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MAX dimerization protein 1 (MAD1) is a transcription suppressor that antagonizes MYC-mediated transcription activation, and the inhibition mechanism occurs mainly through the competition of target genes' promoter MYC binding sites by MAD1. The promoter binding proteins switch between MYC and MAD1 affects cell proliferation and differentiation. However, little is known about MAD1's regulation process in cancer cells. Here, we present evidence that AKT inhibits MAD1-mediated transcription repression by physical interaction with and phosphorylation of MAD1. Phosphorylation reduces the binding affinity between MAD1 and its target genes' promoter and thereby abolishes its transcription suppression function. Mutation of the phosphorylation site from serine to alanine rescues the DNA-binding ability in the presence of activated AKT. In addition, AKT inhibits MAD1-mediated target genes (hTERT and ODC) transcription repression and promotes cell cycle and cell growth. However, mutated S145A MAD1 abrogates the inhibition by AKT. Thus, our results suggest that phosphorylation of MAD1 by AKT inhibits MAD1-mediated transcription suppression and subsequently activates the transcription of MAD1 target genes.

The left ventricular apical systolic dysfunction syndrome was a rare acute cardiac syndrome. Its clinical presentation and electrocardiography were similar to acute myocardial infarction. The syndrome was characterized by transient ventricular wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. Cardiac enzyme was normal or minor elevation. At present, the cause of the syndrome is unknown. In this paper, we describe a 56-year-old female patient. She was admitted in hospital for acute appendititis and the transient left ventricular apical ballooning syndrome. She developed acute heart failure and septic shock in the hospital. The drainage of the appendiceal abscess was done and the heart failure and septic shock recovered completely in a few days.

This study investigated the degradation of anthraquinone reactive dye C.I. Reactive Blue 19 (RB-19) with initial concentration of 100mg L(-1) in aqueous solution by ozone oxidation. The results of UV/VIS and FTIR spectra showed that the anthraquinone structures, nitrogen linkages and amino groups of RB-19 were destroyed under direct ozone reaction. The identification by LC-MS and GC-MS analyses indicated that some organic acids (e.g., phthalic acids) and 1,3-indanone could be the primary degradation products, respectively. The Microtox toxicity of the ozonated RB-19 solution initially increased but subsequently decreased when ozonation time increased. This detoxification accompanied biodegradability enhancement revealed by BOD/COD ratio increasing from 0.15 to 0.33 after 10min of ozonation.

Background/aims: Increased serum iron indices and hepatic iron stores are frequent in patients with chronic hepatitis C (CHC). The antimicrobial peptide hepdicin produced in the liver plays a pivotal role in iron homeostasis., Methodology: To determine the expression of hepcidin, the serum levels of prohepcidin were measured in 58 CHC patients and 144 healthy controls. The hepatic iron stores were scored by Perls' stain on liver biopsy specimens in 39 CHC patients. The serum prohepcidin levels were correlated with biochemical inflammation markers, histological necroinflammation grades, hemoglobin levels and iron status in CHC patients., Results: The concentrations of serum prohepcidin were significantly higher in CHC patients than in healthy controls (142.07 +/- 67.06 vs. 89.07 +/- 37.32 ng/mL, p < 0.001). The CHC patients with positive hepatic iron stains had significantly higher serum prohepcidin levels than the CHC patients without (221.20 +/- 117.74 vs. 123.81 +/- 60.53 ng/mL, p = 0.037). The serum prohepdicin levels were not significantly correlated with the ages (r = -0.041, p = 0.760), hemoglobin (r = 0.127, p = 0.346), alanine aminotransferase (r = -0.032, p = 0.813), transferrin saturation (r = 0.025, p = 0.862), ferritin levels (r = 0.211, p = 0.133) and hepatic inflammation grades (r = 0.153, p = 0.352) in CHC patients., Conclusions: The expression of serum prohepcidin is independent of the degree of hepatic inflammation as measured by the histological activity or aminotransferase level. The serum prohepcidin levels are associated with hepatic iron stains and significantly higher in CHC patients than in healthy controls. Our results suggest that CHC may induce the expression of hepcidin possibly by increased hepatic iron stores.

In the crystal structure of the title compound, C(60)H(70)N(2)O(10)·4CH(3)CN, the calix[4]arene mol-ecule adopts an open-cone conformation with two intra-molecular O-H⋯O hydrogen bonds. The four benzene rings of the calix[4]arene are twisted to the mean plane defined by four methyl-ene C atoms bridging the benzene rings, with dihedral angles ranging from 57.74 (10) to 65.99 (12)°. Two pendant nitro-phenyl rings are nearly perpendicular to each other, the dihedral angle being 70.9 (3)°. The asymmetric unit of the crystal structure contains four acetonitrile solvent mol-ecules, one of which lies in the calix cavity and makes C-H⋯π inter-actions and another links with the calix[4]arene via C-H⋯O hydrogen bonding. One tert-butyl group is disordered over two sets of sites, with a 0.736 (13):0.264 (13) occupancy ratio.

Low power millimeter wave irradiation is widely used in clinical medicine. We describe the effects of this treatment on cultured mesenchymal stem cells (MSCs) and attempted to identify the underlying mechanism. Cells cultured using the whole marrow attachment culture method proliferated dispersedly or in clones. Flow cytometric analyses showed that the MSCs were CD90 positive, but negative for CD45. The negative control group (A) did not express detectable levels of Cbfa1 or Sox9 mRNA at any time point, while cells in the millimeter wave-induced groups (B and C) increasingly expressed both genes after the fourth day post-induction. Statistical analysis showed that starting on the fourth day post-induction, there were very significant differences in the expression of Cbfa1 and Sox9 mRNA between groups A and B as well as A and C at any given time point, between treated groups B and C after identical periods of induction, and within each treated group at different induction times. Transition electron microscopy analysis showed that the rough endoplasmic reticulum of cells in the induced groups was richer and more developed than in cells of the negative control group, and that the shape of cells shifted from long-spindle to near ellipse. Toluidine blue staining revealed heterochromia in the cytoplasm and extracellular matrix of cells in the induced groups, whereas no obvious heterochromia was observed in negative control cells. Induced cells also exhibited positive immunohistochemical staining of collagen II, in contrast to the negative controls. These results show that millimeter wave treatment successfully induced MSCs to differentiate as chondrocytes and the extent of differentiation increased with treatment duration. Our findings suggest that millimeter wave irradiation can be employed as a novel non-drug inducing method for the differentiation of MSCs into chondrocytes.

Germinomas in the central nervous system (CNS) are uncommon tumors and occur usually in the pineal or suprasellar regions. Primary spinal germinoma is extremely rare. Here we reported a rare case of an extramedullary germinoma in a young adult who presented with progressive paraparesis and retention of stool and urine. The MR image features with their differential diagnoses were discussed along with literature review of all previously reported 22 cases.

Myeloid cell leukemia-1 (Mcl-1), a Bcl-2-like antiapoptotic protein, plays a role in cell immortalization and chemoresistance in a number of human malignancies. A peptidyl-prolyl cis/trans isomerase, Pin1 is involved in many cellular events, such as cell cycle progression, cell proliferation, and differentiation through isomerizing prophosphorylated substrates. It has been reported that down-regulation of Pin1 induces apoptosis, and that Erk phosphorylates and up-regulates Mcl-1; however, the underlying mechanisms for the two phenomena are not clear yet. Here, we showed that Pin 1 stabilizes Mcl-1, which is required for Mcl-1 posphorylation by Erk. First, we found expression of Mcl-1 and Pin1 were positively correlated and associated with poor survival in human breast cancer. We then showed that Erk could phosphorylate Mcl-1 at two consensus residues, Thr 92 and 163, which is required for the association of Mcl-1 and Pin1, resulting in stabilization of Mcl-1. Moreover, Pin1 is also required for the up-regulation of Mcl-1 by Erk activation. Based on this newly identified mechanism of Mcl-1 stabilization, two strategies were used to overcome Mcl-1-mediated chemoresistance: inhibiting Erk by Sorafenib, an approved clinical anticancer drug, or knocking down Pin1 by using a SiRNA technique. In conclusion, the current report not only unravels a novel mechanism to link Erk/Pin1 pathway and Mcl-1-mediated chemoresistance but also provides a plausible combination therapy, Taxol (Paclitaxel) plus Sorafenib, which was shown to be effective in killing breast cancer cells.

The crystal structures of the two title thiacalix[4]arene derivatives, C52H64O12S4, (I), and C36H28Br4O12S4, (II), are reported. Compound (I) has crystallographic C2 symmetry and adopts a 1,3-alternate conformation where the four -OCH2CO2Me groups are located alternately above and below the virtual plane (R) defined by the four bridging S atoms. The dihedral angles between the plane (R) and the aromatic rings are 87.17 (7) and 87.60 (8) degrees . Compound (II) has a partial cone conformation in which the pendant -OCH2CO2Me group of the rotated aryl ring is oriented away from the thiacalixarene cavity formed by the other three aryl rings. The dihedral angles between the plane (R) and the aryl rings range from 17.47 (10) to 85.98 (6) degrees . In the supramolecular structure of (II), the molecular components are linked into a two-dimensional framework by a combination of C-H...O hydrogen bonds and C-Br...C interactions. This study demonstrates the usefulness of these motif-generating interactions and thiacalix[4]arene derivatives in crystal engineering.

Objective: To study the effect of inactivated and un-inactivated pharmaco-serum of diabetic rats fed with Chinese herbs Qianggubao decoction on the proliferation of osteoblast cells (OB)cultured in vitro., Methods: OB was isolated from the skull of newly born SD rats aged 1 to 2 days by means of Trypsin-collagenase digestion and identified by image analysis under inverted microscope, V-G collagen staining, ALP staining, calcification nod staining etc. After the OB was identified, in activated and un-inactivated pharmaco-serum of diabetic rats fed with Qianggubao decoction of ferent phase (rats were fed with medicine 3 days or 5 days after last fed with medicine 1 hour or 3 hours) and concentration (5%, 10%, 20%) were added to the OB and incubated. After determined times, the effects of the proliferation of osteoblasts were detected by MTT analysis., Results: There was significant difference between un-inactivated pharmaco-serum and inactivated pharmaco-serum on the proliferation of osteoblasts, and un-inactivated serum had stronger effects to improve the proliferation of osteoblasts (P < 0.01 or P < 0.05)., Conclusion: Un-inactivated and inactivation pharmaco-serum of diabetic rats fed with Chinese herbs Qianggubao decoction can influence the proliferation of, and the un-inactivated pharmaco-serum has stronger effects.

Barrett's esophagus, a columnar metaplasia of the lower esophagus epithelium related to gastroesophageal reflux disease, is the strongest known risk factor for the development of esophageal adenocarcinoma (EAC). Understanding the signal transduction events involved in esophageal epithelium carcinogenesis may provide insights into the origins of EAC and may suggest new therapies. To elucidate the molecular pathways of bile acid-induced tumorigenesis, the newly identified inflammation-associated signaling pathway involving I kappaB kinases beta (IKK beta), tuberous sclerosis complex 1 (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase (S6K1) was confirmed to be activated in immortalized Barrett's CPC-A and CPC-C cells and esophageal cancer SEG-1 and BE3 cells. Phosphorylation of TSC1 and S6K1 was induced in response to bile acid stimulation. Treatment of these cells with the mTOR inhibitor rapamycin or the IKK beta inhibitor Bay 11-7082 suppressed bile acid-induced cell proliferation and anchorage-independent growth. We next used an orthotopic rat model to evaluate the role of bile acid in the progression of Barrett's esophagus to EAC. Of interest, we found high expression of phosphorylated IKK beta (pIKK beta) and phosphorylated S6K1 (pS6K1) in tumor tissues and the Barrett's epithelium compared with normal epithelium. Furthermore, immunostaining of clinical EAC tissue specimens revealed that pIKK beta expression was strongly correlated with pS6K1 level. Together, these results show that bile acid can deregulate TSC1/mTOR through IKK beta signaling, which may play a critical role in EAC progression. In addition, Bay 11-7082 and rapamycin may potentially be chemopreventive drugs against Barrett's esophagus-associated EAC.

Objective: To investigate the effect of Liuwei Dihuang Pill on the number, the surface marker, cell cycle and colony formation of HSC from mouse marrow., Methods: Old Kunming mice were randomly divided into 4 groups: the control group, low, middle and high dose of Liuwei Dihuang Pill group. Then we separated the HSC from marrow after 7 days fed with saline or Liywei Dihuang Pill respectively, numerated monocyte, detected the surface marker and cell cycle of the HSC by FACS and tested the colony forming by semisolid media culture., Results: Among the four groups, there was no obvious difference in the number of MNC, suspended cell and colony. The expression of Sca-1 and CD34 increased in the low and middle dosage group, it meant that the number of HSC elevated by low and middle dosage medicine. The ability of cell proliferation was also higher in the three dosage groups., Conclusion: Liuwei Dihuang Pill activates HSC by increasing the number, proliferation and function of more primitive HSC.

Objective: The purpose of this study was to investigate the relationship between a series of portal hemodynamic parameters obtained with Doppler ultrasonography and portal pressure measured directly from patients with portal hypertension (PHT)., Methods: Fifty-seven patients with a clinical diagnosis of PHT who accepted surgical therapy were investigated. The portal pressure was measured directly intraoperatively. Relevant parameters were compared and measured, including the hepatic artery pulsatility index (HAPI), hepatic artery resistive index (HARI), splenic artery resistive index, splenic artery pulsatility index (SpAPI), congestion index (CI) of the portal vein, hepatic buffer index (HBI), liver vascular index (LVI), and PHT index (PHI)., Results: Doppler parameters for the postprandial HAPI, SpAPI, CI, LVI, HBI, and PHI were statistically different in patients with PHT and healthy control subjects (P<0.05). The portal pressure was significantly correlated with the HARI (r=0.699; P<.001), HAPI (r=0.582; P<.001), LVI (r=-0.501; P=.003), HBI (r=0.441; P=.009), and Child-Pugh scores (r=0.589; P=.044)., Conclusions: The HAPI, LVI, and HBI are indicative indices in patients with PHT, suggesting that color Doppler ultrasonography can be used as a noninvasive evaluation method for PHT degree. The changes in the HAPI, LVI, and HBI that accompany the increase in portal pressure can reflect hepatic resistance and hepatic artery buffer capacity accurately.

Objective: To investigate the effect of folic acid on homocysteine (Hcy)-induced chemokine secretion and NADPH oxidase activity in human monocytes., Methods: Human monocytes from healthy volunteers were incubated with Hcy (100 micromol/L) with or without folic acid (5 micromol/L) for 24 h; MCP-1 and IL-8 were assessed by ELISA. DCFH-DA was added to monitor intracellular ROS production on confocal microscopy. A cytochrome c reduction assay was used to measure NADPH oxidase activity., Results: The Hcy-induced secretion of MCP-1 and IL-8 was significantly reduced by folic acid [(1.88 +/- 0.51) ng/ml vs. (4.36 +/- 0.72) ng/ml vs. (2.40 +/- 0.60) ng/ml and (4.9 +/- 1.9) ng/ml vs. (12.7 +/- 1.5) ng/ml vs. (7.2 +/- 1.9) ng/ml, all P < 0.05]. The Hcy-induced production of ROS was also significantly attenuated by folic acid. Moreover, the Hcy-induced NADPH oxidase activity increase was significantly inhibited by cotreatment with folic acid., Conclusion: Folic acid may attenuate oxidative stress induced by Hcy by reducing NADPH oxidase activity in monocytes.

TNFalpha has recently emerged as a regulator linking inflammation to cancer pathogenesis, but the detailed cellular and molecular mechanisms underlying this link remain to be elucidated. The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis. Here we show that IKKbeta, a major downstream kinase in the TNFalpha signaling pathway, physically interacts with and phosphorylates TSC1 at Ser487 and Ser511, resulting in suppression of TSC1. The IKKbeta-mediated TSC1 suppression activates the mTOR pathway, enhances angiogenesis, and results in tumor development. We further find that expression of activated IKKbeta is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. Our findings identify a pathway that is critical for inflammation-mediated tumor angiogenesis and may provide a target for clinical intervention in human cancer.

Objective: To investigate the effect of Xuefu Zhuyu Decoction (XFZYD) on the number, phenotype, cell cycle and colony formation of bone marrow hematopoietic stem cells (HSC) in mice., Methods: Kunming mice were randomly divided into 4 groups: the control group, the low- (3.25 g/kg), middle- (6.5 g/kg) and high-dose (13.0 g/kg) XFZYD groups. After they were medicated by gastrogavage respectively with saline or corresponding dose of XFZYD for 7 days, their bone marrow HSC were separated and counted. The phenotype Sca and cell cycle of HSC were detected by flow cytometer, and the colony formation was determined with semisolid methyl media culture., Results: No obvious difference in the number of mononuclear cell, suspended cell and colony production was found among all the groups (P > 0.05); while the expression of CD34 and Sca-1 increased in the low-dose XFZYD group, but in the middle-dose XFZYD group increase only showed in Sca-1 expression., Conclusion: XFZYD plays a role of removing blood stasis and promoting regeneration through improving hematopoietic function by means of increasing the number and enhancing the function of premature HSC.

Apoptosis is critical for embryonic development, tissue homeostasis, and tumorigenesis and is determined largely by the Bcl-2 family of antiapoptotic and prosurvival regulators. Here, we report that glycogen synthase kinase 3 (GSK-3) was required for Mcl-1 degradation, and we identified a novel mechanism for proteasome-mediated Mcl-1 turnover in which GSK-3beta associates with and phosphorylates Mcl-1 at one consensus motif ((155)STDG(159)SLPS(163)T; phosphorylation sites are in italics), which will lead to the association of Mcl-1 with the E3 ligase beta-TrCP, and beta-TrCP then facilitates the ubiquitination and degradation of phosphorylated Mcl-1. A variant of Mcl-1 (Mcl-1-3A), which abolishes the phosphorylations by GSK-3beta and then cannot be ubiquitinated by beta-TrCP, is much more stable than wild-type Mcl-1 and able to block the proapoptotic function of GSK-3beta and enhance chemoresistance. Our results indicate that the turnover of Mcl-1 by beta-TrCP is an essential mechanism for GSK-3beta-induced apoptosis and contributes to GSK-3beta-mediated tumor suppression and chemosensitization.

Myeloid cell leukemia-1 (Mcl-1), an antiapoptotic Bcl-2 family member, is overexpressed in many types of human cancer and associates with cell immortalization, malignant transformation, and chemoresistance. Glycogen synthase kinase-3beta (GSK-3beta), a key component of the Wnt signaling pathway, is involved in multiple physiologic processes such as protein synthesis, tumorigenesis, and apoptosis. Here, we report that expression of Mcl-1 was correlated with phosphorylated GSK-3beta (p-GSK-3beta) at Ser(9) (an inactivated form of GSK-3beta) in multiple cancer cell lines and primary human cancer samples. In addition, Mcl-1 was strikingly linked with poor prognosis of human breast cancer, in which the high level of Mcl-1 was related to high tumor grade and poor survival of breast cancer patients. Furthermore, we found that activation of GSK-3beta could down-regulate Mcl-1 and was required for proteasome-mediated Mcl-1 degradation. Under some physiologic conditions, such as UV irradiation, anticancer drug treatment, and inhibition of growth factor pathways, Mcl-1 was down-regulated through activation of GSK-3beta. Our results indicate that Mcl-1 stabilization by GSK-3beta inactivation could be involved in tumorigenesis and serve as a useful prognostic marker for human breast cancer.

Hyperglycemia, advanced glycation end products (AGEs), hyperinsulinemia and dyslipidemia may play roles in the development of diabetes-associated atherosclerosis and post-angioplasty restenosis. Clinically, their effects seem to be synergic. However, few studies have focused on the synergistic action of these factors. In the present study, we investigated whether glycated serum albumin (GSA) has a synergistic effect with insulin on the proliferation of vascular smooth muscle cells (VSMCs). VSMCs were isolated from rat thoracic aortas and cultured in fetal bovine serum (FBS)-free medium for 24 h, then exposed to GSA, insulin or GSA + insulin for 48 h with or without pretreatment of mitogen-activated protein kinase (MAPK) inhibitors or the antioxidant N-acetylcysteine (NAC). Cell growth rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or cell counting. The changes of phosphorylated-p38 MAPK and phosphorylated-C-Jun N-terminal kinase 1/2 (JNK1/2) were measured by Western blot analysis. The results showed that only p38 MAPK, but not JNK was activated by GSA and insulin co-incubation. VSMC proliferation was increased by insulin (10-1000 nmol/L) or GSA (10, 100 microg/mL). Co-incubation of insulin (100 nmol/L) and GSA (100 mug/mL) caused a more potent increase in VSMC proliferation than insulin or GSA incubation alone. p38 MAPK inhibitor, SB203580, as well as NAC, could inhibit the VSMC proliferation induced by co-incubation of GSA and insulin. The results show that insulin enhances GSA-induced VSMC proliferation, which may be mediated through a reactive oxygen species (ROS)-p38 MAPK pathway. The synergism of AGEs and insulin may play a detrimental role in the pathogenesis of diabetic atherosclerosis and post-angioplasty restenosis.

Objective: To investigate the anti-apoptotic effects of mesenchymal stem cells (MSCs) on hypoxia-injured cardiac myocytes., Methods: MSCs were isolated from the bone marrow of 6 - 8 week-old Sprague-Dawley rats. Cardiac myocytes from neonatal rat were cultured under hypoxia, then the hypoxia-injured cardiac myocytes were divided into 3 groups: cultured alone (control group), co-cultured with the MSCs, or co-cultured in MSC-conditioned media in conditions of anoxia (95% N(2) + 5% CO(2), continuous hypoxia group) or normoxia [hypoxia/reoxygen (H/R) group] for 72 hours. The cell apoptosis was measured by Hoechst staining, and Western blotting was used to test the protein expression of Bcl-2 and Bax in the cardiac myocytes., Results: The apoptotic rate of the cardiac myocytes cultured under hypoxia was 51.6% +/- 2.4%, significantly higher than those of the cardiac myocytes co-cultured with MSCs and MSC-conditioned media respectively (15.1% +/- 5.4% and 24.0% +/- 4.2% respectively, both P < 0.001). The apoptotic rate of the H/R group was 20.9% +/- 2.7%, significant higher than that of the MSC group (11.5% +/- 3.7%, P < 0.05), however, not significantly different from that of the MSC-conditioned media group (20.1% +/- 4.2%, P > 0.05). The protein expression of Bcl-2 was not significantly different among different groups. The Bax protein expression of the MSC group and MSC-conditioned media group were 2.28 +/- 0.46 and 3.01 +/- 0.26 respectively, both significantly lower than that of the control group (7.62 +/- 1.28, both P < 0.05). The decreased expression of Bax in the cardiac myocytes was greatly related to the decreasing of apoptosis., Conclusion: Co-cultured MSCs show significant anti-apoptotic effects on cardiac myocytes both in continuous hypoxia and in H/R conditions with the possible mechanism of direct cell to cell interaction and paracrine of cytokines which effect the expression of Bax in the myocytes.

A female patient, aged 62 years, unexpectedly swallowed a removable partial denture (RPD) during the supper. The doctor failed to take out the RPD from her stomach under the gastroscope during the emergency treatment at the first day. 2 days later, the PRD blocked the intestinal tract and its metal clasps penetrated the wall of the intestine near the ileocecal junction, it soon leaded to enterobrosis and diffuse peritonitis. At last, abdominal operation was conducted to take the RPD out from the intestine and enterobrosis was patched up successfully. Diffuse peritonitis was also cured by intravenous infusion of antibiotics for about 1 week.

Niuhuang Jiedu tablets were digested with HNO3-H2O2 system by microwave digestion. The fourteen trace elements of As, Ca, Mg, Al, Mn, Sr, Ba, Se, Ni, Cd, Cu, Zn, Mo and Pb in the solution were determined by ICP-AES. The ICP-AES result proved to be reliable by adding standard recovery experiment to the process. By comparison with the result of chemical experiment, thr present method was accurate, quickly-accessible, and convenient. It was used for Niuhuang Jiedu tablets with result satisfactory.

Objective: To investigate whether hyperthermia can enhance the killing effect of 5- fluorocytosine (5- FC) on human colorectal carcinoma cell lines SW480 transfected with carcinoembryonic antigen (CEA) tissue- specific cytosine deaminase (CD) gene in vitro,and study its mechanism., Methods: Human colorectal carcinoma cell lines SW480 transfected with G1CEACDNa were cultured. The proliferated colonies were treated with the combined therapy of 5-FC and hyperthermia at a temperature of 43 degrees C for 30 min. After eight days, MTT was used to calculate the cellular survival rate,to analyze the killing effect of 5-FC combined with hyperthermia on SW480 cells transfected with CD gene. Flow cytometry was performed to analyze the cellular cycle and transmission electron microscope was used to observe the morphologic changes of SW480 cells after thermochemotherapy., Results: Hyperthermia combined with 5-FC had an enhanced killing effect on SW480-CEACD cells than 5-FC alone (P< 0.05, t =2.403, n=9). Flow cytometry revealed that the proportion of S stage cell increased in the group treated with hyperthermia and 5- FC (P< 0.001, t =7.158, n=6). Transmission electron microscope showed apoptosis after thermo- chemotherapy., Conclusions: Hyperthermia can improve the anti- tumor effect of 5- FC on human colorectal carcinoma cell lines SW480 transfected with CD gene, and the cells were blocked at S stage of cellular cycle and apoptosis was induced following thermochemotherapy.

Objective: To observe the changes of nuclear factor-kappa B (NF-kappaB) in the course of N-methyl-N-nitrosourea (MNU)-induced apoptosis of rat retinal photoreceptor cells and investigate the mechanism of MNU-induced retinal damage., Methods: A single intraperitoneal injection of 60 mg/kg MNU was given to 50-day-old female rats, which were sacrificed at different intervals after MNU treatment. The retinal damage was examined with optical microscopy and photoreceptor cell apoptosis detected by TUNEL assay. Western blotting was performed to analyze the changes in NF-kappaB., Results: Pyknosis of the photoreceptor cell nuclei and disorientation of the outer segment of the photoreceptor layer was observed 24 h after MNU treatment, and the outer nuclear layer and photoreceptor layer were almost completely lost on day 7. Photoreceptor cell apoptosis peaked at 24 h, and in the apoptotic cascade, NF-kappaB p65 protein was only detected 12 and 24 h after MNU treatment, whereas the amount of I kappa B alpha, in contrast, markedly increased in the cytoplasm as well as in the nuclei., Conclusion: MNU-induced retinal damage might be mediated through the signaling pathway of NF-kappaB/I kappa B alpha.

Retinoic acid receptor responder 1 (RARRES1) is a retinoid regulated gene. Its expression is frequently down-regulated through DNA hypermethylation in several types of malignant tissues. This study investigated the clinical significance of RARRES1 protein and its association with RARRES3 protein expression in 161 (26 adenoma, 13 distal normal mucosa and 122 primary colorectal adenocarcinoma) paraffin-embedded colorectal tissues by immunohistochemistry. RARRES1 protein was detected at the highest levels in terminally differentiated cells of normal mucosal tissues and all 26 adenoma tissues. Among 122 colorectal adenocarcinomas, the poorly differentiated adenocarcinomas and Dukes' stage D tumours showed a significant decrease in RARRES1 expression (P < 0.001 and P < 0.01, respectively). RARRES1 expression was significantly (P < 0.001) correlated with RARRES3 expression, which was positively associated with tumour differentiation (P < 0.001). Difference in expression of RARRES1 among 119 patients had no apparent effect on patient survival. Our results suggest the role of RARRES1 in colorectal epithelial differentiation, and the down-regulation of RARRES1 is related to stage D progression.

Objective: To determine the expression of MMP2 mRNA in oral verruvous carcinoma and squamous cell carcinoma., Methods: Thirty cases were divided into 3 groups: verruvous carcinoma (n = 10), well-differentiated squamous cell carcinoma (n = 15) and moderately or poorly differentiated squamous cell carcinoma (n = 5). Reverse transcription polymerase chain reaction (RT-PCR) was used to test the expression of MMP2 mRNA in the carcinoma tissues and matched normal tissues from 3 groups above., Results: The expression of MMP2 mRNA in the carcinoma tissues was significantly higher than that in their matched normal tissues (P < 0.05). The expression of MMP2 mRNA in verruvous carcinoma was significantly higher than that in well-differentiated and moderately or poorly differentiated squamous cell carcinoma (P < 0.05). However, the expression of MMP2 mRNA was not obviously different between well-differentiated and moderately or poorly differentiated squamous cell carcinoma (P > 0.05)., Conclusion: The expression of MMP2 mRNA in oral verruvous carcinoma and squamous cell carcinoma tissues was significantly higher than that in their matched normal tissues. The expression of MMP2 mRNA in verruvous carcinoma was significantly higher than that in squamous cell carcinoma.

We report the case of a 47-year-old male patient who suffered from a malignant phyllodes tumor of the prostate with invasion to the rectum and urinary bladder. The local recurrence at the left scrotum was identified 6 years after radical cystoprostatectomy. Another 2 years after radical orchiectomy showed no evidence of secondary local recurrence or distant metastasis. Histopathologically, both primary and recurrent tumors showed an admixture of stromal and glandular components. However, while extensive squamous metaplasia was identified in the primary tumor, the recurrent tumor had only focal and mild squamous metaplasia. No dependable prognostic factor has been found to date. Here, we describe the morphological features and immunohistochemical presentations of malignant phyllodes tumor of the prostate and review the literature.

Objective: To evaluate the value of combining TIMI myocardial perfusion (TMP) grading with sum ST segment resolution (sumSTR) in prediction of the 2-year outcome and heart function in patients with acute myocardial infarction (AMI) after emergency percutaneous intervention (PCI)., Methods: Seventy-seven consecutive patients of AMI with elevated ST segment, 62 males and 15 females, aged 63 +/- 12 (30-91), underwent PCI. TMP grading was used in combination of electrocardiography to calculate the sumSTR so as to evaluate the effect of myocardial reperfusion. The patients with TMP grade 2-3 and sumSTR > or = 30% were included in the group of better perfusion, and those with the TMP grade 0-1 and sumSTR < 30% were included in the group of lower perfusion. The cardiac events, including death, reinfarction, revascularization, angina pectoris, and heart failure were recorded. The left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) were measured by echocardiography 72 hours and 2 years after the PCI., Results: There were 37 patients in the lower perfusion group and 39 patients in the better perfusion group. Cos regression showed that TMP grade 0-1 associated with sumSTR < 30% was an independent factor for 2-year cardiac events (RR = 13.186, 95% CI 2.149 - 80.917, P = 0.005). The LVEDD 2 years after PCI was 60 mm +/- 4 mm, significantly higher than that 72 hours after PCI (53 mm +/- 4 mm. P < 0.01) in the lower perfusion group. The LVEDD increased by 7.1 mm +/- 1.9 mm two years after PCI in the lower perfusion group, significantly more than that in the better perfusion group (1.5 mm +/- 1.2 mm, P < 0.01). The myocardial perfusion after PCI was closely correlated with the extent of heart function improvement 2 years after (chi(2) = 50.58, P < 0.01)., Conclusion: TMP grading combined with sumSTR helps predict the 2-year outcome and heart function in the patients with AMI after emergency PCI.

Bone marrow monocytic nodules (MNs) can occur in various myeloid disorders. This retrospective review identified 21 patients with myelodysplasia who had unusual and distinct MNs. Eight patients had chronic myelomonocytic leukemia (CMML); 4 had acute myeloid leukemia (AML); and 9 had myelodysplastic/myeloproliferative diseases. In each case, the cells forming MNs expressed strong CD68. MNs appeared to persist even after aggressive chemotherapy, including conventional chemotherapy for 2 AML patients and high-dose chemotherapy preceding allogeneic bone marrow transplantation for 1 CMML patient. Thirteen of 21 patients (62%) died, and acute leukemic transformation was the main cause of death in 3 of 8 patients with CMML. The median survival of the 20 patients with appropriate follow-up was 9.8 months. Our findings demonstrate that MNs are associated with CMML, AML, myelodysplastic syndromes, and myeloproliferative diseases and suggest that MNs are resistant to intensive chemotherapy and patients with bone marrow MNs have a poor prognosis., (Copyright (c) 2005 Wiley-Liss, Inc.)

Aim: To study the protective effect of ligustrazine against photoreceptor cell injury induced by N-methyl-N-nitrosourea (MNU) in Sprague-Dawley (SD) rats., Methods: Ligustrazine injections of different doses were injected intraperitoneally into 47-day female SD rats once a day and a single intraperitoneal injection of MNU 60 mg x kg(-1) was given to 50-day rats. At different intervals after MNU treatment,the animals were sacrificed. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling at 24 h following MNU treatment; peripheral retinal damage was evaluated based on retinal thickness at the d 7 after MNU treatment, and the expression of c-jun and c-fos genes was detected by RT-PCR technique., Results: Ligustrazine injection could remarkably increase total thickness of peripheral retina and decrease apoptotic index of photoreceptor cells induced by MNU in a dose-dependent manner. Compared with MNU-treated rats, the gene expression of c-jun and c-fos was time-dependently down-regulated in ligustrazine-treated group., Conclusion: Ligustrazine injection partially protects against MNU-induced retinal damage by down-modulating the expression of c-jun and c-fos genes to inhibit apoptosis of photoreceptor cells.

Background: Previous studies have showed that photooxidative stress can lead to down-modulation of nuclear factor-kappa B (NF-kappaB) activity causing apoptosis of cultured photoreceptor cells. This study aimed at investigating whether NF-kappaB 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-kappaB 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-kappaB p65 were only detected after MNU treatment for 12 and 24 hours in the nucleus. Conversely, the amounts of IkappaBalpha were markedly increased in the cytoplasm as well as in the nucleus. The activity of NF-kappaB 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-kappaB p65.

Aurora-A, a mitotic serine/threonine kinase with oncogene characteristics, has recently drawn intense attention because of its association with the development of human cancers and its relationship with mitotic progression. Using the gene expression profiles of Aurora-A as a template to search for and compare transcriptome expression profiles in publicly accessible microarray data sets, we identified HURP (encodes hepatoma upregulated protein) as one of the best Aurora-A-correlated genes. Empirical validation indicates that HURP has several characteristics in common with Aurora-A. These two genes have similar expression patterns in hepatocellular carcinoma, liver regeneration after partial hepatectomy, and cell cycle progression and across a variety of tissues and cell lines. Moreover, Aurora-A phosphorylated HURP in vitro and in vivo. Ectopic expression of either the catalytically inactive form of Aurora-A or the HURP-4P mutant, in which the Aurora-A phosphorylation sites were replaced with Ala, resulted in HURP instability and complex disassembly. In addition, HURP-wild-type stable transfectants were capable of growing in low-serum environments whereas HURP-4P grew poorly under low-serum conditions and failed to proliferate. These studies together support the view that the ability to integrate evidence derived from microarray studies into biochemical analyses may ultimately augment our predictive power when analyzing the potential role of poorly characterized proteins. While this combined approach was simply an initial attempt to answer a range of complex biological questions, our findings do suggest that HURP is a potential oncogenic target of Aurora-A.

Aim: To evaluate the effect of tetramethylpyrazine (TMP) injection on retinal damage induced by N-methyl-N-nitrosourea (MNU) in rats and on nuclear factor-kappa B (NF-kappaB) family members., Methods: Female Sprague-Dawley (SD) rats were randomly divided into groups: (i), control group; (ii), model group; and (iii), TMP-injection groups, in which the rats were subdivided into 40 mg/kg, 80 mg/kg and 160 mg/kg groups. Drugs were injected ip into 47-day-old SD rats once a day. At 50 days of age, all rats in the model group and drug groups also received a single ip injection of 60 mg/kg MNU. Rats in group 1 received ip injection of physiological saline. All rats were killed at different times after MNU or physiological saline treatment. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling; retinal damage was evaluated based on retinal thickness and the expression of NF-kappaB family members was detected by Western blot., Results: TMP injections, in a dose-dependent manner, suppressed photoreceptor cell apoptosis and decreased its loss in the peripheral retina. As compared with the MNU-treated group, TMP injection at a dose of 160 mg/kg also time-dependently upregulated the NF-kappaB/p65 protein level in the nucleus and downregulated the IkappaBalpha protein level in the cytoplasm. However, no protective effect of TMP injection on MNU-induced central retinal damage was found., Conclusion: TMP injection partially protects against MNU-induced retinal damage by upregulating the nuclear translocation of p65 to inhibit photoreceptor cells apoptosis.

Background: Retinoid-inducible gene I (RIG1) is a growth regulator protein that exhibits activities to suppress cellular growth and induce cellular differentiation and apoptosis. This study analyzed the expression and regulation of RIG1 in breast cancer cells in vitro and in vivo., Materials and Methods: Expression of RIG1 RNA in breast cancer tissues was analyzed using RNA in situ hybridization. Regulation of RIG1 expression by 17beta-estradiol (E2) was analyzed by semi-quantitative reverse transcription polymerase chain reaction., Results: RIG1 expression in 47 breast cancer tissues was detected mostly in the cytoplasm and in some nuclei. Levels of both cytoplasmic and nuclear RIG1 mRNA were significantly lower in 20 estrogen receptor-positive (ER+) than in 27 ER-negative (ER-) tissues (p < 0.05), in 20 progesterone receptor-positive (PR+) than in 27 PR-negative (PR-) tissues (p < 0.01), and in 14 ER+/PR+ than in 21 ER-/PR-tissues (p < 0.05). Basal levels of RIG1 and ER mRNA were inversely related between ER+ (MCF-7 WS8 and ZR75-1) and ER- (ZR-75-30) breast cancer cells. E2 (1 nM) treatment for two days suppressed RIG1 mRNA levels in MCF-7 WS8 and ZR-75-1 cells, but not in the ER- ZR-75-30 cells. The E2-mediated down-regulation of RIG1 expression was time- and concentration-dependent in ZR-75-1 cells., Conclusion: The negative association between RIG1 and ER expression in breast cancer tissues and down-regulation of RIG1 by E2 in breast cancer cells in vitro suggest that RIG1 expression is negatively regulated by E2 through activation of the ER in ER+ breast cancer cells.

Objective: To investigate the changes of electrocardiogram (ECG) and impact of early invasive strategy in patients with acute coronary syndrome (ACS) without ST-segment elevation., Methods: Five hundred and forty-five consecutive ACS patients without ST-segment elevation were randomly assigned to early conservative treatment group and early invasive treatment group. The combined cardiovascular events, including cardiac death, nonfatal myocardial infarction, nonfatal heart failure, and re-hospitalization due to recurrent ischemia angina, within 30 days and 6 months were analyzed and the effects of varied ECG changes and different intervention strategies on outcomes of patients were evaluated., Results: The incidences of each and combined cardiovascular events were higher in the patients with ST-segment depression than in those without ST-segment depression. ST-segment depression was one of independent predictive factors for an increase in cardiovascular events within 6 months (OR 3.864, 95% CI: 1.668 approximately 9.451, P < 0.001). Early invasive strategy was associated with a lower rate of re-hospitalization due to recurrent ischemia angina within 30 days and a decreased incidence of combined cardiovascular events within 30 days and 6 months in comparison with the early conservative treatment group (all P < 0.05). Subgroup analysis implied that incidences of combined cardiovascular events within 30 days and 6 months decreased significantly only in patients with ST-segment depression treated with early invasive strategy, and no such benefit was seen in the patients without ST-segment depression., Conclusion: ST-segment depression is an effective indicator for identifying those patients with non-ST segment elevation ACS most likely to benefit from early invasive strategy. Early invasive strategy markedly decreases the cardiovascular events in ACS patients with ST-segment depression than early conservative strategy.

Human Aurora kinases have three gene family members: Aurora-A, Aurora-B, and Aurora-C. It is not yet established what the specificity of these kinases are and what signals relayed by their reactions. Therefore, we employed small pool expression screening to search for downstream substrates of Aurora-A. Interestingly, all of the identified Aurora-A substrates were resistant to serve as substrates for Aurora-B or Aurora-C, suggesting that these Aurora family members may have distinct substrate specificity for propagation of diverse signaling pathways, even though they share a conserved catalytic kinase domain. Of the candidate substrates, Aurora-A could increase the functional activity of RalA. Mutational analysis revealed that RalA-Ser194 was the phosphorylation site for Aurora-A. Ectopic expression of V23RalA-WT could enhance collagen I-induced cell migration and anchorage-independent growth in Madin-Darby canine kidney (MDCK) Aurora-A stable cell lines. In contrast, overexpression of V23RalA-S194A in MDCK Aurora-A-stable cell lines abolished the intrinsic migration and transformation abilities of Aurora-A. To our knowledge, this is the first systematic search for the downstream substrates of Aurora-A kinase. Moreover, these results support the notion that Aurora-A may act in concert with V23RalA through protein phosphorylation on Ser194 to promote collagen I-induced cell motility and anchorage-independent growth in MDCK epithelial cells.

Objective: To evaluate the effect of compound branch chain amino acids injection (Aminic) on protein metabolism in patients with radical resection of cardiac carcinoma., Methods: Eighty patients with radical resection of cardiac carcinoma were randomly divided into two groups:study group (40 cases) with compound branch chain amino acids injection (Aminic), and control group(40 cases) with amino acids(MPR- F). The patients received total parenteral nutrition with equal calorie and nitrogen from 1st-7th days after operation by central or peripheral vein with infusing time over 12 hours per day. The change of body weight was observed. The serum levels of total protein, albumin,pre-albumin,transferring, and fibronectin were measured., Results: The body weight was decreased in the two groups after operation, while compared with the study group,the body weight was significantly decreased in the control group (P=0.0250). The positive nitrogen balance recovered two days earlier in study group than that in the control group. Decrease of total protein,albumin were more severe in the control group than those in study group (P=0.0446,P=0.0314 respectively). Compared with the control group,the level of Valine was increased (P=0.0073),and the level of Arginine was decreased more obviously in the study group (P= 0.0212)., Conclusion: The compound branch chain amino acids injection (Aminic) is more beneficial for patients with radical resection of cardiac carcinoma to correct negative nitrogen balance,it can also inhibit decomposition of muscles protein,and improve nutritional conditions.

Aim: To analyze the expression of retinoic acid receptor responder 3 (RARRES3) protein in paraffin-embedded tissues of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), and the correlation of RARRES3 production with tumor differentiation., Methods: Expression of RARRES3 in tissues from 21 CC (10 well-, 7 moderately- and 4 poorly-differentiated) and 32 HCC was determined by immunohistochemistry., Results: Among 21 CC tissues, RARRES3 was detected in 8 (80%) of 10 well-differentiated tumors. Only 2 (18.2%) out of 11 tumors with moderate or poor differentiation showed positive RARRES3 expression. RARRES3 expression in well-differentiated CC was significantly higher than that in tumors with moderate or poor differentiation (Fisher exact test, P<0.01). Expression of RARRES3 was not different between early (I and II) and late (III and IV) stages of CC. Among 30 HCC tissues, 17 (56.7%) weakly expressed RARRES3 in HCC cells, and 25 (83.3%) normal tissues adjacent to HCC expressed the protein. RARRES3 expression was significantly decreased in HCC tissues compared to that in adjacent normal tissues (logistic regression analysis, OR = 0.27, 95% CI (0.11-0.62), P<0.01)., Conclusion: Expression of RARRES3 is positively correlated to well-differentiated CC, which supports the role of RARRES3 in malignant epithelial differentiation of the tumor. The decrease in RARRES3 expression in tissues of HCC and CC with moderate and poor differentiation suggests that altered RARRES3 expression may play a role in the carcinogenesis of the liver and biliary tract.

Background: Cardiovascular diseases, especially coronary artery disease (CAD), are major causes of death in industrialized countries. Elevated concentrations of plasma homocysteine (Hcy) have been associated with an increased risk of CAD. Increased plasma levels of chemokine, characterized by their ability to induce migration and activation of leukocytes, may contribute to the pathogenesis of CAD. This study was designed to investigate the changes of plasma Hcy, monocyte chemoattractant protein-1 (MCP-1) and oxidative stress markers in acute coronary syndrome patients., Methods: A total of 149 subjects were divided into four groups: 50 patients with unstable angina, 30 patients with acute myocardial infarction, 20 coronary restenosis patients after percutaneous coronary intervention and 49 healthy control subjects. Plasma levels of Hcy, MCP-1, malondialdehyde and superoxide dismutase were measured., Results: Plasma levels of Hcy and MCP-1 showed significant increases in unstable angina, acute myocardial infarction and restenosis patients compared with control subjects (P < 0.05, respectively). Plasma levels of malondialdehyde were significantly increased in unstable angina and acute myocardial infarction patients when compared with control subjects (P < 0.05, respectively). Plasma superoxide dismutase levels were significantly reduced in acute myocardial infarction patients when compared with control group (P < 0.01)., Conclusion: Hcy might act as an atherogenic factor through promoting chemokine, reactive oxygen species and oxidized low density lipoprotein production and thereby convert a stable plaque into an unstable potentially occlusive lesion.

F-box proteins, components of SCF ubiquitin-ligase complexes, are believed to be responsible for substrate recognition and recruitment in SCF-mediated proteolysis. F-box proteins that have been identified to function in the SCF complexes to date mostly have substrate-binding motifs, such as WD repeats or leucine-rich repeats in their C termini. However, many F-box proteins lack recognizable substrate-binding modules; whether they can function in the SCF complexes remains unclear. We show here that Fbx7, an F-box protein without WD repeats and leucine-rich repeats, is required for the proteasome-mediated proteolysis of the hepatoma up-regulated protein (HURP). Depletion of Fbx7 by small interfering RNA leads to depression of HURP ubiquitination and accumulation of HURP abundance. In the SCF(Fbx7) complex, Fbx7 recruits HURP through its C-terminal proline-rich region in a Cdk1-cyclin B-phosphorylation dependent manner. Mutation of the multiple Cdk1-cyclin B phosphorylation sites on HURP or the proline-rich region of Fbx7 abolishes the association between Fbx7 and HURP. Thus, Fbx7 is a functional adaptor of the SCF complex with a proline-rich region as the substrate-binding module. In addition to Fbx7, data base analyses reveal two putative mammalian proline-rich region-containing F-box proteins, KIAA1783 and RIKEN cDNA 2410015K21. Taken together, these findings further expound the diverse substrate-recognition abilities of the SCF complexes.

We measured tissue oxygen saturation (StO2) changes during a post-occlusive reactive hyperemia (PORH) test on lower extremities of peripheral vascular disease (PVD) patients and healthy controls. The StO2 changes were measured by the near-infrared tissue oximeter prototyped by ViOptix Inc. We found that PVD indicators may include the post-occlusive StO2 reperfusion rate, the time duration of the reperfusion phase in a PORH test, and the StO2 dispersion rate in reactive hyperemia. We suggest critical values of these indicators for PVD assessments., (Copyright 2004 IOS Press)

Reactive oxygen species (ROS) is involved in autoimmune destruction of islet beta cells, which has been proven to be an important underlying pathogenesis for insulin dependent diabetes mellitus (IDDM). Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide, which has been found to play an important role in protecting myocytes from ROS. We hypothesized that exogenous CGRP gene administration before the pathogenic stage of insulitis might suppress the production of ROS and provide a hopeful therapeutic intervention for autoimmune diabetes. We performed CGRP gene transfer by injecting naked plasmid directly into skeletal muscles of mice with electroporation enhancement to achieve a continuous expression of CGRP in skeletal muscles, and thereby its secretion into the circulation. The effect of CGRP gene transfer on the pathogenesis of diabetes was studied in autoimmune diabetic mice induced by multiple low dose streptozotocin (MLDS). The CGRP gene therapy decreased morbidity of autoimmune diabetes, and significantly ameliorated hyperglycemia in these mice. CGRP gene transfer inhibited the production of ROS and malondialdehyde (MDA). In addition, it enhanced the activity of catalase (CAT) and superoxide dismutase (SOD) significantly. The data suggest that intramuscular CGRP gene transfer ameliorates autoimmune destruction of islet beta cells, resulting in significant reduction in diabetes incidence of MLDS diabetes mice. CGRP benefits might be mediated at least in part by inhibiting the oxidative stress in islet beta cells of these mice.

Previously, 4 cases of myelodysplastic syndrome were reported that had unusual, distinct monocytic nodules in bone marrow. The monocytic nodules, predominantly composed of monocytes with CD68+ immunostaining, had no or low expression of Ki-67 and topoisomerase II alpha. The purpose of the present study was to further define the associated clinical diseases, histologic features, and immunohistochemical characteristics of 21 such cases. Relevant hematopathologic slides of all cases were reviewed, and extensive immunohistochemical staining was performed. Most patients (15/21 [71%]) had monocytosis in the bone marrow, and chronic myelomonocytic leukemia was the most commonly associated clinical disease. In 4 patients, the monocytic nodules also were present in lymph node, spleen, or skin. Immunohistochemical staining results for the monocytes in the nodules were similar to those for plasmacytoid monocytes. Our study established that monocytic nodules can be present in myelodysplastic syndromes, myeloproliferative diseases, and acute myeloid leukemia; verified the monocytic lineage; and revealed the low proliferative state of these cells.

Near-infrared (NIR) spectroscopic imaging technology provides a new modality for measuring changes in total hemoglobin concentration (HbT) and blood oxygen saturation (SO2) in human tissue. The technology can be used to detect breast cancer because cancers may cause greater vascularization and greater oxygen consumption than in normal tissue. Based on the NIR technology, ViOptix, Inc., has developed an optical device that provides two-dimensional mapping of HbT and SO2 in human tissue. As an adjunctive tool to mammography, the device was preliminarily tested in a clinical trial with 50 mammogram-positive patients at the Massachusetts General Hospital. The results of the clinical trial demonstrate that the device can reach as much as 92% diagnostic sensitivity and 67% specificity in detecting ductal carcinoma. These results may indicate that the NIR technology can potentially be used as an adjunct to mammography for breast cancer detection to reduce the number of biopsies performed.

Objective: To study the common clinical manifestations of in-stent restenosis., Methods: Of 431 patients who underwent percutaneous coronary intervention and repeat catheterization between January 1, 1996 and December 31, 2002, 236 consecutive patients with recurrent ischemia and restenosis were identified: 188 patients with (group I) and 48 without (group II) stenting. Patients who developed early acute stent thrombosis were excluded from the study. In the study we compared the clinical manifestations of in-stent restenosis with those of restenosis without stenting., Results: Recurrent clinical ischemia occurred at a mean of 5.3 months in group I and 6.1 months in group II (P > 0.05). Rest angina (Braunwald class 2 and 3, 43% vs 27%, P < 0.05), the combination of rest angina and acute myocardial infarction (43% vs 27%, P < 0.05), and angiographically visible thrombosis (7% vs 0%, P < 0.05) were more frequent in group I than in group II., Conclusion: Acute coronary syndromes are the common clinical manifestations of restenosis in patients undergoing percutaneous coronary intervention and occur more frequently in patients with in-stent stenosis than in those with restenosis without stenting.

Objective: To study the clinical manifestation, angiographic features, and prognosis of myocardial bridge., Methods: A retrospective analysis was made on the data of the clinical manifestation, coronary angiography, and prognosis of 35 patients with myocardial bridge, 29 males and 6 females, with an average age of 52.0 +/- 9.5 years, out of 2 871 patients undergoing coronary angiography 1 January 1996 - 20 February 2001., Results: The detection rate of myocardial bridge, mostly in the middle or distal parts of left anterior descending branch and 24 being isolated myocardial bridge, was 1.22% in coronary angiography. There was a significant difference in the extent of diameter stenosis during systolic stage between the group with atherosclerosis (68% +/- 15%, n = 15) and the group without atherosclerosis (54% +/- 14%, n = 20) in the vessel proximal to myocardial bridge (P < 0.01). The systolic diameter stenosis was more severe in the abnormal ECG group (63% +/- 13%, n = 12) than in the normal ECG group (54% +/- 14%, n = 12), P < 0.05. However, the systolic stenosis extent of myocardial bridge in the patients with typical angina pectoris (58% +/- 15%, n = 11) was not significantly different from that in the patients with atypical angina pectoris (54% +/- 15%, n = 13). The systolic stenosis extent of myocardial bridge were 69% +/- 9% (n = 7) and 58% +/- 16% (n = 26) in the patients with and without left ventricular wall hypertrophy respectively (P = 0.09). No malignant event occurred during the follow-up period of 3 - 50 months., Conclusion: (1) The more severe the extent of systolic diameter stenosis, the more severe the myocardial ischemia and the more the possibility of abnormal ECG. (2) Myocardial bridge tends to promote or accelerate the atherosclerosis of the vessels proximal to it. (3) Left ventricular wall hypertrophy may promote the formation of myocardial bridge clinically. (4) The prognosis of myocardial bridge is good.

Aim: To study the functional alpha1-adrenergic receptor (alpha1-AR) subtypes in human right gastroepiploic artery (RGA)., Methods: The effects of alpha2-AR, alpha1-AR, and alpha1-AR subtype selective antagonists on norepinephrine (NE)-induced vasoconstriction in isolated human RGA were observed by contractile function experiment., Results: Cumulative concentration-response curves for NE were competitively antagonized in RGA by alpha2-AR selective antagonist yohimbine (pA2 6.82+/-0.28, slope 1.12+/-0.40),alpha1-AR selective antagonist prazosin (pA2 9.77+/-0.22, slope 0.90+/-0.22),alpha1A-AR selective antagonists RS17053 (pA2 8.42+/-0.20, slope 0.93+/-0.20) and 5-MU (pA2 8.42+/-0.22, slope 0.88+/-0.18),alpha1D-AR selective antagonist BMY7378 (pA2 6.84+/-0.32, slope 1.05+/-0.17), and alpha1A-,alpha1B-AR selective antagonist WB4101 (pA2 8.88+/-0.20, slope 1.15+/-0.16). The correlation coefficients between these pA2 values of alpha1-AR selective antagonists with pKi values of which obtained from alpha1A-, alpha1B- and alpha1D-AR cloned cells are 0.95, 0.82, and 0.42. After the vessels were pretreated by chlorethylclonidine (CEC), an alpha1B- and alpha1D-AR irreversible alkylating agent, the pD2 values were changed from 5.9+/-0.5 to 5.6+/-0.6 and the maximal contraction was changed from (8.9+/-3.2) g to (8.0+/-3.2) g, respectively. The difference was not significant., Conclusion: In human RGA, the contraction response is mainly mediated by alpha1-AR, of which alpha1A-AR plays an important role, whereas alpha1B- and alpha1D-AR are not involved in the contraction response.

Objective: To investigate the relationship among inflammatory reaction and cytokine levels, nitric oxide (NO) content in aqueous humor after intraocular lens implantation., Methods: Eighteen New Zealand rabbits were divided randomly into 3 groups (each 6 rabbits): (1) control group, (2) extracapsular cataract extraction group (ECCE) and (3) ECCE and posterior chamber intraocular lens implantation group (ECCE + IOL). The inflammation of all experimental rabbit eyes were observed by a zoom-photo slit-lamp microscope 0, 1, 3, 7, 14, 30 days postoperatively, including corneal edema and anterior chamber exudation. Meanwhile, aqueous humor was drawn for white blood cell (WBC) count and classification, as well as for NO(2)(-)/NO(3)(-) and cytokine assays, including interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha). Statistics were taken by SPSS software., Results: (1) The anterior chamber exudation was the most serious and monocyte/macrophage in aqueous humor were the highest in ECCE + IOL group in postoperative 7 - 14 days. (2) The levels of IL-2, TNF-alpha and the content of NO(2)(-)/NO(3)(-) in aqueous humor of ECCE + IOL group were higher than that in ECCE group and control group in the postoperative 1 - 14 days respectively, and they increased to their peak values at the postoperative 3 - 7 days and decreased gradually after postoperative two weeks. (3) The change regularity of IL-2, TNF-alpha, NO(2)(-)/NO(3)(-) and inflammatory reaction in each group were basically similar, i.e. the more serious the reaction, the higher the levels of the contents., Conclusion: The intraocular inflammation after intraocular lens implantation is closely related to the changes of cytokine levels and NO content in aqueous humor.

A 5-year-old male presented with the history of whitish discharge from a midline sinus opening just above the pubis for 2 months. Attempted radiography of the sinus revealed a blind fistula and voiding cystourethrography was normal. The fistula was excised deep to the subpubic space without any evidence of connection to the lower urinary tract. Pathologic evaluation of the lesion revealed a ciliated-columnar lining with stratified-squamous and transitional epithelium. To our knowledge, a subpubic sinus with this unique presentation of epithelium has not been reported previously.