Search

Using electron microscopy and diffraction techniques, as well as first-principles calculations, we demonstrate that as much as 35% of the total Ge atoms in the cubic phase of Ge2Sb2Te5 locate in tetrahedral environments. The Ge-vacancy interactions play a crucial stabilizing role, leading to Ge-vacancy pairs and the sharing of vacancies that clusters tetrahedral Ge into domains. The Ge2Sb2Te5 structure with coexisting octahedral and tetrahedral Ge produces optical and structural properties in good agreement with experimental data and explains the property contrast as well as the rapid transformation in this phase-change alloy.

A new strategy for the highly efficient one-pot synthesis of 3-amino-/alkylthio-cyclobut-2-en-1-ones based on the cyclization of acyl ketene dithioacetals is disclosed. In addition, the rearrangement of 3-amino-cyclobut-2-en-1-ones to 4-quinolone derivatives is described.

Birth defects are the leading cause of infantile mortality, followed by neural tube defects (NTD) and congenital heart defects. Spina bifida and anencephaly are among the most common forms of NTD. NTD etiologies are complex, and are associated with both genetic and environmental factors. Polycomb group proteins are essential for vertebrate development; therefore, the purpose of this study was to determine the role of PcGs in spinal cord morphogenesis in normal and all-trans-retinoic acid (RA)-treated fetal rat models of spina bifida. Pregnant rats were gavage-fed RA, resulting in fetal NTD, and embryos were obtained on day 15.5, 17.5, and 19.5. Western blot and immunohistochemistry were used to reveal PcGs expression in the normal and RA-treated E15.5-19.5 rat sacral cords. Western blot and immunohistochemistry revealed decreased EED, RNF2, SUZ12, and H3K27me3 expression in the normal, E15.5-19.5, rat sacral cords. In addition, the spinal cord of RA-treated rats during embryonic development exhibited altered PcGs protein expression. Administration of excess RA results in NTD. Our results suggest that the Polycomb proteins may be involved in spinal cord development.

Objective: To compare the modified and conventional methods in orotracheal intubation of GlideScope videolaryngoscope., Methods: Sixty patients aged 21-53 years with ASA physical status I-II were scheduled for elective abdominal operation under general anesthesia. After routine anesthesia induction orotracheal intubation was performed with GlideScope videolaryngoscope; the patients were randomly divided into two groups (n=30 in each): Group M received modified orotracheal intubation and Group C received conventional orotracheal intubation. Noninvasive blood pressure and heart rate were recorded before and after anesthesia induction, at intubation, 1 and 3 min after intubation., Results: The time of intubation procedure was significantly longer in Group C than in Group M. BP and HR significantly decreased after intubation, there were no differences between two groups., Conclusion: The modified method can improve the readiness of the procedure but it shows no advantages in prevention of adverse hemodynamic responses during the orotracheal intubetion of videolaryngoscopy.

Objective: To investigate the influence of combined intercostal nerves block-sevoflurane used inhalation anesthesia with laryngeal mask ventilation on the stress response to modified radical mastectomy., Methods: 60 patients with ASA physical status I-II, aged 33-53 years and scheduled for modified radical mastectomy were randomly divided into group I and group II. 30 cases each group. Patients in both groups received modified radical mastectomy under sevoflurane used inhalation anesthesia with laryngeal mask ventilation, and group II received intercostal nerves block before anesthesia induction. Blood samples were taken before anesthesia,at incision, one hour after incision and 5 minutes after the end of surgery for determination of serum concentration of cortisol and angiotension. Blood pressure and heart rate of patients was also recorded during the operation., Results: Compared with the baseline value before anesthesia, serum cortisol and angiotension increased 5 minutes after the end of surgery in both groups, but the concentration in group I were higher than that in group II. At incision the concentration of cortisol in group I were higher than the baseline value and the same time in group II., Conclusion: Combined intercostal nerves block-sevoflurane used inhalation anesthesia with laryngeal mask ventilation can reduce the stress response in patients undergoing modified radical mastectomy.

We present an innovative approach to the production of single-crystal iron oxide nanorings employing a solution-based route. Single-crystal hematite (alpha-Fe2O3) nanorings were synthesized using a double anion-assisted hydrothermal method (involving phosphate and sulfate ions), which can be divided into two stages: (1) formation of capsule-shaped alpha-Fe2O3 nanoparticles and (2) preferential dissolution along the long dimension of the elongated nanoparticles (the c axis of alpha-Fe2O3) to form nanorings. The shape of the nanorings is mainly regulated by the adsorption of phosphate ions on faces parallel to c axis of alpha-Fe2O3 during the nanocrystal growth, and the hollow structure is given by the preferential dissolution of the alpha-Fe2O3 along the c axis due to the strong coordination of the sulfate ions. By varying the ratios of phosphate and sulfate ions to ferric ions, we were able to control the size, morphology, and surface architecture to produce a variety of three-dimensional hollow nanostructures. These can then be converted to magnetite (Fe3O4) and maghemite (gamma-Fe2O3) by a reduction or reduction-oxidation process while preserving the same morphology. The structures and magnetic properties of these single-crystal alpha-Fe2O3, Fe3O4, and gamma-Fe2O3 nanorings were characterized by various analytical techniques. Employing off-axis electron holography, we observed the classical single-vortex magnetic state in the thin magnetite nanorings, while the thicker rings displayed an intriguing three-dimensional magnetic configuration. This work provides an easily scaled-up method for preparing tailor-made iron oxide nanorings that could meet the demands of a variety of applications ranging from medicine to magnetoelectronics.

Objective: To study the effects of different fluids on blood pressure (BP), blood lactate clearance and mortality in patients with septic shock after early fluid resuscitation., Methods: Sixty patients were enrolled and randomly divided into four groups according to the fluids used in resuscitation: normal saline (NS) group (15 cases), hydroxyethyl starch (HES) group (15 cases), 4% hypertonic saline solution (4%NaCl) group (15 cases), hypertonic sodium chloride hydroxyethyl starch 40 solution (HSH40) group, (15 cases). Patients of different groups received fluid resuscitation via central vein, at the same time, received the anti-shock treatment. Hemodynamic parameters, blood lactate clearance and mortality in patients were monitored after resuscitation., Results: The study fluid volume and the total fluid volume in the 4%NaCl group and HSH40 group was lower than that in NS group and HES group significantly (all P<0.01). The mean arterial pressure (MAP) in HSH40 group was significantly higher than in the other three groups 1 hour after the fluid resuscitation (all P<0.01). The 24-hour blood lactate clearance in HSH40 group was also higher than in the other three groups (all P<0.01). The scores of sepsis-related organ failure assessment (SOFA) scores, acute physiology and chronic health evaluation II (APACHE II) scores, and 28-day mortality showed no significant differences among these groups (all P>0.05), but a lowering trend on 28-day mortality could be observed in HSH40 group., Conclusion: The rapid elevation of BP can improve blood lactate clearance in patients with septic shock receiving early fluid resuscitation. Compared with other fluids, HSH40 raises BP more quickly and needs lower total resuscitation volume to achieve the same goal.

Aim: To investigate the effects of ghrelin on delayed gastrointestinal transit in alloxan-induced diabetic mice., Methods: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice group and diabetic mice group treated with ghrelin at doses of 0, 20, 50, 100 and 200 mug/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of ghrelin. Based on the most effective ghrelin dosage, atropine was given at 1 mg/kg 15 min before the ghrelin injection for each measurement. The mice in each group were sacrificed 20 min later and their stomachs, intestines, and colons were harvested immediately. The amount of phenol red was measured. Percentages of GE, IT, and CT were calculated., Results: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice (22.9 +/- 1.4 vs 28.1 +/- 1.3, 33.5 +/- 1.2 vs 43.2 +/- 1.9, 29.5 +/- 1.9 vs 36.3 +/- 1.6, P < 0.05). In the diabetic mice, ghrelin improved both GE and IT, but not CT. The most effective dose of ghrelin was 100 mug/kg and atropine blocked the prokinetic effects of ghrelin on GE and IT., Conclusion: Ghrelin accelerates delayed GE and IT but has no effect on CT in diabetic mice. Ghrelin may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.

A simple and efficient AlCl(3)-mediated C-C coupling reaction between readily available alpha-hydroxyketene-S,S-acetals and various arenes via direct substitution of the hydroxy group in alcohols has been developed. On the basis of this C-C coupling reaction, a series of bio- and pharmacologically important 3,4-disubstituted dihydrocoumarins, difficult to obtain by other methods, were prepared in high yields by a sequential Friedel-Crafts alkylation and intramolecular annulation reaction of alpha-hydroxyketene acyclic-S,S-acetals with phenols under mild conditions.

Objective: To set up a stable primary culture system of Leydig cells with higher purity., Methods: We separated Leydig cells from other testicular cells, such as Sertoli and germ cells, by enzymatic digestion in combination with Percoll density gradient centrifugation and identified Leydig cells by 3beta-HSD staining., Results: The purity achieved by this method was above 95% and the total number of Leydig cells obtained from one testicle was about 1 x 10(6). The cytoplasm of Leydig cells was stained in deep blue by 3beta-HSD staining, and these cells possessed testosterone-secreting capability., Conclusion: Leydig cells can be separated by enzymatic digestion combined with Percoll density gradient centrifugation, and 3beta-HSD staining to identify Leydig cells is simple and feasible with high purity.

Fetuses with homozygous alpha-thalassemia usually die at the third trimester of pregnancy or soon after birth. Hence, the disease could potentially be a target for fetal gene therapy. We have previously established a mouse model of alpha-thalassemia. These mice mimic the human alpha-thalassemic conditions and can be used as preclinical models for fetal gene therapy. We tested a lentiviral vector containing the HS 2, 3, and 4 of the beta-LCR, a central polypurine tract element, and the beta-globin gene promoter directing either the EGFP or the human alpha-globin gene. We showed that the GFP expression was erythroid-specific and detected in BFU-E colonies and the erythroid progenies of CFU-GEMM. For in utero gene delivery, we did yolk sac vessel injection at midgestation of mouse embryos. The recipient mice were analyzed after birth for human alpha-globin gene expression. In the newborn, human alpha-globin gene expression was detected in the liver, spleen, and peripheral blood. The human alpha-globin gene expression was at the peak at 3-4 months, when it reached 20% in some recipients. However, the expression declined at 7 months. Colony-forming assays in these mice showed low abundance of the transduced human alpha-globin gene in their BFU-E and CFU-GEMM and the lack of its transcript. Thus, lentiviral vectors can be an effective vehicle for delivering the human alpha-globin gene into erythroid cells in utero, but, in the mouse model, delivery at late midgestation could not transduce hematopoietic stem cells adequately to sustain gene expression.

Objective: To study the effects of amiloride, an inhibitor of urokinase, on pathological and pathophysiological changes of chronic obstructive pulmonary disease (COPD) model, and to investigate the role of urokinase plasminogen activator system components in the pathogenesis of COPD., Methods: Healthy Wistar rats (n = 24) were randomly divided into a control group, a model group and an amiloride group. After 7 weeks, lung function measurements were performed. The total and different white blood cell counts of bronchoalveolar lavage fluid (BALF) were determined, and collagen deposition of lung sections was observed by picrosirius staining. The expressions of u-PA, u-PAR and PAI-1 in bronchial lung tissues were examined by immunohistochemical analysis., Results: In the model group the expiratory resistance (Re) was significantly higher than that of the control group and the amiloride group, while forced expiratory volume in the 0.3 s/forced expiratory capacity (FEV(0.3)/FVC%) and peak expiratory flow (PEF) were significantly lower than those of the other two groups. Significant increase in total white blood cells and percentage of neutrophils and macrophages in BALF was found in the model group as compared to the control group and the amiloride group. The collagen deposition, mainly type I collagen, in airway walls was significantly increased in the model group. The levels of u-PA, u-PAR and PAI-1 in the model group [(0.166 +/- 0.010), (0.158 +/- 0.024), (0.171 +/- 0.012), respectively] were significantly higher than those in the control group [(0.137 +/- 0.015), (0.122 +/- 0.009), (0.144 +/- 0.005), respectively] and the amiloride group [(0.126 +/- 0.004), (0.120 +/- 0.010), (0.122 +/- 0.004), respectively]. F values were 32.463, 4.094, 79.562 respectively, and all P < 0.001. Moreover, u-PAR protein level was positively correlated with neutrophils in BALF in the model group (r = 0.754, P = 0.031)., Conclusion: Administration of u-PA inhibitor-amiloride significantly alleviated airway inflammation and the pathological changes in COPD rats, suggesting that the u-PA system components are key mediators regulating the inflammatory reaction and tissue remodeling in the pathological process of COPD.

Large strain plasticity is phenomenologically defined as the ability of a material to exhibit an exceptionally large deformation rate during mechanical deformation. It is a property that is well established for metals and alloys but is rarely observed for ceramic materials especially at low temperature ( approximately 300 K). With the reduction in dimensionality, however, unusual mechanical properties are shown by ceramic nanomaterials. In this Letter, we demonstrated unusually large strain plasticity of ceramic SiC nanowires (NWs) at temperatures close to room temperature that was directly observed in situ by a novel high-resolution transmission electron microscopy technique. The continuous plasticity of the SiC NWs is accompanied by a process of increased dislocation density at an early stage, followed by an obvious lattice distortion, and finally reaches an entire structure amorphization at the most strained region of the NW. These unusual phenomena for the SiC NWs are fundamentally important for understanding the nanoscale fracture and strain-induced band structure variation for high-temperature semiconductors. Our result may also provide useful information for further studying of nanoscale elastic-plastic and brittle-ductile transitions of ceramic materials with superplasticity.

Nonylphenol (NP) as an environment contaminant has been demonstrated to adversely affect male reproduction. The main objective of this study was to evaluate NP-induced oxidative stress and toxicity in testicular Sertoli cells. Sertoli cells were exposed to 10-40 microM NP for 24 h. Cell death and growth inhibition were observed by flow cytometric analysis and 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay, while fluorescein diacetate (FDA) and propidium iodide (PI) staining was used to examine the morphological changes following NP exposure. Subsequently, we found that short-term treatment (2 h) of NP caused intracellular accumulation of reactive oxygen species (ROS), which was evaluated by loading of 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) without visible morphological changes. Loss of mitochondrial membrane potential (MMP) was detected following 12 and 24 h treatment of NP and assessment by Rhodamine 123 (Rh123) staining. In addition, incubation with NP for 12 h also increased lipid peroxidation of Sertoli cells. These results indicated that low micromolar concentrations of NP induce an adverse oxidative stress in rat Sertoli cells.

We report on a 4 1/2-year-old girl with clinical features of Teebi hypertelorism syndrome (THS), including a prominent forehead with a widow's peak, heavy and broad eyebrows, hypertelorism, long palpebral fissures, ptosis, a thin upper lip, a grooved chin, and a left preauricular cyst. She required a pacemaker for third degree atrioventricular (AV) block, a finding that has not been previously reported in 36 other patients with THS and for which we were unable to identify other causes. We have reviewed the previous reports of THS and note a characteristic facial appearance with hypertelorism, heavy, broad, and arched eyebrows, a thin upper lip with a long and deep philtrum, and a prominent forehead. Structural cardiac defects were present in five patients, implying that cardiac investigations are warranted in patients with a cardiac murmur and a clinical diagnosis of THS.

The molecular basis in the majority of fragile X patients results from expansion of the CGG repeats in the FMR1 gene causing its transcriptional silencing and deficiency of its encoded protein FMRP. In this communication, we report on a male patient who lacks the characteristic physical features of fragile X and carries a fully methylated mutation, a premutation, a non-methylated full mutation, and a microdeletion encompassing the entire CGG repeat region and 42 bp of upstream flanking sequence. Southern blot analysis revealed that the methylated full mutation accounted for only 10% of his genotype while the premutation/non-methylated full mutation and the microdeletion constituted 37% and 53%, respectively. Immunofluorescent staining of FMRP demonstrated the presence of 22% FMRP in his peripheral blood leukocytes and quantitative RT-PCR revealed a 3.6-fold elevation of FMR1 mRNA levels. Developmental assessments indicated that while he has a learning disability, he does not have mental retardation. Because previous reports had noted that 28% FMRP expression is associated with a characteristic fragile X phenotype, we propose that in our patient the association of 22% FMRP levels with normal physical features and a high-functioning status may have resulted from increased FMRP stability by a mechanism that takes into account the CGG microdeletion and elevated mRNA levels., ((c) 2006 Wiley-Liss, Inc.)

Objective: To investigate the effect of nonylphenol (NP) on testosterone secretion of Leydig cells., Methods: A primary culture system of Leydig cells was set up, followed by identification of Leydig cells with 3beta-HSD staining. After treatment with different concentrations of NP, testosterone secretion was detected and morphological examination was performed., Results: Following treatment with NP, morphologic changes of Leydig cells were detected, with decreased cell density at high doses of NP. Testosterone increased at lower concentrations of NP while decreased at high concentrations of NP., Conclusion: Lower doses of NP can stimulate the secretion of testosterone, but increased exposure to NP will inhibit testosterone secretion of Leydig cells. Besides, high concentrations of NP can cause death of Leydig cells in vitro.

Nonylphenol is the primary final biodegradation product of nonylphenol polyethoxylate (NPE), a non-ionic surfactant that is frequently incorporated into pesticide and detergent formulation. Recent researchers have hypothesized that environmental/ occupational exposure to nonylphenol poses adverse effects on reproductive system of humans and wildlife species. During our study, in vivo and in vitro experiments were performed to examine the effect of nonylphenol on testosterone biosynthesis of rat Leydig cells. In experiment in vivo, serum testosterone (T) as well as luteinizing hormone (LH) levels were detected after animals had been treated with different doses (0 mg/kg/day, 125 mg/kg/day, and 250 mg/kg/day) of nonylphenol for 50 days by gavage, and the final result revealed that testosterone level dramatically declined at the dose of 250 mg/kg/day, while LH level ascended at the dose of 125 mg/kg/day and 250 mg/kg/day. In experiment in vitro, primary cultured Leydig cells were exposed to nonylphenol for 48 h, including low concentrations (0 mg/L, 0.0011 mg/L, 0.0033 mg/L, 0.0055 mg/L, 0.011 mg/L, 0.022 mg/L) and higher concentrations (0.11 mg/L, 0.55 mg/L, 1.1 mg/L, 1.65 mg/L, 2.2 mg/L, 2.75 mg/L, 3.3 mg/L, 5.5 mg/L). Increase of testosterone levels was observed at low concentrations of nonylphenol while reduction was detected at higher concentrations.

In this study, semen samples from fertile and unexplained infertile men were explored for relationships between seminal plasma immunosuppressive factors (SPIFs), semen pH, liquefaction duration and infection of ureaplasma urealyticum (Uu). SPIFs activity was measured by way of counteracting complement. PH was detected by exact pH test paper. Liquefaction duration was observed at 37 degrees C. The results showed that Uu infection ratios of semen samples with abnormal SPIFs, pH or liquefaction duration were markedly higher than those of normal semen samples. It is suggested that Uu infection decreases the level of SPIFs, changes the pH in semen and prolongs the semen liquefaction so as to cause spermatic quality decline. The enhancement of SPIFs level may change the male body against Uu infection.

Objective: To detect the toxic effects of pentachlorophenol (PCP) on cultured rat Sertoli cells., Methods: The viability of Sertoli cells was detected and morphological examination was performed, followed by flow cytometric assay to evaluate the toxic effect of PCP on rat Sertoli cells., Results: MTT assay showed that PCP induced a concentration- and time-dependent decrease in Sertoli cell viability. Flow cytometric assay revealed that the number of dead Sertoli cells grew along with increased exposure to PCP., Conclusion: PCP, with obvious cytotoxic effects, can cause necrosis of Sertoli cells in vitro.

Male Sprague-Dawley (SD) rats were exposed to 4-t-nonylphenol (NP) by gavage at dosages of 0, 125 and 250 mg/kg/day for 50 days. Organ weights of liver, kidney, testis and epididymis were measured. Sperm number in the head of epididymis was counted. Several hormones including testosterone, luteinizing hormone and follicle stimulating hormone were measured. Testicular sections were observed by light and electron microscopy. Terminal dideoxynucleotidyl transferase dUTP nick end labeling assay was performed to probe the apoptotic cells in seminiferous tubules. When rats were treated with nonylphenol at 250 mg/kg/day, the absolute and relative weight of epididymis decreased dramatically, while the relative weights of kidney and liver increased by 14 and 22%, respectively. In addition, the sperm density of the head of epididymis and the testosterone level descended at 250 mg/kg/day. The levels of luteinizing hormone and follicle stimulating hormone increased in both nonylphenol treated groups. Pathological changes were detected by microscopy and the transferase dUTP nick end labeling (TUNEL) assay showed that the number of apoptotic cells in testes increased with nonylphenol in a dose-dependent manner.

Background: Keyhole surgery has developed since the 1990s as a less invasive therapeutic strategy for intracranial lesions, initially for the treatment of intracranial aneurysms. The purpose of this study was to describe and evaluate the results of surgical treatment of lesions in the anterior fossa and sellar region via a supraorbital keyhole approach using eyebrow incisions., Methods: Between April 1994 and July 2003, 54 patients with lesions in the anterior fossa and sellar region were operated on via the supraorbital keyhole approach. The surgical results were studied retrospectively and compared with that of patients with lesions at the same locations but treated via a conventional subfrontal approach., Results: No significant difference in curative effect was found between the conventional subfrontal approach and the supraorbital keyhole approach. However, the supraorbital approach required a much smaller skin incision, causing less surgical trauma, while achieving excellent surgical exposure and good recovery., Conclusion: The supraorbital keyhole approach using an eyebrow incision is safe, effective, and both suitable and convenient for treating lesions in the anterior fossa and sellar region, with almost no adverse consequences on the facial features of patients.

The research on endocrine disrupters has become one of the key directions in the field of environmental medical science. Nonylphenol ethoxylates (NPEs) are widely used in industry and family washing as one of the non-ionic surfactants. NPEs can be degraded biologically to nonylphenol (NP), whose estrogenic effects or toxicity may do harm to the reproductive systems of male fish, amphibians and mammals. Thus it is an urgent affair to develop perfect assays, evaluate the harm of these chemicals to human beings, find the exact mechanism of action and restrict the use of NPEs.

This study investigated the association among male infertility, infection of Ureaplasma urealyticum (Uu), and microelements in semen fluid. Semen analysis and cultivation of Uu are carried out to 165 samples of semen fluid. Then the contents of microelements, such as Cu, Fe, Se, Cd, Mn, and Zn, in the samples are measured respectively by an Inductively Coupled Plasma Quantometer (ICP). The contents of Fe, Se, and Zn in seminal plasma of the normal spermatic quality group are obviously higher than those of the poor spermatic quality group (p<.05), while the content of Cd in seminal plasma of the normal spermatic quality group is obviously lower than that of the poor spermatic quality group (p<.05), and the contents of Cu and Mn show no difference. The contents of Zn, Se, and Cu in seminal plasma infected with Uu are markedly lower than those of seminal plasma not infected with Uu (p<.05), while the content of Cd in seminal plasma infected with Uu is obviously higher than that in samples not infected with Uu, and the contents of Fe and Mn show no statistic difference. The contents of Zn and Se in seminal plasma of the poor spermatic qualitative semen that were infected with Uu are obviously lower than those of seminal plasma not infected with Uu (p<.05), while the content of Cd in seminal plasma of the poor spermatic qualitative semen with Uu infection is markedly higher than that of the normal seminal plasma (p<.05). Uu infection leads to the decrease of the contents of Zn and Se in semen fluid, and therefore causes spermatic quality decline. Lack of Fe or overdose of Cd may also contribute to spermatic quality decline.

The single ion channel signal is stochastic ionic current on the order of 1 pA recorded by patch clamp. Because the weakness of the signal, the background noise always dominates in the recordings, the threshold detector traditionally used in patch clamp to denoise and restore the channel signal can't work satisfactorily. This problem was analyzed mathematically, and a signal restoring and parameters estimating scheme called HMM algorithm was studied. The algorithm has been validated by simulation and the results suggest it performs effectively in the situation of low signal to noise ratio where the threshold detector fails completely.

Nrf2, a member of the "cap 'n collar" group of transcription factors, is important for protecting cells against oxidative damage. We investigated its role in the detoxification of acetaminophen [N-acetyl-p-aminophenol (APAP)]-induced hepatotoxicity. When Nrf2 knockout (Nrf2(-/-)) and wild-type mice were given APAP by i.p. injection, the Nrf2(-/-) mice were highly susceptible to APAP treatment. With doses of APAP that were tolerated by wild-type mice, the Nrf2(-/-) mice died of liver failure. When hepatic glutathione was depleted after a dose of 400 mg/kg of APAP, the wild-type mice were able to compensate and regain the normal glutathione level. In contrast, the glutathione level in the Nrf2(-/-) mice was not compensated and remained low. This was because of the decrease in the gene expression of gcs(H) and gcs(L) as well as gss in the livers of the Nrf2(-/-) mice. In addition, the expression of ugt1a6 and gstpi that detoxify APAP by conjugation was also decreased. This increased susceptibility of the Nrf2(-/-) mice to APAP, because of an impaired capacity to replenish their glutathione stores, compounded with a decreased detoxification capability, highlights the importance of Nrf2 in the regulation of glutathione synthesis and cellular detoxification processes.

Aim: To study the gating kinetics of voltage-dependent K+ channels i n clonal pheochromocytoma (PC12) cells and the effect of nerve growth factor (NGF) on it., Methods: Outward currents of K+ channel were recorded in PC12 cells cultured with or without NGF using cell-attached patch-clamp technique. The kinetic features of K+ channel and the effect of NGF on them were analyzed based on t he fractal model., Results: The fractal dimension D for the closed durations of K+ channel in PC12 cells cultured without NGF was proportional to the absolute value of the pipette potential (Vp). Whereas the fractal dimension D' was inversely proportional to it. Under pipette potentials of 0, -30, -50, and -70 mV, the values of D were 1.75, 1.88, 1.95, and 2; and of D' were 1.51, 1.40, 1.34, and 1.23. After the addition of NGF the changes in the fractal dimensions became more complex. At the same pipette potential, fractal dimensions for K+ channel in PC12 cells cultured with NGF for both the open and closed durations were not greater than those in PC12 cells cultured without NGF. The kinetic setpoints for both the close and open durations did not vary with the pipette potential with values as follows: A (without NGF) = 0.29 +\ -0.05, A(with NGF) = 0.71 +\- 0.06, A' without NGF) = 0.110 +\- 0.020, and A' (with NGF) = 0.38 +\- 0.08., Conclusion: The voltage dependence of D (without NGF) increases the probability of the channel for remaining closed for long durations as the patch is depolarized, and that of D' (without NGF) decreases the probability of the channel for remaining open for long durations as the patch is depolarized. The addition of NG F in the PC12 cell culture accelerates the dynamic process of the K+ channel occurring over long time scales.

Background: von Recklinghausen's neurofibromatosis is a hereditary disease that may affect any organ or system of the body primarily or secondarily, including the vascular system. Among the rare cerebrovascular abnormalities, the most common is stenosis or occlusion of the cerebral artery. Intracranial aneurysms are uncommon., Case Description: A case of an intracranial cerebral aneurysm associated with von Recklinghausen's neurofibromatosis is reported. A 55-year-old woman presented with a history of intermittent headache for 2 months and right oculomotor nerve palsy for 1 month. Widespread cutaneous neurofibromas and angiomas were found over her trunk and limbs with prominent cafe-au-lait spots. X-ray showed that her left lung was compressed by a large mass in the left chest with rib defects and lateral spinal curvature. Right internal carotid angiography revealed a saccular aneurysm between C1 and C2. Craniotomy to clip the aneurysm could not be performed because the mass in her chest made intubation for general anaesthesia almost impossible., Conclusion: The clinical features of this case are discussed together with a review of 15 similar cases in the literature. There are different theories about this disorder. We agree that the malformations are derived not only from ectodermal, but also from mesodermal pathology. In terms of our case, we consider the progression of this disease to be slow.

Hemopoietic stem cells are a distinct population of cells that can differentiate into multilineages of hemopoietic cells and have long-term repopulation capability. A few membrane-bound molecules have been found to be preferentially, but not uniquely, present on the surface of these primitive cells. We report here the identification of a unique 105-kDa glycoprotein on the surface of hemopoietic stem cell line BL3. This molecule, recognized by the absorbed antiserum, is not present on the surface of myeloid progenitors 32D and FDC-P1 cells, EL4 T cells, and NIH 3T3 fibroblasts. This antiserum can also be used to block the proliferation of BL3 cells even in the presence of mitogen-stimulated spleen cell conditioned medium, which is known to have a stimulating activity on BL3 cells. It can also inhibit development of in vitro, fetal liver cell-derived multilineage colonies, but not other types of colonies, and of in vivo bone marrow cell-derived colony-forming unit spleen foci. These data suggest that gp105 plays an important role in hemopoietic stem cell differentiation.

We have established a hemopoietic cell line, BL3, that possesses a rearranged retroviral genome, which we used as a genetic tag for their engraftment into lethally irradiated mice. Analysis of recipients up to 7 months after engraftment indicates that the marker was present in differentiated cells of various hemopoietic organs, in colony-forming cells, pre-CFU-S-forming cells, and in organs of secondary recipients from bone marrow cells of primary recipients. BL3 cells are Thy-1+, Sca-1+, B220-, Mac-1-, and Gr-1-. They express GATA-1 and are able to develop "cobblestones" with stromal cells. They do not express and respond to several hemopoietic growth factors known to facilitate marrow recovery. However, they are negatively regulated by TGF beta and can be stimulated by mitogen-stimulated spleen cell-conditioned medium. We conclude that BL3 cells possess properties of hemopoietic stem cells, including their capability to contribute to long-term repopulation.

We recently showed that hemopoietic stem cells expressing the v-abl oncogene can cause leukemia when injected into lethally irradiated recipient mice. Progenitor cells expressing v-abl did not significantly contribute to disease development, and the leukemia was monoclonal in origin. By serially transplanting v-abl-transduced hemopoietic stem cells into normal, nonirradiated syngeneic recipients, we showed that multiple stem-cell clones do exist in some recipients. These cells fluctuated as normal stem cells do and could home to normal bone marrow. Based on the time course of disease, the recipients developed either an acute or a chronic phase of disorder. All recipients with the acute disease had stem-cell clones with random Abelson murine leukemia virus integration sites. All recipients with the chronic disorder had a specific Abelson murine leukemia virus integration site. We believe this abl-specific integration site, termed ASI, is important in abl-mediated stem-cell leukemogenesis.