Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Massive residual dental cyst: Case report

A case report is presented of a massive residual dental cyst that involved over half an edentulous mandible. Presentation, diagnosis and management of the massive cyst is discussed.     

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.      

Primary total hip replacement--a survey of current practice and identifying changing trends

Primary total hip replacement (THR) surgery is the most commonly performed and successful reconstructive procedure in orthopaedic surgery. We performed a survey of Irish Orthopaedic consultants to elucidate current practices of primary THR in elderly and young patients and identify changing trends. There was an 83% response rate. Most respondents use a cemented THR in elderly patients. 69% use a different THR in younger patients compared to older patients. 9% refer younger patients to hip replacement specialist consultant colleagues. 70% report changing to a new implant or new technique in younger patients and 45% use a hybrid THR, 15% an uncemented THR, 15% perform hip resurfacing and 47% use different bearing surfaces. Only 17% use the Charnley hip prosthesis in younger patients. Young and active patients will place high demands on a new THR and newer techniques, implants and bearing surfaces are being adopted in the hope of better outcomes.     

Presence of the AZF region in a female with an idic(Y)(q11)

In a child with some features of Turner's syndrome, gonosomal mosaicism with an isodicentric nonfluorescent (idic)Y chromosome was detected (mos 45,X/47,X,idic(Y)(q11),idic(Y)(11)/46,X,idic(Y)(q11)). Histopathological examination showed streak gonads with some evidence of ovarian stroma and no sign of gonadoblastoma. Polymerase chain reaction (PCR) analysis in blood lymphocytes and gonadal tissues using primers of seven loci along the Y chromosome, including the sex determined region (SRY), azoospermia factor region (AZF) and the deleted in azoospermia ( DAZ ) gene was positive for all loci tested, confirming the isodicentric character of the Y chromosome and indicating the presence of the AZF region. It is remarkable that the existence of spermatogenesis controlling genes does not play an important role in gonadal development and differentiation in a phenotypic female with some Turner stigmata. The data presented here are briefly discussed with previously-described patients.     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

Computed tomography-directed fine needle aspiration of skull base parapharyngeal and infratemporal fossa masses

Suspicious findings in the parapharyngeal region on computed tomographic (CT) or magnetic resonance imaging studies can be a diagnostic problem. Blind biopsy through the mucosa can be inadequate, since the abnormality is not directly visible. With CT guidance, fine needle aspiration (FNA) of parapharyngeal masses can be performed with a needle confidently placed within the lesion. Vital structures such as the carotid artery are avoided. We present a series of 33 CT-guided FNA on 30 patients to evaluate the safety and the degree of accuracy of the procedure. Most of the patients had been treated previously for local malignancy. All patients had surgical pathologic study, autopsy, or clinical and imaging follow-up to confirm the FNA cytology results. Twenty of the 33 biopsies were positive for malignant cells, confirming recurrence of the primary head and neck malignancy. Of the 33 CT-directed FNA, 13 were negative for malignant cells. Three of these 13 were found to be false-negative FNA. None of the patients had complications from the procedure. CT directed FNA of masses at the skull base or in the parapharyngeal area can be performed safely. A high degree of accuracy is achieved, with 30 (90.9%) accurate in identifying the presence or absence of malignancy in our series.