Hawthorn (Crataegus spp.) is an important pome with a long history as a fruit, an ornamental, and a source of medicine. Fruits of hawthorn are marked by hard stony endocarps, but a hawthorn germplasm with soft and thin endocarp was found in Liaoning province of China. To elucidate the molecular mechanism underlying the soft endocarp of hawthorn, we conducted a de novo assembly of the fruit transcriptome of Crataegus pinnatifida and compared gene expression profiles between the soft-endocarp and the hard-endocarp hawthorn varieties. De novo assembly yielded 52,673 putative unigenes, 20.4% of which are longer than 1,000 bp. Among the high-quality unique sequences, 35,979 (68.3%) had at least one significant match to an existing gene model. A total of 1,218 genes, represented 2.31% total putative unigenes, were differentially expressed between the soft-endocarp hawthorn and the hard-endocarp hawthorn. Among these differentially expressed genes, a number of lignin biosynthetic pathway genes were down-regulated while almost all the flavonoid biosynthetic pathway genes were strongly up-regulated, concomitant with the formation of soft endocarp. In addition, we have identified some MYB and NAC transcription factors that could potentially control lignin and flavonoid biosynthesis. The altered expression levels of the genes encoding lignin biosynthetic enzymes, MYB and NAC transcription factors were confirmed by quantitative RT-PCR. This is the first transcriptome analysis of Crataegus genus. The high quality ESTs generated in this study will aid future gene cloning from hawthorn. Our study provides important insights into the molecular mechanisms underlying soft endocarp formation in hawthorn.
The aim of this study was to investigate the prevalence of interankle systolic blood pressure difference (sIAND) and its influencing factors in community population.
This study included 2849 (65.1±9.4 y) subjects. Blood pressure (BPs) of four limbs was simultaneously measured with 4 electronic sphygmomanometers after 10 min rest in supine position. The difference of systolic BP (SBP) between two ankles was calculated as DETASBP. The criterion for abnormal sIAND was ≥10 mmHg of absolute DeltaSBP, in which the criterion for 1o sIAND was 10–19 mmHg and for 2o sIAND was ≥20 mmHg. Age, gender, smoking, hypertension, family histories of hypertension and diabetes were recorded. Fasting blood glucose and lipids, circumference of hip and waist, and body mass index (BMI) were measured.
The SBP was higher in the right ankle than in the left ankle (158.9±21.8 vs 157.3±21.6 mmHg, P<0.05) and mean DeltaSBP was 6.08±6.26 mmHg. Similar difference was found in both genders. The prevalence of abnormal was 18.5%, in which, the prevalence 1o sIAND was 15.3% and that of 2o sIAND was 3.1%. Multivariate regression analysis showed that age, waist circumference and blood glucose level were the positive factors for DeltaSBP. The normal upper limit for DeltaSBP was 16.7 mmHg in this population, the prevalence of sIAND by≥16 mmHg was 5.8%.
Aging, hypertension, obesity and abnormal glucose metabolism are positive factors for inter-ankle SBP difference.
Nesfatin-1, derived from nucleobindin 2, was recently identified as an anorexigenic signal peptide. However, its neural role in glucose homeostasis and insulin sensitivity is unknown. To evaluate the metabolic impact and underlying mechanisms of central nesfatin-1 signaling, we infused nesfatin-1 in the third cerebral ventricle of high-fat diet (HFD)–fed rats. The effects of central nesfatin-1 on glucose metabolism and changes in transcription factors and signaling pathways were assessed during euglycemic-hyperinsulinemic clamping. The infusion of nesfatin-1 into the third cerebral ventricle markedly inhibited hepatic glucose production (HGP), promoted muscle glucose uptake, and was accompanied by decreases in hepatic mRNA and protein expression and enzymatic activity of PEPCK in both standard diet- and HFD-fed rats. In addition, central nesfatin-1 increased insulin receptor (InsR)/insulin receptor substrate-1 (IRS-1)/AMP-dependent protein kinase (AMPK)/Akt kinase (Akt)/target of rapamycin complex (TORC) 2 phosphorylation and resulted in an increase in Fos immunoreactivity in the hypothalamic nuclei that mediate glucose homeostasis. Taken together, these results reveal what we believe to be a novel site of action of nesfatin-1 on HGP and the PEPCK/InsR/IRS-1/AMPK/Akt/TORC2 pathway and suggest that hypothalamic nesfatin-1 action through a neural-mediated pathway can contribute to increased peripheral and hepatic insulin sensitivity by decreasing gluconeogenesis and promoting peripheral glucose uptake in vivo.
Studies investigating the association between single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and cancer risk report conflicting results. To derive a more precise estimation of the relationship between MTHFD1 polymorphisms and cancer risk, the present meta-analysis was carried out.
A comprehensive search was conducted to determine all the eligible studies about MTHFD1 polymorphisms and cancer risk. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between the MTHFD1 polymorphisms and cancer risk. We investigated by meta-analysis the effects of 2 polymorphisms in MTHFD1: G1958A (17 studies, 12348 cases, 44132 controls) and G401A (20 studies, 8446 cases, 14020 controls). The overall results indicated no major influence of these 2 polymorphisms on cancer risk. For G1958A, a decreased cancer risk was found in acute lymphoblastic leukemia (ALL)/Asians (the dominant: OR = 0.74, 95% CI = 0.58–0.94, P = 0.01; allelic: OR = 0.80, 95% CI = 0.65–0.99, P = 0.04) and other cancers (recessive: OR = 0.80, 95% CI = 0.66–0.96, P = 0.02). For G401A, the data showed that MTHFD1 G401A polymorphism was associated with a decreased colon cancer risk under dominant model (OR = 0.89, 95% CI = 0.80–0.99, P = 0.04).
The results suggest that MTHFD1 G1958A polymorphism might be associated with a decreased risk of ALL and other cancers. Meanwhile, the MTHFD1 G401A might play a protective role in the development of colon cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.
Numerical modeling of the cardiovascular system is becoming an important tool for assessing the influence of heart disease and treatment therapies. In the current study we present an approach for modeling the interaction between the heart and circulatory system. This was accomplished by creating animal specific biventricular finite element models, which characterize the mechanical response of the heart, and coupling them to a lumped parameter model that represents the systemic and pulmonic circulatory system. In order to minimize computation time, the coupling was enforced in a weak (one-way) manner, where the ventricular pressure-volume relationships were generated by the finite element models and then passed into the circulatory system model to ensure volume conservation and physiological pressure changes. The models were first validated by tuning the parameters, such that the output of the models matched experimentally measured pressures and volumes. Then the models were used to examine cardiac function and the myofiber stress in a healthy canine heart and a canine heart with dilated cardiomyopathy. The results show good agreement with experimental measurements. The stress in the case of cardiomyopathy was found to increase significantly, while the pump function was decreased, compared to the healthy case. The total run time of the simulations is less than many fully-coupled models presented in the literature. This will allow for a much quicker evaluation of possible treatment strategies for combating the effects of heart failure, especially in optimization schemes that require numerous finite element simulations.
Finite Element; Lumped Parameter; Cardiac Mechanics
MicroRNAs, non-coding 20–22 nucleotide single-stranded RNAs, result in translational repression or degradation and gene silencing of their target genes, and significantly contribute to the regulation of gene expression. In the current study, we report that miR-182 expression was significantly upregulated in prostate cancer tissues and four cell lines, compared to benign prostatic hyperplasia tissues and normal prostatic epithelial (RWPE-1) cells. Ectopic overexpression of miR-182 significantly promotes the proliferation, increases the invasion, promotes the G1/S cell cycle transition and reduces early apotosis of PC-3 cells, while suppression of miR-182 decreased the proliferation and invasion, inhibits the G1/S cell cycle transition and increase early apotosis of PC-3 cells. Additionally, we demonstrated that miR-182 could downregulate expression of NDRG1 by directly targeting the NDRG1 3′-untranslated region. In conclusion, our results suggest that miR-182 plays an important role in the proliferation of human prostate cancer cells by directly suppressing the tumor supressor gene NDRG1. We uncovered a new epigenetic regulation of NDRG1.
The Acorn CorCap Cardiac Support Device (CSD; Acorn Cardiovascular Inc, St. Paul, MN) is a woven polyester jacket that is placed around the heart and designed to reverse the progressive remodeling associated with dilated cardiomyopathy. However, the effects of the Acorn CSD on myofiber stress and ventricular function remain unknown. We tested the hypothesis that the Acorn CSD reduces end-diastolic (ED) myofiber stress.
A previously described weakly coupled biventricular finite element (FE) model and circulatory model based on magnetic resonance images of a dog with dilated cardiomyopathy was used. Virtual applications of the CSD alone (Acorn), CSD with rotated fabric fiber orientation (rotated), CSD with 5% prestretch (tight), and CSD wrapped only around the left ventricle (LV; LV-only) were performed, and the effect on myofiber stress at ED and pump function was calculated.
The Acorn CSD has a large effect on ED myofiber stress in the LV free wall, with reductions of 55%, 79%, 92%, and 40% in the Acorn, rotated, tight, and LV-only cases, respectively. However, there is a tradeoff in which the Acorn CSD reduces stroke volume at LV end-diastolic pressure of 8 mm Hg by 23%, 25%, 30%, and 7%, respectively, in the Acorn, rotated, tight, and LV-only cases.
The Acorn CSD significantly reduces ED myofiber stress. However, CSD wrapped only around the LV was the only case with minimal negative effect on pump function. Findings suggest that LV-only CSD and Acorn fabric orientation should be optimized to allow maximal myofiber stress reduction with minimal reduction in pump function.
Inflammatory myofibroblastic tumor of the temporal bone is an unusual but distinct disease entity. The most common presenting symptoms are otalgia, otorrhea, hearing loss, facial palsy, and vertigo. We describe here what we believe to be the first reported case of a patient presenting with persistent pulsatile tinnitus. The clinical features, radiological and histopathologic findings, and treatment outcomes of the patient are presented.
A 59-year-old woman of Chinese Han origin presented with complaints of left-sided pulsatile tinnitus and progressive hearing loss for several years. Clinical evaluations revealed a reddish mass behind the intact tympanic membrane, and a moderately severe conductive hearing loss in the left ear. The computed tomographic imaging of the temporal bone demonstrated a slightly ill-defined left middle ear soft tissue mass involving the posterior portion of the mesotympanum and epitympanum, and the mastoid antrum. The patient underwent surgical excision of the lesion which subsequently resolved her symptoms. Postoperative pathology was consistent with an inflammatory myofibroblastic tumor.
An inflammatory myofibroblastic tumor of the temporal bone can present clinically with pulsatile tinnitus and masquerade as venous hum or vascular tumors of the middle ear; therefore, it should be included in the differential diagnosis of pulsatile tinnitus.
Inflammatory Myofibroblastic Tumor; Middle Ear; Pulsatile Tinnitus; Temporal Bone
Herein, we describe the generation of a monomeric large Stokes shift (LSS) red fluorescent protein, mBeRFP, with excitation and emission peaks at 446 and 615 nm, respectively. Compared with two previously reported LSS-RFPs (mKeima and LSS-mKate2), mBeRFP is approximately three times brighter. In addition, mBeRFP is characterized by improved photostability, rapid maturation, an extended lifetime, and a monomeric nature. Additionally, mBeRFP can be paired with the Alexa 647 dye as a FRET donor to detect caspase 3 activity. This FRET pair has an extremely dynamic range and a large Förster radius (approximately 6.5 nm). To demonstrate the applicability of mBeRFP for imaging in living cells, we performed dual-color imaging of mBeRFP and CFP simultaneously excited by a single excitation source, and we demonstrated that these fluorescent proteins allow the clear visualization of the dynamics of Bax during cancer cell apoptosis. Thus, mBeRFP appears to be particularly useful for cellular imaging applications.
We sought to determine regional myofiber stress after Coapsys device (Myocor, Inc., Maple Grove, Minnesota) implantation using a finite element (FE) model of the left ventricle (LV). Chronic ischemic mitral regurgitation (CIMR) is due to LV remodeling after postero-lateral myocardial infarction. The Coapsys device consists of a single trans-LV chord placed below the mitral valve such that when tensioned it alters LV shape and decreases CIMR.
FE models of the LV were based on magnetic resonance images (MRI) obtained before (PRE-OP) and after (POST-OP) CABG + Coapsys in a single patient. To determine the effect of Coapsys and LV pre-stress, virtual Coapsys (VIRTUAL-COAPSYS) was performed on the PRE-OP model. Diastolic and systolic material parameters in the PRE-OP, POST-OP and VIRTUAL-COAPSYS were adjusted so that model LV volume agreed with MRI data. CIMR was abolished in the post-op models. In each case, myofiber stress and pump function were calculated.
Both POST-OP and VIRTUAL-COAPSYS shifted end-systolic (ES) and end diastolic (ED) pressure volume relationships (PVR) to the left. As a consequence and because CIMR was reduced after Coapsys, pump function was unchanged. Coapsys decreased myofiber stress at ED and ES in both the remote and infarct regions of the myocardium. However, knowledge of Coapsys and LV pre-stress was necessary for accurate calculation of LV myofiber stress especially in the remote zone.
Coapsys decreases myofiber stress at ED and ES. The improvement in myofiber stress may contribute to the long term effect of Coapsys on LV remodeling.
Myocardial Infarction; Remodeling; Mitral Valve; Mitral Regurgitation; Mitral Repair; Finite Element; Stress
To evaluate the impact of the Janus kinase 2 single nucleotide polymorphisms (SNPs) on gastric cancer risk.
In this hospital-based, case–control study, the genotypes were identified by polymerase chain reaction–restriction fragment length polymorphism protocols in 661 individuals (359 gastric cancer patients and 302 age and sex matched cancer-free controls).
Both the frequency of A allele in rs2230724 and G allele in rs1887427 were more frequent in patients with gastric cancer (P = 0.013 and 0.001, respectively). Compared with the common genotype, subjects with the (AG+AA) genotypes of rs2230724 and the (AG+GG) genotypes of rs1887427 had a 59% and 98% increased risk of developing gastric cancer, respectively (P = 0.010, adjusted OR = 1.59, 95% CI = 1.12–2.27; P<0.001, adjusted OR = 1.98, 95% CI = 1.39–2.81, respectively). Further stratified analysis showed that the association between the risk of gastric cancer and the rare genotypes of rs2230724 were more profound in the subgroups of elder individuals (>56 years), males, nonsmokers and urban subjects, while the association between the risk and the rare genotypes of rs1887427 persisted in subgroups of younger individuals (≤56 years), males, nonsmokers and both of rural and urban subjects.
The JAK2 gene rs2230724 and rs1887427 polymorphisms are associated with an increased risk of gastric cancer in a Chinese Han population.
Undersized mitral annuloplasty (MA) is the preferred surgical treatment for chronic ischemic mitral regurgitation (CIMR). However, the preferred shape of undersized MA is unclear.
A previously described finite element (FE) model of the LV with mitral valve based on magnetic resonance images of a sheep with CIMR after postero-lateral MI was used. Saddle shape (Edwards Physio II) and asymmetric (IMR ETlogix) MA rings were digitized and meshed. Virtual annuloplasty was performed using virtual sutures to attach the MA ring. LV diastole and systole were performed before and after virtual MA of each type.
Both types of MA reduced the septo-lateral dimension of the mitral annulus and abolished mitral regurgitation. The asymmetric MA was associated with lower virtual suture force in the P2 region but higher force in P1 and P3 regions. Although both types of MA reduced fiber stress at the LV base, fiber stress reduction after asymmetric MA was slightly greater. Neither type of MA affected fiber stress at the LV equator or apex. Although both types of MA increased leaflet curvature and reduced leaflet stress, stress reduction with saddle shape MA was slightly greater. Both MA types reduced stress on the mitral chordae.
The effects of saddle shaped and asymmetric MA rings are similar. FE simulations are a powerful tool that may reduce the need for animal and clinical trials.
Myocardial Infarction; Mitral Valve; Mitral Regurgitation; Mitral Repair; Annuloplasty; Finite Element; Stress
Multiple endocrine neoplasia type 2A (MEN2A), a subtype of MEN2, is characterized by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism. A Han Chinese pedigree with MEN2A was investigated following confirmation of the proband's diagnosis by pathological findings and DNA/biochemical screening. DNA samples from 4 other family members were collected and exon 5, 8, 10, 11, 13, 16 and 18 of the RET proto-oncogene were sequenced and then analyzed. A missense mutation of TGG (Trp) to TGC (Cys) at codon 634 (the classic MEN2A mutation) in exon 11 of the RET gene was detected in 3 family members, including the proband. Sequencing data were compared with the human gene mutation database. Elevated serum calcitonin level was detected initially; medullary thyroid carcinoma was revealed in the 3 cases and adrenal pheochromocytoma was also found in the proband. Elective operations were successfully performed on the adrenal and thyroid glands because of pheochromocytoma and medullary thyroid carcinoma. Our case study confirms that integrated DNA-based/biochemical screening is crucial for early diagnosis of MEN2A and is helpful in the screening of their relatives. In addition, DNA-based screening may occasionally uncover a previously unknown RET sequence.
MEN-2A; RET mutation; medullary thyroid carcinoma; Chinese; RET proto-oncogene; Calcitonin screening; DNA-based screening
Nasopharyngeal carcinoma (NPC) is a very regional malignant head and neck cancer that has attracted widespread attention for its unique etiology, epidemiology and therapeutic options. To achieve high cure rates in NPC patients, theranostic approaches are actively being pursued and improved efforts remain desirable in identifying novel biomarkers and establishing effective therapeutic approaches with low long-term toxicities. Here, we discovered that the scavenger receptor class B type I (SR-B1) was overexpressed in all investigated NPC cell lines and 75% of NPC biopsies, demonstrating that SR-B1 is a potential biomarker of NPC. Additional functional analysis showed that SR-B1 has great effect on cell motility while showing no significant impact on cell proliferation. As high-density lipoproteins (HDL) exhibit strong binding affinities to SR-B1 and HDL mimetic peptides are reportedly capable of inhibiting tumor growth, we further examined the SR-B1 targeting ability of a highly biocompatible HDL-mimicking peptide-phospholipid scaffold (HPPS) nanocarrier and investigated its therapeutic effect on NPC. Results show that NPC cells with higher SR-B1 expression have superior ability in taking up the core constituents of HPPS. Moreover, HPPS inhibited the motility and colony formation of 5-8F cells, and significantly suppressed the NPC cell growth in nude mice without inducing tumor cell necrosis or apoptosis. These results indicate that HPPS is not only a NPC-targeting nanocarrier but also an effective anti-NPC drug. Together, the identification of SR-B1 as a potential biomarker and the use of HPPS as an effective anti-NPC agent may shed new light on the diagnosis and therapeutics of NPC.
Cancer theranostics; nasopharyngeal carcinoma; biomarker; SR-B1; lipoprotein nanocarrier.
In vitro and in vivo studies have suggested that osteopontin (OPN) is associated with many types of cancers. However, no studies have reported the incidence of OPN polymorphisms and the risk of gastric cancer. The aim of this study was to investigate the association between OPN polymorphisms and gastric cancer in a Chinese patient population.
Three genetic variants in the OPN promoter were genotyped using direct sequencing in 200 gastric cancer patients and 200 gender- and age-matched cancer-free controls. The 4-year survival curve was calculated using the Kaplan-Meier method and compared using the log-rank test for each single nucleotide polymorphism (SNP) site. We measured the promoter activity of the -443 T → C polymorphism using a dual luciferase reporter assay.
For the variant at nt -443 (CC), there was a significant difference between the number of patients with stage IV and those with stage I gastric cancer (IA + IB; P = 0.014) and between those with stage IV and all other stages of gastric cancer (IA + IB + II + III; P = 0.02). For the variant at nt -443 (CT), there was a significant difference between the number of gastric cancer patients with stage IV and those with stage II (P = 0.013). The survival rates for patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T). Moreover, significantly higher luciferase activities were observed in the pGL3-C construct compared to the pGL3-T construct.
This study provides the first evidence that variation at nt -443 in the OPN promoter increases the potential for gastric cancer metastasis and subsequent death in the Chinese population.
Osteopontin; Gastric cancer; Polymorphisms; Genetic variants; Metastasis
The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to phorbol 12-myristate 13-acetate (PMA). In sensitive cells, PMA causes Erk MAPK activation and Erk-mediated growth arrest. In resistant cells, PMA induces a low level of Erk activation, without growth arrest. A relatively unexplored aspect of the phenotypes is that resistant cells are more adherent to culture substrate than are sensitive cells. In this study, the roles of the protein tyrosine kinases FAK and Pyk2 in EL4 phenotype were examined, with a particular emphasis on the role of these proteins in metastasis. FAK is expressed only in PMA-resistant (or intermediate phenotype) EL4 cells, correlating with enhanced cell-substrate adherence, while Pyk2 is more highly expressed in non-adherent PMA-sensitive cells. PMA treatment causes modulation of mRNA for FAK (up-regulation) and Pyk2 (down-regulation) in PMA-sensitive but not PMA-resistant EL4 cells. The increase in Pyk2 mRNA is correlated with an increase in Pyk2 protein expression. The roles of FAK in cell phenotype were further explored using transfection and knockdown experiments. The results showed that FAK does not play a major role in modulating PMA-induced Erk activation in EL4 cells. However, the knockdown studies demonstrated that FAK expression is required for proliferation and migration of PMA-resistant cells. In an experimental metastasis model using syngeneic mice, only FAK-expressing (PMA-resistant) EL4 cells form liver tumors. Taken together, these studies suggest that FAK expression promotes metastasis of EL4 lymphoma cells.
cell-substrate adhesion; Erk mitogen-activated protein kinases; tyrosine kinases; T-lymphocytes; tumor promoters; metastasis
Whether a genetic informational nucleic acid is required for the infectivity of transmissible spongiform encephalopathies is central to the debate about the infectious agent. Here we report that an infectious prion formed with bacterially expressed recombinant prion protein plus synthetic polyriboadenylic acid and synthetic phospholipid 1-palmitoyl-2-oleoylphosphatidylglycerol is competent to infect cultured cells and cause prion disease in wild-type mice. Our results show that genetic informational RNA is not required for recombinant prion infectivity.
The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms.
Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days (postnatal days 14th–16th). The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissue. CRD or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-D-aspartic acid (NMDA) NR1 subunit in the L6-S1 spinal cord was examined using Western blot.
The VMR to CRD (≥10mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan rats was significantly higher than the control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (p > 0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared to saline treated rats (p <0.05).
Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does results in overexpression of spinal NR1 subunit in adult rats.
cystitis; visceral hyperalgesia; neonatal; viscero-visceral convergence
Primary malignant melanoma of the duodenum is an unusual oncologic entity. Patients usually present the similar clinical symptoms like other common tumors in this site. And there are no specific radiological features either. The cases with only little melanin pigment or without notable melanin pigment are very misleading, especially in small biopsies or frozen sections. Definite diagnosis depends on both careful histologic examination and the use of proper immunohistochemical stains. Moreover, detailed history and thorough investigation should be made to exclude the preexistence or coexistence of a primary lesion elsewhere. Herein we report the case of a 60-year-old male patient with primary malignant melanoma of the duodenum, which was misdiagnosed as lymphoma or undifferentiated carcinoma in frozen consultation. The patient had achieved disease-free survival for more than 46 months without any evidence of recurrence after surgery.
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1221457317710561.
Malignant melanoma; Primary; Duodenum; Misdiagnosis
The aim of our study was to evaluate the feasibility and clinical effect of laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator for treating small renal cell carcinomas.
The animal experiments of coagulation therapy on the wound tissue bed during partial nephrectomy with an argon beam coagulator were performed on 16 rabbits, which were randomly divided into 4 groups. Groups A and B had renal artery occlusion; the treatment time of coagulation was 4 seconds and 6 seconds, respectively. Groups C and D did not have renal artery occlusion; the treatment time of coagulation was 2 seconds and 4 seconds, respectively. Then 30 clinical operations of laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator were performed.
All 16 rabbits successfully underwent the operation. By the histological examination, the scab depth of the wound tissue bed in groups A, B, C, and D were 2.76±0.17 mm, 3.15±0.15 mm, 2.28±0.16 mm and 2.75±0.06 mm, respectively. Group A differed significantly from groups B and C (P=0.012, 0.007), and group D differed significantly from groups B and C (P=0.002, 0.002). In the clinical study, all 30 patients successfully underwent the operation. The mean operative time was 182 minutes, and the mean blood loss was 280 ml. With a median follow-up time of 37 months, neither local recurrence nor distant metastasis was found by computerized tomography scan.
Laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator can be considered for treating small renal cell carcinomas. However, the indication of this procedure should be highly selected.
renal cell carcinoma; simple enucleation; laparoscopy; animal experiment; clinical study; argon beam coagulator
Objectives: Contractile function in the normally perfused infarct borderzone (BZ) is depressed. However, the impact of reduced BZ contractility on left ventricular (LV) pump function is unknown. As a consequence, there have been no therapies specifically designed to improve BZ contractility. We tested the hypothesis that an improvement in borderzone contractility will improve LV pump function. Methods: From a previously reported study, magnetic resonance imaging (MRI) images with non-invasive tags were used to calculate 3D myocardial strain in five sheep 16 weeks after anteroapical myocardial infarction. Animal-specific finite element (FE) models were created using MRI data and LV pressure obtained at early diastolic filling. Analysis of borderzone function using those FE models has been previously reported. Chamber stiffness, pump function (Starling’s law) and stress in the fiber, cross fiber, and circumferential directions were calculated. Animal-specific FE models were performed for three cases: (a) impaired BZ contractility (INJURED); (b) BZ-contractility fully restored (100% BZ IMPROVEMENT); or (c) BZ-contractility partially restored (50% BZ IMPROVEMENT). Results: 100% BZ IMPROVEMENT and 50% BZ IMPROVEMENT both caused an upward shift in the Starling relationship, resulting in a large (36 and 26%) increase in stroke volume at LVPED = 20 mmHg (8.0 ml, p < 0.001). Moreover, there were a leftward shift in the end-systolic pressure volume relationship, resulting in a 7 and 5% increase in LVPES at 110 mmHg (7.7 ml, p < 0.005). It showed that even 50% BZ IMPROVEMENT was sufficient to drive much of the calculated increase in function. Conclusion: Improved borderzone contractility has a beneficial effect on LV pump function. Partial improvement of borderzone contractility was sufficient to drive much of the calculated increase in function. Therapies specifically designed to improve borderzone contractility should be developed.
myocardial Infarction; borderzone; finite element
The temporal progression in extent and severity of regional myofiber contractile dysfunction in normally perfused borderzone (BZ) myocardium adjacent to a myocardial infarction (MI) has been shown to be an important pathophysiologic feature of the adverse remodeling process in large animal models. We sought, for the first time, to document the presence of impaired contractility of the myofibers in the human BZ myocardium.
Methods and Results
A 62 year-old man who suffered a MI in 1985 and had recently had complete revascularization was studied. Myofiber systolic contractile stress developed in the normally perfused borderzone adjacent to the MI (Tmax_B) and that developed in regions remote from the MI (Tmax_R) were quantified using cardiac catheterization, MRI and mathematical modeling. The resulting finite element model of the patient's beating left ventricle was able to simulate the reduced systolic strains measured using MRI at matching left ventricular pressures and volumes. Tmax_B (73.1 kPa) was found to be greatly reduced relative to Tmax_R (109.5 kPa). These results were found to be independent of assumptions relating to BZ myofiber orientation.
The results of this study document the presence of impaired contractility of the myofibers in the BZ myocardium and support its role in the post MI remodeling process in patients. To fully establish this important conclusion serial evaluations beginning at the time of the index MI will need to be performed in a cohort of patients. The current study supports the importance and demonstrates the feasibility of larger and longer-term studies.
Modeling; Magnetic Resonance Imaging; Cardiac Function; Heart Failure; Bioengineering
Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). The COX-2 polymorphism rs2745557 (+202 C/T) has been extensively investigated as a potential risk factor for PCa, but the results have thus far been inconclusive. This meta-analysis was performed to derive a more precise estimation of the association.
A comprehensive search was conducted to identify all case-control studies of COX-2 rs2745557 polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. Statistical analyses were performed by Review Manage, version 5.0 and Stata 10.0.
A total of 8 available studies were considered in the present meta-analysis, with 11356 patients and 11641 controls for rs2745557. When all groups were pooled, there was no evidence that rs2745557 had significant association with PCa under co-dominant, recessive, over-dominant, and allelic models. However, our analysis suggested that rs2745557 was associated with a lower PCa risk under dominant model in overall population (OR = 0.85, 95%CI = 0.74-0.97, P = 0.02). When stratifying for race, there was a significant association between rs2745557 polymorphism and lower PCa risk in dominant model comparison in the subgroup of Caucasians (OR = 0.86, 95%CI = 0.75-0.99, P = 0.04), but not in co-dominant, recessive, over-dominant and allelic comparisons.
Based on our meta-analysis, COX-2 rs2745557 was associated with a lower PCa risk under dominant model in Caucasians.
The head of bacteriophage T4 is decorated with 155 copies of the highly antigenic outer capsid protein (Hoc). One Hoc molecule binds near the center of each hexameric capsomer. Hoc is dispensable for capsid assembly and has been used to display pathogenic antigens on the surface of T4. Here we report the crystal structure of a protein containing the first three of four domains of Hoc from bacteriophage RB49, a close relative of T4. The structure shows an approximately linear arrangement of the protein domains. Each of these domains has an immunoglobulin-like fold, frequently found in cell attachment molecules. In addition, we report biochemical data suggesting that Hoc can bind to Escherichia coli, supporting the hypothesis that Hoc could attach the phage capsids to bacterial surfaces and perhaps also to other organisms. The capacity for such reversible adhesion probably provides survival advantages to the bacteriophage.
Chronic ischemic mitral regurgitation (CIMR: MR) is associated with poor outcome. However, the effect of CIMR on left ventricular (LV) remodeling after postero-lateral myocardial infarction (MI) remains controversial. We tested the hypothesis that moderate MR accelerates LV remodeling after postero-lateral MI.
Postero-lateral MI was created in 10 sheep. Cardiac MRI was performed 2 weeks before and 2, 8 and 16 weeks after MI. LV and right ventricular (RV) volumes were measured and regurgitant volume (RegurgVolume) calculated as the difference between LV and RV stroke volumes.
Multivariate mixed effect regression showed that LV volumes at end-diastole (ED) and end-systole (ES) and LV sphericity were strongly correlated with both RegurgVolume (p<0.0001, p=0.0086 and p=0.0007 respectively) and %Infarct area (p=0.0156, 0=0.0307, and p<0.0001 respectively). On the other hand, while LV hypertrophy (LV wall volume) increased from 2 to 16 weeks post-MI there was no effect of either RegurgVolume or %Infarct.
Moderate mitral regurgitation accelerates LV remodeling after postero-lateral MI. Further studies are needed to determine whether mitral valve repair is able to slow or reverse MI remodeling after postero-lateral MI.
Myocardial Infarction; Mitral Valve; Mitral Regurgitation; Mitral Repair; Remodeling