大鼠胸腺降黑素受体的鉴定及生物学特性

应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位，该结合位点可以满足特异结合部位的基本条件：１．低结合容量；２．高亲和力；３．可饱和性；４．可逆性；５．对降黑素高度特异性。此外，该特异结合位点具昼夜节律；亚细胞分布的研究表明以细胞核含量最高，线粒体次之，并具有年龄依赖性降低，以出生时最高。     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Propofol versus isoflurane anesthesia under hypothermic conditions: effects on intracranial pressure and local cerebral blood flow after diffuse traumatic brain injury in the rat

BACKGROUND: The aim of this study was to compare the cerebral protective effects of two known protective anesthetics, isoflurane and propofol, when these were used in combination with moderate hypothermia (33-34 degrees C) after diffuse traumatic brain injury (TBI) in the rat. We assessed cerebral protection by measuring local cerebral blood flow (LCBF), mean arterial blood pressure (MABP), cerebral perfusion pressure (CPP) and intracranial pressure (ICP). METHODS: Sixteen female Wistar rats weighing 275 to 350 g were anesthetized and subjected to an accelerated-impact weight-drop model of diffuse TBI. Hypothermia (33-34 degrees C) was induced 45 minutes after TBI (baseline), and was maintained for 180 minutes. The isoflurane group (n = 8) received 70% N(2)O in O(2), and isoflurane at 0.9 +/- 0.04%. The propofol group (n = 8) received 70% N(2)O in O(2) and a propofol infusion (12 mg/kg/hr). LCBF was measured by laser Doppler flowmeter. MABP, ICP, and brain and rectal temperatures were measured every 15 minutes from baseline through 180 minutes. Blood gas and hematocrit testing was also done at baseline and every 60 minutes thereafter to assess the animals' physiological state. RESULTS: In the isoflurane group, MABP and CPP decreased significantly from baseline to 180 minutes (p < 0.05 and p < 0.01, respectively), and MABP was significantly lower than the pressure in the propofol group from 45 minutes through 180 minutes (p < 0.05, p < 0.01). ICP and LCBF remained unchanged in this group. In the propofol group, from baseline to 180 minutes, CPP increased to maximum 120 +/- 8 mmHg at 75 minutes from 98 +/- 5 mmHg (p < 0.05) and ICP fell from 18 +/- 2 mmHg to 7 +/- 1 mmHg (p < 0.01); and the latter was significantly lower than ICP in the isoflurane group (p < 0.05, p < 0.01, p < 0.001). LCBF in this group was significantly higher than LCBF in the isoflurane group in the last 30 minutes of the experiment (p < 0.05). The propofol group showed no change in MABP over the course of the experiment. CONCLUSION: In the clinical setting, propofol anesthesia may be better for use in combination with hypothermia in cases of traumatic brain injury, as it reduces ICP and increases CPP under these conditions.     

Immunologic heterogeneity of diffuse large cell lymphoma

The cellular lineage of 57 diffuse large-cell lymphomas (DLCLs) was determined using a panel of monoclonal antibodies directed against lineage-restricted and -associated T, B, and monocyte antigens. The majority (82%) were of B cell lineage as determined by the expression of sig and/or B1, with the remaining 16% being of T cell lineage and 2%, of monocyte-myeloid lineage. By the expression of other B cell- restricted and -associated antigens, two major and two minor subgroups could be identified. These subgroups expressed the following phenotypes: (1) B1+B4+sIG+B2- (51%); (2) B1+B4+sIg+B2+ (29%); (3) B1+B4+sIg-B2+ (10%); and (4) B1+B4-sIg+B2- (10)%. The morphology of transformed lymphocytes, the weak to absent expression of the early B cell antigens B2 and sIgD, and the absence of the late B cell differentiation antigens PCA-1 and PC-1 suggested that these tumors were the neoplastic counterparts of normal B cells at the mid-stages of differentiation. Further support for the notion that B-DLCLs correspond to transformed B lymphocytes was concluded from the observation that B cells could be identified in normal spleen that expressed the cell surface phenotype and morphological appearance of the majority of B- DLCLs.     

Evaluating the effect of polytetrafluoroethylene and extractum cepae-heparin-allantoin gel in peripheral nerve injuries in a rat model

BACKGROUND:Peripheral nerves can be injured by congenital, mechanical, thermal or chemical causes. Peripheral nerve injuries are increasing in frequency, particularly in countries that are becoming more industrialized. Nerve and extremity injuries result in work loss and high treatment costs, and can lead to separation of patients from their social environment. Failure of nerve repair causes muscle functional losses, sensory losses and painful neuropathies.OBJECTIVES:To compare the effects of condensed polytetrafluoroethylene (cPTFE) and cPTFE-extractum cepae-heparin-allantoin (cPTFE-EHA) gel compound on nerve and functional recovery, and the prevention of adhesion and scar tissue formation after total peripheral nerve injury repaired by primary suture in a rat model.RESULTS:cPTFE alone and cPTFE-EHA gel was found to provide better functional recovery and nerve regeneration compared with primary repair only. In the macroscopic evaluation, the cPTFE-EHA gel was found to have no negative effect on wound healing and, despite increasing extra-neural scar tissue and adhesions, it had no negative effect on nerve function; in addition, it facilitated functional recovery.CONCLUSIONS:Compared with the cPTFE application alone, the application of perineural cPTFE-EHA gel during peripheral nerve surgery appeared to provide better functional recovery without causing any significant changes in epineural and extraneural scar tissue formation.     

Serum carbohydrate antigen 125 levels in nonischemic dilated cardiomyopathy: a useful biomarker for prognosis and functional mitral regurgitation

The authors investigated the prognostic relevance of serum carbohydrate antigen 125 (CA125) levels in nonischemic dilated cardiomyopathy (NICMP) and assessed whether increased levels relate to the degree of functional mitral regurgitation (FMR). Seventy-seven patients with NICMP were enrolled and followed-up for 10 ± 2 months in this prospective study. Receiver-operating characteristic analysis established a cutoff CA125 value of 25 U/mL for predicting mortality. Patients were divided into two groups according to their CA125 levels (CA125 <25 U/mL [n=58] and CA125 ≥ 25 U/mL [n=19]). Patients with high CA125 values had statistically worse functional status, higher B-type natriuretic peptide (BNP) levels, higher left ventricular volumes, lower ejection fraction, higher E/Em ratio, higher pulmonary artery systolic pressure, and more severe FMR. On the multivariate analysis, serum CA125 (P=.002) and severe FMR (P=.04) were identified as the independent predictors of mortality. Serum CA125 levels also correlated with BNP levels and FMR severity (P<.001). Serum CA125 is a powerful prognostic biomarker that is associated with the severity of heart failure, serum BNP levels and several echocardiographic parameters including left ventricular volumes, systolic and diastolic functions, pulmonary artery pressure, and the degree of FMR. Serum CA125 was also shown as an independent predictor of mortality during 10 ± 2 months of follow-up.     

Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

Waist circumference is associated with carotid intima media thickness in peritoneal dialysis patients

Purpose

Atherosclerosis is responsible for the high mortality rate in end-stage renal disease patients. Defining risk factors for atherosclerosis may lead to reduction in cardiovascular disease through modification of these factors. Peritoneal dialysis (PD) patients are subjected to high glucose loads on a daily basis, which results in considerable weight gain and an increase in waist circumference (WC). WC as an indicator of abdominal obesity is a risk factor for atherosclerosis in the general population. Carotid artery intima media thickness (CIMT) measurement is a reliable method for the detection of early atherosclerosis. The aim of this study was to investigate the relationship between WC and CIMT and to define risk factors associated with CIMT in PD patients.

Methods

Fifty-five PD patients and 40 healthy controls were included. Atherosclerosis was assessed using measurement of CIMT. Fasting blood was collected for analysis. Anthropometric parameters (age, weight, BMI, and WC) were measured.

Results

Peritoneal dialysis patients had higher WC (93.9 ± 1.7 vs. 87.3 ± 1.2 cm, p < 0.05) and CIMT (0.70 ± 0.02 vs. 0.57 ± 0.01 mm, p < 0.01) than the control group. On univariate analysis, age, WC, plaque formation, and D/P creatinine were positively correlated with CIMT, whereas residual renal function, albumin, ultrafiltration volume, and D/D0 glucose were negatively correlated. On multivariate analysis, only age, WC, and plaque formation showed correlation (p < 0.001).

Conclusions

Carotid artery intima media thickness is associated with age, plaque formation, and WC in PD patients. WC measurement is a simple, inexpensive, reproducible, and reliable method of evaluating atherosclerosis risk in PD patients and should be assessed at every visit. Appropriate counsel should be provided to patients with greater WC who are deemed to be at risk for atherosclerosis.