Transforming growth factor-beta and gamma-interferon have dual effects on growth of peripheral glia

The influence of transforming growth factor-beta (TGF-beta) and gamma-interferon on DNA synthesis in Schwann cells and enteric glia in culture has been studied. TGF-beta stimulated the DNA synthesis of short-term (less than 2 weeks in culture) Schwann cells, whereas gamma-interferon was ineffective. The stimulatory effect of TGF-beta was additive to the stimulation of DNA synthesis due to axonal membrane fragments. In contrast to their effect on short-term Schwann cells, both TGF-beta and gamma-interferon inhibited DNA synthesis in enteric glial cells and in long-term (over 3 months in culture) Schwann cells. When short-term Schwann cells were stimulated to divide by axolemma or glial growth factor, gamma-interferon did not inhibit this enhanced DNA synthesis although it suppressed DNA synthesis induced by cAMP analogues. These results raise the possibility that TGF-beta and gamma-interferon might have a role in controlling glial proliferation during development and/or regeneration of the peripheral nervous system.     

Schwann Cells Secrete a PDGF-like Factor: Evidence for an Autocrine Growth Mechanism involving PDGF

We have investigated the influence of platelet-derived growth factor (PDGF) in peripheral nervous system gliogenesis using two types of Schwann cell cultures. Short-term Schwann cell cultures grow very slowly, but when maintained in culture for several months the division rate of some cells increases, and cell lines can be established. We show that Schwann cells in both short- and long-term culture possess PDGF receptors and synthesize DNA in response to PDGF. Competitive binding experiments show that Schwann cells express mainly PDGF beta-receptors and respond better to PDGF-BB than to PDGF-AA. Conditioned media from short- and long-term Schwann cell cultures contain PDGF-like mitogenic activity, and anti-PDGF immunoglobin partially inhibits DNA synthesis in long-term Schwann cell cultures. Antibody neutralization experiments and Northern blot analyses both indicate that the predominant PDGF isoform in these cultures is PDGF-BB. PDGF-like activity is also detected in extracts of rat sciatic nerve. Taken together, these results suggest that PDGF-BB may stimulate Schwann cell proliferation in an autocrine manner during normal development.     

EEG correlates of impaired attention performance under secobarbital and chlorpromazine in the monkey

The effects of secobarbital and chlorpromazineupon behavior in a continuous, rapidly presented successive (go-no go) discrimination (attention) task were evaluated in six Macaca mulatta monkeys. Simultaneous monitoring of EEG activity from epidural and subcortical electrodes permitted an evaluation of the nature of altered central nervous system events during erroneous performance (errors of omission) on this task. The computer-assisted analysis of pre-stimulus and post-stimulus EEG frequency activity (baseline crossings) suggests that the best measure of attentive behavior from the pre-stimulus EEG is percentage of beta 2 (25–40 cps) activity. No difference could be observed between drugs or among cerebral placements in this regard. This was determined by comparing measures of EEG frequency, pooled for a given test period, with performance from the same test period. On a trial-by-trial basis, however, the beta 2 measure in the pre-stimulus epoch failed to distinguish correct responses from errors of omission.Separation between correct responses and errors of omission is possible if comparisons are made between the changes in percentage of beta 2 activity in the pre-stimulus vs. post-stimulus epochs. For both drugs, the largest absolute change in beta 2 pre- vs. post-stimulus occurs with correct positive trials and the smallest change with correct negative trials. For secobarbital, no difference could be detected between correct and incorrect positive trials. For chlorpromazine, however, there was significantly less change in beta 2 for incorrect positive than for correct positive trials. The results were interpreted in terms of the hypothesis that secobarbital produces errors by depression of the general level of activation whereas chlorpromazine acts by reducing the sensory input which is necessary for correct discrimination performance.Some of these results were presented to the IXth Meeting of the Collegium Internationale Neuropsychopharmacologicum, Paris, France, July, 1974. Supported by USPHS grant No. MH 12568 from the National Institute of Mental Health. The authors are grateful to Dr. Eva Bakay Pragay for her wise counsel.Research Scientist Awardee K05 14915 of the National Institute of Mental Health.     

Diagnostic accuracy of neuroimaging in pediatric optic chiasm/sellar/suprasellar tumors

Preoperative diagnosis for tumors arising in the optic chiasm/sellar/suprasellar region in children is helpful to determine surgical necessity and approach, given the high operative risk in this area. We evaluated the ability to differentiate tumor type by preoperative neuroimaging. Thirty‐eight of 53 tumors were correctly diagnosed by neuroimaging based on final pathologic diagnosis (prediction accuracy 72%). Prediction accuracies were 87% (20/23) for craniopharyngioma, 79% (11/14) for optic pathway glioma, 64% (7/11) for germ cell tumor, and 0% (0/5) for Langerhans cell histiocytosis. Diagnosis of optic chiasm/sellar/suprasellar tumors in children by imaging alone should be considered when biopsy is considered high risk.     

Noninvasive Assessment of Regional and Global Myocardial Contractility in Normal Control Subjects and in Patients with Dilated Cardiomyopathies

The aim of the present study was to develop a new noninvasive approach for the assessment of regional and global myocardial contractility without the need for pharmacological intervention to alter load. Thirty-four healthy adults and five adults with dilated cardiomyopathy (DCM) were studied. Patients with diabetes mellitus and hyperthyroidism were eliminated from the study. The remainder underwent echocardiography, sphygmomanometric blood pressure determination, and carotid pulse tracings. Left ventricular cross section in the parasternal long-axis four- and two-chamber views was divided into 20 segments. Associated measurements of end-systolic pressure and left ventricular ejection time enabled shortening, shortening rate, and ejection fraction / afterload relationships to be determined. A discriminant analysis showed that the ejection fraction / afterload relationship in patients with DCM differed substantially from that of control subjects and was the most sensitive in this regard. Endocardial shortening, mid-wall shortening, and ejection fraction / afterload relationships demonstrated linearity or nonlinearity for control subjects. This study thus permits the assessment of contractility in individual subjects without the need for drug interventions because load alteration stems from the variation of wall stress from base to apex in the left ventricle. More importantly, the approach may be applied to patients with segmental abnormalities of contractile function.     

MRI Findings in Children with Acute Flaccid Paralysis and Cranial Nerve Dysfunction Occurring during the 2014 Enterovirus D68 Outbreak

BACKGROUND AND PURPOSE:Enterovirus D68 was responsible for widespread outbreaks of respiratory illness throughout the United States in August and September 2014. During this time, several patients presented to our institution with acute flaccid paralysis and cranial nerve dysfunction. The purpose of this report is to describe the unique imaging findings of this neurologic syndrome occurring during an enterovirus D68 outbreak.MATERIALS AND METHODS:Patients meeting a specific case definition of acute flaccid paralysis and/or cranial nerve dysfunction and presenting to our institution during the study period were included. All patients underwent routine MR imaging of the brain and/or spinal cord, including multiplanar T1, T2, and contrast-enhanced T1-weighted imaging.RESULTS:Eleven patients met the inclusion criteria and underwent MR imaging of the brain and/or spinal cord. Nine patients presented with brain stem lesions, most commonly involving the pontine tegmentum, with bilateral facial nerve enhancement in 1 patient. Ten patients had longitudinally extensive spinal cord lesions; those imaged acutely demonstrated involvement of the entire central gray matter, and those imaged subacutely showed lesions restricted to the anterior horn cells. Ventral cauda equina nerve roots enhanced in 4 patients, and ventral cervical nerve roots enhanced in 3, both only in the subacute setting.CONCLUSIONS:Patients presenting with acute flaccid paralysis and/or cranial nerve dysfunction during the recent enterovirus D68 outbreak demonstrate unique imaging findings characterized by brain stem and gray matter spinal cord lesions, similar to the neuroimaging findings described in previous outbreaks of viral myelitis such as enterovirus 71 and poliomyelitis.

Human enteroviruses are ubiquitous pathogens throughout the world and cause a variety of disease states, including respiratory infections, herpangina, hand-foot-and-mouth disease, and aseptic meningitis. Enterovirus D68 (EV-D68), first identified in California in 1962,¹ has been described primarily as a cause of respiratory illness.^2,3 More recently, however, rare cases of CNS disease have been attributed to EV-D68.^4,5In August and September 2014, EV-D68 was responsible for widespread outbreaks of respiratory disease throughout the United States.⁶ Against this backdrop, Children''s Hospital Colorado noted an unusual number of cases of acute flaccid paralysis (AFP) and cranial nerve dysfunction following a febrile upper respiratory illness. This association led the Centers for Disease Control and Prevention to issue a national Health Advisory,⁷ and it was subsequently described in the Morbidity and Mortality Weekly Report.⁸Enteroviruses have been associated with neurologic syndromes previously, most notably enterovirus 71 (EV-71). EV-71 most commonly presents with nonneurologic manifestations but has been associated with multiple outbreaks of AFP and brain stem encephalitis throughout the world.^9–15 MR imaging in affected patients typically reveals a rhombencephalitis affecting the dorsal pons and medulla, and a radiculomyelitis with a predilection for the anterior horn cells of the spinal cord and ventral nerve roots, findings that have also been described in poliomyelitis.^16–19 Although EV-D68 has not been proved as the causative agent in this cluster, these cases demonstrate distinctive imaging features that are very similar to the neuroimaging presentation of both EV-71 and poliovirus.We present an imaging-based report describing in detail the MR imaging findings of neurologic diseases associated with an EV-D68 outbreak.