Triplet repeat instability correlates with dinucleotide instability in primary breast cancer

The expansion of triplet repeat microsatellite sequences is the molecular correlate of anticipation in a number of rare Mendelian neurodegenerative disorders. This finding prompted us to study these sequences in primary breast cancer in which there is evidence of genetic anticipation. We used a PCR/silver stain method to determine whether triplet-repeat instability (TRI) was present in DNA from malignant breast tumors, and analyzed microsatellite instability (MSI) in triplets SCA1, SCA2, SCA3, SCA6, HD, DRPLA and X25-GAA. We studied 54 consecutive primary breast cancers previously analyzed for dinucleotide instability (DI) at 9 loci. Microsatellite instability (TRI and/or DI) was found in 28/54 (52%) cases, ranging from 0 to 56% in each patient. Dinucleotide instability occurred at > or =2 loci in 19/54 (35%) cases and TRI in 6/54 (11%). Considering single locus instability, we found DI in 26/54 (48%) tumors and TRI in 13/54 (24%). Triplets DRPLA and X25-GAA were most frequently unstable (14% of cases); SCA2 instability was not detected. Interestingly, most tumors with TRI had DI (11/13, 85%). There was a correlation between TRI and DI in the same tumor (42 vs 7% in DI+ and DI- tumors respectively, p=0.0028). Furthermore, TRI appears more frequently associated with lymph node metastases and more advanced clinical stages and more frequent in patients <50 years old, with positive steroidal hormone receptor status, positive p185 and negative p53. These findings are of interest because they demonstrate a relationship between TRI and the clinicopathological characteristics of cancer aggressiveness. Triplet repeat alterations can interfere with gene expression and proteomic functions, which suggests they can play a role in the neoplastic progression of mammary cells. Furthermore, the association of TRI and DI in the same tumor suggests that alterations in the DNA repair gene could culminate in selective phenotypes and breast cancer progression in a considerable number of patients.     

Additional antiprotozoal flavonol glycosides of the aerial parts of Helianthemum glomeratum

Bioassay-guided fractionation of the methanol extract of aerial parts from Helianthemum glomeratum afforded five antiprotozoal flavonol glycosides: tiliroside, kaempferol-3-O-(3',6'di-O-E-p-coumaroyl)-betad-glucopyranoside, astragalin, quercitrin and isoquercitrin. The in vitro antiprotozoal assay showed that tiliroside was the most potent antiamoebic and antigiardial compound with IC(50) values of 17.5 microg/mL for Entamoeba histolytica and 17.4 microg/mL for G. lamblia. Isoquercitrin showed selectivity against E. histolytica (IC(50) 14.7 microg/mL) and quercitrin toward G. lamblia (IC(50) 24.3 microg/mL). All isolated compounds were less active than metronidazole and emetine, two antiprotozoal drugs used as positive controls.     

Lyophilization cycle development for a high-concentration monoclonal antibody formulation lacking a crystalline bulking agent

An efficient freeze-dry cycle was developed for a high concentration monoclonal antibody formulation lacking a crystalline bulking agent. The formulation, at multiple protein concentrations, was characterized using differential scanning calorimetry (DSC) and freeze-dry microscopy. At low protein concentrations the glass transition temperature of the maximally freeze-concentrated solution (T(g)') determined by DSC was similar to the collapse temperature determined by freeze-dry microscopy. However, at higher protein concentrations, the difference between collapse temperature and T(g)' became progressively larger. The difference between the onset temperature for collapse and the complete collapse temperature also became progressively larger as protein concentration increased. JMP Design of Experiment studies were used to assess the effect of freezing rate, primary drying shelf temperature, and chamber pressure on primary drying product temperature, length of primary drying, and product quality attributes. Primary drying was shortened significantly by adjusting to conditions where the product temperature substantially exceeded T(g)' without any apparent detrimental effect to the product.     

Cystatin C as a potential marker for relapse in patients with non-Hodgkin B-cell lymphoma

The concentration of cysteine protease inhibitor cystatin C was determined in sera from 59 patients with non-Hodgkin B-cell lymphoma using ELISA. The sera from 43 age and sex matched healthy blood donors served as controls. Cystatin C was significantly increased in sera of patients without therapy (mean 1136+/-SE 105.7ng/ml, p=0.00001) and with therapy (mean 1073+/-52ng/ml, p=0.001) compared to controls (mean 819+/-28ng/ml). The highest levels were determined in sera of patients with a relapse (mean 1680+/-196ng/ml). By using immunofluorescence staining and confocal microscopy we determined immature dendritic cells as a major population of cystatin C positive cells in affected lymph nodes. Our study reports for the first time that cystatin C is a potential marker for relapse in patients with non-Hodgkin B-cell lymphoma.     

Mehr als Vermittlung und Unterstützung

Der Freie Zahnarzt - Der Zahnmedizinische Austauschdienst stellt sich vor. 166 Zahnmedizinstudenten konnten im Jahr 2017 einen finanziellen Zuschuss für ihre Auslandsfamulatur bekommen....     

Pharmacokinetics of First-Line Tuberculosis Drugs in Tanzanian Patients

East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling. In 20 adult TB patients, plasma concentrations were determined just before and at 1, 2, 3, 4, 6, 8, 10, and 24 h after observed drug intake with food to estimate the areas under the curve from 0 to 24 h (AUC_0–24) and peak plasma concentrations (C_max) of isoniazid, rifampin, pyrazinamide, and ethambutol. Acetylator status for isoniazid was assessed phenotypically using the isoniazid elimination half-life and the acetylisoniazid/isoniazid metabolic ratio at 3 h postdose. The geometric mean AUC_0–24s were as follows: isoniazid, 11.0 h · mg/liter; rifampin, 39.9 h · mg/liter; pyrazinamide, 344 h · mg/liter; and ethambutol, 20.2 h · mg/liter. The C_max was below the reference range for isoniazid in 10/19 patients and for rifampin in 7/20 patients. In none of the patients were the C_maxs for pyrazinamide and ethambutol below the reference range. Elimination half-life and metabolic ratio of isoniazid gave discordant phenotyping results in only 2/19 patients. A substantial proportion of patients had an isoniazid and/or rifampin C_max below the reference range. Intake of TB drugs with food may partly explain these low drug levels, but such a drug intake reflects common practice. The finding of low TB drug concentrations is concerning because low concentrations have been associated with worse treatment outcome in several other studies.     

Technical and functional hearing results after unilateral stapes surgery for otosclerosis at Cluj-Napoca University Hospital

The aim of this study was to assess the hearing results after unilateral stapes surgery for otosclerosis at Cluj-Napoca University Hospital, and to evaluate surgical trauma to the inner ear in these patients. The medical records of 387 consecutive patients who underwent unilateral stapes surgery were reviewed. Hearing results were evaluated according to the 1995 American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines and the Glasgow benefit plot. In addition we used Amsterdam plot to give an overview on air conduction gain and bone-conduction differences on an individual level. Results were analyzed separately for patients with preoperative unilateral, bilateral asymmetrical, and bilateral symmetrical hearing loss. Despite good technical hearing results after surgery (closure of the air-bone gap to ≤20 dB in 92 % of patients, air conduction gain of 24 ± 10.00 dB), only 37 % of patients achieved functionally normal, symmetrical hearing. Our results indicated that the pattern of preoperative hearing impairment in patients with otosclerosis can predict postoperative functional hearing results. The type of preoperative hearing impairment had.     

Computer Technology: Implications for Nurse Educators

The purpose of this paper is to discuss implications of computer technology for nursing education. Effects of computer anxiety and strategies to minimize them are presented. Computer assisted instruction (CAI) and interactive videodisc (IVD) are alternative instructional strategies for content dissemination and learning enhancement. Faculty must be cognizant of design factors facilitating usage when selecting programs. Issues of privacy, confidentiality, information security, and impact on nursing practice have risen with increased computer usage.