Mechanism of diuretic-induced hypopotassemia in human hypertension.

Diuretic treatment (hydrochlorothiazide) induced a marked decrease of red cell membrane Na+K+ ATPase activity in excessive potassium loser hypertensive patients. The decreased activity occurred within 2-4 weeks of treatment and returned to baseline in 4-6 weeks after cessation of treatment. Simultaneously, red cell sodium increased, potassium decreased together with increased 24-h urinary excretion.

Modulation of receptors for the colony-stimulating factor, CSF-1, by bacterial lipopolysaccharide and CSF-1.

The ability of the mononuclear phagocyte-specific colony-stimulating factor, CSF-1, to down-regulate its receptor on peritoneal exudate macrophages (PEM) was examined. Because of the essentially irreversible binding of CSF-1 to its receptor at 2 degrees C, unoccupied cell surface receptors could be measured by rapidly cooling PEM to 2 degrees C and determining the amount of 125I-CSF-1 bound at this temperature. On incubation with 125I-CSF-1 at 37 degrees C more receptors were lost than could be accounted for by 125I-CSF-1 binding.

DIRECT ACCESS OF IONS TO THE SQUID STELLATE GANGLION GIANT SYNAPSE BY AORTIC PERFUSION: EFFECTS OF CALCIUM-FREE MEDIUM, LANTHANUM, AND CADMIUM.

The giant synapse in the squid stellate ganglion has served as a model in the understanding of normal synaptic transmission, but has not been used extensively in the study of changes in external ion concentrations or pharmacological agents. This anomaly is due primarily to the substantial diffusion barrier that exists between the synapse and the bathing medium. The present study describes a technique for the rapid introduction of substances into the synapse by perfusion through the arterial blood supply that improves access by at least 50-fold.

Activation of human macrophages. Comparison of other cytokines with interferon-gamma.

Cytokines affecting mononuclear phagocytes were screened for activation of human macrophages to secrete H2O2 and kill toxoplasmas. In contrast to recombinant interferon-gamma (rIFN gamma), the following factors, tested in partially or highly purified form and over a wide range of concentrations, did not augment these functions: native interferon-alpha (nIFN alpha), rIFN alpha A, rIFN alpha D, rIFN beta, colony stimulating factor (type 1) (CSF-1), CSF for granulocytes and macrophages (GM-CSF), pluripotent CSF (p-CSF), tumor necrosis factor (TNF), native interleukin 2 (nIL-2), and rIL-2. Partially purified migration inhibitory factor (MIF) enhanced H2O2-releasing capacity submaximally without inducing antitoxoplasma activity, and warrants further study.

The action of cholinergic agonists on the squid stellate ganglion giant synapse.

Although the giant synapse in the squid stellate ganglion has served as a model in the understanding of the ionic and electrical changes that occur during the release of transmitter from nerve terminals, little is known about the pharmacology of this synapse or the identity of its neurotransmitter. In the present study, the suggestion that acetylcholine (ACh) is the excitatory transmitter at this synapse was tested by exploring the actions of cholinergic agents on the pre- and postsynaptic giant axons and on the excitatory postsynaptic potential (EPSP). A novel arterial perfusion technique that circumvents the diffusion barrier from the bathing medium to the synapse has been used to demonstrate a depolarizing action of ACh and its agonist carbachol on the post- but not the presynaptic axon.

Factors affecting the growth and differentiation of haemopoietic cells in culture.

The proliferation and differentiation of haemopoietic cells are regulated by haemopoietic growth factors (HGFs). Lineage-specific HGFs regulate mature, developmentally late cells while multilineage HGFs regulate the developmentally early precursors. Several studies indicate that the pleiotropic response to HGFs is similar to the effects caused by other growth factor, such as epidermal growth factor and platelet-derived growth factor, on their respective target cells.

Chemical crosslinking of the mononuclear phagocyte specific growth factor CSF-1 to its receptor at the cell surface.

The cell surface receptor for CSF-1 has been identified by affinity labeling intact mouse bone marrow-derived macrophages and intact cells of the murine J774.2 and BAC1 lines, which differ in their specific CSF-1 binding capacities and biological responses. The receptor, labeled by crosslinking to 125I-CSF-1 with disuccinimidyl suberate, is a polypeptide of approximately 165,000 molecular weight, irrespective of cell type.

The congenital undescended scapula. Surgical correction by the woodward procedure.

At The Hospital for Sick Children in Toronto, 21 undescended scapulae were corrected by the Woodward procedure in 20 patients over the past 18 years. The average age at operation was six years six months. The average follow-up period after operation was 8 years 9 months.

Rapid degradation of "new" acetylcholine receptors at neuromuscular junctions.

Acetylcholine receptors at innervated neuromuscular junctions are very stable, with half-lives reported to be 6 to 13 days. Their turnover is described as a first-order process, implying a single population of receptors. In this study, two subpopulations of acetylcholine receptors at normally innervated junctions have been identified.

Effects of age and strain differences on the red nucleus of the mouse mutant Dystonia musculorum.

The mouse mutant Dystonia musculorum exhibits pathological changes in the magnocellular neurons of the red nucleus. The present study shows that allelic differences occur in the age of onset and severity of this pathology. The magnocellular neurons of the Jackson allele (dtJ) almost completely disappear prior to 4 weeks of age while some of these cells are retained in the adult of the Albany strain (dtAlb).

The regulation of macrophage protein turnover by a colony stimulating factor (CSF-1).

CSF-1 is a hemopoietic growth factor that specifically regulates the survival, proliferation, and differentiation of mononuclear phagocytic cells. A homogeneous population of mononuclear phagocytes, bone marrow derived macrophages (BMM), were used to study the regulation of protein turnover by CSF-1. Removal of CSF-1 (approximately 0.

Canine neuroaxonal dystrophy.

Canine neuroaxonal dystrophy, a newly recognized familial disorder in Rottweiler dogs, is characterized by progressive sensory ataxia. Two of four dogs studied clinically were autopsied and the cerebellum was mildly atrophic. Massive numbers of axonal spheroids were present in many regions of the neuraxis but were most prominent in the dorsal horn of the spinal cord and the nuclei gracilis and cuneatus.

Botulinum toxin blocks quantal but not non-quantal release of ACh at the neuromuscular junction.

Botulinum (BOT) toxin is known to block quantal acetylcholine (ACh) release at the neuromuscular junction but little is known about its effect on non-quantal ACh release. We have examined the effect of BOT on non-quantal ACh release directly using a variant of the electrophysiological technique described by Katz and Miledi. This method is based on the observation that non-quantally released ACh results in a small, continual depolarization of the postsynaptic membrane, after inhibition of cholinesterase.

Structure-function studies of a colony stimulating factor (CSF-1).

CSF-1 is a glycoprotein growth factor which specifically stimulates the survival, proliferation, and differentiation of cells of the mononuclear phagocytic lineage. In this study, microgram amounts of radiolabeled murine L-cell and human urinary CSF-1 were isolated in pure form and used to investigate the nature and extent of CSF-1 glycosylation and the requirement of the carbohydrate moiety for its biological and antibody-binding activities. The molecular weight of the preparations examined varied between approximately 47,000 and approximately 76,000.

Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy.

CSF-1 is a hemopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. Receptors for CSF-1 occur exclusively on cells of the mononuclear phagocytic series (precursor leads to monoblast leads to promonocyte leads to monocyte leads to macrophage). Studies of the actions of CSF-1 on freshly explanted macrophages have been complicated by contamination of the primary cell isolates with CSF-1-producing cells and by the heterogeneity of the proliferative responses of individual macrophages.

Distribution of cells bearing receptors for a colony-stimulating factor (CSF-1) in murine tissues.

CSF-1 is a subclass of the colony-stimulating factors that specifically stimulates the growth of mononuclear phagocytes. We used the binding of 125I-CSF-1 at 0 degrees C by single cell suspensions from various murine tissues, in conjunction with radioautography, to determine the frequency of binding cells, their identity, and the number of binding sites per binding cell. For all tissues examined, saturation of binding sites was achieved within 2 h at 2--3 x 10(-10) M 125I-CSF-1.