S U M M A R YThe recent success of pancreatic islet transplantation has generated considerable enthusiasm. To better understand the quality and characteristics of human islets used for transplantation, we performed detailed analysis of islet architecture and composition using confocal laser scanning microscopy. Human islets from six separate isolations provided by three different islet isolation centers were compared with isolated mouse and non-human primate islets. As expected from histological sections of murine pancreas, in isolated murine islets ␣ and ␦ cells resided at the periphery of the ␤ -cell core. However, human islets were markedly different in that ␣ , ␤ , and ␦ cells were dispersed throughout the islet. This pattern of cell distribution was present in all human islet preparations and islets of various sizes and was also seen in histological sections of human pancreas. The architecture of isolated non-human primate islets was very similar to that of human islets. Using an image analysis program, we calculated the volume of ␣ , ␤ , and ␦ cells. In contrast to murine islets, we found that populations of islet cell types varied considerably in human islets. The results indicate that human islets not only are quite heterogeneous in terms of cell composition but also have a substantially different architecture from widely studied murine islets.

The issue of whether brain signals in the absence of peripheral feedback are sufficient to specify accurate movement was evaluated by studying motor performance in patients with loss of somesthetic afferent input as a result of acquired large-fiber sensory neuropathy. With visual guid-ance, movements and postures were impaired relatively little, but when visual guidance was unavailable, the patients exhibited postural drift and gross inaccuracy of movement. Impairments were more apparent for smaller (3°) than for larger (15°) movements. Previous studies that have failed to show major motor impairments in deafferented subjects examined movements involving rather large joint displacements, and this may have been a factor in the failure of these studies to reveal severe deficits. The present results demonstrate a critical role for somesthetic feedback in regulating centrally generated levels of motor output and show that central motor programs deprived of such feedback are unable to subserve accurate motor control.Severe motor impairments in patients with large-fiber sensory neuropathies have been described by clinical neurologists (1-3) and are commonly observed in clinical practice, but results from a number of neuropsychological experiments have raised doubts as to the importance of sensory feedback in active movement (4-7). These "negative" studies revealed only slight motor deficits in deafferented humans, monkeys, cats, and a variety of invertebrates, and it was argued that centrally programmed brain or spinal cord activity could control movement without the need for sensory feedback (8).We reexamined this issue in patients with somesthetic losses due to acquired large-fiber sensory neuropathy, and our results help to resolve the discrepancies between clinical and neuropsychological investigations: whereas motor impairments may seem to be slight when deafferented subjects make relatively large limb displacements, impairments become progressively more apparent as movement size is reduced. Furthermore, somesthetic losses cause profound deficits in the ability of subjects to maintain the steady-state levels of active muscular contraction necessary for postural stability. MATERIALS AND METHODSThe patients who were studied had a peripheral neuropathy with selective involvement of large sensory fibers without clinically evident weakness. Thus, while having excellent muscular strength, the patients exhibited sensory deficits, including absence of position and vibration sense to the level of the most proximal joints; moderate decrease in pinprick, temperature, and light-touch sensation below the shoulders; and absence of deep-tendon reflexes. The loss of inputs fromThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. both cutaneous mechanoreceptors (as shown by deficits in tactile sensitivity) and from muscle receptors (as shown by loss of stretch reflexe...

No abstract

We studied the frequency of oligoclonal immunoglobulin G bands in the cerebrospinal fluid (CSF) of patients with various neurological diseases. We used a micromethod employing sodium dodecyl sulfate polyacrylamide gel electrophoresis that required only 50 microliters of unconcentrated CSF. Oligoclonal bands were detected in the CSF of 95% of the patients with multiple sclerosis, 90% with subacute sclerosing panencephalitis, and 100% with herpes simplex encephalitis, but less frequently in other central nervous system infections. No oligoclonal bands were detected in the CSF of patients with Parkinson, Huntington, Creutzfeldt-Jakob, or herniated disc diseases. Bands were detected in some patients with Alzheimer disease, cerebrovascular accident, idiopathic vertigo, idiopathic seizures, amyotrophic lateral sclerosis, polyneuropathy, and central nervous system glioma. Patients with other conditions infrequently had positive bands. The determination of oligoclonal bands is a useful aid in the diagnosis of multiple sclerosis, subacute sclerosing panencephalitis, and herpes simplex encephalitis. The presence of oligoclonal bands indicates an immunological response but is not diagnostic for a particular condition.