The complete sequence of adeno-associated virus type 1 (AAV-1) was defined. Its genome of 4,718 nucleotides demonstrates high homology with those of other AAV serotypes, including AAV-6, which appears to have arisen from homologous recombination between AAV-1 and AAV-2. Analysis of sera from nonhuman and human primates for neutralizing antibodies (NAB) against AAV-1 and AAV-2 revealed the following. (i) NAB to AAV-1 are more common than NAB to AAV-2 in nonhuman primates, while the reverse is true in humans; and (ii) sera from 36% of nonhuman primates neutralized AAV-1 but not AAV-2, while sera from 8% of humans neutralized AAV-2 but not AAV-1. An infectious clone of AAV-1 was isolated from a replicated monomer form, and vectors were created with AAV-2 inverted terminal repeats and AAV-1 Rep and Cap functions. Both AAV-1- and AAV-2-based vectors transduced murine liver and muscle in vivo; AAV-1 was more efficient for muscle, while AAV-2 transduced liver more efficiently. Strong NAB responses were detected for each vector administered to murine skeletal muscle; these responses prevented readministration of the same serotype but did not substantially cross-neutralize the other serotype. Similar results were observed in the context of liver-directed gene transfer, except for a significant, but incomplete, neutralization of AAV-1 from a previous treatment with AAV-2. Vectors based on AAV-1 may be preferred in some applications of human gene therapy.

No abstract

No abstract

The radiographs of 35 consecutive adult patients with isthmic spondylolisthesis who underwent a transforaminal lumbar interbody fusion (TLIF) with one or two Brantigan carbon fiber cages and pedicle screw instrumentation were evaluated. Anterolisthesis, disk space height, and slip angle were measured in preoperative and postoperative standing neutral radiographs. Anterolisthesis was reduced and disk space height was increased with the TLIF procedure. Average slip angle, however, was not significantly altered. The restoration of lordosis across the listhetic disk space correlated with a more anterior placement of the interbody cage within the disk space. The TLIF technique, performed with the Brantigan cage and pedicle screw instrumentation, appears to be able to restore disk height and reduce forward translation in patients with isthmic spondylolisthesis, but improvement in sagittal alignment is dependent upon anterior placement of the interbody device.

Factors relevant to the successful application of adeno-associated virus (AAV) vectors for liver-directed gene therapy were evaluated. Vectors with different promoters driving expression of human α-1-antitrypsin (α-1AT) were injected into the portal circulation of immunodeficient mice. α-1AT expression was stable but dependent on the promoter. Southern analysis of liver DNA revealed approximately 0.1 to 2.0 provirus copies/diploid genome in presumed head-to-tail concatamers. In situ hybridization and immunohistochemical analysis revealed expression in approximately 5% of hepatocytes clustered in the pericentral region. These results support the use of AAV as a vector for diseases treatable by targeting of hepatocytes.

Patients undergoing anterior cervical fusion have diminished neck motion compared with normal volunteers. Following surgery, they may be expected to gain motion, even when undergoing multilevel fusions. However, these patients are unlikely to regain the neck motion seen among normal individuals without neck complaints.

No abstract

Nerve root anomalies are frequently underrecognized on advanced imaging studies and may account for some percentage of failed spinal surgical procedures. The conjoined nerve root represents the most common nerve root anomaly. It is a well-known cause of false-positive readings for bulging and herniated disks in patients with purely axial neuroimaging studies. A retrospective evaluation of consecutive microsurgical lumbar diskectomies in 80 patients during a 5-year period was undertaken. A total of four patients (5%) were found intraoperatively to have evidence of a conjoined nerve root by the classification of Neidre. None was diagnosed preoperatively. Coronal magnetic resonance imaging offers the best means of visualizing a conjoined nerve root. The chance for a successful operation can be significantly enhanced if the surgeon is prepared to encounter this pathology.