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T Drake

Publications and source records attributed to T Drake.

18 recordsLinked to original sources
PubMed2001

Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study.

BACKGROUND: Carotenoids are hypothesized to explain some of the protective effects of fruit and vegetable intake on risk of cardiovascular disease. The present study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis. METHODS AND RESULTS EPIDEMIOLOGY: Progression of intima-media thickness (IMT) of the common carotid arteries over 18 months was determined ultrasonographically and was related to plasma lutein among a randomly sampled cohort of utility employees age 40 to 60 years (n=480). Coculture: The impact of lutein on monocyte response to artery wall cell modification of LDL was assessed in vitro by quantification of monocyte migration in a coculture model of human intima. Mouse models: The impact of lutein supplementation on atherosclerotic lesion formation was assessed in vivo by assigning apoE-null mice to chow or chow plus lutein (0.2% by weight) and LDL receptor-null mice to Western diet or Western diet plus lutein. IMT progression declined with increasing quintile of plasma lutein (P for trend=0.007, age-adjusted; P=0.0007, multivariate). Covariate-adjusted IMT progression (mean+/-SEM) was 0.021+/-0.005 mm in the lowest quintile of plasma lutein, whereas progression was blocked in the highest quintile (0.004+/-0.005 mm; P=0.01). In the coculture, pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner (P<0.05). Finally, in the mouse models, lutein supplementation reduced lesion size 44% in apoE-null mice (P=0.009) and 43% in LDL receptor-null mice (P=0.02). CONCLUSIONS: These epidemiological, in vitro, and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis.

Adult↗
PubMed1997

Intracoronary adenovirus-mediated transfer of immunosuppressive cytokine genes prolongs allograft survival.

BACKGROUND: Intracoronary transfer and expression of recombinant genes in the intact heart is now feasible. In the transplant setting, local modulation of host immune responses by a genetically modified allograft may offer an attractive alternative to systemic immunosuppression. METHODS: We tested the efficacy and in vivo effect of intracoronary transfer of two immunosuppressive cytokine genes. First-generation E1-deleted adenoviral vectors expressing the Epstein-Barr virus interleukin-10 (AdSvIL10) or human transforming growth factor--beta 1 (AdCMVTGF-beta) were used. Rabbit cardiac allografts were transduced during cold preservation by slow (1 ml/min) intracoronary infusion of 10(10) pfu/gm diluted viral vectors and then implanted heterotopically. Controls included E1-deleted adenovirus (Ad5dI434) and AdCMVLacZ. Beating allografts were collected on day 4 for analysis of gene transfer efficacy and distribution. Additional grafts were used for evaluation of alloreactivity (n = 34). RESULTS: Mean allograft viral uptake was 81% (up to 91%). Polymerase chain reactions and reverse transcription-polymerase chain reactions confirmed the presence and expression of both genes in the grafts. beta-Galactosidase staining in AdCMVLacZ-infected grafts demonstrated efficient gene expression, which was highest (100%) in subepicardial regions. More homogeneous transmyocardial distribution of the transgene (in 25% to 40% of cells) could be achieved by pulsatile slow delivery. Allograft survival was 6.9 +/- 0.9 days in controls (n = 12), 11.1 +/- 1.7 days in AdCMVTGF-beta-infected grafts (n = 11, p < 10(-4)), and 11.2 +/- 3 days in AdSvIL10-infected grafts (n = 11, p < 10(-4)). Histologic scores (blinded) showed significantly (p < 0.005) higher regression coefficients for rejection in controls compared with both cytokine-transduced groups. Perioperative administration of cyclosporine A (INN: ciclosporin) to recipients had no effect on survival of AdCMVTGF-beta-infected grafts but reduced survival of AdSvIL10-infected grafts. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts is efficient and effectively prolongs graft survival. Vectors that would induce long-term expression of such genes may make this approach clinically applicable.

Adenoviridae↗
PubMed1997

Controlled periadventitial administration of verapamil inhibits neointimal smooth muscle cell proliferation and ameliorates vasomotor abnormalities in experimental vein bypass grafts.

OBJECTIVE: Inhibition of early myointimal proliferation may improve longterm patency of vein grafts, but the clinical use of many experimental drugs is limited by systemic toxicity. To determine whether this goal can be achieved by low-dose targeted drug administration, we constructed a polymeric system delivering verapamil and evaluated the effects on local and downstream vein graft morphology, neointimal smooth muscle cell proliferation, and vasomotor function. METHODS: Ethylene-vinyl acetate polymeric delivery systems were constructed, containing 2% verapamil by weight. These are flexible, biocompatible, and nonbiodegradable matrices, delivering the drug at a rate of 10 micrograms/day. The autologous external jugular vein was used to create a carotid artery bypass graft in hypercholesterolemic (n = 22) rabbits. Verapamil-containing matrices (n = 12) or plain polymers (control, n = 10) were wrapped around the proximal third of the veins after reperfusion. Graft vasomotor function was evaluated and was also compared with function of an additional group of normocholesterolemic vein grafts (n = 8). RESULTS: Twenty-eight days after grafting, intimal index (intima/media thickness ratio) was 31% lower, neointima/original lumen surface ratio was 26% lower, and residual luminal area was 71% greater (4.00 +/- 1.2 mm2 versus 2.34 +/- 0.9 mm2, all p < 0.01) under verapamil matrices compared with control grafts. Neointimal smooth muscle cell content was reduced from 45.4% to 28.2%, and net neointimal smooth muscle cell thickness was reduced by 47% (30 microns vs 15.8 microns, both p < 0.01). Verapamil-treated segments distal to the matrices also showed significantly lower neointimal smooth muscle cell density and increased lumen size. Sensitivity to serotoin and vasomotor responses to serotonin, norepinephrine, and sodium nitroprusside in distal segments were significantly lower in verapamil-treated grafts than in controls. CONCLUSIONS: Periadventitial controlled administration of verapamil below 1% of the systemic dose effectively inhibits myointimal hyperplasia in vein grafts. Local polymeric drug delivery may be readily applicable to coronary revascularization operations.

Animals↗
PubMed1992

The poison center as a reservoir for antidotes for veterinary poisoning emergencies.

Animal poisonings account for a significant number of the cases responded to by poison centers. The majority of consultations involve small animals and do not necessitate the use of large amounts of pharmacologic antagonists, such as atropine to treat anticholinesterase pesticide poisonings. However, large animals such as cattle present unique management problems, since phenomenal amounts of antidotes may be needed to treat a herd of cattle, creating a significant economic impact. The most challenging dilemma is providing 24-h availability and a means of acquisition of sufficient quantities of antidotes to reduce the economic impact of large-animal poisonings. In conjunction with a state veterinary medical association, a RPIC serves as a depot for the storage and distribution of emergency veterinary antidotes. Sufficient quantities of atropine, methylene blue, calcium EDTA, sodium nitrite and thiosulfate, and activated charcoal are available via the RPIC to treat a herd of 200 cattle. The antidotes are available only for emergency treatment and with a veterinary prescription. The 24-h nature of the poison center makes it an ideal location to serve the needs of veterinarians.

Animals↗
PubMed1990

Adenovirus hepatitis in two successive liver transplants in a child.

Adenoviruses can produce severe disease, especially in patients who are immunosuppressed. We present a unique case in which adenovirus type 5 was demonstrated retrospectively, by using immunohistochemical methods, in the appendix of a liver transplant donor. The donor had intussusception, which has been associated with adenovirus infection. Both the initial and a second liver transplant in the recipient were severely damaged by adenovirus type 5. These findings were demonstrated immunohistochemically, as well as on electron microscopy. The recipient died due to the infection and ensuing complications.

Adenoviridae Infections↗
PubMed1977

Unexplained infertility. A reappraisal.

During a 30-month period 229 couples were evaluated for infertility at the Naval Regional Medical Center, Oakland. Laparoscopy was used in all cases of otherwise unexplained infertility. The resulting laparoscopic examination of the female partner of 24 such couples demonstrated abnormal findings in 18 (75%). Of these 18 subjects, unsuspected endometriosis was found in 11 (46%) and peritubal adhesions in 7 (29%). Of the 229 couples evaluated, only 8 (3.5%) failed to show some etiologic factor associated with infertility. Thus, the previously reported 10 to 20% incidence of unexplained infertility is too high an estimate in view of the additional information made available through pelvic endoscopy.

Adnexal Diseases↗
PubMedDate not supplied

In vivo cancer gene therapy with a recombinant interleukin-2 adenovirus vector.

Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. In vivo therapy of established murine fibrosarcoma and mammary carcinomas was attempted with intratumoral injections of a recombinant AdV vector in which the human interleukin-2 (IL-2) gene was driven by the cytomegalovirus enhancer/promoter. Delayed growth and rejection of some tumors could be achieved with a cumulative virus dose of 2 to 6 x 10(9) plaque-forming units in two or three divided doses. Lower viral doses were ineffective, and higher doses resulted in animal death due to IL-2 toxicity. Using AdV vectors with the marker genes beta-galactosidase and luciferase, it is clear that even small volume (10 to 20 microL) intratumoral injections result in substantial systemic delivery of a portion of the virus dose. These findings define the potential and limitations of in vivo AdV-based cancer gene therapy and provide support for strategies to develop tumor-specific vectors.

Adenoviridae↗