Distribution of the tensor of the vastus intermedius.

The tensor of the vastus intermedius (TVI) was first described by Grob et al. in 2016. It originates from the anteroinferior greater trochanter and inserts into the upper patella and receives blood and nerves independently of other muscles. It has been overlooked, but since micro-surgery and detailed rehabilitation treatments are being developed, more research on it is warranted. Here we report on the TVI in a Korean cadaveric study. A total of 58 cadavers (41 males and 17 females) were included. Thighs were examined using a standardized dissection protocol. The quadriceps femoris muscle was identified and its components were defined by blunt dissection. A total of 116 lower limbs were dissected. In 40 of them, there was a separately innervated TVI muscle belly between the fasciae of the vastus lateralis (VL) and the vastus intermedius (VI) muscles. TVIs were classed as independent (ID), VI, and VL types according to the relative relationship between the TVI, VL, and VI, and subdivided into two parts: Part 1 was the proximal muscular portion of the TVI attached to the VL or VI, and part 2 was the distal aponeurotic area. TVIs were analyzed in detail via 58 Korean cadavers. We subdivided them on the basis of their location and association with related muscles. A larger study is needed to clarify the function and prevalence of the TVI.

Anatomical Characteristics of the Anterior Jugular Vein and Its Clinical Relevance.

INTRODUCTION: The anterior jugular vein (AJV) is part of the superficial venous drainage system of the head and neck. Recently, interest in AJV is increasing as various surgical procedures have been developed. The authors conducted a cadaveric study to determine characteristics of AJV in Koreans. METHODS: A total of 44 cadavers were dissected. Anatomical characteristics were analyzed for 34 cadavers in which AJV was well observed. RESULTS: In this study, 21 were males and 13 were females. There were 8 cadavers with only 1 AJV from both sides. There was no significant difference in anatomical characteristics according to gender or AJV variation except for a difference in the length of the neck according to gender. However, it was possible to find a safety zone at the main landmark of the neck that could avoid AJV damage. CONCLUSIONS: By using this safety zone, it is possible to prevent damage to the AJV and reduce complications during various surgical procedures on the head and neck.

Delta neutrophil index: A reliable marker to differentiate perforated appendicitis from non-perforated appendicitis in the elderly.

BACKGROUND: Delta neutrophil index (DNI) is a new inflammatory marker and the present study aimed to evaluate the predictive value of the DNI for the presence of a perforation in elderly with acute appendicitis. METHODS: This retrospective observational study was conducted on 108 consecutive elderly patients (≥65 years old) with acute appendicitis treated over a 24-month period. RESULTS: Sixty-nine of the 108 patients (median, IQR: 72, 67-77 years) were allocated to the perforated appendicitis group (63.9%) and 39 to the non-perforated appendicitis group (36.1%). WBC, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and DNI were significantly higher in the perforated group. In multiple logistic regression analyses, initial DNI was the only independent marker that can significantly predict the presence of perforation in multiple regression [odds ratio 9.38, 95% confidence interval (2.51-35.00), P=.001]. Receiver operator characteristic curve analysis showed that DNI is a good predictor for the presence of appendiceal perforation at an optimal cut-off for DNI being 1.4% (sensitivity 67.7%, specificity 90.0%, AUC 0.807). CONCLUSION: Clinicians can reliably differentiate acute perforated appendicitis from non-perforated appendicitis by DNI level of 1.4 or more in elderly patients.

Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells.

The prostate gland contains a high level of intracellular zinc, which is dramatically diminished during prostate cancer (PCa) development. Owing to the unclear role of zinc in this process, therapeutic applications using zinc are limited. This study aimed to clarify the role of zinc and its underlying mechanism in the growth of PCa. ZnCl2 suppressed the proliferation of androgen receptor (AR)-retaining PCa cells, whereas it did not affect AR-deficient PCa cells. In LNCaP and TRAMP-C2 cells, zinc downregulated the expression of AR in a dose- and time-dependent fashion. Zinc-mediated AR suppression accordingly inhibited the androgen-mediated transactivation and expression of the androgen target, prostate specific antigen (PSA). This phenomenon resulted from facilitated protein degradation, not transcriptional control. In studies using mice bearing TRAMP-C2 subcutaneous tumors, the intraperitoneal injection of zinc significantly reduced tumor size. Analyses of both xenograft tumors and normal prostates showed reduced expression of AR and increased cell death. Considering the significant loss of intracellular zinc and the dominant growth-modulating role of AR during PCa development, loss of zinc may be a critical step in the transformation of normal cells to cancer cells. This study provides the underlying mechanism by which zinc functions as a PCa suppressor, and forms the foundation for developing zinc-mediated therapeutics for PCa.

Targeting CD46 Enhances Anti-Tumoral Activity of Adenovirus Type 5 for Bladder Cancer.

CD46 is generally overexpressed in many human cancers, representing a prime target for CD46-binding adenoviruses (Ads). This could help to overcome low anti-tumoral activity by coxsackie-adenoviral receptor (CAR)-targeting cancer gene therapy viruses. However, because of scarce side-by-side information about CAR and CD46 expression levels in cancer cells, mixed observations of cancer therapeutic efficacy have been observed. This study evaluated Ad-mediated therapeutic efficacy using either CAR-targeting Ad5 or CD46-targeting Ad5/35 fiber chimera in bladder cancer cell lines. Compared with normal urothelia, bladder cancer tissue generally overexpressed both CAR and CD46. While CAR expression was not correlated with disease progression, CD46 expression was inversely correlated with tumor grade, stage, and risk grade. In bladder cancer cell lines, expression levels of CD46 and CAR were highly correlated with Ad5/35- and Ad5-mediated gene transduction and cytotoxicity, respectively. In a human EJ bladder cancer xenograft mouse model, with either overexpressed or suppressed CD46 expression levels, Ad5/35-tk followed by ganciclovir (GCV) treatment significantly affected tumor growth, whereas Ad5-tk/GCV had only minimal effects. Overall, our findings suggest that bladder cancer cells overexpress both CAR and CD46, and that adenoviral cancer gene therapy targeting CD46 represents a more suitable therapy option than a CAR-targeting therapy, especially in patients with low risk bladder cancers.

Endotracheal tube-assisted orogastric tube insertion in intubated patients in an ED.

BACKGROUND AND AIMS: Inserting a nasogastric tube (NGT) in intubated patients may be difficult because they cannot follow swallowing instructions, resulting in a high rate of first-attempt failure. We introduce a simple technique for inserting an orogastric tube in an emergency department (ED). METHODS: Fifty-six patients in the ED, who were intubated and required NGT insertion, were randomly allocated to 2 groups. We inserted the NGT using a conventional technique from the nostril (control group) and an endotracheal tube (ET)-assisted technique from the mouth (ET group). The procedures' success rate, insertion duration, and complications were compared between the groups. RESULTS: There was a significantly higher overall success rate in the ET group than the control group (100% vs 64%, P<.001). Endotracheal tube group showed 100% first-attempt success rate, but 50% of the control group failed at first attempt. Mean duration of the first trial was not significantly different between the ET and control groups (58.0±16.9 vs 57.3±29.5 seconds, P=.903), but total time for successful insertion was longer in the control group than the ET group (58.0±16.9 vs 111.7±74.5 seconds, P<.001). There was less NGT kinking and more mucosal bleeding in the ET group than in the control group (0% vs 16%, P=.019; 16% vs 7%, P=.225, respectively). CONCLUSION: Endotracheal tube-assisted orogastric tube insertion technique showed a higher rate of successful insertion and shorter total duration. With this result, ET-assisted orogastric tube insertion would be useful in ED.

Modified carotid sinus massage using an ultrasonography for maximizing vagal tone: a crossover simulation study.

INTRODUCTION: The aim of this study was to ascertain if a modified carotid sinus massage (CSM) using ultrasonography is superior to the conventional CSM for vagal tone generation. METHODS: This was a prospective, crossover, clinical trial including 30 subjects with sinus rhythm. Participants were paired, and they performed 2 types of CSM to each other. To perform the conventional technique, pressure was exerted at the point where the maximal impulse of the carotid pulse was palpated. In the modified technique, participants localized the point of maximal diameter just above the bifurcation of the common carotid artery using ultrasonography and applied pressure to that point. Mean differences between premaneuver and postmaneuver R-R intervals and heart rates were compared. The distance from the midline of the neck (x distance) to the angle of the mandible (y distance) was measured, and the mean distance between the 2 techniques was compared. RESULTS: The baseline mean premaneuver R-R interval and heart rate did not differ significantly between the 2 techniques. The postmaneuver R-R interval and heart rate as well as the mean R-R interval and heart rate differences were significantly greater in the modified CSM. The mean location determined using the modified CSM was located 0.8 cm lateral and 0.8 cm superior to the mean location of the conventional CSM. CONCLUSION: The modified CSM using ultrasonography might be more useful than the conventional CSM in reverting episodes of paroxysmal supraventricular tachycardia and may be a suitable alternative for treating the same in the emergency department.

Pathogenic role of HIF-1α in prostate hyperplasia in the presence of chronic inflammation.

Benign prostatic hyperplasia (BPH) commonly occurs in older men with chronic prostatitis. Although BPH is frequently accompanied by inflammation, it is unclear whether inflammation underlies prostate enlargement. Recently, we reported that hypoxia-inducible factor 1α (HIF-1α), which is known to be induced by proinflammatory cytokines, is involved in testosterone-induced prostate hyperplasia. Therefore, we hypothesized that cytokines secreted from infiltrated macrophages under inflammatory conditions stimulate prostate enlargement by up-regulating HIF-1α. In the present study, we injected lipopolysaccharide (LPS) into rat prostates to mimic prostatitis and evaluated prostate hyperplasia 14days later. Epithelial cells of LPS-treated prostates were found to be highly proliferative and HIF-1α levels in prostate tissues to be elevated. When prostate epithelial cells were incubated in conditioned medium from macrophages activated with LPS, they robustly expressed HIF-1α, and under these conditions IL-1ß, IL-6, and TNF-α cytokines were found to mediate HIF-1α induction. In addition, HIF-1α was found to enhance the expression of Twist, which initiates epithelial-mesenchymal transition (EMT). Furthermore, profound EMT features were observed in LPS-treated rat prostates, and the natural HIF-1α inhibitors ascorbate and curcumin were found to attenuate EMT and prostate hyperplasia both in vivo and in vitro. Based on these results, we propose that HIF-1α mediates prostate enlargement under inflammatory conditions, and we suggest that HIF-1α be viewed as a promising target for blocking the transition from prostatitis to BPH.

Ginsenoside Rg3 inhibits lipopolysaccharide-induced adhesion molecule expression in human umbilical vein endothelial cell and C57BL/6 mice.

Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P- and E-selectin play a key role for initiation of vascular inflammation. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for health promotion in Korea. In this study, we investigated the mechanism by which ginsenoside Rg3 may inhibit ICAM-1 and VCAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC) and C57BL/6 mice. LPS increased ICAM-1 and VCAM-1 expression. Ginsenoside Rg3 prevented LPS-mediated increase of ICAM-1 and VCAM-1 expression. LPS induced IkappaBα (IκBα) degradation within 1 hr. Ginsenoside Rg3 prevented the IκBα degradation stimulated with LPS. Moreover, ginsenoside Rg3 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, which was prevented by ginsenoside Rg3. These data provide a novel mechanism where the ginsenoside Rg3 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing prevention against vascular inflammatory disease.

The application of flipped learning to a gross anatomy dissection course.

We implemented flipped learning for a gross anatomy dissection course and compared its effects on students' motivation and academic achievement with those of traditional dissection methods. We invited 142 first-year medical students at Chonnam National University Medical School to participate in this study. All participants engaged in traditional dissection methods in the first part of the study and flipped learning in the latter part. Medical students' motivation to learn anatomy by cadaveric dissection was measured using the ARCS (Attention, Relevance, Confidence, and Satisfaction) model. Thereafter, all students completed a written examination consisting of 96 multiple-choice questions. The students' mean motivational score regarding attention was significantly higher in association with flipped learning than with traditional learning. However, the students' mean motivational scores regarding relevance, confidence, and satisfaction were not significantly different between the methods. Additionally, the mean anatomy practice test score was significantly higher in association with flipped learning than with traditional learning. The students' motivational scores and anatomy practice test scores associated with flipped learning positively correlated with the extent of learning material completion. The students' responses indicated that flipped learning helped enhance the learning process, improve time management, reduce confusion during practice, and promote independent practice. The application of flipped learning to a cadaveric dissection course increased individual learning motivation, which improved learning activities both in and out of class, as well as academic achievement.

Ginsenoside rg2 inhibits lipopolysaccharide-induced adhesion molecule expression in human umbilical vein endothelial cell.

Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-κB) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaBα (IκBα) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of IκBα expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.

Differences of urease activity and expression of associated genes according to gastric topography.

BACKGROUND: We hypothesize that pH difference between acid-secreting corpus and non-secreting antrum might influence the activity of H. pylori's urease and/or related genes. We therefore measured urease activity and the expression of amiE whose encoded protein that hydrolyzes short-chain amides to produce ammonia. MATERIALS AND METHODS: Fifty-four patients were recruited into this study. Each gastroscopic biopsy specimen collected from the antrum and body of each patient was immediately used to measure urease activity using serial changes of urease activity (ammonia levels) during 60 minutes. Probe specific for amiE was labeled with a biotin nick-translation kit and was used to detect expression of these genes (mRNA) in fresh-frozen gastroscopic biopsy specimens using fluorescent in situ hybridization (FISH). RESULTS: Urease activity at 60 minutes from the gastric antrum and body of all patients infected with H. pylori was 399.5 ± 490.5 and 837.9 ± 1038.9 µg/dL, respectively (p = .004). Urease activity in the antrum was correlated with H. pylori density. Urease activity or H. pylori density in the antrum was significantly correlated with chronic active inflammation; in contrast, this correlation was not found in the gastric body. The expression level of amiE was 1.5 times higher (p < .05) in the gastric body compared with the antrum. CONCLUSION: Topographically, the urease activity in body was much higher than in antrum. The expression level of amiE was higher in the gastric body compared with the antrum.

A heptamethine cyanine dye serves as a potential marker for myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with inhibitory effects on T cell-mediated immune response. MDSCs accumulate under many pathological conditions, including cancers, to avoid anticancer immunity. Unlike mouse MDSCs, common specific surface markers for human MDSCs are not clearly defined, mainly due to the complexity of MDSC subsets. In this study, we investigate specific responses of the infrared dye MHI-148 to MDSCs. Mice bearing 4T1 breast cancer cells were established, and splenocytes were isolated. Flow cytometric analyses demonstrated that MHI-148 was reactive to over 80% of MDSC-specific cells manifesting CD11b+/Gr-1+ acquired from both tumor-bearing mice and naive mice. Cells sorted positive for either CD11b/Gr-1 or MHI-148 were also identical to their counterparts (99.7% and 97.7%, respectively). MHI-148, however, was not reactive to lymphocyte or monocyte populations. To determine whether MHI-148-reactive cells exert inhibitory effects on T cell proliferation, an EdU-based T cell assay was performed. MHI-148 reactive cells significantly reduced T cell proliferation with increased arginase activity and nitrite production. In an attempt to test MHI-148 as a marker for human MDSCs, MHI-148 was specifically reactive to CD11b+/CD33+/CD14- granulocytic MDSCs acquired from selected cancer patients. This study demonstrates that the near-infrared dye MHI-148 specifically reacts to mouse splenocytes with known MDSC-specific markers that have T cell suppressive functions. The dye also selectively binds to a subpopulation of immature myeloid cells acquired from cancer patients. While it is not clear how MHI-148 specifically stains MDSCs, this dye can be a novel tool to detect MDSCs and to predict the prognosis of human cancer patients.

Survivin mediates prostate cell protection by HIF-1alpha against zinc toxicity.

BACKGROUND: The prostate contains extremely high concentrations of zinc, but survives and grows without apparent injury. This begs the question as to how prostate cells avoid the toxic effects of zinc. In a previous study, the authors found that; HIF-1alpha is expressed concomitantly with the accumulation of zinc in the epithelial cells of normal rat prostates, the zinc ion stabilizes HIF-1alpha in prostate cells, and that HIF-1alpha protects prostate cells from zinc toxicity. In the present study, the authors addressed the mechanism responsible for the protective effect of HIF-1alpha in a high zinc environment. METHODS: Immunofluorescent staining, immunoblotting, reverse transcription-polymerase chain reaction, reporter assay, and cell cycle analysis. RESULTS: Survivin was induced by ZnCl(2) in a HIF-1 dependent manner in both DU-145 and PNT2 prostate cells. Furthermore, HIF-1 induced survivin expression at the transcriptional level and the induction of survivin was abolished by HIF-1alpha knock-down. In addition, HIF-1-dependent survivin overexpression promoted prostrate cell survival and prevented cell arrest in the presence of high zinc concentrations, and si-survivin transfected cells under zinc rich conditions contained markedly higher levels of cleaved caspase-9 and PARP than si-con transfected cells. Finally, survivin expression patterns well matched rat prostate proliferation statuses. CONCLUSION: Under zinc rich conditions, prostate epithelial cells HIF-1-dependently express survivin, which promotes prostate cell proliferation, and prevents apoptosis and cell cycle arrest. Accordingly, the HIF-1alpha-survivin pathway appears to facilitate prostate cell survival and growth in zinc rich environments, and this pathway could be a therapeutic target for the treatment of prostate hyperplasia.

Elevated procalcitonin levels in patients with acetaminophen intoxication: two case reports: A CARE-compliant article.

RATIONALE: Procalcitonin (PCT) is used as a biomarker for identifying the occurrence of sepsis. Previous studies have reported high levels of PCT with acetaminophen intoxication without evidence of infection. Here, we report two patients with acetaminophen intoxication with high levels of PCT without showing any symptoms of bacterial infection. PATIENT CONCERNS: This case study examined two unrelated patients with acetaminophen intoxication admitted to emergency at different times. The first patient was admitted to the emergency department after ingesting approximately 8000 mg (153.8 mg/kg) of acetaminophen. On admission, C-reactive protein (CRP), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were normal. PCT and acetaminophen levels were 31.89 ng/mL and below 0.5 µg/mL, respectively. The second patient was admitted to the emergency department 8 h after ingesting ∼23,600 mg (280.6 mg/kg) of acetaminophen. By the second day of admission, GOT and GPT increased to 2508 and 1473 IU/L, respectively. PCT was 45.66 ng/mL with acetaminophen level at 116.9 µg/mL. Both patients were clear of symptoms associated with bacterial infection. DIAGNOSIS: Acetaminophen intoxication. INTERVENTIONS: N-acetylcysteine was given intravenously to both patients for 20 h per protocol. OUTCOMES: Both patients were discharged without complications. LESSONS: Observations suggests that elevated levels of PCT in patients intoxicated with acetaminophen may be associated with involvement of other organs impacted by cytokine stimuli from sterile inflammation resulting from hepatic damage rather than PCT secretion directly caused by hepatic cell damage.

[Effects of a video education program for patients with benign uterine tumors receiving high-intensity focused ultrasound treatment]. / ê³ ê°•ë„ 집속 초음파 치료를 받는 ìžê¶ì–‘ì„±ì¢ ì–‘ 환자의 동영상 교육프로그램 효과.

Purpose: The purpose of this study was to examine the effects of a video education program in women receiving high-intensity focused ultrasound (HIFU) treatment. Methods: This was a quasi-experimental study with a nonequivalent control group non-synchronized design. The participants were 54 patients who had benign uterine tumors and adenomyosis. The data were collected from June to August 2018. A 10-minute video education program on HIFU and post-procedural care was developed based on the literature. The experimental group was provided the video education program with a question-and-answer session for 10 minutes after viewing the video. The control group received usual care (i.e., verbal instructions on post-procedural self-care). The questionnaire survey was conducted twice: before the educational program and before being discharged from the hospital. Differences in uncertainty, emotions, and self-efficacy among patients were analyzed. Data were analyzed using the chi-square test, Shapiro-Wilk test, paired t-test, and t-test with SPSS version 23.0. Results: The participants in the experimental group showed a decrease in uncertainty(t=4.33, p<.001), improvements in anxiety(t=-4.07, p<.001) and depression (t=-3.55,p<.001), and an enhancement ofself-efficacy (t=-4.39,p<.001) compared to the control group. Conclusion: This nursing intervention was effective at reducing uncertainty, improving emotions, and enhancing self-efficacy. This intervention is feasible for use in nursing practice as an aid for patients when considering treatment methods.

HIF-1alpha controls keratinocyte proliferation by up-regulating p21(WAF1/Cip1).

The cyclin-dependent kinase inhibitor p21(WAF1/Cip1) plays a central role in a spatial and temporal balance of epidermal keratinocyte proliferation and growth arrest. However, what controls p21 expression in keratinocytes remains uncertain. Hypoxia-inducible factor 1alpha (HIF-1alpha) does not only express a variety of genes essential for hypoxic adaptation, but also up-regulates p21 so as to slow down cell cycle under hypoxic conditions. In the present study, we examined the role of HIF-1alpha in p21-mediated growth arrest of keratinocyte. Keratinocyte proliferation was arrested in the G1 phase at a high cell density. p21 was also up-regulated in a cell density-dependent manner and was found to be highly expressed in epidermal keratinocytes of normal human skins. In addition, in the same specimens and cells, we noted robust HIF-1alpha expression. HIF-1alpha siRNAs inhibited p21 expression and released the G1 arrest. In vivo, moreover, the intradermal injection of HIF-1alpha siRNA attenuated p21 expression in rat epidermis and induced skin hyperplasia. Mechanistically, we propose that the production of mitochondrial reactive oxygen species and the activation of the MEK/ERK pathway are involved in the HIF-1alpha stabilization in keratinocytes. These results imply that HIF-1alpha functions as an up-stream player in the p21-mediated growth arrest of keratinocytes.

The chemokine receptor CCR4 is expressed and associated with a poor prognosis in patients with gastric cancer.

OBJECTIVES: There is increasing evidence that chemokines and chemokine receptors are causally involved in the metastasis of cancer. Little is known about the possible role of chemokine receptors in the metastasis of gastric cancer. The aim of this study was to investigate the expression of chemokine receptors and their prognostic role in patients with gastric cancer. METHODS: We screened the expression of CCR and CXCR chemokine receptors in 12 gastric cancer cell lines using the semi-quantitative RT-PCR. The expression of CCR4, one of the most commonly expressed chemokines, was confirmed using Western blot and flow cytometry analysis of 8 gastric cancer cell lines. The function of CCR4 was examined using migration and proliferation assays. Then the migratory response of CCR4 was blocked using blocking antibodies. Finally, the clinical significance of the chemokine receptors was explored using tissue microarray methods and immunohistochemical staining of specimens from 753 gastric cancer patients. RESULTS: We found that 6 out of 8 (75.0%) gastric carcinoma cell lines expressed a functional CCR4 for its ligand, chemokine CCL17, as demonstrated by the migration assays, and the migration was inhibited by anti-CCR4 antibodies. The clinical samples evaluated by immunohistochemical assay of tissue microarrays showed that CCR4-positive carcinoma cells were detected in 128 of 753 (17.0%) cases. In addition, there was a significant difference in recurrences between the CCR4-positive and -negative cases (P = 0.009). The patients with CCR4-positive tumors had significantly poorer prognosis than did those with CCR4-negative tumors (5-year survival rate; 71.6% versus 82.5%, respectively, P = 0.008). CONCLUSION: These results suggest that CCR4 and its ligands were associated with increased tumor recurrence and impaired overall survival in patients with gastric cancer.

Hypoxia-inducible factor 1alpha is deregulated by the serum of rats with adjuvant-induced arthritis.

Rheumatoid arthritis (RA) is known to be associated with increased risks of hypoxia-related diseases, whose progresses are critically determined by HIF-1alpha. The authors hypothesized that the hypoxia-related complications of RA are associated with HIF-1alpha deregulation by some factor(s) in RA serum. Arthritis was induced in female Lewis rats by injecting complete Freund's adjuvant. The effects of arthritic rat serum (ARS) on hypoxic responses were investigated by incubating Hep3B cells in ARS. In the presence of ARS, HIF-1alpha was down-regulated and inactivated under hypoxic conditions. ARS inactivated AKT and mTOR, which led to impaired HIF-1alpha protein synthesis. Furthermore, insulin was found to be deficient in ARS and insulin supplementation fully recovered HIF-1alpha synthesis with AKT and mTOR activation. These results suggest that HIF-1alpha deregulation by components in serum is responsible for the RA-associated aggravation of hypoxic diseases in extra-articular tissues.

[Therapeutic effect of allogenic bone marrow transplantation in acute TNBS-induced colitis].

BACKGROUND/AIMS: Bone marrow-derived cells (BMDC) contribute to tissue maintenance under many kinds of pathologic conditions. We carried out a study to see how BMDC play a role in the treatment of experimental murine colitis. METHODS: We divided the animals into 3 groups and treated them with 50% ethanol (control group), 2,4,6-trinitrobenzene sulfinic acid colitis (TNBS group), and TNBS+bone marrow transplant (BMT group). To induce colitis, TNBS (5.0 mg/mouse) dissolved in 50% ethanol was injected into anus weekly for two weeks. Bone marrow transplantations were performed using bone marrow of male transgenic mouse (donor) with green fluorescence protein (GFP) into female wild type mouse (recipient) three weeks before TNBS instillation. All animals were sacrificed, and colons were extracted one week after the last TNBS instillation. We measured microscopic scores of mucosal injury and investigated the GFP expression for bone marrow engraftment. The immunostaining of vimentin and alpha-smooth muscle actin (alpha-SMA) for myofibroblasts was performed. RESULTS: The score of mucosal injury in the TNBS group was much more severe than those in control, and reduced significantly by BMT (p<0.05). GFP-positive cells were almost deposited in pericryptal niche of BMT group but not at all in both control and TNBS group. Most of myofibroblasts stained with both vimentin and SMA also infiltrated into pericryptal niche. But, the number of myofibroblasts stained with vimentin and SMA in both control and TNBS group was smaller than that in BMT group. CONCLUSIONS: BMDC deposited on pericryptal niche might have a significant role in repairing acute experimental murine colitis.