Determination of malignant and invasive predictors in branch duct type intraductal papillary mucinous neoplasms of the pancreas: a suggested scoring formula

Prediction of malignancy or invasiveness of branch duct type intraductal papillary mucinous neoplasm (Br-IPMN) is difficult, and proper treatment strategy has not been well established. The authors investigated the characteristics of Br-IPMN and explored its malignancy or invasiveness predicting factors to suggest a scoring formula for predicting pathologic results. From 1994 to 2008, 237 patients who were diagnosed as Br-IPMN at 11 tertiary referral centers in Korea were retrospectively reviewed. The patients' mean age was 63.1 ± 9.2 yr. One hundred ninty-eight (83.5%) patients had nonmalignant IPMN (81 adenoma, 117 borderline atypia), and 39 (16.5%) had malignant IPMN (13 carcinoma in situ, 26 invasive carcinoma). Cyst size and mural nodule were malignancy determining factors by multivariate analysis. Elevated CEA, cyst size and mural nodule were factors determining invasiveness by multivariate analysis. Using the regression coefficient for significant predictors on multivariate analysis, we constructed a malignancy-predicting scoring formula: 22.4 (mural nodule [0 or 1]) + 0.5 (cyst size [mm]). In invasive IPMN, the formula was expressed as invasiveness-predicting score = 36.6 (mural nodule [0 or 1]) + 32.2 (elevated serum CEA [0 or 1]) + 0.6 (cyst size [mm]). Here we present a scoring formula for prediction of malignancy or invasiveness of Br-IPMN which can be used to determine a proper treatment strategy.     

Clinical review of endogenous endophthalmitis in Korea: a 14-year review of culture positive cases of two large hospitals

Purpose

To identify the clinical features and outcomes of endogenous endophthalmitis in Korea.

Materials and Methods

We reviewed 18 patients with endogenous endophthalmitis at 2 Korean hospitals, treated over a 14 year period between January 1993 and December 2006.

Results

The comorbidities observed in these cases were diabetes mellitus and liver cirrhosis. The most common pathogens, which were found in 7 patients each (38.9%), were Klebsiella pneumonia and Pseudomonas aeruginosa. All patients were treated with systemic antibiotics and fortified topical antibiotics. A surgical approach including vitrectomy was performed in 9 cases (50.0%). The prognosis was generally poor, and visual acuity improved slightly in 6 patients (33.3%).

Conclusion

In this study, diabetes mellitus and Klebsiella pneumonia showed a close relationship with endogenous endophthalmitis, respectively. Endogenous endophthalmitis is a serious risk to sight and careful attention to establishing the diagnosis and management may decrease the ocular morbidity.     

Effects of N-acetylcysteine on TEGDMA- and HEMA-induced suppression of osteogenic differentiation of human osteosarcoma MG63 cells

Triethyleneglycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) are major resinous components of dental restorative materials and dentin bonding adhesives. Resin monomers are known to cause cytotoxicity in mammalian cells via oxidative stress and inhibit differentiation of dental pulp cells and osteoblasts. This study was aimed to investigate whether oxidative stress was involved in the inhibition of TEGDMA- and HEMA-induced differentiation. TEGDMA and HEMA reduced alkaline phosphatase (ALP) activity and the mRNA expression of the osteopontin (OPN) gene in MG63 cells at noncytotoxic concentrations. On the other hand, N-acetylcysteine (NAC) did not affect ALP activity at concentrations below 10 mM. Reduced ALP activity and OPN mRNA expression by TEGDMA were partially recovered via cotreatment with NAC. However, NAC did not exhibit significant effects in HEMA-treated cells. Glutathione (GSH) levels were also down-regulated by both TEGDMA and HEMA. The addition of NAC induced the partial recovery of GSH in cells treated with 0.5 mM TEGDMA. On the other hand, the levels of GSH in HEMA-treated cells were not affected by NAC. These results suggest that oxidative stress is involved in the suppression of differentiation by TEGDMA. Translocation of Nrf2 from the cytoplasm to the nucleus has been known to play a role in the suppression of osteogenic differentiation by oxidative stress. However, Nrf2 did not move into the nucleus in resin monomer-treated MG63 cells, suggesting the contribution of other signaling pathways to the suppressive effects of resin monomers.     

Comparison of diagnostic performance of three real-time PCR kits for detecting Mycobacterium species

Purpose

PCR is widely used for rapidly and accurately detecting Mycobacterium Species. The purpose of this study was to assess the diagnostic performance of three real-time PCR kits and evaluate the concordance with two older PCR methods.

Materials and Methods

Using 128 samples, the five PCR methods were assessed, including an in-house PCR protocol, the COBAS Amplicor MTB, the COBAS TaqMan MTB, the AdvanSure TB/NTM real-time PCR, and the Real-Q M. tuberculosis kit. The discrepant results were further examined by DNA sequencing and using the AdvanSure Mycobacteria Genotyping Chip for complete analysis.

Results

For Mycobacterium tuberculosis (MTB) detection, all five kits showed 100% matching results (positive; N = 11 and negative; N = 80). In non-tuberculous mycobacterium (NTM) discrimination, the AdvanSure yielded two true-positive outcomes from M. intracellulare and one false positive outcome, while the Real-Q resulted in one true-positive outcome and one false negative outcome for each case and another false negative result using the provided DNA samples.

Conclusion

Real-time PCR, yielded results that were comparable to those of the older PCR methods for detecting MTB. However, there were disagreements among the applied kits in regard to the sample test results for detecting NTM. Therefore, we recommend that additional confirmatory measures such as DNA sequencing should be implemented in such cases, and further research with using a larger numbers of samples is warranted to improve the detection of NTM.     

Transient increase of higher-order aberrations after lateral rectus recession in children

The changes of higher-order aberrations (HOAs) after bilateral lateral rectus muscle recession were evaluated. Forty eyes of 20 children were enrolled and their wavefront information was assessed until postoperative 3 months. Even though the root mean square (RMS) of total aberration was not changed, the RMS of HOA was transiently increased at postoperative 1 week and returned to baseline level after 1 month. Among individual Zernike coefficient, secondary astigmatism, quadrafoil, secondary coma, secondary trefoil, and pentafoil showed similar tendency with the RMS of HOA. However, coma, trefoil, and spherical aberration were not changed. Regarding recession amount, it did not correlate with any Zernike coefficient. In summary, our data imply that the HOAs are transiently increased after lateral rectus recession surgery. These results are in collusion with previous reports that strabismus surgery induced transient corneal astigmatism.     

Overexpressions of Cyclin B1, cdc2, p16 and p53 in human breast cancer: the clinicopathologic correlations and prognostic implications

Purpose

The molecular mechanisms that are responsible for the initiation and progression of breast cancers are largely unknown. This study was to analyze the cyclin B1, cdc2, p53 and p16 tumor suppressor genes in human breast cancer.

Materials and Methods

To investigate the role of cyclin B1, cdc2, p53 and p16 in the pathogenesis and progression of breast carcinomas, 98 cases of breast cancers were examined by immunohistochemical method. The correlations of cyclin B1, cdc2, p53 and p16 expression with various clinico-pathologic findings were analysed.

Results

In the normal breast tissues, cyclin B1, cdc2 and p16 were weakly expressed, while p53 was not expressed. On the other hand, cyclin B1, cdc2, p53 and p16 were overexpressed in breast cancer, showing correlation between the expression of cyclin B1 and cdc2 and breast cancers (p=0.00). The overexpressions of cdc2 and p16 were correlated with an infiltrative tumor border pattern and this was statistically significant (p<0.05). In addition, the overexpression of cdc2 was correlated with histologic high grade carcinomas (p=0.00).

Conclusion

Cyclin B1 and cdc2 appeared to be involved in the genesis or progression of breast cancers. In addition, the overexpressions of p16 and p53 may play important roles in more aggressive tumor and the overexpression of cdc2 is associated with progression of tumor to a higher grade of breast carcinomas. The deranged overexpressions of cyclin B1, cdc2, p16 and p53 may play an important role in human breast carcinogenesis.     

Expression and characterization of a second L-amino acid deaminase isolated from Proteus mirabilis in Escherichia coli

L-amino acid deaminases catalyze the deamination of natural L-amino acids. Two types of L-amino acid deaminase have been identified in Proteus species. One exhibits high levels of activity toward a wide range of aliphatic and aromatic L-amino acids, typically L-phenylalanine, whereas the other acts on a relatively narrow range of basic L-amino acids, typically L-histidine. In this study, we cloned, expressed, and characterized a second amino acid deaminase, termed Pm1, from P. mirabilis KCTC 2566. Homology alignment of the deduced amino acid sequence of Pm1 demonstrated that the greatest similarity (96%) was with the L-amino acid deaminase (LAD) of P. vulgaris, and that homology with Pma was relatively low (72%). Also, similar to LAD, Pm1 was most active on L-histidine, indicating that Pm1 belongs to the second type of amino acid deaminase. In agreement with this conclusion, the V(max) and K(m) values of Pm1 were 119.7 (μg phenylpyruvic acid/mg/min) and 31.55 mM phenylalanine, respectively, values lower than those of Pma. The Pml deaminase will be very useful industrially in the preparation of commercially valuable materials including urocanic acid and α-oxoglutarate.     

Responses of spinal dorsal horn neurons to foot movements in rats with a sprained ankle

Acute ankle injuries are common problems and often lead to persistent pain. To investigate the underlying mechanism of ankle sprain pain, the response properties of spinal dorsal horn neurons were examined after ankle sprain. Acute ankle sprain was induced manually by overextending the ankle of a rat hindlimb in a direction of plantarflexion and inversion. The weight-bearing ratio (WBR) of the affected foot was used as an indicator of pain. Single unit activities of dorsal horn neurons in response to plantarflexion and inversion of the foot or ankle compression were recorded from the medial part of the deep dorsal horn, laminae IV-VI, in normal and ankle-sprained rats. One day after ankle sprain, rats showed significantly reduced WBRs on the affected foot, and this reduction was partially restored by systemic morphine. The majority of deep dorsal horn neurons responded to a single ankle stimulus modality. After ankle sprain, the mean evoked response rates were significantly increased, and afterdischarges were developed in recorded dorsal horn neurons. The ankle sprain-induced enhanced evoked responses were significantly reduced by morphine, which was reversed by naltrexone. The data indicate that movement-specific dorsal horn neuron responses were enhanced after ankle sprain in a morphine-dependent manner, thus suggesting that hyperactivity of dorsal horn neurons is an underlying mechanism of pain after ankle sprain.     

Therapy-related myelodysplastic syndrome/acute myeloid leukemia with del(7)(q22) in a patient with de novo AML

A 55-year-old Korean woman was initially diagnosed with acute myelomonocytic leukemia (AML). After induction chemotherapy was performed using cytarabine, idarubicin, and G-CSF, complete remission (CR) was subsequently achieved following reinduction chemotherapy using the same chemotherapeutic agents. Thirty-six months after the initial CR, an increase in immature cells (up to 12.0%) was observed in the patient's bone marrow. Because chromosome analysis revealed a karyotype of 46,XX,del(7)(q22) in all of the analyzed cells, the patient was diagnosed with therapy-related myelodysplastic syndrome (t-MDS). Although the patient subsequently received chemotherapy and G-CSF for neutropenia, t-MDS rapidly progressed after 3 months to therapy-related acute myeloid leukemia (t-AML). Although very rare, de novo AML can progress to a secondary MDS/AML with del(7q) after chemotherapy with cytarabine, idarubicin, and G-CSF. Further investigation into the role of genes located in 7q22 may provide more information about the mechanisms of leukemogenesis.     

Involvement of epidermal growth factor receptor-linked signaling responses in Pseudomonas fluorescens-infected alveolar epithelial cells

Pseudomonas fluorescens is an opportunistic indoor pathogen that can cause severe airway proinflammatory responses. Pulmonary epithelium, like other mucosal epithelial linings of the body, constitutes the first line of defense against airway microbial pathogens. Mucosal epithelial cells can be a sentinel of pathogenic bacteria via stimulation of specific cell surface receptors, including the epidermal growth factor receptor (EGFR) and Toll-like receptor (TLR). This study addressed the involvement of EGFR in airway epithelial pathogenesis by P. fluorescens. Human A549 pneumocytes showed prolonged production of proinflammatory interleukin-8 (IL-8) in response to infection with P. fluorescens, which was via the nuclear factor-kappa B (NF-κB) signaling pathway. Production of proinflammatory cytokine IL-8 was not mediated by P. fluorescens lipopolysaccharide, a representative TLR4 agonist, but was mediated through EGFR-linked signals activated by the opportunistic bacteria. Moreover, EGFR signals were involved in NF-κB signal-mediated production of proinflammatory cytokines. Along with persistent NF-κB activation, P. fluorescens enhanced the EGFR phosphorylation and subsequent activation of downstream mediators, including protein kinase B or extracellular-signal-regulated kinases 1/2. Blocking of EGFR-linked signals increased epithelial susceptibility to pathogen-induced epithelial cell death, suggesting protective roles of EGFR signals. Thus, airway epithelial exposure to P. fluorescens can trigger antiapoptotic responses via EGFR and proinflammatory responses via TLR4-independent NF-κB signaling pathway in human pneumocytes.