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Biomedical subjects

X D Hu

Publications and source records attributed to X D Hu.

17 recordsLinked to original sources

A combined DNA vaccine-prime, BCG-boost strategy results in better protection against Mycobacterium bovis challenge.

In this study, we demonstrated that calves vaccinated with a combined DNA vaccine encoding Ag85B, MPT- 64, and MPT-83 antigens from the Mycobacterium tuberculosis for the priming and subsequently boosting with BCG prior to experimental challenge with virulent Mycobacterium bovis (M. bovis) resulted in improved immune responses over immunizing. Vaccination with the combined DNA/BCG induced higher levels of antigen- specific gamma interferon (IFN-gamma) in whole-blood cultures 4 weeks after final vaccination and the level of antigen-specific IFN-gamma in response to Ag85, MPT-64, and MPT-83 were still higher 4 weeks after challenge when compared to the combined DNA group. There was a significant bias toward induction of CD4+ T cells rather than CD8+ T cells responses, and the mean percentage of CD4+ T cells was increased about 2.6-fold in peripheral blood mononuclear cells (PBMC) cultures in DNA prime-BCG boost vaccination when compared to the nonvaccinated group. In addition, DNA prime-BCG boost vaccination resulted in stronger humoral immune responses, and the levels of the specific antibodies to three antigens were increased two- to 32- fold when compared to the combined DNA group. Vaccination with the combined DNA/BCG induced a high level of protection against an intratracheal challenge with virulent M. bovis, based on a significant enhancement of six pathological and microbiological parameters of protection compared to the nonvaccinated group. Finally, the combined DNA/BCG increased the protective efficacy by more than 10-100-fold as measured by reduced CFU counts in the lungs from calves challenged with M. bovis compared to the combined DNA and BCG groups. These results suggest that use of the prime-boost strategy offers better protection against bovine tuberculosis than does the combined DNA vaccines and BCG.

Animals↗

Combined DNA vaccine encapsulated in microspheres enhanced protection efficacy against Mycobacterium tuberculosis infection of mice.

In a study to develop novel vaccination strategies against tuberculosis, we encapsulated DNA encoding Ag85B, MPT-64 and MPT-83 antigens mixed with dimethyldioctyldecyl ammonium bromide (DDA) into biodegradable poly(dl-lactide-co-glycolide, PLGA) microspheres. Scanning electron microscopy (SEM) analysis demonstrated a uniform microsphere population with a mean diameter of <5microm. Using RT-PCR we were able to demonstrate antigen gene expression in selected tissue. Moreover, in mice injected with PLGA encapsulated DNA, the levels of expression appeared to be higher comparing to those injected with non-encapsulated DNA. Also, C57BL/6 mice immunized with a single dose of PLGA encapsulated DNA produced increased levels of IFN-gamma in the supernatant of spleen cells when cultured in the presence of the recombinant antigens. High levels of specific IgG antibody against the three antigens were also observed. In vaccine/challenge experiments, mice receiving a single dose of PLGA encapsulated DNA were protected against Mycobacterium tuberculosis challenge at levels comparable to groups of mice immunized with three doses of non-encapsulated DNA vaccine or with Mycobacterium bovis BCG.

Adjuvants, Immunologic↗

Combined DNA vaccines formulated either in DDA or in saline protect cattle from Mycobacterium bovis infection.

We tested the effectiveness of combined DNA vaccines encoding antigens Ag85B, MPT64 and MPT83 from Mycobacterium tuberculosis on cattle. Our results showed that calves treated with combined DNA vaccines in the presence of dimethyldioctyldecyl ammonium bromide (DDA) or saline elicited a strong gamma interferon (IFN-gamma) response 1 or 2 months after the third vaccination. All three antigens induced substantial levels of IFN-gamma production 1 month after the bacterial challenge, when the BCG-driven IFN-gamma levels dropped to less than one third of their peak values. Animals receiving combined DNA vaccines produced highest amounts of IgG antibody titer 2 months after the third vaccination. Steady state low IgG levels were found 2 months after bacterial challenge. A few small lung and lymph node lesions were detected in 1/5 animals treated with combined DNA vaccines, whereas 3/5 of BCG-treated and 5/5 of vector-control calves showed larger and significantly more lesions. About 70- to 100-fold fewer bacteria were found in the lungs and lymph nodes of combined DNA vaccine-treated animals compared to those of the control group. Histopathological analyses showed that vaccinated calves possessed substantially improved post-infection lung and lymph node pathology relative to the controls. Our data indicate that combined DNA vaccines may be used in cattle to combat bovine tuberculosis.

Animals↗

Combined DNA vaccines formulated in DDA enhance protective immunity against tuberculosis.

This study evaluated the adjuvant Dimethyldioctyldecyl Ammonium Bromide (DDA) effect on the protective immunity induced by a combination of plasmids containing genes encoding antigens Ag85B, MPT-83, and ESAT-6 from Mycobacterium tuberculosis. The combined DNA vaccines in DDA resulted in significant increases in both specific IgG and splenic T-cell-derived Th1-type cytokine gamma interferon (IFN-gamma) production in response to the three purified antigens when compared to that of combined DNA vaccines in saline. Vaccines in DDA increased the protective efficacy of mice challenged with M. tuberculosis H37Rv as measured by reduced relative CFU counts in their lungs. Mice immunized with the combined DNA vaccines were shown to limit the growth of tubercle bacilli both in lungs and in spleens. Histopathological analyses showed that vaccinated mice had substantially improved postinfection lung pathology relative to the controls. We suggest that our combination of antigens together with DDA formulation may provide a new insight into tuberculosis prevention.

Acyltransferases↗

DDPH inhibited L-type calcium current and sodium current in single ventricular myocyte of guinea pig.

AIM: To investigate the effects of 1-(2, 6-dimethylphenoxy)-2-(3,4-dimethoxyphenyl-ethylamino)propane hydrochloride (DDPH) on L-type calcium current (ICa) and sodium current (INa), and to compare its inhibitory potency with verapamil and mexiletine. METHODS: Whole-cell patch clamp technique was used to record ICa and INa in a single ventricular myocytes of guinea pig. RESULTS: (1) DDPH (3 - 300 micromol . L-1) decreased ICa at 0 mV in a concentration-dependent manner with an IC50 value of 28.5 micromol . L-1 (95 % confidence limits: 14.3 - 42.7 micromol . L-1, n = 8 cells from 8 guinea pigs). Verapamil (0.3 - 30 micromol . L-1) reduced ICa with an IC50 value of 1.8 micromol . L-1 (95 % confidence limits: 1.3 - 2.3 micromol . L-1, n = 6 cells from 6 guinea pigs). Mexiletine 100 micromol . L-1 did not affect ICa (n = 5 cells from 5 guinea pigs, P > 0.05). The degree of use-dependent blocking effect of DDPH 30 micromol/L on ICa was 58 % +/- 13 % (n = 5 cells from 5 guinea pigs, P < 0.01) at 1 Hz and 76 % +/- 11 % (n = 5 cells from 5 guinea pigs, P < 0.01) at 3 Hz. (2) DDPH (20 - 320 micromol . L-1) could also block INa in a concentration-dependent manner with an IC50 value of 89.0 micromol . L-1 (95 % confidence limits: 68.7 - 109.3 micromol . L-1, n = 9 cells from 9 guinea pigs). The IC50 value of mexiletine was 32.2 micromol . L-1 (95 % confidence limits: 11.7 - 52.7 micromol . L-1, n = 5 cells from 5 guinea pigs). Verapamil at the concentration of 10 micromol . L-1 did not affect INa (n = 5 cells from 5 guinea pigs, P > 0.05). The blocking effect of DDPH 80 micromol/L on INa was non use-dependent. CONCLUSION: DPH exhibited inhibitory effects on both ICa and INa, but its inhibitory effect on ICa was weaker than verapamil, and on INa was weaker than mexiletine.

Animals↗

[A clinical study of aortic dissecting].

The clinical features, etiologies, pathogenesis, treatment and prognosis of 70 patients with aortic dissecting were studied. Patients with age ranging from 31 to 70 years consisted 93% of the total. The proportion of proximal to distal types is 0.8: 1. Hypertension was present in 67% and Marfan's syndrome 18% of the patients. The pathologic finding was scattered rupture with myxomatous and cystic necrosis of the mecial elastic fibers. 80% of the patients suffered from the disease without any inducing cause. Of the 76% patients had chest pain, it was very severe in 69%. Chest X-ray, ultrasound, computed tomography and magnetic resonance imaging together with clinical manifestations may accurately diagnose the disease. The sensitivity and specificity of the ultrasound are 97% and 94% respectively. The mortality in hospital with surgical and medical therapy of the proximal type was 14% and 22% respectively, while that of the distal type was 63% and 27% respectively. Rupture of the aneurysm was the cause of death in 68% of the patients.

Adult↗

[Clinical features and prognosis of paroxysmal atrial fibrillation in the elderly].

Eighty one elderly patients with paroxysmal atrial fibrillation were studied with respect to clinical features, effect of antiarrhythmic drugs and prognosis. 35 (43.2%) patients were associated with coronary artery disease and/or hypertension, while 23 (28.4%) patients had no other cardiovascular diseases. The latter condition was significantly less in patients over 60 years old when they had the first paroxysmal attack. Atrial fibrillation became permanent in 18 (22.2%) patients. Left atrial enlargement and abnormal cardiac function were significant independent factors affecting the type of atrial fibrillation. During an observation period of 12-84 months, the incidence of cerebral embolism and cardiac death were 6.1% and 4.9% respectively in all cases. We did not find that the prognosis of patients was affected by the types of atrial fibrillation.

Aged↗

[Preliminary results of three different cannulations for percutaneous transhepatic cholecystic drainage in the interventional gallstone dissolutions].

Three different methods of percutaneous transhepatic gallbladder cathetering drainage were applied in 33 patients undergoing interventional gallstone dissolution. Among them, sheathed needle was used in 6 cases with a success rate of 33%; wire-guided in 16 with a success rate of 50%; and double-sheathed inner needle was successfully used in all the 11 cases. The authors believe that this last method could safely be used in the nonoperative drainage of acute cholecystitis as well as the interventional gallstone dissolutions.

Adolescent↗

[Diabetic myocardiopathy].

Three cases of diabetic myocardiopathy having history of diabetes, angina and left ventricular dysfunction of various degrees and confirmed by coronary angiography and endomyocardial biopsy were reported. Electrocardiography showed significant ST-T changes simulating coronary insufficiency but without definite localization. As to the treatment, nitrate preparations, inotropic agents such as strophanthin K, digoxin etc. were used to relieve the symptoms; insulin was also administered to control the blood glucose level. Diltiazem, a calcium blocker, is also of help in alleviating the symptoms. It is shown in the present study and in the literatures as well that diabetic myocardiopathy is a disease showing intramural microvascular endothelial proliferation and swelling as well as subendothelial accumulation of acid glycogen deposition cells. The transportation of intracellular calcium ions and the cellular metabolism are thus affected, so there are extensive ischemia, focal necrosis and fibrosis in the myocardium with resulting cardiac dysfunction. The authors are, therefore, of the opinion that diabetic myocardiopathy is a specific and separate clinical entity.

Aged↗

[Correlation among electrocardiogram, important risk factors of coronary artery diseases and coronary lesion in patients with chest pain].

Clinical and angiographic data from 103 patients with chest pain were evaluated to determine their correlation with ST-T abnormality in resting electrocardiogram. Univariate analysis suggested that male sex, hypertension, old myocardial infarction, severe coronary lesion, multiple vessel lesion and left ventricular wall motion abnormality significantly increase the likelihood of ST-T abnormality. Multivariate analysis suggested that male sex, hypertension and left ventricular wall motion abnormality were significant independent predictors of abnormal ST-T. It is essential to improve the electrocardiographic accuracy of diagnosing CAD so as to help clinical doctors in preventing and treating this disease.

Adult↗