Biomedical subjects

Brian Davis

Publications and source records attributed to Brian Davis.

7 recordsLinked to original sources

PubMed2006

A 1.5-Mb-resolution radiation hybrid map of the cat genome and comparative analysis with the canine and human genomes.

We report the construction of a 1.5-Mb-resolution radiation hybrid map of the domestic cat genome. This new map includes novel microsatellite loci and markers derived from the 2X genome sequence that target previous gaps in the feline-human comparative map. Ninety-six percent of the 1793 cat markers we mapped have identifiable orthologues in the canine and human genome sequences. The updated autosomal and X-chromosome comparative maps identify 152 cat-human and 134 cat-dog homologous synteny blocks. Comparative analysis shows the marked change in chromosomal evolution in the canid lineage relative to the felid lineage since divergence from their carnivoran ancestor. The canid lineage has a 30-fold difference in the number of interchromosomal rearrangements relative to felids, while the felid lineage has primarily undergone intrachromosomal rearrangements. We have also refined the pseudoautosomal region and boundary in the cat and show that it is markedly longer than those of human or mouse. This improved RH comparative map provides a useful tool to facilitate positional cloning studies in the feline model.

Animals↗

PubMed2006

Does the position of the alimentary limb in Roux-en-Y gastric bypass surgery make a difference?

Intestinal obstruction and other complications have been reported following Roux-en-Y gastric bypass (RYGB) surgery. There is controversy of whether the alimentary limb should be placed in the retrocolic or antecolic position. A retrospective analysis was performed on 444 patients undergoing RYGB surgery for morbid obesity during a six year period. During operation, the surgeon chose the positioning of the 75-cm alimentary limb based upon technical consideration (the presence of adhesions from prior surgical procedures, thickness of the transverse mesocolon and mobility of the small bowel mesentery). Group A (216) patients had placement of the Roux limb anterior to the transverse colon, and group B (228) patients had placement of the limb through an opening created in the transverse mesocolon. The average age was 40 years (range 19-64) and the body mass index ranged from 40 to 75 kg/m2. Patients were followed for 24-86 months (mean 36 months). Any patients lost to follow-up were excluded. The average age of patients in the study was 40 years (range 19-64 years). Patients in both groups were similar in their body mass index and demographic characteristics. Group A had 16 patients (7.4%) that had early intolerance to enteral intake, compared to 13 patients in group B (5.7%, P>0.05). Thirteen patients required reoperation for intestinal obstruction (seven patients in group A and six patients in group B (P>0.05). Development of anastomotic stricture occurred in one patient (0.5%) in group A and three patients (1%, P>0.05) in group B. There were no differences in mean operating room times, hospital length of stay, and excess weight lost. No other complications during the follow-up period were attributed to the position of the alimentary limb. Placement of the Roux limb in the antecolic position is may be technically more feasible in some patients and does not appear to be associated with more complications. It avoids the risk of an internal hernia through the transverse and does not appear to be associated with feeding difficulties in the early or late postoperative period.

Adult↗

PubMed2006

First metatarsal bone: an anatomic study.

BACKGROUND: The purpose of this study was to establish the range of anatomic variations of the first metatarsal bone, including both the angulations of the articular surfaces and the dimensions of the bone in a large sample. METHODS: Four hundred and seventy-eight first metatarsal bones of 239 cadaver specimens were studied. The following parameters were recorded: the distal metatarsal articular angle (DMAA), distal metatarsal articular surface shape, proximal metatarsal articular angle (PMAA), the first metatarsal bone length and width at the mid-region of the shaft, and the existence of a joint between the bases of the first and second metatarsals. These parameters were correlated to the specimen's age, sex, race, height, and weight. The DMAA and PMAA were measured from a digital picture of the first metatarsal bone by a specially designed computer analysis program. RESULTS: Males and African-American race had a longer and wider metatarsal. The joint between the first and second bases was present in 25% of the population. The DMAA ranged from -14 degrees of medial deviation to 30 degrees of lateral deviation with an overall average of 8.21 degrees. The DMAA increased 1 to 3 degrees with every 10 years in age for both right and left bones with a p value of < 0.01 and < 0.001, respectively, and the average increase from 20 to 60 years of age was 4.5 degrees. The PMAA ranged from -13.8 degrees of lateral deviation to 12.7 degrees of medial deviation with an overall average of -1 degrees. PMAA significantly deviated laterally in the presence of a joint between the bases of the first and second metatarsals (p < 0.001). The male and female means for the DMAA and PMAA were nearly equal. CONCLUSIONS: The DMAA had a wider range than reported in the literature, and it increased with age. The first-second metatarsal joint was accompanied by lateral deviation of the PMAA. CLINICAL RELEVANCE: Laterally deviated PMAA could predispose to a varus deformity of the first metatarsal.

Adult↗

PubMed2005

Generation of a packaging cell line for prolonged large-scale production of high-titer HIV-1-based lentiviral vector.

BACKGROUND: A stable packaging cell line facilitates large-scale lentivirus vector manufacture. However, it has been difficult to produce clinical-scale HIV-1-based lentiviral vectors using a packaging cell line, in part due to toxicity of packaging genes, and gene silencing that occurs during the long culture period necessary for sequential addition of packaging constructs. METHODS: To avoid these problems, we developed a three-level cascade gene regulation system designed to remove tetracycline transactivator (tTA) from cytomegalovirus immediate early promoter (CMV)-controlled expression to reduce cytotoxicity from constitutive expression of tTA and leaky expression of packaging genes. We also performed a one-step integration of the three packaging plasmids to shorten the culture time for clonal selection. RESULTS: Although leaky expression of p24 and vector production still occurred despite the three-level regulation system, little cytotoxicity was observed and producer cells could be expanded for large-scale production. Producer cells yielded remarkably stable vector production over a period greater than 11 days with the highest titer 3.5 x 10(7) transducing units (TU)/ml and p24 300 ng/ml, yielding 2.2 x 10(11) TU and 1.8 milligram (mg) p24 from one cell factory. No replication-competent lentivirus (RCL) was detected. Long-term analysis demonstrated that, although the cells are genetically stable, partial gene silencing occurs after 2-3 months in culture; however, the one-step construct integration allowed prolonged vector production before significant gene silencing. Concentrated vector resulted in 90% transduction in CD4+ lymphocytes at 20 TU per cell. CD34+ progenitor cells were transduced at 41-46% efficiency, and long-term initiating culture (LTC-IC) was transduced at 45-51%. CONCLUSIONS: These results demonstrate for the first time HIV-1-based lentiviral vector production on the large scale using a packaging cell line.

Base Sequence↗

PubMed2005

Unilateral segmental Darier disease following Blaschko lines: a case report and review of the literature.

Darier disease (DD) is an autosomal-dominant skin disorder that is characterized by multiple keratotic papules, loss of epithelial adhesion, and abnormal keratinization. We describe an unusual case of late-onset unilateral segmental DD that follows the lines of Blaschko. Our patient did not exhibit other classic findings of DD. Our case and review of the literature suggest that lesions previously classified as acantholytic dyskeratotic epidermal nevi (ADEN) are actually unilateral segmental presentations of DD.

Darier Disease↗

PubMed2004

Safe two-plasmid production for the first clinical lentivirus vector that achieves >99% transduction in primary cells using a one-step protocol.

We report the design of a unique two-plasmid production system for the first lentiviral vector to be evaluated in humans, VRX496. VRX496 is an optimized VSV-G pseudotyped vector derived from HIV-1 that expresses antisense to the HIV envelope gene. We found that a two-plasmid approach to production resulted in higher vector production titers when compared with a three-plasmid approach, which is particularly important for vector production at the large scale. Therefore, we carefully designed a single packaging construct, VIRPAC, for safety by reducing its homology with VRX496 and by insertion of functionally validated genetic elements designed to reduce the risk of generation of a replication-competent lentivirus (RCL). A native cis-acting ribozyme is used to prevent read through into the envelope gene from the upstream gag-pol genes in the packaging vector, thus preventing RNAs containing gag-pol and env together for comparable safety to a three-plasmid system. We demonstrate that there is no significant in vivo vector mobilization using a primary SCID-hu mouse transplantation model, which correlates with the presence of an anti-HIV payload and suggests that inclusion of antisense may be a useful tool to restrict mobilization in other vector constructs. Gene transfer is achieved using a one-step transduction procedure that is simple and clinically translatable, which reaches stable transduction efficiencies of >99% in CD4+ T lymphocytes within 3 days of culture initiation.

Animals↗

PubMed2002

Metastatic prostate carcinoma to bone: clinical and pathologic features associated with cancer-specific survival.

BACKGROUND: The objective of this study was to examine the clinical and pathologic features of metastatic prostate carcinoma to bone in a large cohort of men, and the associations of these features with outcome. METHODS: Sixty-eight men who underwent surgery for metastatic prostate carcinoma to bone for stabilization of a pathologic fracture or impending fracture were studied. Clinical characteristics included the type of treatment for the primary and metastatic prostate carcinoma, age and serum prostate specific antigen (PSA) at the diagnosis of the metastatic prostate carcinoma, radiographic findings of the metastasis (osteoblastic, osteolytic, or mixed), and the number of metastatic sites at the time of the surgery for the metastasis. Pathologic features examined included Gleason score of the metastatic prostate carcinoma. Immunohistochemical stains for MIB-1, cytokeratin, PSA, synaptophysin, chromogranin A, serotonin, estrogen receptor, progesterone receptor, and androgen receptor were performed for all cases. The Kaplan-Meier method was used to estimate cancer-specific survival. The duration of follow-up was defined as the interval from the date of surgery for the metastasis to the date of death or last follow-up. Univariate and multivariate Cox proportional hazards models were fit to assess the features that were associated with death from prostate carcinoma. RESULTS: The average (standard deviation) time from the surgery for the metastasis to death from prostate carcinoma was 1.5 (1.9) years, ranging from 0 days to 10 years, with a median of 1 year. The estimated cancer-specific survival rates at 1 year, 2 years, and 3 years were 54.3%, 28.8%, and 22.9%, respectively. Median cancer-specific survival occurred at 1.1 years. After 4 years of follow-up, there were only seven patients left at risk for death from prostate carcinoma. Features that were found to be significantly associated with death from prostate carcinoma univariately included the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), androgen deprivation therapy before surgery for the metastasis (P = 0.002), presentation with metastasis (P = 0.003), the number of metastatic sites (P = 0.034), Gleason score of the metastasis (P = 0.002), and tumor positivity for chromogranin A (P = 0.041). On multivariate analysis, the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), Gleason score of the metastasis (P < 0.001), and tumor positivity for chromogranin A (P = 0.009) were associated significantly with death from prostate carcinoma. CONCLUSIONS: Although cancer-specific survival for patients after surgery for prostate carcinoma metastatic to bone is poor, assessments of tumor differentiation of the metastasis and chromogranin A positivity provide prognostic information.

Aged↗