Antibody immunosuppressive therapy in solid-organ transplant: Part I

Currently, a wide variety of both polyclonal and monoclonal antibodies are being routinely utilized to prevent and treat solid organ rejection. More commonly, these agents are also administered in order to delay introduction of calcineurin inhibitors, especially in patients with already compromised renal function. While these antibody therapies dramatically reduced the incidence of acute rejection episodes and improved both short and long-term graft survival, they are also associated with an increased incidence of opportunistic infections and neoplastic complications. Therefore, effective patient management must necessarily balance these risks against the potential benefits of the therapy.Key words: monoclonal, polyclonal, induction, transplants, kidney, lung, liver, heart, rejection, complications     

Developing conservation strategies for endemic tree species when faced with time and data constraints: <Emphasis Type="Italic">Boswellia</Emphasis> spp. on Socotra (Yemen)

Many endemic tree species have important scientific, ecological and economic value but the scarcity of information about their biological and ecological features makes it difficult to develop conservation strategies for them. A four-step approach is presented to address this problem, based on the analysis of data collected in a limited-duration field study: (1) Data collected are used to analyse the ecological niche, population structure and regeneration status of the species in question. (2) Several IUCN Red List (RL) parameters, useful for assessing the species’ risk of extinction, are measured, including population counts, number of locations, extent and area of occurrence. (3) The IUCN RL parameters are used together with the other information gathered to set preliminary conservation priorities. (4) The analysis of utilization pattern is used to develop conservation actions specific to the environmental and socio-economic context. To test the applicability of this approach Boswellia spp. of Socotra island were analysed. Ground-rooted species (B. ameero, B. elongata and B. socotrana) were the most abundant and widespread and, according to the spatial analysis, were characterised by a geo-altitudinal zonation. However, the Weibull functions fitted on their stem diameters, and the absence or presence of only a small number of saplings highlighted a poor regeneration status. In the absence of conservation actions, these species will probably be subject to a progressive decline because of uncontrolled grazing. Of the four cliff-rooted species, which grow in sites that are less accessible to livestock, two (B. popoviana and B. dioscorides) were of lower conservation priority and may become the most numerically abundant. Conversely, the other two (B. nana and B. bullata), which may be threatened by stochastic events because of their reduced populations and small number of locations, were considered of very high priority. Different conservation actions were then identified for each species. In particular, for Boswellia species producing gum, the conservation-through-use action was discussed as a potential option.     

In vitro plant regeneration of spinach from mature seed-derived callus

Summary A system for the regeneration of spinach (Spinacia oleracea L.) from mature dry seed explants has been established. The response of two commercial spinach cultivars, ‘Grandstand’ and ‘Baker’, was examined. Callus proliferation was most prominent on MS medium supplemented with 9.3 μM of 6-furfurylaminopurine (kinetin) and 3.39 μM 2,4-dichlorophenoxyacetic acid (2,4-D). Adventitious shoot formation was observed within 8 wk after callus was transferred onto regeneration medium. Shoot regeneration was best from callus induced on 9.3 μM kinetin and 4.56 μM 2,4-D. The regeneration medium contained 9.3 μM kinetin, 0.045 μM 2,4-D, and 2.89 μM gibberellic acid (GA₃). Shoots were rooted on hormone-free medium, and plants grown in a greenhouse showed normal phenotype. This system is beneficial in rapid propagation of spinach plants, particularly when only a limited number of seeds are available.     

Cardiomyopathy induced by incessant ventricular tachycardia originating in the vicinity of the His bundle

A 04-year-old boy was referred to our institution with severe, progressive heart failure of 4-months duration associated with a persistent wide QRS tachycardia with left bundle branch block and severe left ventricular dysfunction. Because of incessant wide QRS tachycardia refractory to antiarrhythmic drugs, he was referred for electrophysiological study. The ECG was suggestive of VT arising from the right ventricle near the His area. Electrophysiological study revealed that origin of tachycardia was septum of the right ventricle, near His bundle, however the procedure was not successful and an inadvertent complete atrioventricular conduction block occurred. The same ventricular tachycardia recurred. A second procedure was performed with a retrograd aortic approach to map the left side of the interventricular septum. The earliest endocardial site for ablation was localized in the anterobasal region of left ventricle near His bundle. In this location, one radiofrequency pulse interrupted VT and rendered it not inducible. The echocardiographic evaluation showed partial reversal of left ventricular function in the first 3 months. The diagnosis was idiopathic parahisian left ventricular tachycardia leading to a tachycardia mediated cardiomyopathy, an extremely rare clinical picture in children.     

ATL-derived exosomes modulate mesenchymal stem cells: potential role in leukemia progression

Background

Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia. We hypothesized that the cargo of ATL-derived exosomes is transferred to MSCs and alter their functional behavior to support the establishment of the appropriate microenvironment for leukemia.

Results

We showed that both ATL cells (C81 and HuT-102) and patient-derived cells released Tax-containing exosomes. The cargo of HuT-102-derived exosomes consisted of miR-21, miR-155 and vascular endothelial growth factor. We demonstrated that HuT-102-derived exosomes not only deliver Tax to recipient MSCs, but also induce NF-κB activation leading to a change in cellular morphology, increase in proliferation and the induction of gene expression of migration and angiogenic markers.

Conclusions

This study demonstrates that ATL-derived exosomes deliver Tax and other leukemia-related genes to MSCs and alter their properties to presumably create a more conducive milieu for leukemia. These findings highlight the contribution of leukemia-derived exosomes in cellular transformation and their potential value as biomarkers and targets in therapeutic strategies.

     

Syncytium gene expression in Glycine max[PI 88788] roots undergoing a resistant reaction to the parasitic nematode Heterodera glycines

The plant parasitic nematode, Heterodera glycines is the major pathogen of Glycine max (soybean). H. glycines accomplish parasitism by creating a nurse cell known as the syncytium from which it feeds. The syncytium undergoes two developmental phases. The first is a parasitism phase where feeding sites are selected, initiating the development of the syncytium. During this earlier phase (1–4 days post infection), syncytia undergoing resistant and susceptible reactions appear the same. The second phase is when the resistance response becomes evident (between 4 and 6 dpi) and is completed by 9 dpi. Analysis of the resistant reaction of G. max genotype PI 88788 (G. max_{[PI 88788]}) to H. glycines population NL1-RHg/HG-type 7 (H. glycines_{[NL1-RHg/HG-type 7]}) is accomplished by laser microdissection of syncytia at 3, 6 and 9 dpi. Comparative analyses are made to pericycle and their neighboring cells isolated from mock-inoculated roots. These analyses reveal induced levels of the jasmonic acid biosynthesis and 13-lipoxygenase pathways. Direct comparative analyses were also made of syncytia at 6 days post infection to those at 3 dpi (base line). The comparative analyses were done to identify localized gene expression that characterizes the resistance phase of the resistant reaction. The most highly induced pathways include components of jasmonic acid biosynthesis, 13-lipoxygenase pathway, S-adenosyl methionine pathway, phenylpropanoid biosynthesis, suberin biosynthesis, adenosylmethionine biosynthesis, ethylene biosynthesis from methionine, flavonoid biosynthesis and the methionine salvage pathway. In comparative analyses of 9 dpi to 6 dpi (base line), these pathways, along with coumarin biosynthesis, cellulose biosynthesis and homogalacturonan degradation are induced. The experiments presented here strongly implicate the jasmonic acid defense pathway as a factor involved in the localized resistant reaction of G. max_{[PI 88788]} to H. glycines_{[NL1-RHg/HG-type 7]}.     

Oxidation of biphenyl by a multicomponent enzyme system from Pseudomonas sp. strain LB400.

Pseudomonas sp. strain LB400 grows on biphenyl as the sole carbon and energy source. This organism also cooxidizes several chlorinated biphenyl congeners. Biphenyl dioxygenase activity in cell extract required addition of NAD(P)H as an electron donor for the conversion of biphenyl to cis-2,3-dihydroxy-2,3-dihydrobiphenyl. Incorporation of both atoms of molecular oxygen into the substrate was shown with 18O2. The nonlinear relationship between enzyme activity and protein concentration suggested that the enzyme is composed of multiple protein components. Ion-exchange chromatography of the cell extract gave three protein fractions that were required together to restore enzymatic activity. Similarities with other multicomponent aromatic hydrocarbon dioxygenases indicated that biphenyl dioxygenase may consist of a flavoprotein and iron-sulfur proteins that constitute a short electron transport chain involved in catalyzing the incorporation of both atoms of molecular oxygen into the aromatic ring.