Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains

PKD1 is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease (ADPKD). Analysis of the predicted protein sequence of the human PKD1 gene, polycystin, shows a large molecule with a unique arrangement of extracellular domains and multiple putative transmembrane regions. The precise function of polycystin remains unclear with a paucity of mutations to define key structural and functional domains. To refine the structure of this protein we have cloned the genomic region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA and has greater complexity with 54 exons compared with 46 in man. Comparative analysis of the predicted protein sequences shows a lower level of homology than in similar studies with identity of 40 and 59% similarity. However key structural motifs including leucine rich repeats (LRR), a C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A region of homology with the sea urchin REJ protein was also confirmed in Fugu but found to extend over 1000 amino acids. Several highly conserved intra- and extra- cellular regions, with no known sequence homologies, that are likely to be of functional importance were detected. The likely structure of the membrane associated region has been refined with similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels highlighted over part of this area. The overall protein structure has therefore been clarified and this comparative analysis derived structure will form the basis for the functional study of polycystin and its individual domains.      

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

SCREENING PROCEDURES IN PEDIATRICS

Pediatric health screening procedures, both prenatal and postnatal, have a tremendous potential in improving the health status of children and in turn reducing the resource burden on the parents and the State. The existing recommendations, inherent problems and different screening procedures are discussed. The need for suitable mass screening pediatric procedures in the Indian context is stressed.KEY WORDS: Pediatric screening procedures     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

Merits of multicolor imaging for tractional retinal detachment

Purpose:To compare multicolor imaging (MCI) with Optos color fundus photography (OCFP) for the evaluation of morphology and extent of preretinal membranes in diabetic tractional retinal detachments (TRD).Methods:In this retrospective study, 30 eyes with diabetic TRDs were imaged using the MCI feature of the Heidelberg Spectralis Spectral-domain optical coherence tomography (SD-OCT) and color photo using the Optos Daytona ultra-widefield fundus camera. Two investigators independently graded and determined the agreeability between the two modalities with respect to the extent of the TRD and preretinal membranes on the SD-OCT B-scan images.Results:The MCI provided better visualization of the attachments and traction points of the posterior hyaloid face and preretinal membranes and is comparable to the SD-OCT B-scan images. The inter-rater agreeability rates for OCFP had a Kappa (κ) value of 0.37, while the MCI had a κ value of 0.46. When comparing between images of different wavelengths, grading using infrared reflectance (IR) had a poor agreement (−0.04 ± 0.04) while green reflectance (GR) (0.46 ± 0.32) and blue reflectance (BR) (0.53 ± 0.19) had a moderate agreement. The composite MCI and GR images also had comparatively higher intraclass coefficient when compared to the OCFP (0.25 [−0.09–0.55]) and IR (−0.03 [−0.39–0.34]) images.Conclusion:MCI is more sensitive for determining the extent of TRDs and for the detection of secondary membranes when compared to OCFP, thus, aiding in better surgical planning.     

Fabrication of Diamond Based Sensors for Use in Extreme Environments

Electrical and magnetic sensors can be lithographically fabricated on top of diamond substrates and encapsulated in a protective layer of chemical vapor deposited single crystalline diamond. This process when carried out on single crystal diamond anvils employed in high pressure research is termed as designer diamond anvil fabrication. These designer diamond anvils allow researchers to study electrical and magnetic properties of materials under extreme conditions without any possibility of damaging the sensing elements. We describe a novel method for the fabrication of designer diamond anvils with the use of maskless lithography and chemical vapor deposition in this paper. This method can be utilized to produce diamond based sensors which can function in extreme environments of high pressures, high and low temperatures, corrosive and high radiation conditions. We demonstrate applicability of these diamonds under extreme environments by performing electrical resistance measurements during superconducting transition in rare earth doped iron-based compounds under high pressures to 12 GPa and low temperatures to 10 K.