Peroxisomal proliferator activated receptor-γ deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3)

Background  

Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG encoding peroxisomal proliferator-activated receptor-γ. Both dominant-negative and haploinsufficiency mechanisms have been suggested for this condition.     

Pathophysiologic concentrations of lysophosphoglycerides quantified by electron microscopic autoradiography

Lysophosphoglycerides accumulate in ischemic myocardium and appear to contribute to malignant dysrhythmia. Exposure of normoxic isolated Purkinje fibers or ventricular muscle strips to exogenous lysophosphatidyl choline (LPC) results in rapid, yet reversible, electrophysiologic derangements analogous to changes associated with ischemia in vivo. However, subcellular, local concentrations required for induction of electrophysiologic effects have not yet been elucidated unambiguously. The present study was designed to delineate the subcellular distribution and the sarcolemmal concentration of LPC by quantitative electron microscopic autoradiography after exposure of canine ventricular muscle strips to 3H-methyl LPC (200 microM) for 10 minutes. Tissue was processed for electron microscopy with a new procedure developed specifically to spatially fix choline phosphatides and render them insoluble in lipid solvents. Grain distributions were analyzed in the same group of cells that had been monitored electrophysiologically while superfused with LPC. LPC significantly decreased the resting membrane potential, action potential amplitude, duration, Vmax of phase 0, and conduction time. Grains were concentrated in the membranous organelles of cardiac myocytes. Myocyte sarcolemma exhibited the highest grain density (129 grains/100 micron2 versus a background of 0.27 grains/100 micron2). Calculations based on grain densities, emulsion sensitivity, exposure time, and specific activity indicated that the sarcolemma incorporated 5.4 X 10(6) LPC molecules/micron3 of membrane volume corresponding to approximately 1% of total sarcolemmal phospholipid. Since incorporation of only this small amount of lysophosphoglyceride into the sarcolemma was sufficient to elicit electrophysiologic disturbances, the observed accumulation of lysophosphoglycerides induced by ischemia appears to be sufficient to contribute to malignant dysrhythmia in vivo.     

Absence of simian virus 40 (SV40) DNA in lymphoma samples from Tasmania, Australia

AIMS: It has been postulated that the recent world-wide increase in the incidence of non-Hodgkin's lymphoma (NHL) may have been caused by human infection with simian virus 40 (SV40) (a lymphotropic monkey virus that was introduced to man from contaminated poliovirus vaccines between 1955 and 1963); therefore, we set out to determine the incidence of SV40 DNA positivity in lymphoma samples from patients in Tasmania, Australia. METHODS: One hundred lymph node samples, 50 from patients with lymphomas and 50 from controls, were tested using PCR amplification of three SV40-specific primer pairs followed by dot-blot hybridisation. RESULTS: All of the samples tested contained amplifiable DNA, but none contained amplifiable SV40 sequences with any of the primer sets used. CONCLUSIONS: Our results demonstrate absence of SV40 in the lymphoid tissues of our study population in Tasmania, Australia. SV40 does not explain the increasing incidence of NHL in our population.     

Heterogeneity in synaptic transmission along a Drosophila larval motor axon

At the Drosophila melanogaster larval neuromuscular junction (NMJ), a motor neuron releases glutamate from 30-100 boutons onto the muscle it innervates. How transmission strength is distributed among the boutons of the NMJ is unknown. To address this, we created synapcam, a version of the Ca2+ reporter Cameleon. Synapcam localizes to the postsynaptic terminal and selectively reports Ca2+ influx through glutamate receptors (GluRs) with single-impulse and single-bouton resolution. GluR-based Ca2+ signals were uniform within a given connection (that is, a given bouton/postsynaptic terminal pair) but differed considerably among connections of an NMJ. A steep gradient of transmission strength was observed along axonal branches, from weak proximal connections to strong distal ones. Presynaptic imaging showed a matching axonal gradient, with higher Ca2+ influx and exocytosis at distal boutons. The results suggest that transmission strength is mainly determined presynaptically at the level of individual boutons, possibly by one or more factors existing in a gradient.     

Microbicides 2006 conference

Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition.     

Morphological and immunohistological study of testicular lymphomas

We have studied normal testis, seminomas and malignant lymphomas of the testis using routine stains and a panel of antibodies directed against lymphoid and basement membrane antigens. The results show that normal testis contains, at most, a minor population of T-lymphocytes: seminomas contain mixed T- and B-cell populations with a predominance of B-lymphocytes; and most primary lymphomas are B-cell tumours of large centroblastic type. Solid testicular lymphomas presenting secondarily to acute lymphoblastic leukaemias showed intact seminiferous tubular basement membranes with predominantly interstitial lymphomatous infiltrates, whereas the tubules in primary cases were over-run by lymphoma cells and basement membranes were disrupted.     

Advancement to independent living: a model behavioral program for the intermediate care of adults with behavioral and emotional problems

This article describes and evaluates the treatment effectiveness of a behaviorally oriented intermediate day-care clinic for adults with psychiatric disturbances. The goals of the program included reducing the number of psychiatric hospital admissions and readmissions, providing a community-based controlled environment to assist patients in the modification of specific problem behavior, improving interpersonal relations with "significant others" in the natural environment, teaching patients how to use community resources, and preparing them for employment and/or continued outpatient treatment. The program was structured so that patients advance through a series of four achievement levels for a variety of extrinsic and intrinsic reinforcers. While in the program, patients were introduced to available community resources, and were gradually phased into follow-up services. Results showed that 79% of all patients thus far treated partially, if not completely, advanced through the levels. There was also a high probability that a patient would advance from any given level. Outside-clinic behavior showed sustained improvement, with the authors concluding that the day-care clinic offered promise for the future.