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The epidermal growth factor receptor (EGFR) activates several signaling cascades in response to epidermal growth factor stimulation. One of these signaling events involves tyrosine phosphorylation of signal transducer and activator of transcription (STAT), whereas another involves activation of the phosphatidylinositol 3-OH kinase pathway. Two possibilities for STAT activation exist: a janus kinase (JAK)-dependent and a JAK-independent mechanism. Herein, we demonstrate that EGFR overexpression in primary esophageal keratinocytes activates STAT in a JAK-dependent fashion with the functional consequence of enhanced cell migration, which can be abolished by use of a JAK-specific inhibitor, AG-490. We determined the mechanisms underlying the signal transduction pathway responsible for increased cell migration. Stimulation of EGFR induces Tyr701 phosphorylation of STAT 1 and initiates complex formation of STAT 1 and STAT3 with JAK1 and JAK2. Thereafter, the STATs translocate to the nucleus within 15 min. In addition, we found that activation of this signaling pathway results in matrix metalloproteinase-1 (MMP-1) activity. By contrast, Akt activation does not impact the EGFR-STATs-JAKs complex formation and nuclear translocation of the STATs with subsequent MMP-1 activity, although Akt activation may contribute to cell migration through an independent mechanism. Taken together, we find that the recruitment of the STAT-JAK complex by EGFR is responsible for keratinocyte migration that, in turn, might be mediated by MMP-1 activation. epidermal growth factor receptor: Akt; cell migration

The epidermal growth factor receptor (EGFR) activates several signaling cascades in response to epidermal growth factor stimulation. One of these signaling events involves tyrosine phosphorylation of signal transducer and activator of transcription (STAT), whereas another involves activation of the phosphatidylinositol 3-OH kinase pathway. Two possibilities for STAT activation exist: a janus kinase (JAK)-dependent and a JAK-independent mechanism. Herein, we demonstrate that EGFR ovemxpression in primary esophageal keratinocytes activates STAT in a JAK-dependent fashion with the functional consequence of enhanced cell migration, which can be abolished by use of a JAK-specific inhibitor, AG-490. We determined the mechanisms underlying the signal transduction pathway responsible for increased cell migration. Stimulation of EGFR induces Tyr701 phosphorylation of STAT1 and initiates complex formation of STAT1 and STAT3 with JAK1 and JAK2. Thereafter, the STATs translocate to the nucleus within 15 min. In addition, we found that activation of this signaling pathway results in matrix metalloproteinase-1 (MMP-1) activity. By contrast, Akt activation does not impact the EGFR-STATs-JAKs complex formation and nuclear translocation of the STATs with subsequent MMP-1 activity, although Akt activation may contribute to cell migration through an independent mechanism. Taken together, we find that the recruitment of the STAT-JAK complex by EGFR is responsible for keratinocyte migration that, in turn, might be mediated by MMP-1 activation. [ABSTRACT FROM AUTHOR]

Objectives: Currently, serum total amylase, pancreatic isoamylase (P-amylase), lipase, trypsin(ogen), phospholipase A2 (PLA2), and elastase I are advocated to be useful in diagnosing pancreatic diseases. However, the most useful among the above six enzymes in patients with impaired renal function has not been fully clarified. We, therefore, studied the relation of the serum levels of the above enzymes and creatinine clearance (CrCl) in normal controls and patients with chronic renal insufficiency or failure. Methods: PLA2 and elastase I were assayed by RIA, trypsin(ogen) by EIA and others by activity. Subjects were 24 healthy controls and 47 patients with impaired renal function and no apparent pancreatic diseases. Results: 1) Elastase I was significantly elevated only in patients with a CrCl of 10 ml/min or less, whereas others were elevated already in patients with a CrCl below 40 ml/min; 2) in 12 patients with a CrCl between 13 and 39 ml/min, lipase tended to be less frequently raised than others, except elastase I, although the difference was statistically insignificant; 3) in 28 patients with a CrCl between 40 and 74 ml/min, lipase was less frequently elevated than others, except elastase I and PLA2; 4) in seven patients with a CrCl of 10 ml/min or below, elastase I tended to be less frequently elevated than others, although the difference was statistically insignificant; and 5) the degree of elevation was within 2.5 times the upper limits of reference values in all enzymes, except trypsin(ogen) (within 4.8 times). Conclusions: Elastase I was least vulnerable to impaired renal function followed by lipase. We, therefore, recommend combined assays of elastase I and lipase for detecting pancreatic diseases in patients with renal insufficiency. When cut-off levels are set at 2.5 times the upper limit of reference values, P-amylase or PLA2 can replace lipase. [ABSTRACT FROM AUTHOR]

A rare kind of malignant lymphoma, called primary effusion lymphoma (PEL) is associated with human herpesvirus 8 (HHV-8), and characterized by lymphomatous effusion in the bodily cavities. Although the initial clinical presentation of primary effusion lymphoma-like lymphoma (PEL-LL) is similar to that of PEL, PEL-LL is HHV-8 negative and has a favorable prognosis. A PEL-LL diagnosis was made after an 88-year-old man was admitted to our hospital with a pleural effusion. His disease regressed after effusion drainage. He demonstrated disease progression to diffuse large B-cell lymphoma after two years and ten months. Our example demonstrates that aggressive B-cell lymphoma can develop from PEL-LL.

Lymphoblastic lymphoma (LBL) is a rare hematologic malignancy that originates from immature lymphocytes and usually expresses terminal deoxynucleotidyl transferase (TdT). Here, we report a case of TdT-negative B-LBL. A 71-year-old male patient presented to a hospital with shortness of breath. His chest computed tomography showed a mediastinal mass. Tumor cells did not express TdT but expressed MIC2, which led to LBL diagnosis. MIC2 is a useful marker for LBL diagnosis.

Hepatitis B virus (HBV) is one of the major viruses causing acute hepatitis. Recently, the incidence of acute hepatitis with genotype A has been increasing in Japan. The aim of this study was to investigate acute hepatitis B (AHB) in Okayama prefecture, with special attention to HBV genotype A. AHB patients who visited one of 12 general hospitals in Okayama prefecture between 2006 and 2010 were retrospectively analyzed. Over the course of the study period, 128 patients were diagnosed with AHB. Sexual transmission was supposed in the majority of patients (78 patients, 61%), including 59 (76%) having sex with heterosexual partners. The genotypes of HBV were assessed in 90 patients (70%), of whom 27 patients were infected with genotype A, 5 with genotype B, and 58 with genotype C. The prevalence of genotype A was significantly higher among male patients (28.7%), aged 20-29 (35.6%, p＜0.01), among men who had sex with men (100%, p＜0.005), and among patients having sex with unspecified partners (44.8%, p＜0.005). Genotype A was not a significant factor associated with delayed HBsAg disappearance. Caution should be exercised with regard to sexually transmissible diseases in order to slow the pandemic spread of AHB due to genotype A.

The concept of Team-Based Learning (TBL) was developed in the late 1970s by Larry Michaelsen, who wanted students to enjoy the benefits of small group learning within large classes in the business school environment. In contrast to problem-based learning (PBL), which is student centered, TBL is typically instructor centered. Recently, TBL is being used as a teaching method in over 60 health science professional schools in the US and other countries. In the present study, the impact of adopting TBL in teaching pharmaceutical care practices to students was evaluated. Students were required to answer a set of multiple-choice questions individually in individual readiness assessment test (IRAT) before the TBL sessions to assess their level of preparation. The same set of questions was then reattempted by the group readiness assessment test (GRAT) during TBL. Comparing the scores obtained in the GRAT and IRAT before the first TBL session, the scores from the GRAT were always higher than those of the IRAT, indicating that TBL has encouraged active learning. In addition, students were surveyed about their level of satisfaction with TBL and written comments about TBL were solicited. The results of the questionnaire showed that 87.3±9.3% of the students were satisfied. Moreover, no student commented that TBL was in any way inferior to the PBL. Implementation of a TBL approach was successfully integrated into the pharmaceutical care education course. In order to further improve the usefulness of TBL in teaching pharmaceutical care, a hybrid teaching approach that also comprises PBL and a lecture-based course is desirable.

The relationship between pancreatic fibrosis and apoptosis of pancreatic acinar cells has not been fully elucidated. We reported that taurine had an anti-fibrotic effect in a dibutyltin dichloride (DBTC)-chronic pancreatitis model. However, the effect of taurine on apoptosis of pancreatic acinar cells is still unclear. Therefore, we examined apoptosis in DBTC-chronic pancreatitis and in the AR42J pancreatic acinar cell line with/without taurine. Pancreatic fibrosis was induced by a single administration of DBTC. Rats were fed a taurine-containing diet or a normal diet and were sacrificed at day 5. The AR42J pancreatic acinar cell line was incubated with/without DBTC with taurine chloramines. Apoptosis was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. The expression of Bad and Bcl-2 proteins in the AR42J cells lysates was detected by Western blot analysis. The apoptotic index of pancreatic acinar cells in DBTC-administered rats was significantly increased. Taurine treatment inhibited pancreatic fibrosis and apoptosis of acinar cells induced by DBTC. The number of TUNEL-positive cells in the AR42J pancreatic acinar cell lines was significantly increased by the addition of DBTC. Incubation with taurine chloramines ameliorated these changes. In conclusion, taurine inhibits apoptosis of pancreatic acinar cells and pancreatitis in experimental chronic pancreatitis.

Plain abdominal radiography is a very basic examination and plays an important role in primary care. The objectives of this study were to clarify colon distributions on plain abdominal radiographs. Forty-three healthy volunteers underwent gastric fluoroscopy, and 2 hours later, plain abdominal radiography in the supine position. A region of interest (ROI) was defined uniformly on each X-ray image to divide the image into 600 zones. The area corresponding to the large bowel within the ROI was divided into 4 segments (ascending colon, transverse colon, descending colon, and sigmoid colon + rectum). The percentage of barium in each segment relative to the total volume of barium used was calculated to evaluate the percent ROI occupancy. The large bowel covered 76.7% of the entire ROI, with the percent duplication being 55%. The duplicated area corresponded to the transverse colon region. When the method proposed by Arhan et al. was used, the percentage of the colon actually present in each segment relative to that determined theoretically was 99.6% for the right colon segment, 92.2& for the left colon segment, and 92.2% for the sigmoid/rectal segment. However, in cases in which the transverse colon descended partially from the fifth lumbar vertebra, the percentage occupied by the sigmoid colon + rectum decreased to 57.2%. We applied a new large bowel segmentation method especially for patients with ptosis, by devising a line joining the lateral side of the right lesser pelvis and the lower ends of both sacroiliac joints.