2005年 · 第118卷第13期

Background It is known that the brain structure changes with normal aging. The Objective of this study was to quantify the anisotropy and average diffusion coefficient (DCavg) of the brain in normal adults to demonstrate the microstructure changes of brain with aging. Methods One hundred and six normal adults were examined with diffusion tensor imaging (DTI). The fractional anisotropy (FA), 1-volume ratio (1-VR), relative anisotropy (RA) and average diffusion coefficient (DCavg) of different anatomic sites of brain were measured, correlated with age and compared among three broad age groups. Results Except in lentiform nucleus, the anisotropy increased and DCavg decreased with aging. Both anisotropy and DCavg of lentiform nucleus increased with aging. The normal reference values of DTI parameters of normal Chinese adult in major anatomic sites were acquired. Conclusions DTI data obtained noninvasively can reflect the microstructural changes with aging. The normal reference values acquired can serve as reference standards in differentiation of brain white matter diseases.

Background The insufficiency of the proximal landing zone (PLZ) is a frequent factor challenging the applicability and efficacy of endovascular repair (EVR) for thoracic aortic disorders. This study discusses two strategies for conquering this challenge. Methods Ten patients underwent EVR for thoracic aortic diseases during a one-year period ending June 30, 2004. Nine patients had DeBakey type Ⅲ dissecting aortic aneurysm (DAA), and one had descending thoracic aortic aneurysm (DTAA). The PLZ, defined as the distance from the origin of the left subclavian artery (LSA) to the primary entry tear of the dissection or to the proximal aspect of DTAA, was less than 15 mm in all instances. EVR with intentional coverage of the LSA without any supportive bypass was employed in 6 patients with DAA, and the preliminary right-left carotid and left carotid-subclavian bypass combined with EVR in the DTAA and other 3 DAA cases. Results Technical success was achieved in all the patients. The patient with DTAA died from hemispheric cerebral infarction and subsequent multiple system organ failure following an uneventful recovery from the cervical reconstruction performed 1 week previously. In cases receiving the EVR with intentional coverage of the LSA, in two patients dizziness occurred, which noticeably resolved after intravenous administration of mannitol for 4 to 5 days, and a drop in blood pressure of the left arm was noted in all the cases, but remained clinically silent. No neurological deficits or limb ischaemia developed perioperatively or during the followup, ranging from 3 to 12 months, and complete thrombosis of the thoracic aortic false lumen was revealed on CT at 3 months in the 9 patients with DAA. Conclusions Both the intentional bypass absent coverage of the LSA and the adjunctive surgical bypass appear to be feasible and effective in managing the insufficiency of the PLZ during the endovascular thoracic aortic repair.

Background Acute myocardial infarction can result in left ventricular aneurysm, which may in turn cause congestive heart failure, ventricular arrhythmia and thromboembolic events. This study evaluates Results achieved with a modified linear closure of left ventricular aneurysms during off-pump coronary artery bypass surgery. Methods From January 2001 to May 2004, 75 patients were operated on for nonruptured, postinfarctional, left ventricular aneurysm during off-pump coronary artery bypass surgery. Repair was completed on the beating heart to minimize ischaemia and allow assessment of wall function and viability to guide closure. All patients presented with symptoms of angina and congestive heart failure or ventricular arrhythmia. The majority (75%) of the patients were in NYHA functional class Ⅲ or Ⅳ. Preoperative ejection fraction was 26%±9%. The mean left ventricular, end diastolic diameter was (57.5±7.1) mm. The ventricular preoperative and postoperative performances were compared. Χ2 test and Student’s t test were used to analyse the outcomes. A P value less than 0.05 was considered significant. Results Hospital mortality was 1.3% (1/75). Coronary artery bypass was performed with an average of (3.3±1.2) grafts per patient. At the time of followup, all the patients had no symptoms. The mean NYHA class and ejection fraction increased significantly (P<0.001). The mean left ventricular, end diastolic diameter decreased significantly (P<0.001). Conclusions Surgical closure of left ventricular aneurysm can be performed during off-pump coronary artery bypass. The operation is associated with a low inhospital mortality and morbidity. A postoperative improvement in the early term cardiac functions and symptoms and quality of life was documented, increasing our expectations of an increased long-term survival.

Background The NASG gene has been confirmed as a tumor-suppressor gene candidate related to nasopharyngeal carcinoma (NPC) by previous studies. We further investigated the expression and the role of NASG in the homogeneous tissue cells by microdissecting the samples of tissue from human NPC, and introduced a new way to study the expression of specific genes in tumor tissue. Methods The RNAlater reagent was used to preserve the samples of tissue from the nasopharynx of NPC patients. The samples were microdissected to harvest the homogeneous tissue cells and then total RNA was isolated from them. The antisense RNA (aRNA) was amplified from the total RNA by "in vitro transcription (IVT)". We investigated NASG expression in the homogeneous tumor cells of NPC (22 samples) and compared it with that in the pure epithelial pillar cells of normal nasopharyngeal (10 samples) by semi-quantitative reverse transcription-polymerase chain reaction (sqRT-PCR). Results The high quality total RNA could be harvested from the microdissected homogeneous tissue cells of the nasopharynx, then sufficient aRNA was derived from it. NASG gene expression was identified using aRNA by sqRT-PCR and showed that there was significant difference between the average value of case groups and that of control group (t=-5.275, df=30, P<0.001). The NASG gene in the subgroups WHOII tended to express lower levels than those in the subgroup WHO Ⅲ although this difference was not statistically siginificant (t=-1.584, df=20, P=0.129>0.05). Conclusions Microdissection was an effective method to obtain the homogeneous tissue cells of nasopharyngeal tissue (including the samples of NPC and non-NPC) in our study. Sufficient aRNA from amplifiying total RNA could be used in sqRT-PCR to analyse the expression of NASG in the pure tissue cells. NASG should be a tumor-suppression gene candidate regarding to NPC.

Background Previous studies have showed that photooxidative stress can lead to down-modulation of nuclear factor-κappa B (NF-κB) activity causing apoptosis of cultured photoreceptor cells. This study aimed at investigating whether NF-κB was involved in photoreceptor cells apoptosis induced by N-methyl-N-nitrosourea (MNU) in rats. Methods A single intraperitoneal injection of 60 mg/kg MNU was given to 50-day-old female rats. At different intervals after MNU treatment，the animals were sacrificed. Retinal damage was examined by a light microscope. The apoptotic index of the photoreceptor cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). NF-κB was analysed by Western blot and Transcriptin Factor Assay Kits. Results The pyknosis of the photoreceptor nuclei and the disorientation of the outer segment of the photoreceptor layer was seen after MNU treatment for 24 hours. The outer nuclear layer and photoreceptor layer were almost completely lost at 7 days. Photoreceptor cells apoptosis reached the peaked value at 24 hours. In apoptotic cascade, the protein levels of NF-κB p65 were only detected after MNU treatment for 12 and 24 hours in the nucleus. Conversely, the amounts of IκBα were markedly increased in the cytoplasm as well as in the nucleus. The activity of NF-κB p65 in the nucleus was down-modulated in the end. Conclusions MNU-induced photoreceptor cell destruction was attributed to the apoptotic process by down-regulating the activation of NF-κB p65.

Background Previous studies showed that the role of Fas ligand (FasL) is not consistent in the pathogenesis of autoimmune thyroiditis. This study was designed to investigate the effects of FasL on the pathogenesis of experimental autoimmune thyroiditis (EAT) using CMV-human FasL (hFasL) transgenic mice. Methods Transgenic mice ubiquitously expressing hFasL were used as an animal model of EAT by injection of porcine thyroglobulin (pTg). Expression of hFasL was detected by RT-PCR and Western blot. The activity of hFasL transgenic thyrocytes killing Jurket cells was determined. CMV-hFasL transgenic mice and wild type (WT) mice were immunized with pTg and killed 28 days later to evaluate the lymphocytic infiltration of their thyroids. The number of CD4+ and CD8+ lymphocytes from the spleen was detected using FACS. The serum interferon-γ (IFN-γ) concentration was measured by ELISA. Results hFasL expression in the thyroid of CMV-hFasL transgenic mice was confirmed. After co-incubation of Jurket thymocytes with thyroid tissues of CMV-hFasL transgenic mice, the percentage of apoptotic cells in the CMV-hFasL transgenic thyroid group was significantly higher than that of the control WT thyroid group [(23.4±4.3)% vs (6.6±2.5)%, P<0.01]. On day 28 after immunization with pTg, the infiltration index of lymphocytes in thyroids of the CMV-hFasL transgenic mice was significantly lower than that of the WT mice [(1.0±0.5) vs (2.1±0.7), P<0.001]. Moreover, the number of CD4+ and CD8+ lymphocytes of the spleen and serum IFN-γ concentration were significantly decreased in the CMV-hFasL transgenic mice. Conclusions FasL plays an important role in the pathogenesis of autoimmune thyroiditis. Transgenic mice ubiquitously expressing hFasL may strongly inhibit lymphocytic infiltration of the thyroid of EAT and ameliorate the course of this disease.

Background Ageing is associated with increased incidence of dyslipidemia. To investigate potential molecular mechanisms, the effects of age and fibrate administration on peroxisome proliferator-activated receptor α(PPARα) expression in livers of young and old rats were studied. Methods A total of 16 young (2-month-old) and 16 old rats (24-month-old) were randomly assigned to a control group and fenofibrate group (fenofibrate in a total therapeutic dosage of 0.5% in ratio to each treated rat weight in 14 days). RT-PCR was applied to evaluate hepatic mRNA expression of PPARα and its target genes. Western blotting was used to determine PPARα protein level in liver tissue. Results When compared with 2-month-old rats, the liver tissue from 24-month-old rats showed reduced expression of PPARα mRNA (52%, P<0.05) and protein (109%, P<0.01). Consequently, the mRNA levels of PPAR target genes, LPL, ACO, ACS and CPT-1 were markedly lowered by 19%, 8%, 13% and 9% respectively, and apoCIII increased by 24% in livers from 24-month-old rats, compared with values obtained from 2-month-old rats (P<0.05). Fenofibrate therapy significantly lowered plasma triglyceride and total cholesterol levels in old rats, accompanied with improvement in hepatic expression of genes, including LPL, ACO, ACS, CPT-1 and apoCIII, but no change was found in PPARα expression in livers from either 24-month or 2-month-old rats. Conclusions The decrease in the hepatic PPARα expression is probably directly related to the lipid metabolic disturbances observed in old animals. The beneficial effects of fenofibrate administration in old rats suggests that fibrates may be useful for treating lipid disturbances in old people.

Background Although 32P-glass microspheres (32P-GMS) have been used in internal radiotherapy for malignant tumors, it has been one of the key obstacles to improve the effect of radiotherapy. We investigated the cellular and hypersensitive effect of combined use of low dose of cisplatin and interstitial injection of 32P-GMS on mouse solid tumor S180. Methods The mice with solid tumor S180 were randomly divided into four groups (controls, cisplatin therapy, 32P-GMS therapy and combination therapy). The specimens of the mice were sectioned two weeks after treatment and weighed. The death rate of tumor cells and the inhibition rate of tumor were calculated respectively. The cell cycle and apoptosis rate were evaluated with flow-cytometry. The ultrastructural changes of the four groups were observed by a transmission electron microscope. The data were analyzed by the chi-square test. Results The growth of tumor was slower in the combination therapy group than in the simple therapy groups by macrography. The inhibition rate and the death rate of tumor cells of the combination therapy group were significantly higher than those of the control group and the other two simple therapy groups (P<0.05). More cell damages were displayed in the combination therapy group than in the other groups under the light and electronic microscope. Conclusion Low-dose cisplatin combined with interstitial injection of 32P glass microspheres could be used as an effective hypersensitive regimen for the internal radiotherapy of mouse solid tumor S180.