardation (IUGR) and premature labour. In this hospital based study on 602 admitted patients of falciparum malaria which included 314 males, 243 non-pregnant females and 45 pregnant females, there was significantly increased mortality rate in females (18.4%) in comparison to males (7.64%, p < 0.001). The mortality rate was highly significant in pregnant females (37.77%) in comparison to non-pregnant females (14.81%) and males (7.64%; p < 0.001). Severe anaemia with Hb < 5 gm% was observed more commonly in pregnant patients (20.0%) in comparison to non-pregnant patients (4.11%). Incidence of malaria infection was more in primi gravida and second gravida. Pregnancy related complications in the form of preterm live births, intra-uterine death (IUD), still births and abortions were more in primi parous than multiparous patients. As the pregnancy is associated with increased incidence and adverse outcome of P.falciparum malaria infection, chemoprophylaxis should be made an integral part of antenatal care along with antianaemia therapy to reduce the risk of serious maternal and fetal complications.