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Chakraborty Bhaswat S. Sardessai Manik S. Jaworski Theodore J. Midha Kamal K. Hawes Edward M. 《Pharmaceutical research》1987,4(3):207-213
For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized. 相似文献
3.
Theodore Berk MD Robert F. Crochelt BA Dr. Steven R. Peikin MD 《Digestive diseases and sciences》1986,31(5):502-505
Obese Zucker rats are less responsive than their lean littermates to the effects of cholecystokinin-octapeptide on satiety and pancreatic growth and exocrine function. We hypothesized that the hyperphagia observed in obese Zucker rats may be caused by a decreased pyloric contractile response to cholecystokinin, resulting in an increased rate of gastric emptying, decreased postprandial gastric distention, and thus decreased satiety. Pyloric muscle strips from six obese Zucker rats and six lean littermates were mounted in separate tissue baths and isometric contraction was measured in response to acetylcholine and cholecystokinin-octapeptide. The dose-response curves for acetylcholine-and cholecystokinin-octapeptide-stimulated pyloric muscle contraction were similar for both the obese and the lean rats. (For cholecystokinin, D50 obese=4.0±0.6 nM, D50 lean=3.4±0.2 nM;P=0.16). We conclude that the decreased satiety response to cholecystokinin-octapeptide observed in obese Zucker rats is not secondary to a decreased pyloric responsiveness to cholecystokinin.This work was supported by NIH grant AM28303-03. 相似文献
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E Gadelha Figueiredo M Castillo De la Cruz N Theodore P Deshmukh M C Preul 《Minimally invasive neurosurgery》2006,49(1):37-42
We describe a modified keyhole laminoforaminotomy (LF) using anatomic landmarks on the posterior aspect of the cervical vertebral body to decompress the intervertebral foramen with minimal bone removal. Twenty-four procedures were performed at C3-4, C4-5, and C5-6; 12 at C6-7; and 3 at C7-Tl. Facets and laminae structures were identified based on relative surgical perspectives. Bony resection was limited as follows: 1) inferior limit; inferior border of the superior facet; 2) superior limit, superior border of the superior facet; 3) lateral limit, a vertical line linking the junction of the lamina-facet to the lateral end of the superior limit; and 4) lateral aspect of the dural sac. Fluoroscopy was used to confirm that the intervertebral space was reached. The amount of bony removal was quantified for the superior and inferior laminae and facets. The length of the exposed nerve root was measured. The intervertebral foramen was exposed and the intervertebral disc reached in all specimens. Fluoroscopy showed that the center of the exposure remained at the same height with the intervertebral space. The mean length of the nerve root was 4.6 mm; the mean percentage of bony resection was 21.8%, 7.5%, 11.3%, and 11.5% for the superior and inferior laminae and facets, respectively. Opening the intervertebral foramen posteriorly consistently exposed sufficient nerve root length and allowed access to the intervertebral disc. The technique offers the most direct and safest method of decompressing the intervertebral foramen while minimizing bony resection. This simple surgical procedure may help reduce postoperative morbidity. 相似文献
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Brenda M Sandmaier Storb Rainer Yanfang Liu Erlinda B Santos Eileen Bryant Friedrich G Schuening H Joachim Deeg Kristy Seidel Theodore Graham 《Transplant immunology》1996,4(4):271-274
920 cGy total body irradiation (TBI) is adequate for consistently successful engraftment of marrow from dog leukocyte antigen (DLA)-identical littermates; however, the dose is inadequate to ensure a marrow graft from DLA-nonidentical unrelated donors. Such mismatched grafts are successful only after 1800 cGy, given in three fractions. While anti-T-cell reagents enhance engraftment of DLA-identical littermate marrow after 920 cGy, they fail to be effective in the DLA-nonidentical setting. However, a monoclonal antibody (mAb) to CD44, S5, was found to be very effective in enhancing engraftment of DLA-nonidentical marrow. The current study asked whether mAb S5 was also effective in the setting of DLA-identical littermate transplants. To this purpose, the TBI dose was lowered to 450 cGy, a dose after which 70% of such grafts failed. Four dogs were treated with antibody S5, 0.2 mg/kg on days −7 though −2 (per previously published protocol), given 450 cGy TBI followed by marrow grafts from their DLA-identical littermates. All four dogs rejected their grafts; two of these died from marrow aplasia, and two survived with endogenous marrow recovery. This result was not statistically significantly different from that in 17, historical (n = 5) and concurrent (n = 12), control dogs where 11 of 17 animals rejected. Even if ten experimental animals were transplanted and all six remaining dogs engrafted, the results still would not have been significantly different from control. This result is in contrast to the successful engraftment promoted by pretreatment with antibody S5 of DLA-nonidentical unrelated dogs, consistent with the notion that different host cells are involved in graft rejection in the two disparate histocompatibility settings. 相似文献
8.
Theodore Colton Laurence Freedman Tony Johnson David MaChin 《Statistics in medicine》1989,8(6):639-639
9.
The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies. 总被引:4,自引:0,他引:4
Daniel A Hamstra Kuei C Lee Joseph M Tychewicz Victor D Schepkin Bradford A Moffat Mark Chen Kenneth J Dornfeld Theodore S Lawrence Thomas L Chenevert Brian D Ross Juri T Gelovani Alnawaz Rehemtulla 《Molecular therapy》2004,10(5):916-928
To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy. 相似文献
10.
Victor M. Neira Corey Sawchuk Kenneth S. Bonneville Victor Chu Theodore E. Warkentin 《Journal canadien d'anesthésie》2007,54(6):461-466
PURPOSE: To describe the management of severe acute intracardiac thrombosis in a patient who underwent redo multiple valve replacement and valvular repair. The diagnostic features, associated risk factors, and anesthetic management are reviewed. CLINICAL FEATURES: A 67-yr-old woman undergoing redo mitral and aortic mechanical valve replacement and tricuspid annuloplasty under aprotinin prophylaxis exhibited severe refractory hypotension that began immediately after protamine reversal of intraoperative heparin anticoagulation following separation from cardiopulmonary bypass. Intraoperative transesophageal echocardiography revealed severe thrombosis in the right atrium, right ventricle and pulmonary artery. The patient was managed by immediate reheparinization and return to cardiopulmonary bypass (CPB), surgical thrombectomy, and intraoperative administration of recombinant tissue-plasminogen activator. After removal of the thrombi, and separation from CPB, no further protamine was given. One hundred units of blood products and two surgical re-explorations were required to manage subsequent massive postoperative bleeding. Acute heparin-induced thrombocytopenia (HIT) was ruled out using sensitive assays for HIT antibodies. After 16 days in the intensive care unit and 30 more days in hospital, the patient was subsequently transferred to a chronic care facility and succumbed several weeks later. CONCLUSION: Acute intraoperative thrombosis is a rare and potentially fatal complication of cardiac surgery. Intraoperative transesophageal echocardiography was essential for rapid diagnosis in this case. Multiple interacting prothrombotic factors (e.g., aprotinin use, acquired antithrombin deficiency, long pump time, post-protamine status, transfusion of blood components) were likely contributing factors related to this rare complication. 相似文献