Comparison of viral gene-deleted adenoviral vectors with the E1-deleted adenoviral vector in islets.
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Adenoviridae↗
Biomedical subjects
J Shen
Publications and source records attributed to J Shen.
mu-Opioid receptor downregulation contributes to opioid tolerance in vivo.
The present study examined the contribution of downregulation of mu-opioid receptors to opioid tolerance in an intact animal model. Mice were implanted subcutaneously with osmotic minipumps that infused etorphine (50-250 microg/kg/day) for 7 days. Other mice were implanted subcutaneously with a morphine pellet (25 mg) or a morphine pellet plus an osmotic minipump that infused morphine (5-40 mg/kg/day) for 7 days. Controls were implanted with an inert placebo pellet. At the end of treatment, pumps and pellets were removed, and saturation binding studies were conducted in whole brain ([3H]DAMGO) or morphine and etorphine analgesic ED(50)s were determined (tail-flick). Morphine tolerance increased linearly with the infusion dose of morphine (ED(50) shift at highest infusion dose, 4.76). No significant downregulation of mu-receptors in whole brain was observed at the highest morphine treatment dose. Etorphine produced dose-dependent downregulation of mu-opioid receptor density and tolerance (ED(50) shift at highest infusion dose, 6.97). Downregulation of mu-receptors only occurred at the higher etorphine infusion doses (> or =150 microg/kg/day). Unlike morphine tolerance, the magnitude of etorphine tolerance was a nonlinear function of the dose and increased markedly at infusion doses that produced downregulation. These results suggest that mu-opioid receptor downregulation contributes to opioid tolerance in vivo. Therefore, opioid tolerance appears to rely upon both "receptor density-dependent" and " receptor density-independent" mechanisms.
Animals↗
Age-related decrease in the N-methyl-D-aspartateR-mediated excitatory postsynaptic potential in hippocampal region CA1.
Glutamatergic fast synaptic transmission is known to be altered with age in a region-specific manner in hippocampus of memory-impaired old rats. In the present experiment, presynaptic fiber potentials and non-N-methyl-D-aspartate (NMDAR) and NMDAR-mediated synaptic responses in CA1 were compared in three ages of behaviorally characterized male F-344 rats. In the CA1 region, old rats showed approximately equivalent reductions in non-NMDAR- and NMDAR-excitatory postsynaptic potential amplitudes for a given size of presynaptic fiber potential. There was no change in magnitude of the presynaptic response itself at any stimulus level. These results are consistent with the hypothesis that there is a reduction in the number of Schaffer collateral synapses per presynaptic axon. This pattern of results in CA1 is very different from what is known to occur at the perforant path-granule cell synapse. In fascia dentata the non-NMDAR-mediated excitatory postsynaptic potential is increased in amplitude, although the NMDAR-mediated excitatory postsynaptic potential is reduced for a given presynaptic input. These data suggest that age-related functional alterations in neurotransmitter receptor subtypes occur differentially between closely-related anatomical subregions.
Aging↗
Two opposite effects of ATP on the apparent sensitivity of the cGMP-gated channel of the carp retinal cone.
Effects of ATP on the activity of cGMP-gated channels from carp cone photoreceptors were studied. In 29% of the patches examined (N = 45), ATP (1 mM) enhanced a current evoked by cGMP (20 microM, up to about 100%), in 33%. ATP suppressed it by up to about 90%, and in the remaining 38%, ATP had no effect. ATP showed similar effects on a current evoked by 8-bromoguanosine 3',5'-cyclic monophosphate (2 microM, enhancing in 42% of the patches, suppressing in 25%, no effect in 33%, N = 12), suggesting that the effects were not through modulation of the phosphodiesterase. Both of the effects, enhancement and suppression, were produced by a change in apparent affinity for cGMP, since (1) the maximum current evoked by cGMP of the saturating concentration (> or = 1 mM) was not affected, and (2) the K1/2 value decreased by approximately 45% (N = 2) or increased by approximately 25% (N = 2). A lower pH (approximately 6) facilitated the enhancing effect. ATP-gamma-S (1 mM) showed a suppressing effect in 80% of the patches and no effect in 20% of the patches (N = 10). However, ATP-gamma-S did not show an enhancing effect. Thus, ATP had two opposite effects through different mechanisms on the apparent sensitivity of the channel to cGMP; increasing and decreasing.
Adenosine Triphosphate↗
A novel selenocystine-beta-cyclodextrin conjugate that acts as a glutathione peroxidase mimic.
A novel artificial glutathione peroxidase mimic consisting of a selenocystine-di-beta-cyclodextrin conjugate (selenium-bridged-6, 6'-amino-selenocystine-6,6'-deoxy-di-beta-cyclodextrin), in which selenocystine is bound to the primary side of beta-cyclodextrin through the two amino nitrogen groups of selenocystine, was synthesized. The glutathione peroxidase activities of the mimic-catalyzed reduction of H(2)O(2), tert-butylhydroperoxide, and cumene hydroperoxide by glutathione are 4.1, 2.11, and 5.82 units/micromol, respectively. The first activity was 82 and 4.2 times as much as that of selenocysteine and ebselen, respectively. Studies on the effect of substrate binding on the glutathione peroxidase activity suggest that it is important to consider substrate binding in designing glutathione peroxidase mimics. The detailed steady-state kinetic studies showed that the mimic-catalyzed reduction of H(2)O(2) by glutathione followed a ping-pong mechanism, which was similar to that of the native glutathione peroxidase.
Binding Sites↗
Acupuncture: evidence and implications for cancer supportive care.
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Acupuncture↗
Cytologic and histologic review of atypical glandular cells (AGC) detected during cervical cytology screening.
This article is to determine the clinical significance and underlying pathology among patients with atypical glandular cells (AGC) identified during cervical Papanicolau (Pap) smear screening. AGC slides were searched from 51,412 computerized files of the cytology laboratory of Mackay Memorial Hospital during a 29-month period. The results of clinical evaluations were reviewed and an experienced gynecologic cytopathologist who was not involved in the original cytologic diagnosis and was not aware of the clinical results of the follow-up examinations rechecked all AGC slides. We used the z score to determine whether different results were achieved after the gynecologic cytopathologist rechecked the slides. We further analyzed all slides with different cytologic diagnoses and compared results with the histologic diagnoses. Forty-nine cases were initially identified as AGC. Among these, 29 were reviewed and identified as AGC again, and the result of biopsies revealed that they were all chronic cervicitis, ie, negative for malignancy or premalignancy. The other 20 cases were reviewed and diagnosed as non-AGC. Among the results of cytologic examinations, seven had inflammation, two had atypical squamous cells of undetermined significance (ASC-US), ten had high-grade cervical intraepithelial neoplasia (CIN), and one had adenocarcinoma. The results of histologic diagnosis included eight cases with normal tissue, two with CIN grade 1, eight with high-grade CIN, one with microinvasive squamous cell carcinoma, and one with adenocarcinoma. Histologic results revealed 20.4%1 (10/49) and 50% 1(10/20) at initial cytologic diagnosis of AGC and expert-reviewed non-AGC, respectively, which were finally at least high-grade CIN. According to the gynecologic cytopathologist's diagnosis, 59.2%1 (29/49) of cases would have eliminated unnecessary histologically diagnostic procedures. In conclusion, clinicians should be careful about the significance of the cytologic diagnosis of AGC, because there may actually be an underlying pathology, which can be identified by a pathologist who is an expert in gynecologic cytopathology. The interobserver variation in diagnosing AGC favors specialized training in gynecologic cytopathology. In addition, prompt diagnostic interventions, including colposcopy, endocervical curettage, and/or endometrial biopsy, should be performed after confirmation of the diagnosis of non-AGC by an experienced gynecologic cytopathologist.
Adenocarcinoma↗
Solubilization and pharmacokinetic behaviors of sodium cholate/lecithin-mixed micelles containing cyclosporine A.
The purpose of this study was to investigate the solubilization capacity of sodium cholate/lecithin-mixed micelles and to evaluate the potential of mixed micelles as a carrier of cyclosporine A for intravenous infusion. The mixed micelles were prepared by coprecipitation technique. The formulation components and preparation procedures, which may affect the solubilization of cyclosporine A, were studied. The dilution stability of cyclosporine A-containing mixed micelles was investigated. Pharmacokinetic behaviors of mixed micelles in rabbits after intravenous infusion were compared with Sandimmun. Results showed the strategies to increase the solubility of cyclosporine A include lowering the molar ratio of sodium cholate to lecithin, increasing the concentration of lecithin, and reducing the ionic strength of the dispersion medium and temperature. The largest solubility was found to be 5.42 +/- 0.16 mg/ml. The leakage of mixed micelles in 5% glucose (5.84%) was much less than that in saline solution (36.7%). The relative bioavailability of mixed micelles versus Sandimmun was 112 +/- 20%, and statistical analysis demonstrated both preparations were bioequivalent. Sodium cholate/lecithin-mixed micelles are promising carriers in the intravenous delivery of cyclosporine A, considering their capability of large-scale production and low-toxic property.
Animals↗
Effect of naloxone on the haemodynamics and the outcome of experimental acute pancreatitis in dogs.
Endogenous opioid peptides may play a role in the genesis of pancreatic damage in acute pancreatitis. The effects of naloxone on the haemodynamic changes in acute pancreatitis were investigated by inducing it in dogs with pancreatic ductal injection of fresh trypsin-bile mixture. In the control group (n = 8), acute pancreatitis was characterized haemodynamically by falls in the maximum positive and negative dP/dt (+/- dP/dt), cardiac output (CO) and cardiac index (CI), and increases in the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) as well as an early reduction of pancreatic blood flow (PBF). In another set of eight dogs (naloxone group), naloxone was given intravenously 10 min after the induction of acute pancreatitis (80 micrograms/kg as a bolus + 80 micrograms/kg/h for 3 h). Compared with untreated dogs, naloxone significantly increased PBF and the +/- dP/dtmax; prevented the significant decreases in CO and CI and increases in PVR and SVR, and reduced significantly the severity of pancreatitis, as assessed by both the histological staging and the mortality rate. These results suggest that naloxone limits the progression of acute pancreatitis from oedematous to haemorrhagic form. It is proposed that endogenous opioid peptides may play a role in the pathophysiology of acute pancreatitis.
Acute Disease↗
Overexpression of cyclin D1 and c-Myc gene products in human primary epithelial ovarian cancer.
Cyclin D1 and c-Myc are key participants in the cell-cycle pathway, in which aberrancies have been associated with malignant transformation. To date, data on the relationship of expression of these proteins and histologic subtype of epithelial ovarian cancer are still scarce and discordant. Immunohistochemical analysis was performed on 12 normal ovaries and 47 cases of serous, mucinous, endometrioid, and clear cell ovarian carcinomas. No abnormal expression of cyclin D1 or c-Myc was demonstrated in any of the 12 normal ovarian specimens. However, compared to normal ovarian tissues, overexpression of cyclin D1 and c-Myc was observed in 42.6% (20/47) and 65.9% (31/47) of tumors examined, respectively. There was no significant difference of overexpression of cyclin D1 or c-Myc gene products between these four histologic subtypes of ovarian adenocarcinomas. This study shows that cyclin D1 and c-Myc are frequently overexpressed in epithelial ovarian carcinomas, but they are not correlated with a particular histologic subtype. Although our preliminary results need to be validated in a larger number of tumors, the abnormal expression of cyclin D1 and c-Myc in epithelial ovarian cancer reaffirms the notion that they are crucial components in the pathway of tumorigenesis and deserve further study.
Cyclin D1↗
Recurrent retroperitoneal myxoid liposarcoma during pregnancy: a case report and literature review.
Retroperitoneal liposarcoma in pregnancy is rare, and only a few cases of primary liposarcoma during pregnancy have been reported. To the best of our knowledge, there is no published report of retroperitoneal liposarcoma that was previously treated and recurred during pregnancy. Our patient was diagnosed with a pelvic mass on ultrasound at 12-weeks' gestation. The mass was found to be a retroperitonal, well-differentiated myxoid liposarcoma and was radically excised at the time of cesarean delivery at 36-weeks' gestation. However, the tumor recurred soon and progressed rapidly, and the patient eventually died of the disease. A thorough sonographic investigation and timing of surgery may be critical in terms of finding a surgically resectable lesion and leading to a more favorable prognosis.
Adult↗
Efficient gene transfer and expression in islets by an adenoviral vector that lacks all viral genes.
Although adenoviral vector-mediated gene transfer has significant potential for gene therapy, host immune responses to virally expressed proteins and small insert capacity may limit its clinical application. In order to overcome these disadvantages, a new adenoviral vector that lacks all viral genes has been developed. Using the green fluorescent (GFP) gene as a reporter gene, we investigated the efficiency of gene transfer by this all-viral-genes-deleted and minimal cis-element remaining adenoviral vector (miniAd-GFP) in islets in vitro and ex vivo, and compared it with the E1-deleted adenoviral vector (E1-GFP). One day after in vitro infection, GFP was expressed in both miniAd-GFP- and E1-GFP-infected islets. The percentage of GFP-positive single cells was not significantly different between miniAd-GFP-infected islets and E1-GFP-infected islets. When these islets were transplanted into syngeneic diabetic mice, both miniAd-GFP- and E1-GFP-infected islet grafts reversed diabetes, and normal blood glucose levels were maintained for over 20 weeks posttransplantation. Mild lymphocyte infiltration was found in all E1-GFP-infected islet grafts at all time points. However, this was not seen in most miniAd-GFP-infected islet grafts. Our results indicate that gene transfer by an adenoviral vector that lacks all viral genes is as efficient as E1-deleted adenoviral vector-mediated gene transfer in islets. Furthermore, this adenoviral vector might be less immunogeneic than the E1-deleted adenoviral vector.
Adenoviridae↗
Immunolocalization of cellular fibronectins in the normal liver, cirrhosis, and hepatocellular carcinoma.
Cellular (c) fibronectins (Fn) differ biochemically, immunologically, and functionally from plasma fibronectins (pFn). Most existing data on Fn distribution in the normal and diseased liver require revision because those studies were based on reagents that did not distinguish pFn from cFn and predated the development of specific cFn monoclonal antibodies (Mabs). We immunostained cryosections of normal adult livers (n = 5), cirrhotic livers (n = 20), and livers with hepatocellular carcinoma (HCC) (n = 10) by the avidin-biotin-complex method with specific Mabs to the extradomains A and B (EDA, EDB) and oncofetal (Onc) isoforms of cFn. Selected samples were stained with an antiserum to pFn; fetal livers served as controls. Normal and cirrhotic livers showed EDA-cFn staining in the portal, septal, and perisinusoidal matrix; its distribution was more restricted than that of pFn. In cirrhosis, EDA-cFn reactions were strongest at sites of piecemeal necrosis and around proliferating ductules in biliary cirrhosis. EDA-cFn reactions were consistently most intense in the matrix of HCC. Distinct from adult normal and cirrhotic livers, reactions for EDB- and Onc-cFn were noted exclusively in most cases of HCC. We conclude that the only cFn isoform indigenous to the normal adult liver matrix is EDA-cFn. Enhanced EDA-cFn in cirrhotic livers may serve as indicator of active stromal remodeling. The restriction of EDB- and Onc-cFn to a large subset of HCC and the putative role of cFn in modulating cell-matrix adhesive interactions would suggest that the emergence of these molecules may be related to the variably invasive and metastatic properties of these tumors.
Adult↗
Morphologic analysis of normal human lumbar dorsal root ganglion by 3D MR imaging.
BACKGROUND AND PURPOSE: The dorsal root ganglion (DRG) of the spinal nerve has been considered a key structure in the mechanism of low-back pain and radicular symptoms. The purpose of this study was to clarify the normal morphologic features and variations of the lumbar DRGs in a healthy population by using 3D MR imaging. METHODS: 3D fast-field echo (FFE) with water selective excitation coronal MR images of lumbar spine obtained in 115 healthy volunteers were further reconstructed into a radial stack of 15 coronal images by using maximum intensity projection technique. The DRGs from L1 through L5 were assessed for the location, signal intensity, architecture, and dimensions. RESULTS: Most DGRs were foraminal in location. Only 5.7% of the L5 DGRs were located intraspinally. The sizes of L1, L2, and L5 DRGs in men were larger than those in women (P < .05). The dimensions of the DRGs gradually increased from L1 to L5 (P < .0001). The biganglia (2 ganglial components) frequently occurred in the L4 and L3 DRGs, whereas the singular ganglion (1 ganglial component), in the L5 and L1 DRGs. CONCLUSION: The normal anatomy and variants of the lumbar DRG could be better demonstrated by 3D MR imaging with water selective excitation technique. The relatively larger and more proximally located DRGs in the lower lumbar region may be more susceptible to compression. An appreciation of normal anatomy and variants of DRGs radiologically is helpful for the diagnosis and proper treatment for radiculopathy.
Adolescent↗
A single-base deletion in the 3'-coding region of glycogen-debranching enzyme is prevalent in glycogen storage disease type IIIA in a population of North African Jewish patients.
Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of glycogen-debranching enzyme (AGL). The overall incidence of the disease is about 1:100,000 life births in the USA; however, it is unusually frequent among North African Jews in Israel (prevalence 1:5,400, carrier prevalence 1:35). All North African Jewish GSD III patients examined have both liver and muscle involvement. While all patients showed the characteristic features related to the liver enzyme deficiency, the peripheral muscular impairment varied from minimal to severe, with neuromuscular involvement. A single mutation in the AGL gene, the deletion of T at position 4,455 (4,455delT) in homozygous form, was found in this patient population. The mutation 4,455delT results in the change of 17 amino acids at the carboxy terminus of the AGL protein (1,486-1,502) and truncation of the last 30 amino acids of the normal AGL 1,532 amino acids. The mutation appears to be ethnic specific as it was not seen in 18 patients of different ethnic origins. This is the first report of a mutation in the AGL gene affecting a considerable number of GSD III patients in a defined population.
Adult↗
The effect of heparinization on intra-abdominal infection and acute pulmonary failure.
UNLABELLED: Acute severe purulent peritonitis is still a very life-threatening disease condition. The primary cause of death is multiple organ failure (MOF) where acute respiratory distress syndrome (ARDS) is the initial trigger. Studies have shown that heparin has a cytoprotective effect and stimulates an increase in cardiopulmonary function systematically. METHODS: Twenty-one Sprauge Dawley rats were used as an animal model by puncturing the distal wall of intestine and ligating the appendix without interfering with the continuity of intestinal tract. In the formal experiments, 100 rats were divided into two groups and equal amounts of distilled water was given intraperitoneally. Total mortality and early mortality rate were recorded. Abdominal autopsies and blood gas analyses were performed and lung tissue samples were taken for light and electronic microscope analyses. RESULTS: The mortality rate was not statistically significant. But early death rate, the average survival times and the rate of abscess formation were significantly lower in the heparin treated group. The histological study of the experimental specimen showed that in the control group, the incidence of ARDS was higher and there was a more severe ARDS-like change, especially polymorphonuclear neutrophil leukocytes infiltration into alveolar and interstitial spaces. Blood gas analysis demonstrated the beneficial aspects of heparin administration. CONCLUSIONS: Heparin can increase the early survival rate and increase the survival time of rats with experimental acute severe purulent peritonitis, and proves to be beneficial in preventing infection induced lung injury during sepsis. We conclude that the effect of heparin on the survival rate is related to less pulmonary function deterioration, thereby preventing ARDS and the triggering of MOF.
Acute Disease↗