Nucleic acid distribution pattern as a possible biomarker for metabolic activities of neoplastic cells: a digitally-aided fluorescence microscopy study on normal and neoplastic lymphocytes of acute and chronic canine lymphocytic leukemia

<p>Abstract</p> <p>Background</p> <p>Metabolic states of neoplastic cells are increasingly being relied upon for diagnostic and prognostic assessment of neoplastic conditions. The nucleic acid distribution pattern of cells in general, in terms of degree of condensation of the nuclear chromatin and overall spread of the nucleic acid within the nuclear and cytoplasmic compartments, can reflect the metabolic state of the cell. This simple but logical concept appears not be put into consideration to date as numerous attempts are being made towards formulating reliable biomarkers for rapid diagnosis, prognosis and subsequent therapeutic interventions for neoplastic conditions. We comparatively evaluated nucleic acid distribution patterns of normal lymphocytes and neoplastic cells of lymphocytic lineage, employing light and fluorescence microscopy procedures, as well as digital imaging analytical methods.</p> <p>Results</p> <p>The results demonstrate distinctiveness in the pattern of nucleic acid distribution for the normal lymphocytes and three lymphocytic neoplastic cell-types of canine lymphocytic leukemia that are categorized as small, intermediate and large neoplastic lymphocytes. Variably-shaped cytoplasmic processes laden with single-stranded nucleic acids (SSNA) were observed for the small and intermediate-sized neoplastic lymphocytes, compared with large neoplastic lymphocytes and the normal lymphocytes; the latter two categories of cells being virtually devoid of similar processes. Prominent cytoplasmic and nuclear clumps of SSNA, indicative of a higher rate of metabolic activity, were also observed within the neoplastic cells compared with fewer and narrower SSNA of the normal cells.</p> <p>Conclusion</p> <p>The comparative relative increases of SSNA in cytoplasmic processes and other cellular areas of small and intermediate-sized neoplastic lymphocytes is reflective of greater metabolic activity in neoplastic cells in general compared with their normal cellular counterparts.</p

Experimental Study on Brucella abortus Strain RB51 Vaccinated Water Buffalo (Bubalus bubalis) Challenged with Virulent B. abortus Strain during Pregnancy

The study was conducted to determine the efficacy of Brucella abortus strain RB51 (RB51) vaccine in preventing abortion in pregnant water buffalo (Bubalus bubalis) experimentally challenged using the intravenous route, with a local pathogenic strain of B. abortus biovar 1 (Trinidad 1). Thirty-two female water buffalo calves aged 6-10 months were randomly divided into three groups for the vaccination trial using the subcutaneous route: Group I animals received recommended dose (RD) vaccine twice 4 weeks apart, Group II was vaccinated twice 18 weeks apart and Group III (control) received saline once. At approximately 6 months of pregnancy following natural breeding, the animals were challenged by the intravenous route with 2.5 x 108 to 4.4 x 108 colony forming units of a local strain of B. abortus, Trinidad 1. Blood samples were collected, pre-challenge and post-challenge, for serological assay using the BPAT and the animals were monitored for clinical signs. The bacteriological study was also performed on tissues of the dams and their calves. The frequency of abortion/stillbirths/early neonatal deaths was 55.6% (5/9), 42.9% (3/7) and 40.0% (2/5) for Groups I, II and III dams respectively (P&gt;0.05; ?2). For calves from infected dams, the frequency of isolation of B. abortus Trinidad 1 from the abomasal and rectal swabs was 100.0%, 80.0% and 100.0% for Groups I, II and III animals respectively (P&gt;0.05). It was concluded that vaccination of water buffalo with the RB51 vaccine using the recommended dose was ineffective in preventing infection, abortion, stillbirths, and neonatal deaths

Achilles tendinopathy alters stretch shortening cycle behaviour during a sub-maximal hopping task

Objectives To describe stretch shortening cycle behaviour of the ankle and lower limb in patients with Achilles tendinopathy (AT) and establish differences with healthy volunteers. Design Between-subjects case-controlled. Methods Fifteen patients with AT (mean age 41.2 ± 12.7 years) and 11 healthy volunteers (CON) (mean age 23.2 ± 6.7 years) performed sub-maximal single-limb hopping on a custom built sledge-jump system. Using 3D motion analysis and surface EMG, temporal kinematic (lower limb stiffness, ankle angle at 80 ms pre-contact, ankle angle at contact, peak ankle angle, ankle stretch amplitude) and EMG measures (onset, offset and peak times relative to contact) were captured. Data between AT and CON were compared statistically using a linear mixed model. Results Patients with AT exhibited significantly increased lower limb stiffness when compared to healthy volunteers (p \u3c 0.001) and their hopping range was shifted towards a more dorsiflexed position (p \u3c 0.001). Furthermore, ankle stretch amplitude was greater in AT compared with healthy volunteers (p \u3c 0.001). A delay in muscle activity was also observed; soleus onset (p \u3c 0.001), tibialis anterior peak (p = 0.026) and tibialis anterior offset (p \u3c 0.001) were all delayed in AT compared with CON. Conclusions These findings indicate that patients with AT exhibit altered stretch-shortening cycle behaviour during sub-maximal hopping when compared with healthy volunteers. Patients with AT hop with greater lower limb stiffness, in a greater degree of ankle dorsiflexion and have a greater stretch amplitude. Likewise, delayed muscle activity is evident. These findings have implications in terms of informing the understanding of the pathoaetiology and management of AT

A case of transplacental transmission of Theileria equi in a foal in Trinidad

Equine piroplasmosis due to Theileria equi and Babesia caballi is endemic in Trinidad. A case of equine piroplasmosis due to T. equi was diagnosed in a thoroughbred foal at 10 h post-partum. A high parasitaemia (63%) of piroplasms was observed in a Wright-Giemsa® stained thin blood smear from the foal. In addition, the 18S rRNA gene for Babesia/Theileria was amplified from DNA extracted from the blood of the foal and the mare. Amplified products were subjected to a reverse line blot hybridization assay (RLB), which confirmed the presence of T. equi DNA in the foal. The mare was negative by RLB but was positive for T. equi using a nested PCR and sequence analysis. In areas where equine piroplasmosis is endemic, severe jaundice in a post-partum foal may be easily misdiagnosed as neonatal isoerythrolysis. Foals with post-partum jaundice should be screened for equine piroplasmosis, which may be confirmed using molecular methods if available

Prevention of LPS-Induced Acute Lung Injury in Mice by Mesenchymal Stem Cells Overexpressing Angiopoietin 1

Using a mouse model of acute respiratory distress syndrome, Duncan Stewart and colleagues report that rescue with mesenchymal stem cells expressing human angiopoietin 1 can avert lung injury from lipopolysaccharide

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist