Quantification of diagnostic biomarkers to detect multiple sclerosis lesions employing (1)H-MRSI at 3T.

Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) enables the quantification of metabolite concentration ratios in the brain. The major purpose of the current work is to characterize NAA/Cho, NAA/Cr and Myo/Cr in multiple sclerosis (MS) patients, and to estimate their reproducibility in healthy controls. Twelve MS patients and five healthy volunteers were imaged using (1)H-MRSI at 3T. Eddy current correction was performed using a single-voxel non-water suppressed acquisition on an external water phantom. Time-domain quantification was carried out using subtract-QUEST technique, and based on an optimal simulated metabolite database. Reproducibility was evaluated on the same quantified ratios in five normal subjects. An optimal database was created for the quantification of the MRSI data, consisting of choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate (Lac), lipids, myo-inositol (Myo) and glutamine + glutamate (Glx). Decreasing of NAA/Cr and NAA/Cho ratios, as well as an increase in Myo/Cr ratio were observed for MS patients in comparison with control group. Reproducibility of NAA/Cr, NAA/Cho and Myo/Cr in control group was 0.98, 0.87 and 0.64, respectively, expressed as the squared correlation coefficient R (2) between duplicate experiments. We showed that MRSI alongside the time-domain quantification of spectral ratios offers a sensitive and reproducible framework to differentiate MS patients from normals.

Intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and represent new targets for therapy.

BACKGROUND: Sialophorin is a transmembrane sialoglycoprotein. Normally, the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signalling, apoptosis, migration and proliferation. METHODS: Normal breast tissue and primary breast tumours were analysed by immunohistochemistry for sialophorin expression. The sialophorin-positive breast cancer cell line MCF7 was engineered to stably express either non-targeted or sialophorin-targeted small interfering RNA (siRNA). Assays were then performed in vitro to assess apoptosis, intracellular adhesion, transendothelial migration and cytotoxicity. An orthotopic mouse model assayed ability to produce tumours in vivo. RESULTS: Normal breast epithelial cells exhibit expression of the N-terminal domain of sialophorin in the cytoplasm but not the nucleus. The majority of these normal cells are also negative for expression of the C-terminal domain. In contrast, malignant breast epithelial cells exhibit N-terminal expression both in the cytoplasm and nucleus and the majority express the C-terminus in the nucleus. Using differential patterns of intracellular expression of the N and C termini of sialophorin, we define six subtypes of breast cancer that are independent of histological and receptor status classification. Targeting sialophorin with siRNA resulted in the MCF7 breast cancer cell line exhibiting increased homotypic adhesion, decreased transendothelial migration, increased susceptibility to apoptosis, increased vulnerability to lysis by natural killer cells and decreased ability to produce tumours in mice. CONCLUSION: Our results indicate that intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and that sialophorin represents a novel therapeutic target.

Pre-transplant calcium-phosphate-parathormone homeostasis as a risk factor for early graft dysfunction.

While good organ quality and ideal transplant conditions eliminate many of the know factors that compromise initial graft function (IGF), poor early graft function (EGF) still occurs after living donor kidney transplantation (LDKT). Uncontrolled pre-transplant hypercalcemia and hyperparathyroidism are associated with impaired allograft function. Between April 2004 and January 2006, data were collected on 354 LDKT recipients including 252 males and 102 females, to determine risk factors for poor EGF, defined as either delayed or slow graft function (DGF or SGF). Of the 354 recipients, 318 (89%) had IGF, 22 (6.2%) had SGF and 14 (4%) had DGF. Donor female gender (P = 0.04) and duration on dialysis (P = 0.02) were associated with poor EGF. Recipients with DGF had higher serum phosphate (P = 0.07) and calcium x phosphate product ( P = 0.01) than recipients with IGF and SGF. The serum parathormone (PTH) levels were higher in recipients with SGF and DGF although the difference was not statistically significant (P = 0.1). Serum calcium levels did not correlate with the occurrence of poor EGF (P = 0.9). Our study suggests that serum phosphate and calcium x phosphate product serve as risk factors for DGF while serum PTH level may play a role as a risk factor for SGF and DGF.

Serum zinc, copper, magnesium, proteins and superoxide dismutase in leprosy patients on multidrug therapy--a follow-up study.

Serum zinc, copper, magnesium, total proteins and albumin-globulin fractions and superoxide dismutase (SOD) were estimated in 80 untreated patients with TT/BT/BL/LL type of leprosy and in 40 controls. The investigations were repeated on day 30, 60 and 120 after starting multidrug therapy (MDT-WHO) on the patients. Serum zinc was significantly lowered in all types of leprosy on days 0 and 30. Serum copper was significantly raised in all types of leprosy. This was not significant in BT/TT cases on 60, 120 days. There was a correlation between serum zinc and copper levels and the severity and type of leprosy. The lowering of serum magnesium values were not significant. With therapy, there was a shift of all the three elements towards normal values. Serum total proteins reduction was not significant. Serum albumin was significantly lowered in all types of leprosy. Serum globulin was significantly raised in all types of leprosy. This rise in TT/BT was not significant on day 60 and 120 after starting treatment. Serum SOD was significantly reduced in all the untreated cases. It gradually increased with the clinical improvement under MDT.