Robert Staudinger

Identification of a New Quaternary Neutralizing Epitope on Human Immunodeficiency Virus Type 1 Virus Particles

ABSTRACT The selection of human monoclonal antibodies (MAbs) specific for human immunodeficiency virus (HIV) type 1 by binding assays may fail to identify Abs to quaternary epitopes on the intact virions. The HIV neutralization assay was used for the selection of human MAb 2909, which potently neutralizes SF162 and recognizes an epitope on the virus surface but not on soluble proteins. Three regions of gp120, the V2 and V3 loops and the CD4 binding domain, contribute to the epitope recognized by MAb 2909. The existence of such a unique MAb, which defines a complex epitope formed by a quaternary structure, suggests that there may be other new neutralizing HIV epitopes to target with vaccines.

Remission of HIV myelopathy after highly active antiretroviral therapy

To the Editor: We read with interest the case report by R. Staudinger and K. Henry1 describing the clinical improvement in a patient with AIDS-associated myelopathy after the use of highly active antiretroviral combination therapy. This is the first reported case of improvement of myelopathy with antiretroviral agents, and it may have important implications in the understanding of the pathogenesis and treatment of this rare but disabling complication of HIV infection. However, a number of considerations must be made before accepting the conclusions that the improvement resulted from antiretroviral treatment. First, we think that the authors should have quantified the evaluation of spinal cord function in order to strengthen their conclusions. Objective measurement of spinal cord function, such as central conduction time (CCT) of the somatosensory evoked potentials (SEPs), can be used to monitor the clinical progression of the disease.2 Neurophysiologic tests would have supported the clinical diagnosis at baseline and repeat SEPs could have helped determine whether the observed clinical improvement was accompanied by improved …

Teaching NeuroImages: “Penguin” or “hummingbird” sign and midbrain atrophy in progressive supranuclear palsy

An 82-year-old man presented to us with a 2-year history of progressive difficulty walking. On examination, he had bradykinesia, bradyphrenia, …

Interaction of soluble CD4 with the chemokine receptor CCR5.

The chemokine receptor CCR5 is constitutively associated with the T cell co-receptor CD4 in plasma cell membranes. The CD4-CCR5 complex exhibits distinct binding properties for macrophage inflammatory protein 1beta (MIP-1beta) and enhanced G-protein signaling as compared with those of CCR5 alone. Here we report that recombinant soluble CD4, when refolded into its dimeric form, allosterically modulates CCR5 and decreases the affinity for its natural ligand MIP-1beta. Monomeric soluble CD4 had little inhibitory effect on CCR5. In contrast, the two-domain amino-terminal fragment of soluble CD4 was able to completely inhibit the interaction of CCR5 with MIP-1beta. Thus, we suggest that various conformational states of CD4 exist, which differ markedly with regard to inhibiting the interaction of CCR5 with its ligand MIP-1beta. R5-tropic HIV-1 glycoprotein 120, but not interleukin-16, the natural agonist, or X4-tropic glycoprotein 120, inhibited MIP-1beta binding to CCR5 in the presence of monomeric and dimeric soluble CD4.

Cerebral Aneurysm in Lyme Neuroborreliosis with Regression After Medical Treatment

Lyme disease in the United States is caused predominantly by the spirochete Borrelia burgdorferi and affects multiple organ systems. Lyme Borreliosis infrequently involves the peripheral and central nervous system, and the term Neuroborreliosis is used for the latter case. The most common manifestations of Neuroborreliosis include cranial neuropathy and lymphocytic meningitis. It can also cause cerebral vasculitis leading to both wall thickening and endothelial obliteration. Other manifestations include stroke, with over 50 documented cases, and rarely nonaneurysmal subarachnoid hemorrhage and intraparenchymal hemorrhage. Intracranial aneurysm detected in the setting of Lyme Borreliosis infection has been previously documented in four cases [3,4]. However, the existence of a causal relationship between Lyme infection and intracranial aneurysm has been debated. We discuss these cases, and present our own case of a man with Lyme Neuroborreliosis with an intracranial aneurysm which regressed upon completion of treatment with ceftriaxone.