Effect of mild whole body hyperthermia on cytotoxic action of N-methyl-N'-nitro-N-nitrosoguanidine in Swiss mice

Studies were carried out to ascertain the efficacy of mild whole body hyperthermia (WBH) as a modifier of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) cytotoxicity in mice. Adult Swiss male mice, 6-8 weeks old, weighing about 25 g were exposed to mild WBH (39 degrees C, 1 h) in a precision temperature controlled environmental chamber maintained at 50-60% relative humidity. Twenty-four hours after treatment, animals were administered with different doses of MNNG either by intraperitoneal (i.p.) injections or by feeding through drinking water and were monitored for survival. The studies revealed that the exposure of animals to mild WBH, 24 h prior to MNNG administration results in an increase in survival and recovery in mean body weight compared with those administered with MNNG only. This suggests that prior WBH treatment can effectively reduce the MNNG cytotoxicity in mice.     

Multiple myeloma: an old disease with new hope for the future

Multiple myeloma is a currently incurable malignancy of terminally differentiated plasma cells. It typically occurs in older patients (median age 71 years). Clinical manifestations result from monoclonal protein (immunoglobulin) production and its accumulation in the serum and/or urine, anemia, lytic bone disease, hypercalcemia, renal insufficiency, and immune deficiency. Myeloma cells have low proliferative activity--most myeloma experts opine that the initial oncogenic event occurs 10-15 years before clinical disease manifestation. In addition, myeloma cells develop multiple chromosomal abnormalities, which may explain the native resistance of myeloma patients to conventional therapy and our inability to completely eradicate the disease. Indeed, with conventional therapy, only 5% of patients achieve complete response. Minimal improvement has been observed with conventional therapies over the past 20-30 years; the median duration of initial response remains approximately 18 months with median survival in the 36-month range. However, recent clinical trials have established high-dose therapy with autologous hematopoietic stem cell transplant as superior to conventional therapy: complete remission rates of 25-30% can be affected with median survival exceeding 5 years. Newer approaches to improve treatment outcomes are in active clinical trials including: more potent induction regimens utilizing thalidomide, alone or in combination with dexamethasone; tandem transplants to improve complete remission rates; newer approaches to maintenance therapy using thalidomide with corticosteroids; non-myeloablative therapy with allogeneic transplant; and post-transplant vaccinations.     

Physiological aspects of pig-to-primate renal xenotransplantation

BACKGROUND: Few data exist on the physiological aspects of pig-to-primate renal xenotransplantation. METHODS: Use of organs transgenic for human decay accelerating factor has allowed assessment of the metabolic and hormonal functions of these xenografts. RESULTS: Porcine renal xenografts largely maintain plasma electrolyte homeostasis. An increase in proteinuria was detected that may result from graft injury. In contrast to allotransplantation a severe anaemia developed requiring recipient treatment with exogenous human erythropoietin. CONCLUSIONS: Our experience provides qualified encouragement for the likely physiological compatibility of pig and primate species, but identifies areas where a xenograft may not match the performance of an allograft.     

Glucose phosphate isomerase (GPI) Tadikonda: Characterization of a novel Pro340Ser mutation

After a thirty-year lag, we serendipitously reestablished contact with a patient with glucose phosphate isomerase deficiency and hydrops fetalis first reported in 1987. We now provide a clinical update and provide results of mutation analysis in this patient, from Southern India. The patient now an adult female of 36 years of age has moderate anemia but requires no transfusions except with some intercurrent illnesses. Exome sequencing studies showed a homozygous c.1018C>T (Pro340Ser) mutation in exon 12 of the glucose phosphate isomerase gene and later confirmed by direct sequencing. This mutation has not been previously described. To our knowledge, this is also the first known homozygous mutation in the hydrophobic core of the protein and is a highly deleterious mutation by in silico analysis and by clinical history in the family. Flow cytometry studies of band 3 content with eosin maleimide showed a unique tail of red cells on histograms, reflecting the dense red cells (presumably ATP depleted) seen on blood smears; similar findings were seen in patients with pyruvate kinase and phosphoglycerate kinase deficiency.     

Complete nucleotide sequence of cherry virus A (CVA) infecting sweet cherry in India

Cherry virus A (CVA) is a graft-transmissible member of the genus Capillovirus that infects different stone fruits. Sweet cherry (Prunus avium L; family Rosaceae) is an important deciduous temperate fruit crop in the Western Himalayan region of India. In order to determine the health status of cherry plantations and the incidence of the virus in India, cherry orchards in the states of Jammu and Kashmir (J&K) and Himachal Pradesh (H.P.) were surveyed during the months of May and September 2009. The incidence of CVA was found to be 28 and 13% from J&K and H.P., respectively, by RT-PCR. In order to characterize the virus at the molecular level, the complete genome was amplified by RT-PCR using specific primers. The amplicon of about 7.4 kb was sequenced and was found to be 7,379 bp long, with sequence specificity to CVA. The genome organization was similar to that of isolates characterized earlier, coding for two ORFs, in which ORF 2 is nested in ORF1. The complete sequence was 81 and 84% similar to that of the type isolate at the nucleotide and amino acid level, respectively, with 5′ and 3′ UTRs of 54 and 299 nucleotides, respectively. This is the first report of the complete nucleotide sequence of cherry virus A infecting sweet cherry in India.     

Automated analysis of small animal PET studies through deformable registration to an atlas

Purpose

This work aims to develop a methodology for automated atlas-guided analysis of small animal positron emission tomography (PET) data through deformable registration to an anatomical mouse model.

Methods

A non-rigid registration technique is used to put into correspondence relevant anatomical regions of rodent CT images from combined PET/CT studies to corresponding CT images of the Digimouse anatomical mouse model. The latter provides a pre-segmented atlas consisting of 21 anatomical regions suitable for automated quantitative analysis. Image registration is performed using a package based on the Insight Toolkit allowing the implementation of various image registration algorithms. The optimal parameters obtained for deformable registration were applied to simulated and experimental mouse PET/CT studies. The accuracy of the image registration procedure was assessed by segmenting mouse CT images into seven regions: brain, lungs, heart, kidneys, bladder, skeleton and the rest of the body. This was accomplished prior to image registration using a semi-automated algorithm. Each mouse segmentation was transformed using the parameters obtained during CT to CT image registration. The resulting segmentation was compared with the original Digimouse atlas to quantify image registration accuracy using established metrics such as the Dice coefficient and Hausdorff distance. PET images were then transformed using the same technique and automated quantitative analysis of tracer uptake performed.

Results

The Dice coefficient and Hausdorff distance show fair to excellent agreement and a mean registration mismatch distance of about 6?mm. The results demonstrate good quantification accuracy in most of the regions, especially the brain, but not in the bladder, as expected. Normalized mean activity estimates were preserved between the reference and automated quantification techniques with relative errors below 10?% in most of the organs considered.

Conclusion

The proposed automated quantification technique is reliable, robust and suitable for fast quantification of preclinical PET data in large serial studies.     

Respiratory viral infection in lower airways of asymptomatic children

Aim: The aim of this study was to determine if asthmatic children have viruses more commonly detected in lower airways during asymptomatic periods than normal children. Methods: Fifty‐five asymptomatic children attending elective surgical procedures (14 with stable asthma, 41 normal controls) underwent non‐bronchoscopic bronchoalveolar lavage. Differential cell count and PCR for 13 common viruses were performed. Results: Nineteen (35%) children were positive for at least one virus, with adenovirus being most common. No differences in the proportion of viruses detected were seen between asthmatic and normal ‘control’ children. Viruses other than adenovirus were associated with higher neutrophil counts, suggesting that they caused an inflammatory response in both asthmatics and controls (median BAL neutrophil count, 6.9% for virus detected vs. 1.5% for virus not detected, p = 0.03). Conclusions: Over one‐third of asymptomatic children have a detectable virus (most commonly adenovirus) in the lower airway; however, this was not more common in asthmatics. Viruses other than adenovirus were associated with elevated neutrophils suggesting that viral infection can be present during relatively asymptomatic periods in asthmatic children.     

Sugar-sweetened carbonated beverage consumption correlates with BMI,waist circumference,and poor dietary choices in school children

Background  

The prevalence of obesity and overweight is increasing globally. Frequently coexisting with under-nutrition in developing countries, obesity is a major contributor to chronic disease, and will become a serious healthcare burden especially in countries with a larger percentage of youthful population. 35% of the population of Saudi Arabia are under the age of 16, and adult dietary preferences are often established during early childhood years. Our objective was to examine the dietary habits in relation to body-mass-index (BMI) and waist circumference (W_C), together with exercise and sleep patterns in a cohort of male and female Saudi school children, in order to ascertain whether dietary patterns are associated with obesity phenotypes in this population.