Pericardial effusion in a dog concurrent with carcinoma of unknown primary origin.

BACKGROUND: Pericardial effusion (PE) due to secondary metastasis has rarely been reported in dogs. CASE DESCRIPTION: This case describes clinical signs and further diagnostics regarding metastatic carcinoma of unknown primary origin (CUP) in refractory PE of a dog. FINDINGS/TREATMENT AND OUTCOME: A nine-year-old, castrated male Shih Tzu dog was referred for evaluation of cough and dyspnea. On presentation, tachypnea, intermittent cough, and muffled heart sounds were noted. Thoracic radiography, electrocardiography, and echocardiography confirmed a PE. No mass lesion was detected at the heart base, aorta, or right atrium (RA). Analysis of the PE showed hemorrhagic cytology, and an idiopathic hemorrhagic PE was tentatively diagnosed. The dog responded to conservative treatment with steroid and diuretics, but the clinical sign recurred. Further evaluation with multi-detector computed tomography (MDCT) was non-diagnostic. The dog died 457 days after initial presentation. Necropsy and histopathology revealed metastatic CUP origin. CONCLUSION: This case illustrated a rare cause of recurrent PE in dogs.

Correction: Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer.

The original version of this article contained error in Figure 2e. In Figure 2e, the 6th colony image of T47D cells treated with shMSI2 was inadvertently replaced with a duplicate of 7th colony image. However, the conclusions reported in the manuscript are not affected by figure replacement. The authors regret that these errors were made and apologize for the confusion and inconvenience. The correct version of this figure panel appears in the Author Correction associated with this Article.

Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer.

Musashi RNA-binding protein 2 (MSI2) has important roles in human cancer. However, the regulatory mechanisms by which MSI2 alters breast cancer pathophysiology have not been clearly identified. Here we demonstrate that MSI2 directly regulates estrogen receptor 1 (ESR1), which is a well-known therapeutic target and has been shown to reflect clinical outcomes in breast cancer. Based on gene expression data analysis, we found that MSI2 expression was highly enriched in estrogen receptor (ER)-positive breast cancer and that MSI2 expression was significantly correlated with ESR1 expression, including expression of ESR1 downstream target genes. In addition, MSI2 levels were associated with clinical outcomes. MSI2 influenced breast cancer cell growth by altering ESR1 function. MSI2 alters ESR1 by binding specific sites in ESR1 RNA and by increasing ESR1 protein stability. Taken together, our findings identified a novel regulatory mechanism of MSI2 as an upstream regulator of ESR1 and revealed the clinical relevance of the RNA-binding protein MSI2 in breast cancer.

Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the intracranial hemorrhage in two dogs: a case report.

Two dogs with generalized seizures were evaluated. The dogs were diagnosed with traumatic intracranial hemorrhages based on the history, neurological examinations, and magnetic resonance imaging (MRI) of the brain. Treatment was started with oxygen, prednisolone and anticonvulsant agents. No further seizure activity was observed after treatment in both dogs, however cushing reflex was detected in case 1 and a left-sided hemi-paresis was detected in case 2. Further supportive treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) was attempted. No abnormal signs were noted in either of the dogs and no recurrence was noted 16 and 14 months later, in case 1 and 2, respectively. These cases indicate that a combination of rhG-CSF treatment with previous therapy could be used in dogs with traumatic brain injury.

Conjugated polyelectrolyte nano field emission adlayers.

Here we report on a straightforward and rapid means of enhancing the field electron emission performance of nascent vertically aligned multi-walled carbon nanotubes by introducing a polar zwitterionic conjugated polyelectrolyte adlayer at the vacuum-emitter interface. We attribute the observed 66% decrease in turn-on electric field to the augmented emitter micro-morphology and shifted surface band structure. The composite emitters can be optically modulated by exploiting the absorption cross-section of the solution cast adlayer, which increases the local carrier concentration which broadens the effective electrostatic shape of the emitter during optical excitation. Assessment via scanning anode field emission microscopy reveals a 25% improvement in DC time stability, a significant reduction in long-term hysteresis shift, and a threefold increase in bandwidth during pulsed mode operation.

The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma.

Melphalan (L-PAM) has been an integral part of multiple myeloma (MM) treatment as a conditioning regimen before stem cell transplant (SCT). After initial response, most treated patients experience relapse with an aggressive phenotype. Increased glutathione (GSH) in MM may mediate resistance to L-PAM. We demonstrated that the GSH synthesis inhibitor buthionine sulfoximine (BSO) synergistically enhanced L-PAM activity (inducing 2-4 logs of cell kill) against nine MM cell lines (also in the presence of marrow stroma or cytokines) and in seven primary MM samples (combination indices <1.0). In MM cell lines, BSO significantly (P<0.05) depleted GSH, increased L-PAM-induced single-strand DNA breaks, mitochondrial depolarization, caspase cleavage and apoptosis. L-PAM depleted GSH, but GSH rapidly recovered in a L-PAM-resistant MM cell line unless also treated with BSO. Treatment with N-acetylcysteine antagonized BSO+L-PAM cytotoxicity without increasing GSH. In human MM xenografted into beige-nude-xid mice, BSO significantly depleted MM intracellular GSH and significantly increased apoptosis compared with L-PAM alone. BSO+L-PAM achieved complete responses (CRs) in three MM xenograft models including maintained CRs >100 days, and significantly increased the median event-free survival relative to L-PAM alone. Combining BSO with L-PAM warrants clinical testing in advanced MM.

Ischemic diabetic retinopathy as a possible prognostic factor for chronic kidney disease progression.

PURPOSE: To assess the value of diabetic retinopathy (DR) severity as a possible predictive prognostic factor for the progression of chronic kidney disease (CKD). PATIENTS AND METHODS: Retrospective cohort study. Patients (51) who were initially diagnosed with DR and CKD were enrolled and their medical records were evaluated. The following ophthalmic factors were assessed by fluorescein angiography at the initial visit: area of capillary nonperfusion, presence of neovascularization and vitreous hemorrhage, and DR grade. The effect of these factors on CKD progression over the 2-year period of the study, defined as doubling of serum creatinine or the development of end-stage renal disease requiring dialysis or renal transplant, was evaluated. RESULTS: The study included 51 patients with DR and CKD; of these, 11 patients (21.6%) were found to have proliferative DR (PDR) and seven patients (13.7%) had high-risk PDR at baseline. Patients with ischemic DR, who showed extensive capillary nonperfusion (≥ 10 optic disc areas) in the retina, had a greater risk for CKD progression (hazard ratio = 6.64; P = 0.002). CONCLUSION: We found that extensive capillary nonperfusion in the retina greatly increased the risk of progression of CKD in patients with DR. This suggests that the retina and the kidney may have shared risk factors for microvascular disease secondary to diabetes mellitus, and emphasizes the need for a team approach to diabetes care.

The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment. METHODS: We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital. RESULTS: In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS. CONCLUSIONS: NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.

Expression and localization of 20α-hydroxysteroid dehydrogenase (20α-HSD) in porcine reproductive tissues during pregnancy.

The aims of this study were to determine the specific site of 20α-HSD expression in the reproductive tissues on day 30 of pregnancy and during pre-parturition. 20α-HSD mRNA was demonstrated to have the highest expression in the placenta on day 30 of pregnancy and in the ovary during pre-parturition. Weak mRNA expression was observed in the uterus and ovary on day 30 of pregnancy. However, the mRNA was not expressed in the oviduct on day 30 of pregnancy. The mRNA was also specifically detected in the placenta on day 30 of pregnancy by northern blot analysis. Western blot analysis indicated that the expression pattern of the 20α-HSD protein in the reproductive tissues was similar to that of 20α-HSD mRNA. Immunohistochemical analysis also revealed that the pig 20α-HSD protein was localized in the trophoblast villus in the placenta on day 30 of pregnancy. It was highly expressed in the glandular epithelial cells of the endometrium and the luminal epithelial cells of the uterus. The 20α-HSD protein was highly localized in the large luteal cells of the ovary on day 30 of pregnancy and during pre-parturition. Taken together, our study demonstrated that the pig 20α-HSD mRNA and protein are mainly localized in the trophoblast villus in the placenta on day 30 of pregnancy. The expression of the protein is also localized in the large luteal cells of the ovary. In addition, the protein is highly expressed in the glandular epithelial cells of the endometrium and the luminal epithelial cells of the uterus.

Gene expression and localization of 20α-hydroxysteroid dehydrogenase (HSD) in reproductive tissues during early pregnancy of cattle.

The enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD) catalyzes the conversion of progesterone to its inactive form, 20α-hydroxyprogesterone, and this enzyme has an important role in the regulation of luteal function in mammals. It has previously been determined that the 20α-HSD gene is primarily expressed by large luteal cells during the late stage of the estrous cycle. In the present study, the amounts of mRNA were determined in cultured cells of the corpus luteum (CL) cells. The localization of 20α-HSD was also determined in ovaries, placenta, and endometrium during early pregnancy. The amount of 20α-HSD mRNA in cultured luteal cells increased with time and by treatment with the luteolysis agent prostaglandin F2α (PGF2α). Immunofluorescence assays detected increased protein in cultured luteal cells. The 20α-HSD mRNA and protein were present in the ovaries, placenta, and endometrium on Days 30, 60, and 90 of pregnancy. In particular, gene expression was much greater in the ovary than in the placenta and endometrium. Immuno-histochemical analysis indicated that bovine 20α-HSD was primarily localized in ovarian large luteal cells, placental cytotrophoblast villus, and glandular epithelial cells of the endometrium during early pregnancy. Furthermore, in situ analyses demonstrated colocalization of 20α-HSD mRNA and protein. Taken together, results of the present study indicate that 20α-HSD mRNA and protein are co-localized in large luteal cells, the placenta, and the endometrium during early pregnancy, suggesting that 20α-HSD regulates mechanisms involved in the maintenance of early pregnancy.

Unusual congenital pulmonary anomaly with presumed left lung hypoplasia in a young dog.

A seven-month-old, entire, male miniature schnauzer dog was referred with acute vomiting, inappetence and depression primarily as a result of a gastric foreign body (pine cones). During investigations, thoracic radiographs revealed increased volume of the right lung lobes, deviated cardiomediastinal structures and elevation of the heart from the sternum. Thoracic computed tomography revealed left cranial lung lobe hypoplasia and extension of the right cranial lung parenchyma across the midline to the left hemithorax. Branches of the right pulmonary vessels and bronchi also crossed the midline and extended to the left caudal lung lobe. These findings suggested that the right and left lungs were fused. In humans this finding is consistent with horseshoe lung, which is an uncommon congenital malformation. To the authors' knowledge, this case represents the first report of such a pulmonary anomaly in a dog.

Common stress and serum cortisol and IL-12 levels in missed abortion.

To investigate stress levels, serum cortisol levels, and changes in IL-12 concentration in patients with missed abortion. Patients with missed abortion (n = 48) were age and gestational age-matched with normal early pregnancy cases (n = 48). All subjects completed a stress evaluation survey questionnaire about common stressors. Venous blood samples were collected at 07.00 hours, and serum cortisol and IL-12 concentrations were measured by electrochemiluminescence immunoassay and ELISA methods, respectively. Missed abortion patients demonstrated a significantly higher number of common stressors and higher serum cortisol levels compared to controls (both p < 0.05). Dilation and curettage did not lead to significant differences in serum cortisol and IL-12 levels (p > 0.05). Stress and immunity alterations of the immune system may contribute to the aetiology of missed abortion.

Ovarian and placental expression of 20α-hydroxysteroid dehydrogenase during pregnancy in deer.

The enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD) catalyzes the conversion of progesterone to its inactive form, 20α-hydroxyprogesterone. This enzyme has been shown to play a critical role in the regulation of luteal function in experimental animals. In this study, we cloned and expressed the gene encoding elk deer 20α-HSD from reproductive placental and ovarian tissues. PCR, 3'- and 5'-RACE, and northern blot analysis were performed for the cloning and characterization of deer 20α-HSD gene. We expressed recombinant deer 20α-HSD protein and used western blot analysis to determine protein expression levels in the placenta and ovary during pregnancy. The full cDNA sequence of 20α-HSD was used to clone an open reading frame encoding 323 amino acids and consisting of 1142 bp. The nucleotide sequence of deer 20α-HSD showed high homology with the sequences of the bovine (96%), goat (96%), and human (83%) 20α-HSD genes. 20α-HSD mRNA was strongly expressed in the placenta on days 30, 60, and 70 of pregnancy. A high level of the protein was also detected in the placenta but not in fetal skin tissue. The recombinant 20α-HSD protein produced in mammalian cells and bacterial systems had a molecular weight of approximately 37-kDa. The deer 20α-HSD protein signal was specifically localized in the basal part of the primary chorionic villi and chorionic stem villus of the placenta during early pregnancy. The 20α-HSD protein was also intensively localized in the larger luteal cells of the corpus luteum during pregnancy.

Cancel all Hollidays for SLX4 mutations: identification of a new Fanconi anemia subtype, FANCP.

SLX4, a coordinator of structure-specific endo-nucleases, is mutated in a new Fanconi anemia subtype Stoepker et al. (2011) Nature Genetics 43:138-141. Mutations of the SLX4 gene in Fanconi anemia Kim et al. (2011) Nature Genetics 43:142-146.

Responses of wild plant species to polycyclic aromatic hydrocarbons in soil.

Responses of plants to polycyclic aromatic hydrocarbons (PAHs) contamination were determined with fifty-five Korean wild plants. Responsiveness of species was evaluated based on germination and shoot weight and shoot length of plants grown in soil spiked with four PAHs (pyrene, fluorene, phenanthrene and fluoranthene). Seeds of test plants were germinated with mixtures of PAHs of 0, 10, 30, 100, 300 mg kg(-1) spiked in soil. Seed germination of test plants changed when subjected to PAHs. As compared to control germination percentages ranged from 0 (completely inhibited) to 242.9% (highly promoted) of control at 300 mg kg(-1) of PAHs. In germination responses, Fabaceae plants were much less affected (105% of control) compared to species belonging to Caryophyllaceae (18.7% of control), which showed highly susceptible responses. Results demonstrated that seed germination was affected by species-specific responses to PAHs. In seedling growth experiments on Bromus tectorum and Veronica persica, species classified as highly susceptible in germination experiments, a low No Observed Effect Concentration (NOEC) of 10 mg kg(-1) was observed. On the other hand, NOEC was 100 mg kg(-1) in Bromus japonicus and Cerastium holosteoides var. hallaisanense, which were also classified as highly susceptible by the germination experiment. However, most species classified as susceptible showed high NOEC of greater than 10 mg kg(-1). EC(50) values of test species ranged from 2.87 x 10(2) (Humulus japonicus) to 8.05 x 10(81) mg kg(-1) (Bidens bipinnata) based on shoot length. The wide range of EC(50) for shoot weight suggests that shoot weight is more appropriate as an endpoint for PAHs toxicity than shoot length for determining the susceptibility of plant species to PAHs. It was confirmed that dose-response of plants to PAHs spiked soil can be used to estimate critical concentration of PAHs inhibiting early establishment of plants in contaminated fields.

Calf-contouring surgery of gastrocnemius hypertrophy: selective neurectomy of the sural nerve.

Generally, Asians tend to have obese calves that are shorter and thicker than those of Caucasians. The cause of the enlarged calves is either an excess of subcutaneous fat or calf muscular hypertrophy, but some patients have both conditions. These features are accentuated by the contraction of the calf muscles when patients stand in tiptoe position or wear high heels. In the case of calf muscular hypertrophy without excessive subcutaneous fat, manipulation of the calf muscle is an effective method for reducing calf circumference. From January 2005 to December 2006, the authors performed selective sural neurectomy for 20 patients who complained of obese calves. Using a popliteal incision, the sural nerve branches to the medial and/or lateral gastrocnemius muscles were dissected from the posterior tibial nerve. Using a nerve stimulator, the branches with the most contractile portions were resected in 1 cm lengths at the distal ends. One medial branch was resected in 15 patients, and two branches were resected in 5 patients. In the case of a lateral neurectomy, only one branch was resected. Ultrasound-assisted liposuction was combined for five patients who also showed excessive subcutaneous fat. The patients ranged in age from 19 to 29 years (mean, 23 years). The follow-up period varied from 6 to 18 months. The circumferential change was checked 6 months postoperatively 15 cm below the medial condyle and 15 cm above the medial malleolus. These average circumferences were reduced, respectively, from 36.6 and 32.5 cm to 35.5 and 32.2 cm. In gait analysis performed at 6 months postoperatively, the calf muscle power was slightly reduced to 95% of the preoperative state, but still remained above the normal range. Subjectively, no patient complained of muscle weakness or gait disturbance. One patient showed lower leg edema after mountain climbing that subsided after 1 day of rest. The authors believe a selective neurectomy technique can be an effective method for treating obese calves.

Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia.

BACKGROUND: This randomized, double-blind, prospective study was undertaken to evaluate the effects of magnesium sulphate on anaesthetic requirements and postoperative analgesia in patients undergoing total i.v. anaesthesia (TIVA). METHODS: Fifty patients who underwent gynaecological surgery were randomly divided into two groups. Before induction of anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and then 15 mg kg(-1) h(-1) i.v. by continuous infusion. The control group (Group S) received the same amount of isotonic saline. TIVA (propofol+remifentanil) was administered under bispectral index monitoring during anaesthesia induction and maintenance. Rocuronium was administered before orotracheal intubation and during surgery when the train-of-four count was 2 or more. After operation, patient-controlled analgesia with a solution of ketorolac and morphine was used and the consumption of this solution was recorded. Pain scores at rest and upon movement were evaluated 30 min, 4, 24, and 48 h after surgery. RESULTS: Patients in Group M required less rocuronium than those in Group S [mean (SD) 0.44 (0.09) vs 0.35 (0.07) microg kg(-1) min(-1), P<0.05]. The total amounts of propofol and remifentanil administered were similar in the two groups. Postoperative pain scores, cumulative analgesic consumption, and shivering incidents were significantly lower in Group M (P<0.05). Mean arterial pressure just after intubation and during the immediate postoperative period was also significantly lower in Group M (P<0.05). CONCLUSIONS: I.v. magnesium sulphate during TIVA reduced rocuronium requirement and improved the quality of postoperative analgesia.