c-myc amplification coexistent with activating N-ras point mutation in the biphenotypic leukemic cell line RED-3

While activation of the protooncogene c-N-ras is observed regularly in acute myelogenous leukemia, amplification of c-myc in AML cells or derived lines is uncommon. In particular, concurrent ras/myc activation, which has been shown to be critical in several elegant models of malignancy, has been demonstrated in a very small number of human tumors or derivative cell lines. A cell line, RED-3, is described which was derived from cells of a patient with aggressive acute leukemia which exhibits many markers of lineage infidelity. DNA from this cell line contains an activating point mutation of c-N-ras as well as 20-30-fold amplification of c-myc. After HL-60, this is the second example of ras/myc activation in AML derived cells and demonstrates that this lesion is not unique to HL-60. Rather, it may be important in leukemogenesis in a small proportion of AML patients.     

The effect of fluoride on fertilized eggs of a freshwater fish, Catla catla (Hamilton)

The eggs of Catla catla were exposed to 2 fluoride media, (1) effluent dilutions containing 1.86, 3.21, 7.12, 9.56, and 16.23 ppm fluoride, and (2) fluoride (NaF) solutions containing 1.86, 3.56, 7.34, 10.01, and 16.68 ppm fluoride. The eggs exposed to 1.86 ppm fluoride (in both media) hatched at the end of 6 h, while in rest of the fluoride concentrations hatching was delayed by 1–2 h. The eggs showed decreases in water and protein and increase in fluoride contents. Toxicity of fluoride to eggs was more related to the availability of fluoride ions, than to the total fluoride in the media.     

Bioavailability of imipramine tablets relative to a stable isotope-labeled internal standard: Increasing the power of bioavailability tests

A new methodology for comparative bioavailability testing is described in which each drug formulation is compared with a stable isotope-labeled variant of the drug that is consumed orally in solution at the same time the tested formulation is ingested. The methodology is used to determine the comparative bioavailabilities of two commercially available brands of imipramine hydrochloride. The power of the new methodology to detect differences between drug formulations, when, in fact, such differences exist, is shown to be superior to that of conventional bioavailability tests.This study was supported by Contract 223-75-3006, DHEW/Public Health Service, Food and Drug Administration, Rockville, Maryland.     

Analytical Methods Validation: Bioavailability,Bioequivalence and Pharmacokinetic Studies

Pharmaceutical Research -     

A longitudinal study on physical growth of children of different birth weight groups from birth to 5 years

Summary A statistical analysis of the physical growth of 1858 children of different birth weight groups in an urban community of Delhi, during the age period from birth to 5 years, is presented. The relative growth pattern of weight, height, head and chest circumferences is discussed. The literature related to the subject is briefly reviewed. From the Longitudinal Morbidity and tality Survey of Children Unit, Indian Council Medical Research, Postal Address: Flat 32, mkar Market, New Delhi-1.     

The Centers for Mendelian Genomics: a new large-scale initiative to identify the genes underlying rare Mendelian conditions

Next generation exome sequencing (ES) and whole genome sequencing (WGS) are new powerful tools for discovering the gene(s) that underlie Mendelian disorders. To accelerate these discoveries, the National Institutes of Health has established three Centers for Mendelian Genomics (CMGs): the Center for Mendelian Genomics at the University of Washington; the Center for Mendelian Genomics at Yale University; and the Baylor-Johns Hopkins Center for Mendelian Genomics at Baylor College of Medicine and Johns Hopkins University. The CMGs will provide ES/WGS and extensive analysis expertise at no cost to collaborating investigators where the causal gene(s) for a Mendelian phenotype has yet to be uncovered. Over the next few years and in collaboration with the global human genetics community, the CMGs hope to facilitate the identification of the genes underlying a very large fraction of all Mendelian disorders; see http://mendelian.org.     

Radiosynovectomy using yttrium-90, phosphorus-32 or rhenium-188 radiocolloids versus corticoid instillation for rheumatoid arthritis of the knee

Background  

Radiosynovectomy (RSO) is widely used in rheumatoid arthritis (RA). Commercially available radiopharmaceuticals are costly, and therefore new agents may be of interest. Radiocolloids labelled with less costly and more accessible radionuclides are of interest to developing countries. We investigated the efficacy of different formulations in RA.     

Use of anti‐CD20 antibody in the treatment of post‐transplant glomerulonephritis

Damodar A, Mustafa R, Bhatnagar J, Panesar M, Gundroo A, Zachariah M, Blessios G, Tornatore K, Weber‐Shrikant E, Venuto R. Use of anti‐CD20 antibody in the treatment of post‐transplant glomerulonephritis.
Clin Transplant 2011: 25: 375–379. © 2010 John Wiley & Sons A/S. Abstract: Post‐transplant glomerulonephritis (PTGN) accounts for 4–10% of late graft loss. Six consecutive patients who developed PTGN 3–72 months post‐transplant presented to our center with deteriorating kidney function and proteinuria. Three had focal segmental glomerulosclerosis; one had membranoproliferative glomerulonephritis Type 1; one recurrent membranous nephropathy; and one recurrent immunoglobin A nephropathy. All six were treated with an aggressive immunosuppression regimen including rituximab, pulse steriods and/or maximization of mycophenolic acid and calcineurin inhibitor therapy. Four of the six patients received plasma exchange. The patients were followed for a minimum of nine months after treatment. Proteinuria decreased from 7.2 ± 4.4 to 1.4 ± 1.5 g (p = 0.04), while mean estimated glomerular filtration rate was 31.2 ± 13.1 and 42.5 ± 21.7 mL/min (p = 0.07) at nine months. No adverse events were noted. These observations suggest that immune modulating therapy may be of benefit in the treatment of PTGN.