Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Frequency and species distribution of gliotoxin-producing Aspergillus isolates recovered from patients at a tertiary-care cancer center

Aspergillus isolates (n = 103) collected from cancer patients were screened to determine the taxonomic distribution and quantity of gliotoxin production. Gliotoxin was detected in 93% of Aspergillus fumigatus, 75% of A. niger, 25% of A. terreus, and 4% of A. flavus cultures. Gliotoxin concentrations were highest in cultures of A. fumigatus.     

Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection

Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV) infections are described. One patient had primary HHV-7 infection and reactivated EBV infection. The other had primary HHV-7 and EBV infections. These cases indicated that HHV-7 is capable of inducing infectious mononucleosis-like illness. Multiple herpesvirus infection in one of the patients also suggests that interaction among herpesviruses can occur in vivo. The consequence of this interaction may have clinical implications.     

The Third World Integrative Medicine Congress Abstracts (Excerption)

The 3rd World Integrative Medicine Congress (3rd WIMCO) was held on September 22-24, 2007 in Guangzhou, China. The Congress has showed the academic achievements of integrative medicine in the recent five years covering a wide range of fields, such as basic and experimental research; clinical research; theory, education and management research; new drug research and development; and application of evidence-based medicine.     

Percutaneous nephrolithotripsy under assisted local anaesthesia for high risk patients: Is it effective?

ObjectivesThe aim of the present study is to evaluate the feasibility and safety of performing PNL under local anesthesia in a selected group of patients who are at high risk for general anesthesia.Patients and methodsForty seven patients underwent PNL under local anesthesia. There were 38 males and 9 females with a mean age of 62 years. All patients were at medical high-risk for general anesthesia, with an American Society of Anesthesiologists (ASA) score of 3. The indications for local anesthesia in this study were obstructed single functioning kidney with azotemia in 29 patients, hepatic insufficiency in 8 patients, cardiac problems in 7 patients and 3 patients had hepatocellular carcinoma. The mean stone size was 2.7 cm (range 2–3.1 cm). Local infiltration with 10–20 cc of 2% lidocaine at the site of puncture was used in all cases. Narcotics were given 30 min prior to the procedure and medazolam was given intraoperatively upon demand. Utrasound guided puncture was performed in all cases and tract dilatation was then done under fluoroscopy using high pressure balloon catheter in 35 and Alken's metal dilators in 12 cases. Stones were then retrieved after disintegration in the same cession in 33 patients, while the other 14 patients underwent staged PNL, where a 12 Fr. nephrostomy tube was placed in the first stage, followed by tract dilatation and stone retrieval one week later.ResultsOut of 47 patients included, 44 had successful PNL either one stage (30 patients) or two stages (14 patients). Only 3 patients could not tolerate pain and the procedure was terminated after placement of nephrostomy tube and stone retrieval was completed later under general anesthesia.ConclusionOur results demonstrated that PNL under local anesthesia with narcotics and sedatives seems to be a satisfying solution for the treatment of a selected group of patients with renal pelvic stones and who have high anesthetic risk. However, additional studies with different groups of patients are required to validate our results.