Da Vinci SP robotic approach to colorectal surgery: two specific indications and short-term results.

BACKGROUND: Da Vinci® Single Port (dvSP) was recently developed. Its application in colorectal surgery is under investigation. The aim of this study was to explore the safety and feasibility of dvSP for intersphincteric (dvSP-ISR), right colectomy (dvSP-RC), and transverse colectomy (dvSP-TC). Surgical indication and short-term results were analyzed. METHODS: All consecutive patients from a prospective database of patients who underwent dvSP-ISR, dvSP-RC, and dvSP-TC at Korea University Anam Hospital from November 2020 to December 2021, were analyzed. Perioperative, pathological, and oncological short-term outcomes were analyzed. RESULTS: A total of 7 dvSP-ISR, 5 dvSP-RC, and 1 dvSP-TC were performed. Median age was 56.0 (55.0-61.0) years for the dvSP-ISR and 54.0 (44.7-63.5) years for the dvSP-RC/TC. Median body mass index was 22.8 (17.1-24.8) kg/m2 for the dvSP-ISR and 23.6 (20.8-26.9) kg/m2 for the dvSP-RC/TC. All dvSP-ISR patients received neoadjuvant long-course chemoradiotherapy, including one patient with squamocellular carcinoma who was treated with 5-fluorouracil (5-FU)/mitomycin. All other patients, excluding one dvSP-RC patient with Crohn's disease, had an adenocarcinoma. Median operation time was 280 (240-370) minutes for the dvSP-ISR and 220 (201-270) minutes for the dvSP-RC/TC. Estimated blood loss was insignificant. No intraoperative complications or conversions to multiport/open surgery was reported. Median post-operative stay was 7.0 (6.0-10.0) days for the dvSP-ISR and 5.0 (4.0-6.7) days for the dvSP-RC/TC. Quality of mesorectum was complete for six patients, and nearly complete for one. Median number of retrieved lymph nodes were 21 (17-25) for the dvSP-ISR and 28 (24-49) for the dvSP-RC/TC. Proximal and distal resection margins were tumor free. Four patients experienced post-operative complications not related to the platform which were: ileus, voiding dysfunction, infected pelvic hematoma, and wound infection. Median follow-up was 9 (6-11) months and 11 (7-17) months for the dvSP-ISR and dvSP-RC/TC, respectively. Two patients had systemic recurrence; all others were tumor free. CONCLUSIONS: The dvSP platform is safe and feasible for intersphincteric resection with right lower quadrant access, and right/transverse colectomy with suprapubic access. Further studies are needed to evaluate benefit differences compared to multiport robotic platform.

A multicentre comparative study between laparoscopic and open surgery for intussusception in adults.

AIM: Intussusception in adults is rare and requires surgery in most cases. While abdominal laparoscopic surgery (LS) is becoming more popular, there are few reports on the outcomes of adult intussusception treated with LS. This study compared the feasibility of LS vs open surgery (OS) for adult intussusception. METHOD: We reviewed retrospectively the medical records of adult patients with intussusception from three tertiary hospitals between 2000 and 2016. The patients were divided into LS and OS groups, and their surgical outcomes were compared. RESULTS: Surgery was indicated in 71 patients with intussusception (41 LS and 30 OS). The median age of the patients was 49.0 and 51.5 years in the LS and OS groups, respectively (P = 0.930). Overall, nine (12.7%) patients had a negative laparotomy or laparoscopy with spontaneous reduction of the intussusception. Conversion to OS from LS was necessary in one patient (2.4%). The operative time and intra-operative and postoperative complication rates were not significantly different. However, there were more serious complications such as bowel perforation and major vessel injury in the LS group. The patients in the LS group had a shorter time to first food intake and hospital stay vs patients in the OS group (4.0 vs 6.0 days, P < 0.001, and 7.0 vs 10.5 days, P < 0.001, respectively). CONCLUSION: LS may be feasible for adult intussusception; there may be more severe intra-operative complications than in OS.

Safety, feasibility, and short-term outcomes in 588 patients undergoing minimally invasive ileal pouch-anal anastomosis: a single-institution experience.

PURPOSE: A laparoscopic approach to proctocolectomy and ileal pouch-anal anastomosis (IPAA) in patients with chronic ulcerative colitis and familial adenomatous polyposis has grown in popularity secondary to reports of small series demonstrating short-term patient benefits. Limited data exist in large numbers of patients undergoing laparoscopic ileal pouch-anal anastomosis (L-IPAA). We aimed to analyze surgical outcomes in a large cohort of patients undergoing L-IPAA. METHODS: From a prospectively maintained surgical database, 30-day surgical outcome data were reviewed for all L-IPAA performed for chronic ulcerative colitis and familial adenomatous polyposis from 1999 to 2012. Demographics, operative approach, and operative and postoperative complications were analyzed. RESULTS: A total of 588 L-IPAA ileal pouch-anal anastomoses were performed predominantly for chronic ulcerative colitis (93.9 %). The mean age was 36.2 years, and 54.3 % were male, with a mean BMI of 24.1 kg/m(2). Three-stage operations were performed in 17.7 %. The mean operating time of the patients excluding 3-stage operation was 269.4 min. Minimally invasive techniques included hand-assist in 55 % and straight laparoscopy in 45 %. Conversion to open occurred in 8.8 %. Median length of stay was 5 days. There was no mortality. Complications occurred in 36.9 % of patients: Clavien grade I (17.5 %), grade II (72.8 %), and grade III (9.7 %). Analysis of the grouped data over time demonstrated a statistically significant reduction in operative time (p < 0.001) and an increase in the ratio of hand-assisted over straight laparoscopy (p = 0.001). CONCLUSIONS: Minimally invasive IPAA performed using either a laparoscopic or hand-assisted technique is safe, can be performed with low conversion rates, and confers beneficial perioperative outcomes.

NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism.

OBJECTIVE: Obesity is a major health problem associated with high morbidity and mortality. NSAID-activated gene (NAG-1) is a TGF-ß superfamily member reported to alter adipose tissue levels in mice. We investigated whether hNAG-1 acts as a regulator of adiposity and energy metabolism. DESIGN/SUBJECTS: hNAG-1 mice, ubiquitously expressing hNAG-1, were placed on a control or high-fat diet for 12 weeks. hNAG-1-expressing B16/F10 melanoma cells were used in a xenograft model to deliver hNAG-1 to obese C57BL/6 mice. RESULTS: As compared with wild-type littermates, transgenic hNAG-1 mice have less white fat and brown fat despite equivalent food intake, improved glucose tolerance, lower insulin levels and are resistant to dietary- and genetic-induced obesity. hNAG-1 mice are more metabolically active with higher energy expenditure. Obese C57BL/6 mice treated with hNAG-1-expressing xenografts show decreases in adipose tissue and serum insulin levels. hNAG-1 mice and obese mice treated with hNAG-1-expressing xenografts show increased thermogenic gene expression (UCP1, PGC1α, ECH1, Cox8b, Dio2, Cyc1, PGC1ß, PPARα, Elvol3) in brown adipose tissue (BAT) and increased expression of lipolytic genes (Adrb3, ATGL, HSL) in both white adipose tissue (WAT) and BAT, consistent with higher energy metabolism. CONCLUSION: hNAG-1 modulates metabolic activity by increasing the expression of key thermogenic and lipolytic genes in BAT and WAT. hNAG-1 appears to be a novel therapeutic target in preventing and treating obesity and insulin resistance.

Sarcopenia and sarcopenic obesity and their association with dyslipidemia in Korean elderly men: the 2008-2010 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Recently, aging has been shown to be associated with sarcopenic obesity (SO), of which decreased muscle mass and increased fat mass are features. Sarcopenia and obesity alone are known to be associated with abnormal lipid metabolism. However, it remains unclear whether SO has greater adverse effects on dyslipidemia than on sarcopenia or obesity alone. AIM: We aimed to investigate the association between SO and dyslipidemia in elderly Koreans. SUBJECTS AND METHODS: This study was based on data collected during the 2008-2010 Korea National Health and Nutrition Examination Survey. We included 1,466 men and 2,017 women aged 65 years and over. Sarcopenia was indicated in participants with height- or weight-adjusted appendicular skeletal muscle that was 1 standard deviation below the sex-specific mean for the young reference group, and obesity was defined as a body mass index ≥ 25 kg/m(2). Dyslipidemia was defined according to the National Cholesterol Education Program-Adult Treatment Panel III. RESULTS: After adjusting for confounding factors, the SO group had a higher risk for dyslipidemia [odds ratio (OR) 2.82 (95 % confidence interval 1.76-4.51)] than the obese group [2.12 (1.11-4.07)] and sarcopenic group [1.46 (1.01-2.11)] (p < 0.001) only in men. Furthermore, the SO group in men had the highest OR for hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, hyper-low-density lipoprotein cholesterolemia, and a high ratio of triglyceride to high-density lipoprotein cholesterol even after further adjustments. CONCLUSIONS: In Korean elderly men, SO was associated with an increased risk for dyslipidemia compared with sarcopenia or obesity alone.

Complete mesocolic excision with D3 lymph node dissection in laparoscopic colectomy for stages II and III colon cancer: long-term oncologic outcomes in 168 patients.

BACKGROUND: There is emerging evidence that complete mesocolic excision (CME) for colon cancer produces favorable oncologic outcomes. The applicability of CME technique in laparoscopic colectomy has not been fully explored. The aim of our retrospective study was to evaluate the feasibility of the CME technique with D3 lymphadenectomy in laparoscopic colectomy and its short- and long-term outcomes. METHODS: Between September 2006 and December 2009, 168 laparoscopic colectomies were performed for stages II and III colon cancer. Prospectively, collected data on demographics, tumor characteristics, complications, and outcomes were analyzed retrospectively. RESULTS: Eighty-seven patients (51.8 %) had stage II colon cancer, and 81 patients had stage III cancer. The mean operative time was 196.0 ± 61.2 min. The overall morbidity rate was 17.8 %, which included anastomotic leak in 10 patients (5.9 %). There was no operative mortality. The number of lymph nodes harvested was 27.8 ± 13.6. With a median follow-up of 57.3 months, locoregional recurrence and systemic metastasis developed in 6 (3.6 %) and 14 patients (8.3 %), respectively. Seven patients died of causes related to cancer, and all had stage III cancer. Disease-free survival at 5-years was 95.2 % for patients with stage II and 80.9 % for patients with stage III. CONCLUSIONS: Standardization of laparoscopic CME and D3 lymphadenectomy is expedient. The technique is associated with acceptable morbidity and provides excellent oncologic outcomes for stage II and stage III colon cancer. A longer follow-up is needed to validate the enhancement of oncological outcome related to this surgical concept.

Magnetic Resonance Imaging-Negative Cerebral Amyloid Angiopathy: Cerebrospinal Fluid Amyloid-ß42 over Amyloid Positron Emission Tomography.

BACKGROUND: Cerebral amyloid angiopathy (CAA) pathology is becoming increasingly important in Alzheimer's disease (AD) because of its potential link to amyloid-related imaging abnormalities, a critical side effect observed during AD immunotherapy. Identification of CAA without typical magnetic resonance imaging (MRI) markers (MRI-negative CAA) is challenging, and novel detection biomarkers are needed. METHODS: We included 69 participants with high neuritic plaques (NP) burden, with and without CAA pathology (NP with CAA vs. NP without CAA) based on autopsy data from the Alzheimer's Disease Neuroimaging Initiative. Two participants with hemorrhagic CAA markers based on MRI were excluded and the final analysis involved 36 NP without CAA and 31 NP with CAA. A logistic regression model was used to compare the cerebrospinal fluid (CSF) amyloid-ß42 (Aß42), phosphorylated tau181, and total tau levels, the amyloid positron emission tomography (PET) standardized uptake ratio (SUVR), and cognitive profiles between NP with and without CAA. Regression models for CSF and PET were adjusted for age at death, sex, and the last assessed clinical dementia rating sum of boxes score. Models for cognitive performances was adjusted for age at death, sex, and education level. RESULTS: NP with CAA had significantly lower CSF Aß42 levels when compared with those without CAA (110.5 pg/mL vs. 134.5 pg/mL, p-value = 0.002). Logistic regression analysis revealed that low CSF Aß42 levels were significantly associated with NP with CAA (odds ratio [OR]: 0.957, 95% confidence interval [CI]: 0.928, 0.987, p-value = 0.005). However, amyloid PET SUVR did not differ between NP with CAA and those without CAA (1.39 vs. 1.48, p-value = 0.666). Logistic regression model analysis did not reveal an association between amyloid PET SUVR and NP with CAA (OR: 0.360, 95% CI: 0.007, 1.741, p-value = 0.606). CONCLUSIONS: CSF Aß42 is more sensitive to predict MRI-negative CAA in high NP burden than amyloid PET.

Stylet- or forceps-guided tube exchanger to facilitate GlideScope intubation in simulated difficult intubations--a randomised controlled trial.

The GlideScope videolaryngoscope is widely used in the management of the difficult airway. However, passing the tracheal tube through the vocal cords can be awkward, and the use of a stylet to guide insertion is recommended. This randomised controlled trial evaluated a forceps-guided tube exchanger as an alternative to the stylet to aid intubation with the GlideScope in patients undergoing anaesthesia, with a simulated difficult airway created by the application of a semi-rigid cervical collar. Data were analysed from 178 patients randomly assigned to undergo intubation using either the stylet (n = 88) or a forceps-guided tube exchanger (n = 90). All intubations were completed successfully, with first attempt rates of 93.2% using the stylet and 94.4% using the exchanger (p = 0.597). The mean (SD) intubation time was 67.8 (28.7) s in the stylet group and 66.1 (15.5) s in the forceps-guided tube exchanger group (p = 0.11). The frequency of sore throat 1 h after extubation was 34.1% in the stylet group and 2.2% in the tube exchanger group (p < 0.001); 24 h after extubation the corresponding figures were 40.0% and 11.1% (p < 0.001). Using a forceps-guided tube exchanger may offer an advantage over a stylet in guiding tracheal intubation when the GlideScope is used.

NAG-1/GDF15 transgenic mouse has less white adipose tissue and a reduced inflammatory response.

NAG-1/GDF15 is a TGF- ß superfamily member with poorly characterized biological activity proposed to inhibit inflammatory cytokine production. Transgenic mice expressing human NAG-1/GDF15 (NAG-1 (Tg/Lox) ) are leaner with lower body weight and are resistant to chemically or genetically induced intestinal tumors. Because of the link between obesity, inflammation, and cancer, we examined whether these mice exhibit a reduced response to inflammatory stimuli. The NAG-1 (Tg/Lox) mice had a reduced inflammatory response to LPS based on the serum levels of cytokines KC, IL-6, MCP-1, and TNF α . In contrast to literature reports and our in vivo results, NAG-1 did not inhibit LPS-induced cytokine expression in vitro in RAW264.7 cells, mouse peritoneal macrophages, or mouse liver Kupffer cells, suggesting that NAG-1/GDF15 does not directly inhibit LPS-induced inflammatory cytokine production. However, NAG-1 (Tg/Lox) mice have less white adipose tissue, the major source of inflammatory adipokines including leptin. Basal and LPS-treated serum leptin and mRNA levels in the adipose tissue of NAG-1 (Tg/Lox) mice were lower than those in WT mice. We propose that the reduced white adipose tissue and reduced leptin expression may be responsible, in part, for the reduced inflammatory response to LPS and the decrease in intestinal tumors observed in NAG-1 (Tg/Lox) mice.

Risk factors for local recurrence and long term survival after minimally invasive intersphincteric resection for very low rectal cancer: Multivariate analysis in 161 patients.

INTRODUCTION: Intersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR. MATERIALS AND METHODS: Retrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis. RESULTS: Median follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976-6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941-11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015-9.838); p < 0.001) was a prognostic factor on multivariate analysis. CONCLUSIONS: This study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS.

Review paper: Cancer chemopreventive compounds and canine cancer.

Canine cancer has become more prevalent in recent years because of increased life expectancy and greater attention to the health of pets. The range of cancers seen in dogs is as diverse as that in human patients, and despite more intensive therapeutic interventions, fatality rates remain unacceptably high in both species. Chemoprevention is therefore an important means of confronting this disease. Because domestic pets share our environment, greater cross-application and study of the protumorigenic and antitumorigenic factors in our shared environment will benefit all species, leading to the development of new families of less toxic antitumorigenic compounds based on novel and established molecular targets. Currently, the most interesting cancer preventive agents are nonsteroidal anti-inflammatory drugs, peroxisome proliferator-activated receptor-gamma ligands, and dietary compounds. This article provides an overview of what is known about how these agents affect molecular signaling in neoplastic disease, with reference to reported application and/or study in dogs where available.

Infrared vacuum-ultraviolet laser pulsed field ionization-photoelectron study of CH3Br+ (X(2)E(3/2)).

By preparing methyl bromide (CH3Br) in selected rotational levels of the CH3Br(X(1)A1; v1 = 1) state with infrared (IR) laser excitation prior to vacuum-ultraviolet (VUV) laser pulsed field ionization-photoelectron (PFI-PE) measurements, we have observed rotationally resolved photoionization transitions to the CH3Br(+)(X(2)E(3/2); v1(+) = 1) state, where v1 and v1(+) are the symmetric C-H stretching vibrational mode for the neutral and cation, respectively. The VUV-PFI-PE origin band for CH3Br(+)(X(2)E(3/2)) has also been measured. The simulation of these IR-VUV-PFI-PE and VUV-PFI-PE spectra have allowed the determination of the v1(+) vibrational frequency (2901.8 +/- 0.5 cm(-1)) and the ionization energies of the origin band (85 028.3 +/- 0.5 cm(-1)) and the v1(+) = 1 <-- v1 = 1 band (84 957.9 +/- 0.5 cm(-1)).

Combined surgery and postoperative radiotherapy for oropharyngeal squamous cell carcinoma in Korea: analysis of 110 cases.

The treatment of oropharyngeal squamous cell carcinoma (OSCC) remains controversial. This study reviews the authors' experience of treating OSCC, evaluates the oncologic outcome and assesses the factors affecting local/regional recurrence. A retrospective analysis of 110 consecutive OSCC patients treated primarily by surgery and/or postoperative radiotherapy was carried out. 82% of patients had advanced disease (stage III or IV). The 5-year overall survival and disease specific survival rates (DSSR) were 58% and 65%, respectively. The DSSR of the soft palate or posterior pharyngeal wall, tonsillar area, and base of tongue were 80%, 62%, and 51%, respectively (P<0.05). The 5-year DSSR according to the American Joint Committee on Cancer stages was 94% for early stage and 56% for advanced stage (P<0.05). The overall recurrence rate was 38% (42 patients). The most frequent site of recurrence was the neck (46%). Only 14% of patients with recurrences were treated successfully. Positive resection margins and the presence of pathologic lymph nodes influenced the recurrence at the primary lesion and in the neck, respectively, in a statistically significant manner. Surgery and postoperative radiotherapy provided a superior outcome in patients with advanced OSCC. A randomized study is required to assess the oncologic and functional superiority of surgery or chemoradiation.

Expression of Gab1 lacking the pleckstrin homology domain is associated with neoplastic progression.

An in vitro transformation system of carcinogen-treated Syrian hamster embryo (SHE) cell cultures represents multistep genetic and nongenetic changes that develop during the neoplastic progression of normal cells to tumor cells in vivo. During this neoplastic progression, SHE cells demonstrate an altered response to epidermal growth factor (EGF). In the present report, we examined the role of the adapter protein Gab1 (Grb2-associated binder-1) in the neoplastic progression of SHE cells. We used two asbestos-transformed SHE cell clones in different neoplastic stages: a 10W+8 clone, which is immortal and retains the ability to suppress the tumorigenicity of tumor cells in cell-cell hybrid experiments, and a 10W-1 clone, which has lost this tumor suppressor ability. 10W+8 cells expressed full-length 100-kDa Gab1 and associated 5.2-kb mRNA. Upon repeated cell passaging, 10W-1 cells showed increasing expression of a novel 87-kDa form of Gab1 as well as 4.6-kb mRNA with diminishing expression of the original 100-kDa Gab1. cDNA encoding the 87-kDa Gab1 predicts a form of Gab1 lacking the amino-terminal 103 amino acids (Gab1(Delta1-103)), which corresponds to loss of most of the pleckstrin homology (PH) domain. Gab1(Delta1-103) retains the ability to be phosphorylated in an EGF-dependent manner and to associate with the EGF receptor and SHP-2 upon EGF stimulation. The endogenous expression of Gab1(Delta1-103) in 10W-1 cells appeared closely related to EGF-dependent colony formation in soft agar. Moreover, transfection and expression of Gab1(Delta1-103), but not Gab1, in 10W+8 cells enhanced their EGF-dependent colony formation in soft agar. These results demonstrate that Gab1 is a target of carcinogen-induced transformation of SHE cells and that the expression of a Gab1 variant lacking most of the PH domain plays a specific role in the neoplastic progression of SHE cells.

NAG-1/GDF15 accumulates in the nucleus and modulates transcriptional regulation of the Smad pathway.

Protein dynamics, modifications and trafficking are all processes that can modulate protein activity. Accumulating evidence strongly suggests that many proteins have distinctive roles dependent on cellular location. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor-ß (TGF-ß) superfamily protein that has a role in cancer, obesity and inflammation. NAG-1 is synthesized and cleaved into a mature peptide, which is ultimately secreted into the extracellular matrix (ECM). In this study, we have found that full-length NAG-1 is expressed in not only the cytoplasm and ECM, but also in the nucleus. NAG-1 is dynamically moved to the nucleus, exported into cytoplasm and further transported into the ECM. We have also found that nuclear NAG-1 contributes to inhibition of the Smad pathway by interrupting the Smad complex. Overall, our study indicates that NAG-1 is localized in the nucleus and provides new evidence that NAG-1 controls transcriptional regulation in the Smad pathway.

Robotic rectal cancer surgery: literature review and perspective.

Surgical treatment of patients with rectal cancer is challenging. The concept of robotic surgery is attractive and has earned considerable interest after its successful implementation in the fields of urology and gynecology. Recently, robotic surgery for rectal cancer with total mesorectal excision (TME) has also obtained an increasing amount of attention in the colorectal field. In this review, we introduce the commonly performed methods of robotic rectal surgery and discuss results to date and future perspectives.

Genomic structure and polymorphism of the human thromboxane synthase-encoding gene.

Thromboxane synthase (TS) is a cytochrome P-450 (CYP450) enzyme catalyzing the conversion of prostaglandin endoperoxide (PGH2) into thromboxane A2 (TxA2) which plays a crucial role in hemostasis and cardiovascular diseases. Twelve genomic clones containing the DNA encoding the human TS gene (hTS) were isolated and characterized to determine the exon/intron boundaries and restriction maps of the nearly contiguous structure of the gene. The hTS contains 13 exons spanning more than 150 kb. Its first five exons, divided by relatively large introns, spread over 100 kb, but encode less than one third of the full-length TS transcript. Southern analysis indicates that the human haploid genome contains a single copy of the TS gene. Although multiple transcription start points (tsp) are utilized, transcription of hTS is primarily TATA-independent, as determined by promoter-directed reporter gene expression in transfected cells. A dinucleotide (CA) repetitive sequence identified in the ninth intron of the gene exhibits allelic polymorphism. At least four distinctive alleles, containing from 13 to 20 copies of the CA repeats, have been detected.

The porcine thromboxane synthase-encoding cDNA: sequence, mRNA expression and enzyme production in Sf9 insect cells.

A full-length cDNA encoding porcine thromboxane synthase (TS) was isolated and sequenced. The open reading frame encodes a 534-amino acid (aa) protein (M(r) 60,451) which shares more than 75% identity with TS from other species and is 30% homologous to several enzymes of the cytochrome P-450 III family. Sequence comparison among porcine (p), human (h), and murine (m) TS indicated conservation of eight Cys residues and one putative N-glycosylation site. Several highly conserved regions were identified at the near N terminus, middle and C terminus. The most divergent region lies at aa residues 290-325, within which a Lys308 residue was unique to pTS. Between aa residues 70 and 90, considerable divergence was observed in mTS. Northern analysis showed that the pTS gene was expressed as a 2.3-kb transcript primarily in lung, kidney and thymus. A high-titer recombinant (re-) baculovirus containing pTS cDNA was developed to conduct a time course study of enzyme production in Spodoptera frugiperda (Sf9) cells. TS activity was detectable in the microsomes of Sf9 cells 12-h post-infection and reached maximum by 48 h. The produced TS resembles purified pTS in catalysis, as well as inhibition by a substrate analog inhibitor.

Evaluation of eicosanoids and NSAIDs as PPARgamma ligands in colorectal carcinoma cells.

The activation of peroxisome proliferator activated receptor gamma (PPARgamma) may play a role in the control of colorectal carcinogenesis. The expression of PPARgamma was examined by Western blotting in human colorectal tumors and matched normal adjacent tissues, as well as in various colorectal carcinoma cell lines. In the tissues, the expression of PPARgamma was elevated in tumors relative to the adjacent normal tissues. Each colorectal carcinoma cell line expressed PPARgamma. The ability of various eicosanoids to bind PPARgamma in colorectal carcinoma cells was investigated using luciferase reporter assays. The well-known PPARgamma ligands, troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2) strongly induced PPARgamma binding activity. Products of lipoxygenases displayed moderate binding activity, while other prostaglandins and fatty acids displayed little or no reporter activation. The activation of PPARgamma by 13(S)-HODE, the major metabolite of 15-lipoxygenase-1 from linoleic acid, was concentration dependent reaching maximum at 10 micro M (35-fold activation). The endogenous production of 13(S)-HODE by expression of 15-LO-1 did not activate PPARgamma. The ability of various nonsteroidal anti-inflammatory drugs (NSAIDs) to induce PPARgamma activation was also evaluated. The conventional NSAIDs that inhibit both cyclooxygenases (COX-1 and COX-2) also induced PPARgamma binding activity. In general, however, neither COX-1- nor COX-2-specific inhibitors induced the activation of PPARgamma. Taken together, the metabolites of 15-lipoxygenase and the conventional NSAIDs were confirmed as exogenous ligands for PPARgamma in colorectal carcinoma cells.

High intraocular pressure is associated with cardiometabolic risk factors in South Korean men: Korean National Health and Nutrition Examination Survey, 2008-2010.

OBJECTIVE: Elevated intraocular pressure (IOP) contributes to the progression of visual defects such as glaucoma. This study determined whether metabolic syndrome (MetS) and cardiovascular risk factors are associated with IOP in South Korean men. METHODS: We analyzed data on 4875 men who participated in the Korean National Health and Nutrition Examination Survey 2008-2010. We recorded the values for age, weight, height, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), insulin, homeostasis model assessment of estimated insulin resistance (HOMA-IR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), non-HDL-C (NHDL-C), and TG/HDL-C, as well as sociodemographic factors. IOP was measured using Goldmann applanation tonometry. RESULTS: Weight, BMI, WC, SBP, DBP, FBG, insulin, HOMA-IR, TC, LDL-C, TG, NHDL-C, TG/HDL-C, and the prevalence of MetS differed significantly among the three groups with IOP (P<0.05). Mean IOP was higher in subjects who were obese and had hypertension, diabetes mellitus, MetS, abdominal obesity, high TG, high FBG, or high BP compared with normal subjects (P<0.005). Analysis using Pearson's correlation coefficient showed that all cardiometabolic risk factors were significantly associated with IOP (P<0.005), with the exception of WC and HDL-C. A multivariate linear regression analysis showed that IOP was positively correlated with BMI, SBP, DBP, FBG, HOMA-IR, TC, LDL-C, TG, NHDL-C, and TG/HDL-C after adjusting for all covariates (all P<0.05). CONCLUSIONS: Cardiometabolic risk factors, including the components of MetS, are associated with increased IOP.