An active particle can convert its internal energy into mechanical work. We study a generalized energy-depot model of an overdamped active particle in a ratchet potential. Using well-known biological parameters for kinesin-1 and modeling ATP influx as a pulsed energy supply, we apply our model to the molecular motor system. We find that our simple model can capture the essential properties of the kinesin motor such as forward stepping, stalling, backward stepping, dependence on ATP concentration, and stall force. Our model might be quite universal in the sense that it is able to describe dynamics of various types of motors as long as realistic parameters for each motor species are adopted.

Purpose

To analyze minimum 2-year clinical and radiological follow-up results of primary total knee replacement arthroplasty (TKRA) with metal block augmentation for tibial bony defect.

Materials and Methods

We analyzed 67 cases (52 patients) of primary TKRA with metal block augmentation for tibial bony defects from March 1999 and March 2008. Clinical results were evaluated using the Knee Society clinical rating system and the Western Ontario and McMaster University (WOMAC) score. Radiologic results were evaluated using the Knee Society roentgenographic evaluation system.

Results

The mean knee score and function score improved from 42.0 and 45.6 preoperatively to 94.5 and 85.4 postoperatively. At last follow-up, the mean WOMAC score was 16.8. The incidence of radiolucent lines was 10% (7 cases) during the follow-up period, but there was no case of progression. There were no statistically significant differences between the groups divided according to the block size (below 5 mm and over 8 mm) and between the stem and no-stem groups for all parameters.

Conclusions

Primary TKRA with a metal block produced satisfactory results for the minimum 2-year follow-up and can be considered as a simple and effective method for the treatment of tibial bony defect in primary TKRA.

Abstract

The efficiency of embryonic stem (ES) cell derivation relies on an optimized culture medium and techniques for treating preimplantation stage embryos. Recently, ES cell derivation from the preblastocyst developmental stage was reported by removing the zona pellucida from embryos of the most efficient strain for ES cell derivation (129Sv) during early preimplantation. Here, we showed that ES cells can be efficiently derived and maintained in a modified medium (MEMα), from preblastocysts of a low-efficiency mouse strain (a hybrid consisting of 50% B6, 25% CBA, and 25% DBA). Preblastocyst-derived ES cell lines were normal in terms of pluripotency-related protein expression, and chromosome number. Also, preblastocyst-derived ES cell lines from various culture conditions showed pluripotency in vivo through teratoma analysis. Interestingly, ES cell lines produced from preblastocysts and blastocysts, regardless of the derivation culture conditions, are nearly indistinguishable by their global gene expression profiles.

A bacterium designated M1-1 was isolated from the gills of a Korean rockfish, Sebastes schlegeli Hilgendorf, after high hydrostatic pressure processing. Studies of 16S rRNA phylogeny and comparative genomics demonstrated that the isolate belongs to Staphylococcus saprophyticus subsp. saprophyticus. Here, we report the draft genome sequence of S. saprophyticus subsp. saprophyticus M1-1 (KACC 16562).

AIM: To investigated the incidence of diversion colitis (DC) and impact of DC symptoms on quality of life (QoL) after ileostomy reversal in rectal cancer.

METHODS: We performed a prospective study with 30 patients who underwent low anterior resection and the creation of a temporary ileostomy for the rectal cancer between January 2008 and July 2009 at the Department of Surgery, Korea University Anam Hospital. The participants totally underwent two rounds of the examinations. At first examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom were performed 3-4 mo after the ileostomy creations. At second examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom and QoL were performed 5-6 mo after the ileostomy reversals. Clinicopathological data were based on the histopathological reports and clinical records of the patients.

RESULTS: At the first examination, all of the patients presented with inflammation, which was mild in 15 (50%) patients, moderate in 11 (36.7%) and severe in 4 (13.3%) by endoscopy and mild in 14 (46.7%) and moderate in 16 (53.3%) by histology. At the second examination, only 11 (36.7%) and 17 (56.7%) patients had mild inflammation by endoscopy and histology, respectively. There was no significant difference in DC grade between the endoscopic and the histological findings at first or second examination. The symptoms detected on the first and second questionnaires were mucous discharge in 12 (40%) and 5 (17%) patients, bloody discharge in 5 (17%) and 3 (10%) patients, abdominal pain in 4 (13%) and 2 (7%) patients and tenesmus in 9 (30%) and 5 (17%) patients, respectively. We found no correlation between the endoscopic or histological findings and the symptoms such as mucous discharge, bleeding, abdominal pain and tenesmus in both time points. Diarrhea was detected in 9 patients at the second examination; this number correlated with the severity of DC (0%, 0%, 66.7%, 33.3% vs 0%, 71.4%, 23.8%, 4.8%, P = 0.001) and the symptom-related QoL (r = -0.791, P < 0.001).

CONCLUSION: The severity of DC is related to diarrhea after an ileostomy reversal and may adversely affect QoL.

This paper reports that arrays of three-dimensional (3D), bowtie-shaped Au nanoparticle dimers can exhibit extremely high nonlinear absorption. Near-field interactions across the gap of the 3D bowties at the localized surface plasmon resonance wavelengths resulted in an increase of more than four orders of magnitude in local field intensity. The imaginary part of the third-order nonlinear susceptibility (Im χ(3)) for the 3D bowtie arrays embedded in a dielectric material was measured to be 10−4 esu, more than two orders of magnitude higher than reported for other metal nanoparticle-dielectric composites. Moreover, 3D dimers with increased nanoscale structure (such as folding) exhibited increased optical nonlinearity. These 3D nanoantennas can be used as critical elements for nanoscale nonlinear optical devices.

Gross hematuria secondary to vesical varices is an unusual presentation. We report such a case recurrent gross hematuria in a male patient who had a history of bladder substitution with ileal segments that had been treated by balloon-occluded percutaneous transhepatic obliteration of vesical varices.

MicroRNAs (miRNAs) participate in diverse biological functions and carcinogenesis by inhibiting specific gene expression. We previously reported that suppression of adenine nucleotide translocase 2 (ANT2) by using the short hairpin RNA (shRNA) approach has an antitumor effect in several cancer cells. We here examined the influence of ANT2 on expression of miRNAs in hepatocellular carcinoma (HCC) to further elucidate the tumor-suppressive mechanism of ANT2 shRNA. We first carried out screening for miRNAs, whose expression is regulated by ANT2 suppression in the Hep3B HCC cell line using miRNA microarrays. Validation of candidate miRNAs was done by incorporating clinical samples, and their effects on the tumorigenesis of HCC were studied in vitro and in vivo. miR-636 was one of the miRNAs whose expression was highly upregulated by ANT2 suppression in miRNA microarray analysis, as confirmed by real-time reverse transcription-polymerase chain reaction. Notably, miR-636 was markedly downregulated in HCC tissues compared with matched non-neoplastic liver in clinical samples. Restoration of miR-636 in Hep3B cells led to significant reduction of cell proliferation and colony formation. miR-636 restoration resulted in a decreased level of Ras, one of the putative targets of miR-636, and inactivation of its signaling pathway. Moreover, tumorigenesis was efficiently suppressed by miR-636 in an in vivo tumor xenograft model of HCC. The data suggest that miR-636 might function as a tumor suppressor miRNA affecting HCC tumorigenesis via downregulation of Ras, and that ANT2 suppression by shRNA could exert an anticancer effect by restoring miR-636 expression in HCC.

Patients with pulmonary arterial hypertension (PAH) and heart failure (HF) display many abnormalities in respiratory gas exchange. These abnormalities are accentuated with exercise and track with disease severity. However, use of gas exchange measures in day-to-day clinical practice is limited by several issues, including the large number of variables available and difficulty in data interpretation. Moreover, maximal exercise testing has limitations in clinical populations due to their complexity, patient anxiety and variability in protocols and cost. Therefore, a multivariable gas exchange index (MVI) that integrates key gas exchange variables obtained during submaximal exercise into a severity score that ranges from normal to severe-very-severe is proposed. To demonstrate the usefulness of this index, we applied this to 2 groups (PAH, n = 42 and HF, n = 47) as well as to age matched healthy controls (n = 25). We demonstrate that this score tracks WHO classification and right ventricular systolic pressure in PAH (r = 0.53 and 0.73, P ≤ 0.01) and NYHA and cardiac index in HF (r = 0.49 and 0.74, P ≤ 0.01). This index demonstrates a stronger relationship than any single gas exchange variable alone. In conclusion, MVI obtained from light, submaximal exercise gas exchange is a useful approach to simplify data interpretation in PAH and HF populations.

We report here a case of inguinal sparganosis, initially regarded as myeloid sarcoma, diagnosed in a patient undergone allogeneic hematopoietic transplantation (HSCT). A 56-year-old male patient having myelodysplastic syndrome was treated with allogeneic HSCT after myeloablative conditioning regimen. At day 5 post-HSCT, the patient complained of a painless palpable mass on the left scrotum and inguinal area. Pelvic magnetic resonance imaging and computed tomography revealed suspected myeloid sarcoma. Gun-biopsy was performed, and the result revealed eosinophilic infiltrations without malignancy. Subsequent serologic IgG antibody test was positive for sparganum. Excisional biopsy as a therapeutic diagnosis was done, and the diagnosis of sparganosis was confirmed eventually. This is the first report of sparganosis after allogeneic HSCT mimicking myeloid sarcoma, giving a lesson that the physicians have to consider the possibility of sparganosis in this clinical situation and perform adequate diagnostic and therapeutic approaches.

Background/Aims

The relationship between Runt-related transcription factor 3 (RUNX3) gene inactivation and various solid tumors has been reported; however, little information is available about RUNX3 in thyroid cancers.

Methods

We evaluated the DNA methylation of RUNX3 in 13 papillary thyroid cancer tissues and four thyroid cancer cell lines. Additionally, using reverse transcriptase-polymerase chain reaction, we analyzed RUNX3 gene expression in several thyroid cancer cell lines after treating with the demethylating agent 5-aza-2'-deoxycytidine (DAC).

Results

RUNX3 was hypermethylated in many thyroid cancer cell lines and in 10 of the 12 papillary thyroid cancer tissues. Treatment with DAC increased the expression of RUNX3 in some thyroid cancer cell lines.

Conclusions

We suggest that RUNX3 is associated with thyroid carcinogenesis, and RUNX3 methylation is a potentially useful diagnostic marker for papillary thyroid cancer.

Neural retina leucine zipper (Nrl), a key basic motif leucine zipper (bZIP) transcription factor, modulates rod photoreceptor differentiation by activating rod-specific target genes. In searching for factors that might couple with Nrl to modulate its transcriptional activity through posttranslational modification, we observed the novel interactions of Nrl with c-Jun N-terminal kinase 1 (JNK1) and HIV Tat-interacting protein 60 (Tip60). JNK1 directly interacted with and phosphorylated Nrl at serine 50, which enhanced Nrl transcriptional activity on the rhodopsin and Ppp2r5c promoters. Use of an inactive JNK1 mutant or treatment with a JNK inhibitor (SP600125) significantly reduced JNK1-mediated phosphorylation and transcriptional activity of Nrl in cultured retinal explants. We also found that Nrl activated rhodopsin and Ppp2r5c transcription by recruiting Tip60 to promote histone H3/H4 acetylation. The binding affinity of phospho-Nrl for Tip60 was significantly greater than that of the unphosphorylated Nrl. Thus, the histone acetyltransferase-containing Tip60 behaved as a coactivator in the Nrl-dependent transcriptional regulation of the rhodopsin and Ppp2r5c genes in the developing mouse retina. A transcriptional network of interactive proteins, including Nrl, JNK1, and Tip60, may be required to precisely control spatiotemporal photoreceptor-specific gene expression during retinal development.

Introduction

When a pulmonary nodular lesion is detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in a patient with post-surgical papillary thyroid carcinoma with undetectable serum-stimulated thyroglobulin levels and negative 131I whole body scan, diagnosis and management of the nodule may be confusing.

Case presentation

We describe two post-surgical patients with papillary thyroid carcinoma who showed pulmonary nodular lesions detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography. In both cases serum-stimulated thyroglobulin levels were undetectable and nodular lesions were not detected by 131I whole body scan. In the first case, a 64-year-old Asian woman showed one focal increased fluorodeoxyglucose uptake lesion in the right lower lobe of one of her lungs. Based on the histologic study, the pulmonary nodular lesion was diagnosed as a solitary pulmonary metastasis from papillary thyroid carcinoma. In the second case, a 59-year-old Asian woman showed a new pulmonary nodule in the right lower lobe. The computed tomography scan of her chest revealed a 9mm nodule in the anterior basal segment and another tiny nodule in the posterior basal segment of the right lower lobe. Six months later, both nodules had increased in size and miliary disseminated nodules were also seen in both lungs. Based on their histology, the pulmonary nodular lesions were considered to be primary lung adenocarcinoma.

Conclusions

The present cases emphasize that physicians should be cautious and make efforts for an accurate diagnosis of pulmonary nodules detected on F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid carcinoma with no evidence of metastasis such as negative 131I whole body scan and undetectable stimulated serum thyroglobulin levels.

Purpose

To identify the prostate cancer detection rate on the patients who had second prostate biopsy out of the patients who were reported negative in their first biopsy.

Materials and Methods

From July 2006 to February 2012, prostate biopsy was performed on 843 patients with over 4 ng/ml and on 618 biopsy negative patients PSA was performed from between 6 months and 9 months after biopsy. On 164 patients, second biopsy was performed, and 42 patients were selected. If there was less than 10% change between PSA before the prostate biopsy and PSA measured during 6 to 9 months after the first biopsy it was considered as no change. If above 10% increase, it was considered increase and if above 10% decrease it was considered as decrease.

Results

The cancer detection rate in PSA increase group was 20%, the detection rate in no change in PSA level but still over the normal range group 8.3%, and that in the PSA decrease group was 0%. When comparing prostate cancer group and non-cancer group, it is more probable to have prostate cancer when they are older, prostate volume is smaller and PSA density is higher.

Conclusions

The second biopsy is strongly recommended when PSA level shows no change or increase, age is older, prostate volume is smaller or PSA density is higher.

Genetic polymorphisms are important factors in the effects and toxicity of chemotherapeutics. To analyze the pharmacogenetic and ethnic differences in chemotherapeutics, major genes implicated in the treatment of acute lymphoblastic leukemia (ALL) were analyzed. Eighteen loci of 16 genes in 100 patients with ALL were analyzed. The distribution of variant alleles were CYP3A4*1B (0%), CYP3A5*3 (0%), GSTM1 (21%), GSTP1 (21%), GSTT1 (16%), MDR1 exon 21 (77%), MDR1 exon 26 (61%), MTHFR 677 (63%), MTHFR 1298 (29%), NR3C1 1088 (0%), RFC1 80 (68%), TPMT combined genotype (7%), VDR intron 8 (11%), VDR FokI (83%), TYMS enhancer repeat (22%) and ITPA 94 (30%). The frequencies of single nucleotide polymorphisms (SNPs) of 10 loci were statistically different from those in Western Caucasians. Dose percents (actual/planned dose) or toxicity of mercaptopurine and methotrexate were not related to any SNPs. Event free survival (EFS) rate was lower in ITPA variants, and ITPA 94 AC/AA variant genotypes were the only independent risk factor for lower EFS in multivariate analysis, which was a different pharmacogenetic implication from Western studies. This study is the first pharmacogenetic study in Korean pediatric ALL. Our result suggests that there are other possible pharmacogenetic factors besides TPMT or ITPA polymorphisms which influence the metabolism of mercaptopurine in Asian populations.

Changes in meat quality traits are strongly associated with alterations in postmortem metabolism which depend on genetic variations, especially nonsynonymous single nucleotide variations (nsSNVs) having critical effects on protein structure and function. To selectively identify metabolism-related nsSNVs, next-generation transcriptome sequencing (RNA-Seq) was carried out using RNAs from porcine liver, which contains a diverse range of metabolic enzymes. The multiplex SNV genotyping analysis showed that various metabolism-related genes had different nsSNV alleles. Moreover, many nsSNVs were significantly associated with multiple meat quality traits. Particularly, ch7:g.22112616A>G SNV was identified to create a single amino acid change (Thr/Ala) at the 145th residue of H1.3-like protein, very close to the putative 147th threonine phosphorylation site, suggesting that the nsSNV may affect multiple meat quality traits by affecting the epigenetic regulation of postmortem metabolism-related gene expression. Besides, one nonsynonymous variation, probably generated by gene duplication, led to a stop signal in porcine testicular carbonyl reductase (PTCR), resulting in a C-terminal (E281-A288) deletion. Molecular docking and energy minimization calculations indicated that the binding affinity of wild-type PTCR to 5α-DHT, a C21-steroid, was superior to that of C-terminal-deleted PTCR or human carbonyl reductase, which was very consistent with experimental data, reported previously. Furthermore, P284 was identified as an important residue mediating the specific interaction between PTCR and 5α-DHT, and phylogenetic analysis showed that P284 is an evolutionarily conserved residue among animal carbonyl reductases, which suggests that the C-terminal tails of these reductases may have evolved under evolutionary pressure to increase the substrate specificity for C21-steroids and facilitate metabolic adaptation. Altogether, our RNA-Seq revealed that selective nsSNVs were associated with meat quality traits that could be useful for successful marker-assisted selection in pigs and also represents a useful resource to enhance understanding of protein folding, substrate specificity, and the evolution of enzymes such as carbonyl reductase.

OBJECTIVE

To investigate whether waist circumference (WC), calf circumference (CC), and waist-to-calf ratio (WCR) are associated with carotid atherosclerosis in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

This was an observational study performed in 3,694 Korean patients with type 2 diabetes. Anthropometric measures and carotid ultrasound were performed on each subject. Carotid atherosclerosis was defined as having a clearly isolated focal plaque or mean carotid intima-media thickness (CIMT) ≥1.1 mm.

RESULTS

CIMT and the frequency of carotid atherosclerosis were higher with increasing WC quartiles and decreasing CC quartiles. There was an augmentative effect of CC and WC on the frequency of carotid atherosclerosis, which was dramatically higher in both the highest WC quartile and lowest CC quartile. However, except for the relationship between the quartile of CC with the frequency of carotid atherosclerosis in men, those associations disappeared after adjusting for potential confounders. In contrast, WCR was significantly related to CIMT (only in women) and carotid atherosclerosis, even after adjustment (adjusted odds ratio for carotid atherosclerosis for the highest quartile of WCR compared with the lowest quartile being 1.178 [95% CI 1.026–1.353] and 1.276 [1.053–1.545] in men and women, respectively).

CONCLUSIONS

A low CC and high WC seems to be associated with a carotid atherosclerotic burden in Korean diabetic patients. In particular, compared with each circumference, WCR is independently associated with carotid atherosclerosis. However, the cross-sectional nature of the study limits conclusions regarding the direction or causality. Further longitudinal study is warranted in this and other ethnic groups.

Purpose

We evaluated whether the clinicopathological factors of papillary thyroid microcarcinoma (PTMC), especially tumoe size, are associated with subcinical central lymph node metastasis.

Materials and Methods

A total of 160 patients diagnosed with PTMC who underwent total thyroidectomy with bilateral central lymph node dissection were enrolled in this study. All patients were clinically lymph node negative PTMC. Patients were divided into 2 groups according to the size of tumor (≤5 mm vs. >5 mm). Clinicopathologic risk factors for subclinical central lymph node metastasis were analyzed.

Results

Subclinical central lymph node metastasis was detected in 61 (38.1%). Patients with tumors ≤5 mm had a lower frequency of extrathyroidal extension, multifocality and subclinical central lymph node metastasis. On multivariate analysis, only male and tumor size >5 mm were independent predictors of subclinical central lymph node metastasis; age, multifocality, bilaterality, extrathyroidal extension, lymphvascular invasion and lymphocytic thyroiditis were not.

Conclusion

In this study, male and tumor size >5 mm were two independent predictive factors for subclinical central lymph node metastasis in PTMC. These are easier factors to assess before surgery than other factors when planning the central lymph node dissection. However, further long-term follow-up studies are needed to confirm the prognostic significance of subclinical central lymph node metastasis in PTMC.

Purpose

We aimed primarily to investigate the level of health-related quality of life (HRQoL), lower urinary tract symptoms (LUTS), and depression in older adults and secondly to identify the impact of LUTS and depression on HRQoL.

Methods

A community-based cross-sectional study was conducted from April to November 2010. Participants were recruited from five community senior centers serving community dwelling older adults in Jeju city. Data analysis was based on 171 respondents. A structured questionnaire was used to guide interviews; the data were collected including demographic characteristics, body mass index, adherence to regular exercise, comorbidities (hypertension, diabetes mellitus, and osteoarthritis), depression, urinary incontinence, LUTS (measured via the International Prostate Symptom Score [IPSS]), and HRQoL as assessed by use of the EQ-5D Index. Stepwise multiple regression analysis was used to test predictors of HRQoL.

Results

Eighteen percent (18.6%) of the respondents reported depressive symptoms. The mean LUTS score was 8.9 (IPSS range, 0 to 35). The severity of LUTS, was reported to be mild (score, 0 to 7) by 53% of the respondents, moderate (score, 8 to 19) by 34.5%, and severe (score, 20 to 35) by 12.5%. HRQoL was significantly predicted by depression (Partial R2=0.193, P<0.01) and LUTS (Partial R2=0.048, P=0.0047), and 24% of the variance in HRQoL was explained.

Conclusions

LUTS and depression were the principal predictors of HRQoL in older adults.

AIM: To evaluate the impact of surgical volume on nationwide hospital mortality after pancreaticoduodenectomy (PD) for periampullary tumors in South Korea.

METHODS: Periampullary cancer patients who underwent PD between 2005 and 2008 were analyzed from the database of the Health Insurance Review and Assessment Service of South Korea. A total of 126 hospitals were divided into 5 categories, each similar in terms of surgical volume for each category. We used hospital mortality as a quality indicator, which was defined as death during the hospital stay for PD, and calculated adjusted mortality through multivariate logistic models using several confounder variables.

RESULTS: A total of eligible 4975 patients were enrolled in this study. Average annual surgical volume of hospitals was markedly varied, ranging from 215 PDs in the very-high-volume hospital to < 10 PDs in the very-low-volume hospitals. Admission route, type of medical security, and type of operation were significantly different by surgical volume. The overall hospital mortality was 2.1% and the observed hospital mortality by surgical volume showed statistical difference. Surgical volume, age, and type of operation were independent risk factors for hospital death, and adjusted hospital mortality showed a similar difference between hospitals with observed mortality. The result of the Hosmer-Lemeshow test was 5.76 (P = 0.674), indicating an acceptable appropriateness of our regression model.

CONCLUSION: The higher-volume hospitals showed lower hospital mortality than the lower-volume hospitals after PD in South Korea, which were clarified through the nationwide database.