Regulation of single potassium channels by serotonin in the cell bodies of the tail mechanosensory neurons ofAplysia californica

Sensory neurons in the pleural ganglion ofAplysia mediate the afferent portion of the tail withdrawal reflex. Previous work has shown that in these neurons and in the siphon sensory neurons ofAplysia, serotonin modulates a steady-state non-inactivating potassium current called the S current. Using the technique of patch clamping, we have examined the kinetics of single potassium channels and found that they share the properties of the S potassium channel of the siphon sensory neurons. This channel has an elementary slope conductance of73 ± 9.98pS(x±S.E.M.) and shows Goldman rectification. It is active at the resting potential and does not inactivate with maintained depolarization. Bath application of serotonin in a majority of experiments decreased the functional number of channels in the patch.     

Freiberg’s Infraction in Identical Twins: A Case Report

Freiberg's infraction is an ostechondrosis of a lesser metatarsal head resulting in degeneration of the metatarsophalangeal joint. Several mechanisms have been suggested in its pathenogenesis. Freiberg first described the entity and believed single impact trauma was the underlying cause. Repetitive biomechanical microtrauma is the most widely accepted etiologic theory. Other factors contributing to its development include aseptic necrosis, ischemia, and a congenital predisposition. We present a case report of Freiberg's infraction occurring in identical twins involving multiple metatarsals in various stages of degeneration. One of the twins was affected unilaterally whereas the other twin was affected bilaterally. Both twins had involvement of the second metatarsal on the same side extremity. The occurrence of Freiberg's infraction in identical twins suggests that an underlying congenital predisposition to the condition may play more of a role than previously considered.     

Effects of heterozygosity for the E180 splice mutation causing growth hormone receptor deficiency in Ecuador on IGF-I, IGFBP-3, and stature.

CONTEXT & OBJECTIVE: The Ecuadorian GH receptor deficiency (GHRD)/Laron syndrome population is the only large cohort with a single GHR mutation (E180 splice), permitting identification of numerous carrier and noncarrier first-degree relatives, to ascertain effects of heterozygosity on GH-dependent IGF-I and IGFBP-3 concentrations and on growth. DESIGN: First-degree relatives (n=212) of GHRD patients had specimens taken for IGF-I, IGFBP-3, and GHR genotyping. Normal statured (n=40) and short statured (n=40) unrelated controls had measurement of IGF-I, IGFBP-3, and stature. RESULTS: There were no significant differences between heterozygous and homozygous normal relatives in IGF-I or IGFBP-3 standard deviation scores (SDS). Heterozygous relatives had lower mean height SDS than did homozygous normals, but with extensive overlap between genotype groups in both child and adult relatives. Height SDS in general did not relate to IGF-I or IGFBP-3 concentrations. CONCLUSIONS: GH-dependent IGF-I and IGFBP-3 secretion is not affected by heterozygosity for the E180 splice mutation that causes GHRD/Laron syndrome in the Ecuadorian population. Heterozygosity is associated with reduction in mean statural SDS, but this is not sufficient to be clinically important and not mediated through measurable differences in circulating IGF-I or IGFBP-3 related to genotype.     

Coronary artery vasospasm causing acute myocardial infarction in a heart transplant recipient.

The etiology of cardiac allograft vasculopathy is not known, but may be preceded by both endothelial cell and smooth muscle dysfunction of the epicardial coronary arteries. We here report a case of acute, reversible coronary artery vasospasm which caused a myocardial infarction in a cardiac transplant recipient. The patient had a complex post-transplant course, including an episode of severe vascular rejection several months before this presentation. Interestingly, the event was captured in its early stages because the patient presented with chest pain: a rare event because of the denervation of the transplanted heart. Our ability to document the etiology of this patient's myocardial infarction supports the concept that cardiac allograft vasculopathy is a progressive disease that, in its early stages, may include a reversible component of abnormal vasoreactivity.     

IDEC-131 (Anti-CD154), Sirolimus and Donor-Specific Transfusion Facilitate Operational Tolerance in Non-Human Primates

CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.     

Canadian Consensus Recommendations for the Optimal Use of Enfuvirtide in HIV/AIDS Patients.

BACKGROUND AND OBJECTIVES: An eight-member group consisting of Canadian infectious disease and immunology specialists and a family physician with significant experience in HIV management was convened to update existing recommendations, specifically intended for use by Canadian HIV-treating physicians, on the appropriate use of enfuvirtide in HIV/AIDS patients with resistance to other antiretroviral drugs. METHODS: Evidence from the literature and expert opinions of the group members formed the basis of the guidelines. Comments on the draft guidelines were obtained from other physicians across Canada with HIV expertise. The final guidelines represent the group's consensus agreement. RESULTS AND CONCLUSIONS: The recommendations were developed to guide physicians in optimal practices in patient selection for enfuvirtide treatment and subsequent patient management. The issues considered include positive predictors of response to enfuvirtide, stage of disease, optimization of the background regimen, early indicators of enfuvirtide response, and patient education and support.     

Development of neurochemical separation of ON and OFF channels at retinal ganglion cells

Anatomical and physiological segregation of neurons into ON (brightening detector) and OFF (darkening detector) channels in the retina and subsequent visual system ensure the high sensitivity required for contrast detection and spatial discrimination. This segregation is finest at the visual axis. Neurochemically, ON and OFF ganglion cells at the visual axis seem to be distinguished by different inhibitory transmitters but not excitatory transmitters. Microiontophoretic studies of inhibitory transmitters on the retinal ganglion cells in kittens and adult cats suggest that this neurochemical distinction is poor in immature ganglion cells at the visual axis. Initially both ON and OFF cells seem to be supplied by GABAergic, glycinergic, and catecholaminergic amacrine cells, but in adults, ON cells remain supplied only by GABAergic amacrines, while OFF cells are supplied by glycinergic amacrines. Postnatal elimination of multiple inputs and strengthening of the appropriate inputs, as seen in the central nervous system, also seem to occur at the retinal neurotransmitter synapses during development.