Rockefeller University

About: Rockefeller University is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 15867 authors who have published 32938 publications receiving 2940261 citations. The organization is also known as: Rockefeller University & Rockefeller Institute.

Dendritic cells in the T‐cell areas of lymphoid organs

Abstract: Substantial numbers of dendritic cells (DCs) are found in the T-cell areas of peripheral lymphoid organs such as the spleen, lymph node and Peyer's patch. By electron microscopy these DCs (also called interdigitating cells) form a network through which T-cells continually recirculate. The cytological features of DCs in the T-cell areas, as well as a number of markers detected with monoclonal antibodies, are similar to mature DCs that develop from other sites such as skin and bone marrow. Some markers that are expressed in abundance are: MHC II and the associated invariant chain, accessory molecules such as CD40 and CD86, a multilectin receptor for antigen presentation called DEC-205, the integrin CD11c, several antigens within the endocytic system that are detected by monoclonal antibodies but are as yet uncharacterized at the molecular level, and, in the human system, molecules termed S100b, CD83 and p55. DCs in the periphery can pick up antigens and migrate to the T-cell areas to initiate immunity. However, there are new observations that DCs within the T-cell areas also express high levels of self-antigens and functional fas-ligand capable of inducing CD4+ T-cell death. We speculate that there are at least 2 sets of DCs in the T-cell areas, a migratory myeloid pathway that brings in antigens from the periphery and induces immunity, and a more resident lymphoid pathway that presents self-antigens and maintains tolerance.

Kinetic Analysis of Secretory Protein Traffic and Characterization of Golgi to Plasma Membrane Transport Intermediates in Living Cells

Abstract: Quantitative time-lapse imaging data of single cells expressing the transmembrane protein, vesicular stomatitis virus ts045 G protein fused to green fluorescent protein (VSVG-GFP), were used for kinetic modeling of protein traffic through the various compartments of the secretory pathway. A series of first order rate laws was sufficient to accurately describe VSVG-GFP transport, and provided compartment residence times and rate constants for transport into and out of the Golgi complex and delivery to the plasma membrane. For ER to Golgi transport the mean rate constant (i.e., the fraction of VSVG-GFP moved per unit of time) was 2.8% per min, for Golgi to plasma membrane transport it was 3.0% per min, and for transport from the plasma membrane to a degradative site it was 0.25% per min. Because these rate constants did not change as the concentration of VSVG-GFP in different compartments went from high (early in the experiment) to low (late in the experiment), secretory transport machinery was never saturated during the experiments. The processes of budding, translocation, and fusion of post-Golgi transport intermediates carrying VSVG- GFP to the plasma membrane were also analyzed using quantitative imaging techniques. Large pleiomorphic tubular structures, rather than small vesicles, were found to be the primary vehicles for Golgi to plasma membrane transport of VSVG-GFP. These structures budded as entire domains from the Golgi complex and underwent dynamic shape changes as they moved along microtubule tracks to the cell periphery. They carried up to 10,000 VSVG-GFP molecules and had a mean life time in COS cells of 3.8 min. In addition, they fused with the plasma membrane without intersecting other membrane transport pathways in the cell. These properties suggest that the post-Golgi intermediates represent a unique transport organelle for conveying large quantities of protein cargo from the Golgi complex directly to the plasma membrane.

A biochemical and pharmacological suggestion about certain mental disorders.

Abstract: Recent findings in this laboratory1' 2 and elsewhere3 , 4have permitted an understanding of some aspects of mental diseases in relation to the hormone-like compound, serotonin. Furthermore, these findings lead directly to a suggestion for a logical treatment of diseases known as \"schizophrenia.\" The experimental observations have been made solely on laboratory animals, but they have reached a point where clinical trials in human psychiatric patients are required to test the validity of the conclusions. Being only biochemists, we are unable to do these experiments on patients and can only hope that this paper will stimulate those who are professionally qualified to undertake in man what we cannot pursue further in laboratory animals. This discussion is going to revolve about serotonsin,5 or enteramine, if Erspamer's terminology is followed.6 Serotonin is one of the latest hormone-like substances to be discovered. Chemically it has been shown to have the structure given in Figure 1.7 Being a simple molecule, it has been synthetically produced without great difficulty8' 9 and is thus readily available. It was discovered because it is the vasoconstrictor long known to form in the serum when blood clots. Erspamer's works with it, done independently of that of Rapport, et al.,5 on the vasoconstrictor material, was based on the abundant occurrence of this new compound in the enterochromaffinic cells of the gastric and intestinal mucosa. Serotonin has now been isolated from several different organs, including the brain, of a wide variety of animal forms.'0-'2 There can be no doubt of its wide-spread occurrence in living things. Furthermore, a variety of pharmacological properties in isolated organs and tissues has been demonstrated, in addition to the vasoconstrictor effect. 13 The pharmacological properties which have been described thus far are attributable in large part to the ability of serotonin to cause various smooth muscles to contract; but there are indications that it has other effects which may become more clearly defined as time for study of them goes by. Aside from the occurrence and importance of serotonin, a second general idea is prerequisite to this discussion. It is now well known that several classes of drugs are related. chemically to individual hormones and other essential metabolites.14' 15 In fact, a major part of the pharmacological effects of these drugs is attributed to a specific interference with the biological functioning of these metabolites to which the drugs are related structurally. That is, the drugs are antimetabolites. Our thinking and experimentation about certain mental disorders has been in the following vein. Several synthetic compounds have been produced which are very closely related in structure to serotonin. These were shown to antagonize, in a competitive fashion, the contractions of artery walls caused by serotonin.16' 17 Also, the fact that the ergot alkaloids are structurally related to serotonin Was appreciated, and it was demonstrated that several of these actually did antagonize

Ascending central gustatory pathways.

Abstract: The central gustatory pathways of the albino rat have been traced using a combined electrophysiological-neuroanatomical technique. Gustatory responses in the medulla were recorded in the region of the solitary nucleus which receives the seventh nerve primary afferents. Fibers traced from lesions of these recording sites did not cross as expected into the medial lemniscus, but instead travelled rostrally to terminate ipsilaterally in a small celled area dorsal and ventral to the brachium conjunctivum as it enters the pons. Since gustatory responses could be recorded in this region it represents a previously undescribed secondary “pontine taste area.” Lesions of PTA result in degeneration of a bilateral ascending pathway travelling in the dorsomedial tegmentum to terminate in the classical gustatory nuclei of the thalamus. Other fibers in this pathway continue rostrally and distribute in the subthalamus, dorsolateral hypothalamus and subpallidal gray in the ventral forebrain. These findings in a mammal resemble those established nearly three quarters of a century ago by Herrick ('05) in the carp, and confirm his prediction that “broad lines of similarity [would be found] between both the peripheral and central gustatory paths in all vertebrates”.

Stress Down-Regulates Corticosterone Receptors in a Site-Specific Manner in the Brain*

Abstract: We have examined whether corticosterone receptor number within the brain can be regulated by its own ligand and whether such autoregulation reduces receptor number after the sustained secretion of corticosterone during repeated stress. Glucocorticoid receptors were measured in cytosolic preparations from acutely adrenalectomized rats using [1,2,6,7-3H] dexamethasone; maximal binding and receptor affinity parameters were determined by Scatchard analysis. Sustained elevations of circulating corticosterone, whether by repeated stress or exogenous corticosterone administration, did not change receptor affinity for [3H] dexamethasone, but significantly reduced cytosolic corticosterone receptor number. This reduction in total receptor number could not be attributed to residual tissue contamination with endogenous corticosterone after adrenalectomy or to translocation of cystosolic receptors to cell nuclei. The receptor reductions were anatomically specific, occurring in the hippocampus and amygdala, but not in ...