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41.
Purpose. To determine whether the non-toxic pentameric B subunit of Cholera toxin (CTB) binding to ganglioside GM1 on both the lipid vesicles and epithelial cells may provide a means to target lipid vesicles to mucosal cells expressing surface GM1.
Methods. Sonicated lipid vesicles containing ganglioside GM1 were prepared. Inter-vesicle cross-linking due to pentameric CTB binding to these GM1 vesicles was determined with a sub-micron particle analyzer. Association of CTB to GM1 vesicles was analyzed with continuous sucrose gradient centrifugation. CTB-mediated binding of GM1 vesicles to human mucosal epithelial cells (Caco-2 and HT-29), mucous membranes of mouse trachea, and nasal tissues were detected with fluorescent labeled vesicles.
Results. An increase in lipid particle size due to binding of CTB to lipid vesicles and inter-vesicles cross-linking was detected. At a 30-to-1 mole ratio of membrane-bound GMl-to-CTB, optimum increase in GM1 vesicle aggregation, was detected. Under such conditions, all the added CTB molecules were associated with GM1 vesicles. Time course analysis showed that inter-vesicles cross linking by CTB was detectable within 10 min. and reached a maximum value at 60 min. CTB associated GM1-vesicles bind to mucosal epithelial cells HT-29 and Caco-2 with similar affinity [Kd = 7.8 × 10–4 M lipid (Caco-2) and 7.6 × 10–4 M lipid (HT-29)]. GM1 mediated binding specificity was demonstrated by blocking with anti-GMl antibody and the insignificant degree of CTB-associated GM1 vesicle binding to GM1 deficient C6 cells.
Conclusions. The CTB-mediated GM1 binding to multiple membrane surfaces provides selective localization of GM1 vesicles to GM1 expressing mucosal cells and tissues. The strategy may be useful in localizing drugs and proteins to gut and respiratory tract mucosa. 相似文献
42.
Post-transplantation diabetes is better controlled after conversion from prednisone to deflazacort: a prospective trial in renal transplants 总被引:2,自引:0,他引:2
Yu Seun Kim Myoung Soo Kim Soon Il Kim Seung Kil Lim Ho Yung Lee Dae Suk Han Kiil Park 《Transplant international》1997,10(3):197-201
It is well known that long-term use of steroids plays a decisive role in the development of glucose intolerance and diabetes
mellitus (DM). Deflazacort, an oxazoline derivative of prednisolone, has been introduced as a potential substitute for conventional
steroids in order to ameliorate glucose intolerance. We initiated a randomized study of conversion from prednisone to deflazacort
in kidney transplantation (Tx) recipients presenting with pre-Tx or post-Tx DM to ascertain whether or not the switch to deflazacort
would ameliorate the diabetic state. Forty-two recipients in the conversion group were compared with 40 patients on prednisone
(the control group) in a prospective manner. The dose reduction of insulin or oral blood glucose-lowering agents, the adequacy
of glucose control, and the development of side effects were the criteria for evaluating outcome. In the conversion group,
patients were switched to deflazacort at a dose ratio of 6 mg deflazacort to 5 mg prednisone. During the mean follow-up period
of 13.2 months, neither graft dysfunction nor acute rejection developed in the conversion group. Improvement in blood glucose
control in the conversion group was noted. When the conversion group was stratified into pre- or post-Tx DM, promising effects
were clearly evident in the post-Tx DM patients. More than 50 % dose reduction of blood glucose-lowering agents was possible
in 42.3 % of post-Tx DM patients. In conclusion, it was readily possible to control blood glucose better in post-Tx DM recipients
without seriously affecting the immunosuppressive activity after conversion to deflazacort.
Received: 20 August 1996 Received after revision: 25 November 1996 Accepted: 6 December 1996 相似文献
43.
Yeong Shik Kim Kyung Shin Park Ho Koon Park Sung Whan Kim 《Archives of pharmacal research》1994,17(5):337-342
Carbohydrate analysis is important in studying structure and activity of complex polysaccharides. New analytical method was
applied to get an information on the composition of polysaccharides showing antitumor activity. Monosaccharides were labeled
with 7-amino-1,3-naphthalenedisulfonic acid (7-AGA) by reductive amination and separated by HPLC. Five kinds of polysaccharides
fromBasidiomycetes were hydrolyzed and analyzed in combination with electrophoresis and HPLC. At the same time, alditol acetate derivatives
were prepared and analyzed by gas chromatography. Two different techniques using different derivatization methods showed very
similiar results. The monosaccharides fromCoriolus versicolor andLentinus eodes were mainly composed of D-glucose, while those fromGanoderma lucidium andCordyceps militaris were glucose and galactose.Phellinus linteus composed of glucose, galactose, mannose, arabinose and fucose. The HPLC method with fluorescence detector was very sensitive
compared to other methods. 相似文献
44.
45.
C M Yang T M Dwyer P M Mohan I K Ho J M Farley 《Toxicology and applied pharmacology》1990,104(3):375-385
Subacute (daily) administration of diisopropylfluorophosphate (DFP) to male swine (Yorkshire white) resulted in a 97% inhibition of cholinesterase and a decrease of [3H]quinuclidinyl benzilate [( 3H]QNB) binding sites in homogenates of striata by approximately 50% after 14 days. The maximal density of receptors (Bmax) decreased from 2.1 +/- 0.3 to 1.0 +/- 0.2 pmole/mg protein. There was no significant change in the dissociation constant (Kd) for [3H]QNB binding (control: 52.6 +/- 10.7 pM; 7-day: 57 +/- 2.8 pM). Carbachol displacement of [3H]QNB binding yielded data best fit by a two-binding site model. The dissociation constants were KiL = 115 +/- 62 microM (55 +/- 3%) and KiH = 1.8 +/- 0.7 microM (45 +/- 3%), respectively, for the low- and high-affinity states. Seven-Day treatment with DFP reduced the percentage of high-affinity receptors to 22 +/- 8.6%, but affected neither the low- nor the high-affinity Kd (100 +/- 20 and 2 +/- 0.6 microM). With the addition of Mg2+, striatal homogenates had low- and high-affinity receptors in the proportion of approximately 1 to 1. In the presence of Gpp(NH)p + Mg2+ the ratio of high- to low-affinity receptors was 3:1 in homogenates of control tissue (to 26 +/- 5%). This treatment had no effect on this ratio in homogenates of tissue from 7-day DFP-treated swine (3:1) since it was already 3:1. Pirenzepine displacement of [3H]QNB binding was best described by a two-binding site model, with Ki values of 38 +/- 14 and 201 +/- 78 nM, which represent 74 and 26% of the binding sites, respectively. The high affinity Kd value was unchanged following 7 days of DFP treatment (24 +/- 5 nM). There appears to be little change in the displacement curves for pirenzepine inhibition of [3H]QNB binding. This suggests that about 75% of the receptors are of the M1 subtype. Thus, subacute administration of DFP causes not only a decrease in the number of receptors, but also a change in the proportion of agonist affinity states which is related to the interaction of the guanine nucleotide binding protein and the muscarinic receptor. 相似文献
46.
Efficacy of radical neck dissection for the control of cervical metastasis after radiotherapy for nasopharyngeal carcinoma 总被引:5,自引:0,他引:5
Fifty-one patients who had persistent or recurrent neck disease from nasopharyngeal carcinoma after radiotherapy underwent radical neck dissection. The follow-up period ranged from 0.5 to 9 years (median: 2 years). Multiple cervical lymph node involvement was present in 51% of the patients (26 of 51). Malignant cells were detected in 88% of the resected specimens (45 of 51). The clinical sign of fixation of lymph node is the only factor that affects the successful control of neck disease (p = 0.04). Extracapsular extension of the nodal disease was present, and 35% of the lymph nodes were adherent to surrounding structures at operation (18 of 51). There was one hospital mortality and the overall morbidity was minimal. The actuarial survival at 5 years was 38%, and the probability of control of neck disease was 66%. Radical neck dissection is effective in controlling post-irradiation cervical metastasis from nasopharyngeal carcinoma. 相似文献
47.
48.
49.
Jong-Moon Lee Kun-Woo Park Woo-Keun Seo Moon Ho Park Changsu Han Inho Jo Sangmee Ahn Jo 《Movement disorders》2007,22(16):2446-2449
There have been a few studies and inconsistent results regarding the coincidence of Parkinson's disease (PD) and atherosclerotic diseases, such as cerebrovascular disease. Carotid intima-media thickness (IMT) is a known marker for subclinical atherosclerosis. The aim of this study was to investigate the carotid IMT between PD patients and controls. We studied 43 patients with PD and 86 matched controls. The carotid IMT in PD patients was significantly smaller than in controls (0.796 +/- 0.179 mm vs. 0.913 +/- 0.237 mm, P < 0.05). In multivariate analysis, the carotid IMT was inversely associated with the duration of levodopa medication and the severity of PD. These results suggest that PD patients have a lower risk of atherosclerosis. 相似文献
50.
Paired kidney analysis of tacrolimus and cyclosporine microemulsion-based therapy in Chinese cadaveric renal transplant recipients 总被引:5,自引:0,他引:5
Chi Yuen Cheung Kim Ming Wong Hoi Wong Chan Yan Lun Liu Yiu Han Chan Ho Sing Wong Wai Leung Chak Koon Shing Choi Ka Foon Chau Chun Sang Li 《Transplant international》2006,19(8):657-666
Few studies used paired kidneys for comparison between tacrolimus and cyclosporine in renal transplantation. Most of the published data used whole blood trough levels for drug monitoring. However, the use of limited sampling strategy and abbreviated formula to estimate the 12-h area under concentration-time curve (AUC(0-12)) allowed better prediction of drug exposure. Sixty-six first cadaveric renal transplant recipients receiving paired kidneys were randomized to receive either tacrolimus-based (n = 33) or cyclosporine microemulsion (Neoral)-based therapies (n = 33). Abbreviated AUC(0-12) was used for drug monitoring and dose titration. Mean follow-up duration was 2.8 +/- 2 years. The patient and graft survival were comparable. Fewer incidence of acute rejection was observed in tacrolimus group (15% vs. 27.3%) though the difference was not significant (P = 0.23). The absolute value and the rate of decline of creatinine clearance were both significantly better in tacrolimus-treated patients. Prevalence of hypertension, post-transplant diabetes mellitus, infection, and malignancy were similar in both groups. Prevalence of hypercholesterolemia (11/33 vs. 4/33) and gum hypertrophy (6/33 vs. 1/33) was more common in cyclosporine-treated patients (P = 0.04 in both parameters). This was the first prospective, randomized study with paired kidney analysis showing the renal function was significantly better in tacrolimus-treated patients than in cyclosporine-treated patients. 相似文献