Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen

Streptococcus mutans is the leading cause of dental caries (tooth decay) worldwide and is considered to be the most cariogenic of all of the oral streptococci. The genome of S. mutans UA159, a serotype c strain, has been completely sequenced and is composed of 2,030,936 base pairs. It contains 1,963 ORFs, 63% of which have been assigned putative functions. The genome analysis provides further insight into how S. mutans has adapted to surviving the oral environment through resource acquisition, defense against host factors, and use of gene products that maintain its niche against microbial competitors. S. mutans metabolizes a wide variety of carbohydrates via nonoxidative pathways, and all of these pathways have been identified, along with the associated transport systems whose genes account for almost 15% of the genome. Virulence genes associated with extracellular adherent glucan production, adhesins, acid tolerance, proteases, and putative hemolysins have been identified. Strain UA159 is naturally competent and contains all of the genes essential for competence and quorum sensing. Mobile genetic elements in the form of IS elements and transposons are prominent in the genome and include a previously uncharacterized conjugative transposon and a composite transposon containing genes for the synthesis of antibiotics of the gramicidin/bacitracin family; however, no bacteriophage genomes are present.     

The oncology treatment of patients who use oral anticoagulants is connected with high risk of bleeding complications

The data about risk for bleeding complications during anticoagulation in cancer patients with different oncology treatment are conflicting. To investigate the rate of bleeding in the course of oral anticoagulants, during treatment of malignant diseases, we conducted a retrospective study including 75 patients on stable anticoagulation prior to commencing their different oncology treatment. All patients were treated according to the consiliar decision, made based on the localization and pathohistological findings of the malignant disease. During their treatment the regular laboratory monitoring of INR was done. Every dose of oral anticoagulants, INR changes, as well as the size and localization of bleeding were recorded. During all the malignancy treatment 22 (30%) of patients were overanticoagulated. In 15 (20%) patients it was associated with bleeding, while 3 (4%) of them had to be transfused with fresh frozen plasma to stop the major bleeding. Most bleeding complications occurred in the group of patients treated with chemotherapy or with analgesics in the group with advanced disease. None of the bleeding complications were observed in patients treated with irradiation and surgery alone, where the bridging of oral anticoagulants with low molecular weight heparin was done before surgery. The oncology treatment of patients who take oral anticoagulants was connected with high risk for bleeding especially if chemotherapy as a therapeutic options was used. Therefore physicians should be aware of this risk and carefully monitor the intensity of anticoagulant therapy, especially during the first treatment weeks when the risk of bleeding is greatest.     

Conceptual knowledge is underpinned by the temporal pole bilaterally: convergent evidence from rTMS

Conceptual knowledge provides the basis on which we bring meaning to our world. Studies of semantic dementia patients and some functional neuroimaging studies indicate that the anterior temporal lobes, bilaterally, are the core neural substrate for the formation of semantic representations. This hypothesis remains controversial, however, as traditional neurological models of comprehension do not posit a role for these regions. To adjudicate on this debate, we conducted 2 novel experiments that used off-line, low-frequency, repetitive transcranial magnetic stimulation to disrupt neural processing temporarily in the left or right temporal poles (TPs). The time required to make semantic decisions was slowed considerably, yet specifically, by this procedure. The results confirm that both TPs form a critical substrate within the neural network that supports conceptual knowledge.     

Study on histogenesis of enterochromaffin-like carcinoid in autoimmune atrophic gastritis associated with pernicious anemia

BACKGROUND/AIM: Autoimmune atrophic fundic gastritis induces the pernicious anemia (PA), as well as the changes in both epithelium and endocrine cells of gastric mucosa. The most important complications are: achlorhydria, hypergastrinemia, gastric cancer and enterochromaffin-like (ECL) carcinoid. The aim of this study was to examine ECL carcinoid histogenesis in A-gastritis associated with PA. METHODS: During the period from 2000-2006, 65 patients with PA and 30 patients of the control group were examined. Histopathological examination was done in endoscopical biopsies of gastric mucosa fixed in 10% formaldehyde. Paraffin sections were stained with classic hematoxylin-eosin (HE); histochemical AB-PAS (pH 2.5), cytochemical argyrophilic Servier-Munger's and immunocytochemical PAP methods for G cell identification and chromogranin A antibodies - specific marker for neuroendocrine ECL cells. Both G and ECL cells were counted per 20 fields, of surface 0.0245312 mm2 by a field. Basal gastrin serum levels were also examined by using radioimmunoassay (RIA) method. The obtained results were statisticaly calculated by using Student's t test. RESULTS: Marked antral G cell hyperplasia associated with corporal ECL hyperplasia was found. ECL cell hyperplasia was of simplex, linear, adenomatoid type to the pattern of intramucous ECL cell carcinoid. An average number of G cells was statistically significant in the patients with PA as compared to the control group (p < 0.05) as well as an average number of ECL cells. CONCLUSION: We concluded that antral G cell hyperplasia accompanied by gastrinemia induces ECL hyperplasia and ECL corporal carcinoid in A-gastritis and that their histogenesis develops trough simple, linear and adenomatoide hyperplasia.     

Gastrointestinal stromal tumors--microscopic and immunihistochemical features

BACKGROUND/AIM: Gastrointestinal (GI) stromal tumors (GIST) are the most common mesenchymal tumors of GI tract. The most frequent localization is gastric (60-70%) followed by intestinal localization (20-30%). The histogenesis, classification, diagnostic criteria and biological behavior of GIST are still discussable. Gastrointestinal stromal tumors are thought to originate from interstitial pacemaker intestinal cells of Cajal. Histologic appearance of a GIST is complicated and biologic potential unpredictable. The aim of of tha study was to investigate anatomic localization, the size of the tumor, incapsulation, microscopic and immunohistochemical characteristics. METHODS: The study involved 21 GIST taken by a complete resection in the period from 1994-2006. The analysed parameters were the localization, size, microscopic (mitotic index, nectosis, bleeding, invasivity) and immunohistochemical characteristics (CD117 (c-kit), CD34, desmin, vimentin, smooth muscle actin and s-100 protein expression. RESULTS: Gastrointestinal stromal tumors (n=21) size varied from 10-150 mm were most frequently gastric localised with predominance of malignant tumors (85.72%). Most GIST were comprised of a uniform spindle cell population, but some were dominated by epitheloid cells. Eosinophilic cells stained CD117, CD34 and vimentin positively, were usually arranged in fascicles with the presence of skeinoid fibers. Positive correlation of biologic potential and tumor size, haemorrhagia and mitotic index were found, so as negative correlation of biologic potential and incapsulation. CONCLUSION: The above results, a specially localization, tumor size, mitotic index, CD117, CD34 and vimentin positivity, may be helpful for setting of a widespread criteria for diagnostic and differential diagnosis of GIST and their use in practice and therapy.     

Amodal semantic representations depend on both anterior temporal lobes: Evidence from repetitive transcranial magnetic stimulation

The key question of how the brain codes the meaning of words and pictures is the focus of vigorous debate. Is there a “semantic hub” in the temporal poles where these different inputs converge to form amodal conceptual representations? Alternatively, are there distinct neural circuits that underpin our comprehension of pictures and words? Understanding words might be primarily left-lateralised, linked to other language areas, while semantic representation of pictures may be more bilateral. To elucidate this debate, we used offline, low-frequency, repetitive transcranial magnetic stimulation (rTMS) to disrupt neural processing temporarily in the left or right temporal poles. During the induced refractory period, participants made judgements of semantic association for verbal and pictorial stimuli. The efficiency of semantic processing was reduced by rTMS, yet a perceptual task of comparable difficulty was unaffected. rTMS applied to the left or right temporal poles disrupted semantic processing for words and pictures to the same degree, while rTMS delivered at a control site had no impact. The results confirm that both temporal poles form a critical substrate within the neural network that supports conceptual knowledge, regardless of modality.     

KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer

The anti-epidermal growth factor receptor (anti-EGFR) cetuximab has been proven to be efficient in metastatic colorectal cancer. The molecular mechanisms underlying the clinical response to this drug remain unknown. Genetic alterations of the intracellular effectors involved in EGFR-related signaling pathways may have an effect on response to this targeted therapy. In this study, tumors from 30 metastatic colorectal cancer patients treated by cetuximab were screened for KRAS, BRAF, and PIK3CA mutation by direct sequencing and for EGFR copy number by chromogenic in situ hybridization. Eleven of the 30 patients (37%) responded to cetuximab. A KRAS mutation was found in 13 tumors (43%) and was significantly associated with the absence of response to cetuximab (KRAS mutation in 0% of the 11 responder patients versus 68.4% of the 19 nonresponder patients; P = 0.0003). The overall survival of patients without KRAS mutation in their tumor was significantly higher compared with those patients with a mutated tumor (P = 0.016; median, 16.3 versus 6.9 months). An increased EGFR copy number was found in 3 patients (10%) and was significantly associated with an objective tumor response to cetuximab (P = 0.04). In conclusion, in this study, KRAS mutations are a predictor of resistance to cetuximab therapy and are associated with a worse prognosis. The EGFR amplification, which is not as frequent as initially reported, is also associated with response to this treatment.     

HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin (Adriamycin [ADM]). Evidence from our recent study indicates that node-positive patients respond to cyclophosphamide, methotrexate, and fluorouracil (CMF) regardless of HER2 status. We address the issue of whether therapy regimens including CMF and ADM versus CMF alone have the same therapeutic effect in patients with HER2+ and HER2- tumors in terms of relapse-free survival (RFS) and overall survival (OS). METHODS: Archival specimens of the primary tumors from 506 patients in a prospective clinical trial were stained with the anti-HER2 monoclonal antibody CB11. Originally, patients were randomly allocated to receive either 12 courses of intravenous CMF or eight courses of the same regimen followed by four cycles of ADM. RFS and OS were analyzed by a Cox model taking into account treatment, HER2 status, and the interaction between treatment and HER2 status, adjusting for the effect of other known clinical and biopathologic factors. RESULTS: Analysis of survival rates indicates a possible differential effect of treatment in the patients grouped according to HER2 status. Improved RFS and OS were observed in the HER2+ subgroup after treatment with CMF plus ADM versus CMF alone. With a median follow-up of 15 years, the hazard ratio (HR) for RFS was 0.83 in HER2+ tumors and 1.22 in HER2- tumors. The effect of treatment was more evident on OS in HER2+ patients (HR = 0.61; CI, 0.32 to 1.16) than in HER2- patients (HR = 1.26). CONCLUSION: Our data indicate that adding ADM to CMF might be beneficial for patients with HER2+ tumors.     

BPC-157,一种胃十五肽的抗焦虑作用:休克探查/埋藏试验和明暗试验(英文)

AIM: To study anxiolytic effect of a gastric pentade-capeptide, BPC-157. METHODS: In shock probe/burying test, pentadecapeptide BPC-157 (10 μg/kg, 10ng/kg, ip), diazepam (0.075, 0.0375 mg/kg, ip),and an equivolume of saline (5 mL/kg, ip) were givenat 30 min prior test. In light/dark test, the same dosageof diazepam, BPC-157, and saline were given at 45 minPrior procedure. RESULTS: Shock probe/buryingtest: rats treated with either diazepam or pentadecapeptideBPC-157 were much less afraid after the shock: almost