A serendipitous isolate of Histoplasma capsulatum

This is a report of an unexpected laboratory diagnosis of Histoplasma capsulatum. The fungus was isolated from an acute cellulitic lesion on the forearm of an elderly male patient with a functioning renal transplant. The patient resides within the environs of Brisbane and has not travelled outside Australia. We consider the isolation of H. capsulatum from a rare site in a patient resident in a non-endemic area indicative of a latent opportunistic infection in an immunocompromised patient.     

Histamine excites GABAergic cells in the rat substantia nigra and ventral tegmental area in vitro

We have investigated the effect of histamine (HA) on spontaneous firing of dopaminergic (DA) and GABAergic neurons in the substantia nigra (SN) and the ventral tegmental area (VTA) of the rat in vitro. Single-unit extracellular recordings were obtained and drugs were bath applied. In both regions application of HA (10 and 100 μM) did not affect the firing frequency of DAergic cells, but increased the firing of GABAergic neurons. The histamine-induced excitation was blocked by the H₁ receptor antagonist mepyramine (1 μM), but was unaffected by application of the H₂ antagonist cimetidine (50 μM) or the H₃ antagonist thioperamide (10 μM). Our results suggest that histamine does not directly inhibit dopaminergic neurons in SN and VTA, but rather that this inhibition is mediated through histamine-induced excitation of GABAergic neurons.     

Fragilitas ossium (fro/fro) in the mouse: A model for a recessively inherited type of osteogenesis imperfecta

The fragilitas ossium (fro/fro) in the mutation in the mouse has been demonstrated to have clinical, radiographic and morphologic manifestations similar to those which arise in autosomal recessive forms of osteogenesis imperfecta (OI) occurring in humans. Approximately 90% of mutant offspring in the mouse were perinatally lethal with clinical and roentgenographic findings similar to those of OI type II subgroup A in humans. The 10% of mutant mice surviving follow a course very similar to severe progressively deforming OI type III. In surviving mice, there is progressive fore-limb and hind-limb bowing in the absence of a high fracture frequency.     

Immunopathologic Role of Proteoglycan Antigens in Rheumatoid Joint Disease

Cell-mediated immunity to proteoglycan antigens was assessed by leucocyte migration inhibition and by lymphocyte stimulation tests in patients with rheumatoid arthritis or with ankylosing spondylarthritis, in patients with relapsing synovitis after a single trauma to their knee joints, and in healthy donors. Both tests revealed a sensitization in most of the patients examined with various proteoglycan antigens derived from human cartilaginous tissues, rheumatoid synovial fluid, and species-common antigen of bovine nasal cartilage. Anybodies against proteoglycan antigens of human articular cartilage were detected by solid-phase radioimmunoassay in eleven out of twenty-nine sera from patients with rheumatoid arthritis and in four out of six rheumatoid synovial fluids. The results suggest that the cartilage antigenic components released by an inflammatory process or trauma may trigger a vicious circle of chronic inflammation and joint destruction.     

Alteration in the pattern of nerve terminal protein immunoreactivity in the perforant pathway in Alzheimer's disease and in rats after entorhinal lesions.

Neurons in layer II of the entorhinal cortex consistently develop neurofibrillary tangles in Alzheimer's disease (AD). Experimental neuroanatomical studies have shown that these neurons give rise to the perforant pathway, a major excitatory projection to the hippocampal formation, which terminates in a discrete pattern in the outer portion of the molecular layer of the dentate gyrus. The distribution of two nerve terminal associated proteins, synaptophysin and NT75, was studied in the molecular layer of the dentate gyrus in AD and control cases to determine whether Alzheimer neuronal pathology is associated with loss of synaptic markers. In parallel studies, the effect of ablation of the entorhinal cortex in rats was evaluated. In AD as compared to controls, a decrease in synaptophysin immunostaining was evident in the terminal zone of the perforant pathway. NT75 nerve terminal immunostaining was too weak to interpret in the human hippocampal formation. Both synaptophysin and NT75 immunoreactivity were found in association with some neuritic plaques. In rats, entorhinal lesions resulted in diminished immunoreactivity for both synaptophysin and NT75 in the perforant pathway terminal zone. These results suggest that nerve terminal protein loss is a concomitant feature of neuronal pathology in AD.     

Correlations of Monocyte Phagocytic Receptor Expressions with Serum Immune Complex Level in Systemic Lupus Erythematosus

The expression of FcγRI, FcγRII, and FcγRIII (the IgG receptors CD64, CD32, CD16) as well as CR3 (the C3bi receptor, CD11b) on monocytes in the blood of patients with systemic lupus erythematosus (SLE) was investigated. The relationship between the receptor expression and the serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity (FI) of the FcγRII of patients' monocytes stained by specific monoclonal antibodies (MoAb IV3) was very close to statistical significance ( P = 0.052). The expression (FI) of CR3 (using MoAb OKM1) on monocytes of patients was also decreased, but not significantly. The detected decrease of FcγRII and CR3 was inversely correlated with the high circulating immune complex level in patients' sera. At the same time, FcγRI expression on SLE monocytes (using MoAb 32) was significantly elevated and this change was in parallel with the serum IC concentration.     

Large and small conductance calcium-activated potassium channels in the GH3 anterior pituitary cell line

Single Ca²⁺-activated K⁺ channels were studied in membrane patches from the GH₃ anterior pituitary cell line. In excised inside-out patches exposed to symmetrical 150 mM KCl, two channel types with conductances in the ranges of 250–300 pS and 9–14 pS were routinely observed. The activity of the large conductance channel is enhanced by internal Ca²⁺ and by depolarization of the patch membrane. This channel contributes to the repolarization of Ca²⁺ action potentials but has a Ca²⁺ sensitivity at –50 mV that is too low for it to contribute to the resting membrane conductance. The small conductance channel is activated by much lower concentrations of Ca²⁺ at –50 mV, ad its open probability is not strongly voltage sensitive. In cell-attached patches from voltage-clamped cells, the small conductance channels were found to be active during slowly decaying Ca²⁺-activated K⁺ tails currents and during Ca²⁺-activated K⁺ currents stimulated by thyrotropin-releasing hormone induced elevations of cytosolic calcium. In cell-attached patches on unclamped cells, the small conductance channels were also active at negative membrane potentials when the frequency of spontaneously firing action potentials was high or during the slow afterhyperpolarization following single spontaneous action potentials of slightly prolonged duration. The small conductance channel may thus contribute to the regulation of membrane excitability.