Presumed primary cardiac mast cell tumor, pericardial effusion, and arrhythmia in a dog.

A 13-year-old female spayed border collie cross presented for pericardial effusion, arrhythmia, and a suspected cardiac mass. Echocardiogram revealed severe thickening and hypokinesis of the interventricular septum with a heterogenous, cavitated myocardium, concerning for neoplasia. Electrocardiogram revealed predominantly accelerated idioventricular rhythm with frequent periods of nonsustained ventricular tachycardia. Occasional prolonged PR intervals terminating in an aberrantly conducted QRS complex were present. These beats were postulated to represent either first-degree atrioventricular block with aberrant QRS conduction or atrioventricular dissociation. Cytology of the pericardial effusion revealed atypical, suspected neoplastic, mast cells. The patient was euthanized, and postmortem examination confirmed full-thickness infiltration of the interventricular septum by a mast cell tumor, with metastasis to the tracheobronchial lymph node and spleen. Given the anatomic location of the mass, the observed atrioventricular nodal conduction delay may represent neoplastic infiltration of the atrioventricular node. Neoplastic infiltration of the ventricle was suspected to cause the accelerated idioventricular rhythm and ventricular tachycardia. To the authors' knowledge, this is the first reported case of a primary cardiac mast cell tumor causing arrhythmia and pericardial effusion in a dog.

Large seasonal fluctuations in whole-tree carbohydrate reserves: is storage more dynamic in boreal ecosystems?

BACKGROUND AND AIMS: Carbon reserves are a critical source of energy and substrates that allow trees to cope with periods of minimal carbon gain and/or high carbon demands, conditions which are prevalent in high-latitude forests. However, we have a poor understanding of carbon reserve dynamics at the whole-tree level in mature boreal trees. We therefore sought to quantify the seasonal changes in whole-tree and organ-level carbon reserve pools in mature boreal Betula papyrifera. METHODS: Non-structural carbohydrate (NSC; soluble sugars and starch) tissue concentrations were measured at key phenological stages throughout a calendar year in the roots, stem (inner bark and xylem), branches and leaves, and scaled up to estimate changes in organ and whole-tree NSC pool sizes. Fine root and stem growth were also measured to compare the timing of growth processes with changes in NSC pools. KEY RESULTS: The whole-tree NSC pool increased from its spring minimum to its maximum at bud set, producing an average seasonal fluctuation of 0.96 kg per tree. This fluctuation represents a 72 % change in the whole-tree NSC pool, which greatly exceeds the relative change reported for more temperate conspecifics. At the organ level, branches accounted for roughly 48-60 % of the whole-tree NSC pool throughout the year, and their seasonal fluctuation was four to eight times greater than that observed in the stemwood, coarse roots and inner bark. CONCLUSIONS: Branches in boreal B. papyrifera were the largest and most dynamic storage pool, suggesting that storage changes at the branch level largely drive whole-tree storage dynamics in these trees. The greater whole-tree seasonal NSC fluctuation in boreal vs. temperate B. papyrifera may result from (1) higher soluble sugar concentration requirements in branches for frost protection, and/or (2) a larger reliance on reserves to fuel new leaf and shoot growth in the spring.

Hepatic alveolar hydatid disease (Echinococcus multilocularis), a mimic of liver malignancy: a review for the radiologist in non-endemic areas.

Alveolar hydatid disease or alveolar echinococcosis (AE) is caused by the parasite Echinococcus multilocularis and is increasingly seen as an imported disease in non-endemic areas such as the UK. It is rare compared to cystic echinococcosis (CE), but like CE commonly affects the liver. AE does have imaging features that can aid in diagnosis, but is often initially misdiagnosed as liver malignancy. It is usually fatal if untreated, underscoring the importance of early diagnosis. This review highlights the role of imaging in AE diagnosis with the broader objective of increasing radiologists' awareness of this unusual, but increasingly prevalent disease.

Metformin Discontinuation prior to FDG PET/CT: A Randomized Controlled Study to Compare 24- and 48-hour Bowel Activity.

Purpose To investigate the relationship of 24- and 48-hour metformin discontinuation to bowel uptake of fluorine 18 fluorodeoxyglucose (FDG) on PET/CT scans. Materials and Methods Patients with diabetes who were treated with metformin and referred for FDG PET/CT were randomized to three equal groups based on duration of metformin discontinuation: 24 hours, 48 hours, and no discontinuation (control group). Two interpreters blinded to the study groups assessed FDG uptake in multiple segments of small and large bowel qualitatively and semiquantitatively by using maximum standardized uptake values (SUVsmax). Differences in age, sex, weight, dose of metformin, duration of metformin treatment, blood glucose levels, and FDG dose injected were assessed. Data were analyzed with analysis of variance when passing normality, and by nonparametric testing when not. Results Ninety study participants (62 male, 28 female; median age, 70 years) were enrolled from July 2010 through March 2012. There were no differences between study groups in weight, blood glucose levels 3 days prior to scanning, or normal organ uptake. Large bowel SUVmax was lower after 24 hours (4.10 ± 2.00 vs 5.42 ± 2.36; P = .020) and 48 hours (2.63 ± 0.88 vs 5.42 ± 2.36; P ˂ .001) of metformin discontinuation than for no discontinuation (control), and for 48 hours versus 24 hours of discontinuation (P = .0015). Small bowel SUVmax was lower after 24 hours (2.86 ± 0.67 vs 3.73 ± 1.08 [control]; P ˂ .001) and 48 hours (2.78 ± 0.73 vs 3.73 ± 1.08 [control]; P ˂ .001) of metformin discontinuation versus no metformin discontinuation, but not for 48 hours versus 24 hours of discontinuation (P = .57). Examination-day blood glucose levels increased after 48-hour withdrawal of metformin (8.41 mmol/L ± 2.86 vs 6.83 mmol/L ± 2.13 [control]; P = .002). Conclusion Metformin discontinuation for 48 hours prior to PET/CT was associated with lower accumulation of fluorodeoxyglucose in the bowel, compared to when there was no discontinuation (control group) or 24-hour discontinuation of metformin. © RSNA, 2018.

Are node-based and stem-based clades equivalent? Insights from graph theory.

Despite the prominence of "tree-thinking" among contemporary systematists and evolutionary biologists, the biological meaning of different mathematical representations of phylogenies may still be muddled. We compare two basic kinds of discrete mathematical models used to portray phylogenetic relationships among species and higher taxa: stem-based trees and node-based trees. Each model is a tree in the sense that is commonly used in mathematics; the difference between them lies in the biological interpretation of their vertices and edges. Stem-based and node-based trees carry exactly the same information and the biological interpretation of each is similar. Translation between these two kinds of trees can be accomplished by a simple algorithm, which we provide. With the mathematical representation of stem-based and node-based trees clarified, we argue for a distinction between types of trees and types of names. Node-based and stem-based trees contain exactly the same information for naming clades. However, evolutionary concepts, such as monophyly, are represented as different mathematical substructures in the two models. For a given stem-based tree, one should employ stem-based names, whereas for a given node-based tree, one should use node-based names, but applying a node-based name to a stem-based tree is not logical because node-based names cannot exist on a stem-based tree and visa versa. Authors might use node-based and stem-based concepts of monophyly for the same representation of a phylogeny, yet, if so, they must recognize that such a representation differs from the graphical models used for computing in phylogenetic systematics.

Characterization of 32 novel microsatellite loci for population and mating system studies using Campostoma anomalum (central stoneroller).

The central stoneroller (Campostoma anomalum) is an abundant, widespread and sexually dimorphic stream minnow that is a useful model for mating system studies as well as a sentinel species for understanding population-level processes for fishes in headwater communities. We developed one genomic library enriched for dinucleotide repeats and isolated 48 putative, novel microsatellite loci. Of those, we present 32 polymorphic and independent microsatellite markers with 3 to 16 alleles per locus and heterozygosity ranging from 0.23 to 0.95. Hence, these markers will be useful for future behavioural, ecological and evolutionary studies using C. anomalum.

Characterization of 35 novel microsatellite loci for ecological and evolutionary studies of the bluntnose minnow (Pimephales notatus).

The bluntnose minnow (Pimephales notatus) is abundant and widespread with a broad ecological niche. This species is also sexually dimorphic with strong competition between males during the mating season. We developed two genomic libraries enriched for microsatellite repeats - one dinucleotide and one tetranucleotide - and isolated 48 putative, novel microsatellite loci. Of those, we present 35 polymorphic and statistically independent microsatellite markers with two to 18 alleles per locus and heterozygosities ranging from 0.04 to 1. These markers will be useful for future behavioural, ecological, evolutionary and mating system studies using P. notatus.

Twenty-three microsatellite DNA loci for population genetic studies and parentage assignment in orangethroat darter, Etheostoma spectabile.

The genus Etheostoma is a species-rich and ecologically important group of fishes in North America. The orangethroat darter (Etheostoma spectabile) is widely distributed and abundant in headwater streams throughout the central Midwest, and is an excellent model for ecological and mating system studies. We developed 23 novel, polymorphic, and independent microsatellite loci for E. spectabile. We found from two to 14 alleles per locus, and observed heterozygosities ranged from 0.39 to 1.0. These markers, in combination with others isolated from Etheostoma taxa, will be useful for ecological and evolutionary studies in the genus.

Perinucleolar compartment prevalence has an independent prognostic value for breast cancer.

The perinucleolar compartment (PNC) is a multicomponent nuclear structure enriched with RNAs transcribed by RNA pol III and RNA binding proteins. Studies in cultured cells showed an association between PNC and transformed phenotype. To evaluate the relationship between structure and malignancy in vivo, we examined PNC prevalence (the percentage of cells containing at least one PNC) in normal and cancerous paraffin-embedded breast tissues using immunohistochemistry against a PNC-associated protein. Five hundred nuclei in the most active area of each sample were scored for PNC prevalence. The results show that PNC prevalence significantly correlates with the progression of breast cancer (by the criteria of staging). PNC prevalence in primary tumors, lymph nodes, and distant metastases shows a stepwise increase from a median of 23% in primary tumors to approximately 100% in distant metastases. In addition, univariate and multivariate (controlling for tumor size and grade) analyses show that early-stage patients with invasive ductal carcinomas containing a higher PNC prevalence have a significantly poorer prognosis. These findings link PNC prevalence with the progression of breast cancer in vivo and suggest that PNC-containing cells have metastatic advantages. These findings also show the potential of PNC prevalence as a prognostic marker for breast cancer.

Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast.

AIMS: Invasive micropapillary carcinoma (IMPC) is a rare variant of ductal carcinoma of the breast and is characterized by high metastatic potential and an aggressive clinical course. This tumour is hence ideal for studying the mechanism underlying tumour biological behaviour, especially metastasis. Cell adhesion molecules, such as CD44 and E-cadherin (Ecad), and angiogenesis are considered important in the invasion and metastasis of tumours. METHODS AND RESULTS: We immunohistochemically analysed 23 IMPCs for expression of a standard form of CD44 (CD44s), Ecad, and CD34 to measure microvessel density (MVD). Results are compared with the changes observed in 23 tubular carcinomas (TCs), another variant of ductal carcinoma that rarely metastasizes. Evaluation of haematoxylin and eosin (H&E) sections showed a higher prevalence of lymph-vascular invasion (19/23, 83%) and regional lymph node involvement (12/15, 80%) in IMPCs; whereas no lymph-vascular invasion or lymph node metastasis was identified in TCs. Loss or reduction of CD44s immunoreactivity was significantly frequent in IMPC (39%) compared with TC (4%) (P = 0.0098), and was associated with positive axillary lymph nodes and lymph-vascular invasion. All cases of IMPC and TC strongly expressed Ecad. MVD (in five 200x fields) was significantly higher in IMPC (88 +/- 37) than in TC (57 +/- 16) (P = 0.001). In the IMPC group, MDV was higher in cases with positive lymph node(s) (P = 0.048), and cases with loss or reduction of CD44s expression (P = 0.011). The same trend was also demonstrated in cases with lymph-vascular invasion (P = 0.077). Moreover, the vessels in IMPC had much smaller calibres with thinner walls than those in TC. CONCLUSIONS: Loss of the CD44 adhesion molecule and high MVD may play a significant role in the high incidence of lymph-vascular permeation and metastasis in IMPC.

Prediction of breast cancer size by ultrasound, mammography and core biopsy.

Neoadjuvant chemotherapy and non-surgical tumor ablation rely upon imaging studies to determine tumor size. In this study the accuracy of ultrasound (US) mammography and core biopsy in determining tumor size was examined in 202 patients with Stages I and II breast cancer. The most accurate single modality for determining tumor size was mammography with a correlation coefficient of 0.66, followed by US (r = 0.48) and core biopsy (r = 0.28). Size measurements were less accurate in lobular than ductal cancers. The combination of the three modalities understaged 25% of the tumors > 1cm in size, and overstaged 10% of those < 1cm. The inability to accurately determine tumor size has important implications for the use of non-surgical ablation.

Oolong tea increases metabolic rate and fat oxidation in men.

According to traditional Chinese belief, oolong tea is effective in the control of body weight. Few controlled studies, however, have been conducted to measure the impact of tea on energy expenditure (EE) of humans. A randomized cross-over design was used to compare 24-h EE of 12 men consuming each of four treatments: 1) water, 2) full-strength tea (daily allotment brewed from 15 g of tea), 3) half-strength tea (brewed from 7.5 g tea) and 4) water containing 270 mg caffeine, equivalent to the concentration in the full-strength tea treatment. Subjects refrained from consuming caffeine or flavonoids for 4 d prior to the study. Tea was brewed each morning; beverages were consumed at room temperature as five 300 mL servings. Subjects received each treatment for 3 d; on the third day, EE was measured by indirect calorimetry in a room calorimeter. For the 3 d, subjects consumed a typical American diet. Energy content of the diet was tailored to each subject's needs as determined from a preliminary measure of 24-h EE by calorimetry. Relative to the water treatment, EE was significantly increased 2.9 and 3.4% for the full-strength tea and caffeinated water treatments, respectively. This increase over water alone represented an additional expenditure of 281 and 331 kJ/d for subjects treated with full-strength tea and caffeinated water, respectively. In addition, fat oxidation was significantly higher (12%) when subjects consumed the full-strength tea rather than water.

Expression of epithelial mucins Muc1, Muc2, and Muc3 in ductal carcinoma in situ of the breast.

Epithelial mucins are glycoproteins secreted by epithelial cells and their carcinomas. At least nine mucin genes have been identified, and their products (MUC1-MUC9) are expressed in various epithelia. MUC1 is a mucin expressed in breast epithelial cells, whereas MUC2 and MUC3 are primarily intestinal mucins. Although MUC1 and MUC2 expression has been documented in invasive ductal carcinoma of the breast, mucin expression in pure ductal carcinoma in situ (DCIS) has not been investigated. Sixty-one of 105 cases of DCIS without coexisting infiltrating carcinoma diagnosed during a 30-month period were selected as having sufficient tissue for study. Paraffin-embedded tissue sections were stained using immunohistochemical techniques with mouse monoclonal anti-MUC1, anti-MUC2, and rabbit-specific polyclonal anti-MUC3 antibodies. Immunoreactive epitopes of MUC1, MUC2, and MUC3 were expressed in DCIS in 61, 19, and 16 of 61 cases, respectively. MUC2 and MUC3 staining intensity in DCIS was markedly less than that observed for MUC1. Luminal and/or cytoplasmic patterns of staining were observed for MUC1. MUC2 and MUC3 showed only cytoplasmic staining. Cytoplasmic-only staining of MUC1 was associated with a higher grade of DCIS. Any MUC2 staining was also associated with a higher grade of DCIS. Coexpression of MUC2 and MUC3 was present in only 6 of 61 cases, and MUC3 staining was unrelated to the grade of DCIS. Cytoplasmic expression of MUC1 and MUC2 appears to be associated with a higher grade of DCIS. MUC3 expression appears to be independent of grade and expression of MUC1 and MUC2. The relationship of mucin expression and grade warrants further study.

PHP-HT (VitaResc Biotech).

VitaResc (formerly Apex) is developing PHP-HT, pyridoxalated hemoglobin polyoxyethylene conjugate, for the potential treatment of nitric oxide-induced shock (characterized by hypotension), associated with various etiologies, initially in septic shock. A phase I safety study and an initial phase I/II patient trial for NO-induced shock have been completed, and VitaResc has enrolled patients in three of five planned cohorts in a continuation of these trials to include a protocol of continuous infusion and dose escalation [330680,349187,390918]. The results from the dose escalation trials are expected to provide the basis for a randomized, controlled phase II/III pivotal trial of PHP-HT [390918]. VitaResc has licensed PHP-HT exclusively from Ajinomoto for all indications, worldwide, except Japan [275263]. Ajinomoto originally developed the human derived and chemically modified hemoglobin preparation as a blood substitute, but no development has been reported by the company since 1997 [275277,303577]. The other potential indications of PHP-HT include shock associated with burns, pancreatitis, hemodialysis and cytokine therapies [275277]. VitaResc expects the annual market potential of PHP-HT to exceed 1 billion dollars [330680].

Developmentally regulated rpd3p homolog specific to the transcriptionally active macronucleus of vegetative Tetrahymena thermophila.

A clear relationship exists between histone acetylation and transcriptional output, the balance of which is conferred by opposing histone acetyltransferases (HATs) and histone deacetylases (HDACs). To explore the role of HDAC activity in determining the transcriptional competency of chromatin, we have exploited the biological features of Tetrahymena as a model. Each vegetative cell contains two nuclei: a somatic, transcriptionally active macronucleus containing hyperacetylated chromatin and a transcriptionally silent, germ line micronucleus containing hypoacetylated histones. Using a PCR-based strategy, a deacetylase gene (named THD1) encoding a homolog of the yeast HDAC Rpd3p was cloned. Thd1p deacetylates all four core histones in vitro. It resides exclusively in the macronucleus during vegetative growth and is asymmetrically distributed to developing new macronuclei early in their differentiation during the sexual pathway. Together, these data are most consistent with a potential role for Thd1p in transcriptional regulation and suggest that histone deacetylation may be important for the differentiation of micronuclei into macronuclei during development.

Are malignant cells displaced by large-gauge needle core biopsy of the breast?

OBJECTIVE: The purpose of this paper is to determine the rate of tumor displacement resulting from large-gauge needle core biopsy in patients with breast carcinoma. MATERIALS AND METHODS: Three hundred fifty-two cancer excisions in patients who had undergone large-gauge needle core biopsy were evaluated for evidence of tumor displacement. Three needle procedures were compared: vacuum-assisted, automated gun, and core biopsy guided by palpation. Needle track visualization, presence and amount of tumor displacement, tumor morphology, and interval between core biopsy and surgical excision were recorded for each case. RESULTS: Seventy-six cases showed tumor displacement of one or two cell clusters, and 38 cases-showed displacement of multiple tumor fragments. Tumor displacement was identified in 37% of automated gun specimens, 38% of specimens obtained with palpable guidance, and 23% of specimens obtained with a vacuum-assisted needle. Tumor displacement was seen in 42% of patients with an interval between biopsy and excision of less than 15 days, in 31% of patients with an interval of 15-28 days, and in 15% of tumors excised more than 28 days after core biopsy (p < .005). CONCLUSION: Tumor cell displacement was observed in 32% of patients who had undergone large-gauge needle core biopsy. The incidence and amount of tumor displacement was inversely related to the interval between core biopsy and excision. This relation suggests that tumor cells do not survive displacement.