Comparison of full genome sequences between two hepatitis B virus strains with or without preC mutation (A1896) from a single Korean hepatocellular carcinoma patient

This report describes the full-length sequences of 2 HBV clones from a hepatocellular carcinoma (HCC) patient, one with preC mutation (1896A) and the other without preC mutation. The high level of discrepancy in mutation frequency between these 2 strains was observed in the Core (C) region among 4 ORFs. These data support previous results that Korean HBV strains, belonging to genotype C2, are prone to mutations. It is possible that the mutations (BCP and preC mutations) associated with the HBeAg defective production might contribute to the diversity of mutations related to HBV persistence, playing an important role in hepatocarcinogenesis in this patient.     

Diagnostic Efficacy of 18F-FDG PET/MRI in Peripheral Nerve Injury Models

The aim of this study was to evaluate the diagnostic efficacy of ¹⁸F-FDG PET/MRI in two different peripheral neuropathic pain models using the injured rat sciatic nerves. Twelve rats, with operation on left sciatic nerves, were evenly divided into three groups: sham surgery (control group), crushing injury and chronic constriction injury (CCI) (experimental groups). The nerve damage was assessed at 3 weeks postoperatively using following methods: paw withdrawal threshold values (RevWT), maximum standardized uptake values on PET/MRI images (SUVR), and counting the number of myelinated axons in proximal and distal sites of nerve injury (MAxR). The results were quantified and statistically analyzed. Compared to the control group, the crushing injury demonstrated significant differences in RevWT (p < 0.0001) and SUVR (p = 0.027) and the CCI group demonstrated significant differences in RevWT (p < 0.0001), SUVR (p = 0.001) and MAxR (p = 0.048). There were no significant differences between the two experimental groups for all assessments. Correlation analysis demonstrated that RevWT and SUVR assessments were highly correlated (r = -− 0.710, p = 0.010), and SUVR and MAxR were highly correlated (r = 0.611, p = 0.035). However, there was no significant correlation between RevWT and MAxR. The PET scan may be a valuable imaging modality to enable noninvasive, objective diagnosis of neuropathic pain caused by peripheral nerve injury. Also, MRI fused with PET may help clarify the anatomic location of soft tissue structures, including the peripheral nerves.

     

Activation of 5'-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2

Metformin is one of the most commonly used first line drugs for type II diabetes. Metformin lowers serum glucose levels by activating 5'-AMP-activated kinase (AMPK), which maintains energy homeostasis by directly sensing the AMP/ATP ratio. AMPK plays a central role in food intake and energy metabolism through its activities in central nervous system and peripheral tissues. Since food intake and energy metabolism is synchronized to the light-dark (LD) cycle of the environment, we investigated the possibility that AMPK may affect circadian rhythm. We discovered that the circadian period of Rat-1 fibroblasts treated with metformin was shortened by 1 h. One of the regulators of the period length is casein kinase Iepsilon (CKIepsilon), which by phosphorylating and inducing the degradation of the circadian clock component, mPer2, shortens the period length. AMPK phosphorylates Ser-389 of CKIepsilon, resulting in increased CKIepsilon activity and degradation of mPer2. In peripheral tissues, injection of metformin leads to mPer2 degradation and a phase advance in the circadian expression pattern of clock genes in wild-type mice but not in AMPK alpha2 knock-out mice. We conclude that metformin and AMPK have a previously unrecognized role in regulating the circadian rhythm.     

A human papillomavirus testing system in women with abnormal Pap results: a comparison study with follow-up biopsies

OBJECTIVE: To evaluate the efficacy of INFORM HPV using the SurePath collection method in women whose Pap tests indicated abnormal results. STUDY DESIGN: Ninety-two women from the gynecology clinics at The University of Texas M.D. Anderson Cancer Center who had Pap tests and underwent follow-up biopsies were selected for the study. This included 51 women with atypical squamous cells of undetermined significance (ASCUS), 23 women with low-grade squamous intraepithelial lesion (LSIL), 15 women with high-grade squamous intraepithelial lesion (HSIL) and 3 women with negative Pap results. The INFORM HPV, an in situ hybridization assay, testing for oncogenic types of HPV was performed, and the results were compared with follow-up biopsies. RESULTS: The positive rate of the INFORM HPV increased with higher grades of cytology diagnoses. The sensitivity of the INFORM HPV testing for predicting high-grade cervical intraepithelial neoplasia (CIN 2/3) also increased with higher grades of cytology diagnoses. A negative predictive value (NPV) of 94.9% and a specificity of 80.4% for predicting CIN 2/3 were observed in the ASCUS group. CONCLUSION: Using SurePath Pap specimens, the INFORM HPV lacks sufficient sensitivity and NPV for predicting CIN 2/3 in women with ASCUS. Therefore, use of the test as a triage tool is limited.     

Microarray analysis of gene expression profile in the corpus cavernosum of hypercholesterolemic rats after chronic treatment with PDE5 inhibitor

Gene expression changes in the corpus cavernosum of hypercholesterolemic rats were not fully assessed, which were not previously known to be associated with hypercholesterolemia-related erectile dysfunction (ED). To provide molecular insight into pathophysiology of hypercholesterolemia-related ED and to investigate the effects of Udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on gene expression, we performed microarray gene expression analysis via gene discovery methods using GenoCheck platinum cDNA chip (Ansan, S. Korea). Sixteen male Sprague-Dawley rats were fed 2% cholesterol diet for 5 months. Half of them were orally treated with Udenafil (20 mg/kg/day) simultaneously. Eight age-matched rats fed normal diet were served as normal control. RNA was extracted from corpus cavernosum and microarray analysis was performed. Decreased erectile responses and hypercholesterolemia were observed in hypercholesterolemic control group. In microarray analysis, 122 candidate genes were noted to be altered based on the magnitude of expression changes, which includes 44 down-regulated and 78 up-regulated genes compared with the age-matched normal controls. These changes were, however, significantly attenuated by treatment with Udenafil. Out of the 78 up-regulated genes, 8 genes were significantly decreased by the chronic treatment with Udenafil. The altered genes were cytochrome oxidase biogenesis protein OXA1, skeletal muscle myosin heavy chain, lipophilin, fast skeletal muscle isoforms beta/alpha, myosin light chain 3, cytochrome c oxidase, adipocyte fatty acid binding protein and one EST gene. In contrast, among the 44 down-regulated genes, Kruppel-like factor 5 and cyclin D1 genes were increased after the Udenafil treatment. These results provide the molecular basis for understanding the pathogenesis of hypercholesterolemia-related ED and offer clues on determining the underlying action mechanism of a PDE5 inhibitor.     

A Novel Geriatric Screening Tool in Older Patients with Cancer: The Korean Cancer Study Group Geriatric Score (KG)-7

Geriatric assessment (GA) is resource-consuming, necessitating screening tools to select appropriate patients who need full GA. The objective of this study is to design a novel geriatric screening tool with easy-to-answer questions and high performance objectively selected from a large dataset to represent each domain of GA. A development cohort was constructed from 1284 patients who received GA from May 2004 to April 2007. Items representing each domain of functional status, cognitive function, nutritional status, and psychological status in GA were selected according to sensitivity (SE) and specificity (SP). Of the selected items, the final questions were chosen by a panel of oncologists and geriatricians to encompass most domains evenly and also by feasibility and use with cancer patients. The selected screening questions were validated in a separate cohort of 98 cancer patients. The novel screening tool, the Korean Cancer Study Group Geriatric Score (KG)-7, consisted of 7 items representing each domain of GA. KG-7 had a maximal area under the curve (AUC) of 0.93 (95% confidence interval (CI) 0.92−0.95) in the prediction of abnormal GA, which was higher than that of G-8 (0.87, 95% CI 0.85–0.89) within the development cohort. The cut-off value was decided at ≤ 5 points, with a SE of 95.0%, SP of 59.2%, positive predictive value (PPV) of 85.3%, and negative predictive value (NPV) of 82.6%. In the validation cohort, the AUC was 0.82 (95% CI 0.73−0.90), and the SE, SP, PPV, and NPV were 89.5%, 48.6%, 77.3%, and 75.0%, respectively. Furthermore, patients with higher KG-7 scores showed significantly longer overall survival (OS) in the development and validation cohorts. In conclusions, the KG-7 showed high SE and NPV to predict abnormal GA. The KG-7 also predicted OS. Given the results of our studies, the KG-7 could be used effectively in countries with high patient burden and low resources to select patients in need of full GA and intervention.     

Efficacy of Gastric Balloon Dilatation and/or Retrievable Stent Insertion for Pyloric Spasms after Pylorus-Preserving Gastrectomy: Retrospective Analysis

Purpose

We retrospectively investigated the feasibility and clinical efficacy of balloon dilatation and subsequent retrievable stent insertion, when necessitated, for pyloric spasms after pylorus-preserving gastrectomy (PPG).

Materials and Methods

Forty-five patients experiencing pyloric spasms after PPG underwent fluoroscopic balloon dilations to alleviate obstructive symptoms due to delayed gastric emptying. Patients showing poor response to balloon dilation underwent subsequent retrievable stent insertion. Safety of the procedures was analyzed, and subjective symptoms and objective signs of pyloric spasms were analyzed and compared before and after treatment.

Results

Thirty-three patients (73.3%, 33/45) showed good response to balloon dilatation requiring no further treatment (balloon group). Conversely, 12 patients (26.7%, 12/45) showed poor or no response after balloon dilation requiring subsequent stent insertion (stent group). Balloon dilations and/or stent insertions were safely performed in all patients except one patient who suffered a transmural tear after balloon dilatation. In both groups, mean subjective symptom score was significantly improved and mean pyloric canal-to-height of the adjacent vertebral body ratio was significantly increased after the procedures (P <.05).

Conclusion

Balloon dilation is a safe and effective treatment for patients with pyloric spasms after PPG. In patients refractory to balloon dilations, retrievable stent placement can be a safe alternative tool.     

Impact of Postoperative Chemoradiotherapy versus Chemotherapy Alone on Recurrence and Survival in Patients with Stage II and III Upper Rectal Cancer: A Propensity Score-Matched Analysis

Purpose

To compare the impact of postoperative chemoradiotherapy (CRT) versus adjuvant chemotherapy alone on recurrence and survival in patients with stage II and III upper rectal cancer undergoing curative resection.

Materials and Methods

From our institutional database, 190 patients who underwent primary curative resection between 2003 and 2010 for stage II or III upper rectal cancer were identified. None of the patients received preoperative CRT. Of these, 136 patients received postoperative chemotherapy alone (the CTx group) and 54 patients received postoperative CRT (the CRT group). The CRT group had poorer prognostic features (pT4, pN2, poor differentiation, or involved resection margin) compared with the CTx group. To reduce the impact of treatment selection bias on treatment outcomes, propensity score-matching analysis was used.

Results

The matched cohort consisted of 50 CRT and 50 CTx patients with a median follow-up period of 76 and 63 months, respectively. In the matched cohort, CRT resulted in an improved 5-year local control (98.0% vs. 85.2%, p = 0.024) and overall survival rate (89.9% vs. 69.8%, p = 0.021) compared with CTx. In the subgroup analysis to identify subpopulations of patients that benefit most from receiving CRT, local recurrence did not occur in patients who did not have poor prognostic features regardless of the receipt of CRT. For patients with any poor prognostic features, CRT resulted in an improved 5-year local control compared with CTx (96.4% vs. 70.7%, p = 0.013).

Conclusions

After adjusting for clinicopathologic factors by propensity score-matching, postoperative CRT was associated with improved local control and overall survival in stage II and III upper rectal cancer. Our results suggest that surgery followed by chemotherapy alone is acceptable for patients who did not have poor prognostic features, while additional radiotherapy should be given for patients who have any poor prognostic features.     

Age-Related Changes in Sentence Production Abilities and Their Relation to Working-Memory Capacity: Evidence from a Verb-Final Language

Objectives

This study investigated the best predictor to capture age-related changes in passive-sentence production using a constrained sentence-production paradigm and explored the role of working-memory capacity in relation to the task demands of the sentence-production tasks.

Methods

A total of 60 participants participated in the study ranging in age from 21 to 86. All were administered a syntactic-priming and a sentence-completion task under either canonical or noncanonical word-order conditions.

Results

Age was significantly and negatively correlated with sentence-production tasks, and the most demanding condition with a noncanonical word order under the syntactic priming paradigm was the best predictor of aging. Working-memory capacity was significantly and positively correlated with all conditions, but the significant correlation remained only for the most demanding condition (the priming task with a noncanonical word order) after controlling for age.

Discussion

Sentence-production abilities were vulnerable to aging, and these effects manifested most clearly when the task demands were high enough to tax individuals’ cognitive capacity. Working-memory capacity partially accounted for age-related changes in sentence-production abilities.     

Response of primary rabbit kidney proximal tubule cells to estrogens

The effects of estrogens on the growth and function of primary rabbit kidney proximal tubule (RPT) cells have been examined in hormonally defined phenol red–free medium. 17β-estradiol was observed to stimulate growth at dosages as low as 10⁻¹⁰ M. The growth stimulatory effects of 17β-estradiol were mitigated in the presence of hydrocortisone, suggesting that these two steroid hormones acted at least in part by common mechanisms. The effects of other steroids known to interact with the estrogen receptor were examined. Alpha estradiol was found to be growth stimulatory over a concentration range of 10⁻⁹ to 10⁻⁸ M, albeit to a lower extent than beta estradiol. In addition, the anti-estrogen tamoxifen was also growth stimulatory (unlike the case with the human mammary tumor cell line MCF-7). The effects of several metabolic precursors of 17β-estradiol were examined, including testosterone, which was growth stimulatory, and progesterone, which was growth inhibitory. The growth stimulatory effects of 17β-estradiol, alpha estradiol, and tamoxifen could possibly be explained by their interaction with an estrogen receptor. Indeed, metabolic labelling and immunoprecipitation studies indicated the presence of such an estrogen receptor in the primary cultures. The rate of biosynthesis of the estrogen receptor was found to be affected by the presence of exogenously added 17β-estradiol. 17β-estradiol was also observed to increase the activity of two brush border enzymes, alkaline phosphatase and gamma glutamyl transpeptidase, during the growth phase of the primary cultures. J Cell Physiol 178:35–43, 1999. © 1999 Wiley-Liss, Inc.