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Biomedical subjects

E E Benarroch

Publications and source records attributed to E E Benarroch.

At least 19 recordsLinked to original sources
PubMed2001

CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity.

We have defined a new paraneoplastic immunoglobulin G (IgG) autoantibody specific for CRMP-5, a previously unknown 62-kd neuronal cytoplasmic protein of the collapsin response-mediator family. CRMP-5 is in adult central and peripheral neurons, including synapses, and in small-cell lung carcinomas. Since 1993, our Clinical Neuroimmunology Laboratory has detected CRMP-5-IgG in 121 patients among approximately 68,000 whose sera were submitted for standardized immunofluorescence screening because a subacute neurological presentation was suspected to be paraneoplastic. This makes CRMP-5 autoantibody as frequent as PCA-1 (anti-Yo) autoantibody, second only to ANNA-1 (anti-Hu). Clinical information, obtained for 116 patients, revealed multifocal neurological signs. Most remarkable were the high frequencies of chorea (11%) and cranial neuropathy (17%, including 10% loss of olfaction/taste, 7% optic neuropathy). Other common signs were peripheral neuropathy (47%), autonomic neuropathy (31%), cerebellar ataxia (26%), subacute dementia (25%), and neuromuscular junction disorders (12%). Spinal fluid was inflammatory in 86%, and CRMP-5-IgG in 37% equaled or significantly exceeded serum titers. Lung carcinoma (mostly limited small-cell) was found in 77% of patients; thymoma was in 6%. Half of those remaining had miscellaneous neoplasms; all but two were smokers. Serum IgG in all cases bound to recombinant CRMP-5 (predominantly N-terminal epitopes), but not to human CRMP-2 or CRMP-3.

Amino Acid Sequence↗
PubMed2000

Involvement of the ventrolateral medulla in parkinsonism with autonomic failure.

OBJECTIVE: To determine whether patients with PD and autonomic failure (AF), manifested primarily with orthostatic hypotension (OH), have a consistent loss of tyrosine hydroxylase (TH) neurons in the rostral ventrolateral medulla (RVLM), similar to that occurring in patients with multiple system atrophy (MSA) and AF, and to determine whether there is loss of nicotinamide, adenine dinucleotide phosphate (NADPH) diaphorase (NADPH-d) RVLM neurons in both groups of patients. METHODS: The numbers of TH and NADPH-d neurons in the RVLM was assessed in brain sections obtained at autopsy from five patients with suspected PD and OH, six patients with MSA, two patients with corticobasal ganglionic degeneration and no AF, and 10 control subjects with no history of neurologic disease. Cell numbers were compared among groups and correlated with their final neuropathologic diagnosis. RESULTS: The number of TH neurons in the RVLM of patients with PD and OH were not significantly different from control subjects, and there were marked individual variations. The TH cell numbers in the RVLM were significantly higher (p < 0.06) in patients with PD than in patients with MSA, despite a similar degree of severity of OH. As a group, patients with PD and OH had reduced numbers of NADPH-d cells in the RVLM compared with control subjects, but again there were marked individual variations. NADPH-d cell numbers were reduced consistently and more markedly in patients with MSA. CONCLUSION: Unlike the case in patients with MSA, the number of TH neurons in the RVLM is highly variable in patients with PD and is unlikely to contribute significantly to the pathophysiology of OH. As a group, patients with PD have reduced numbers of NADPH-d neurons in the RVLM, but some patients had cell counts similar to control subjects. On the other hand, NADPH-d cell depletion in the RVLM is a consistent finding in MSA and may contribute to cardiorespiratory dysfunction in this disorder.

Aged↗
PubMed1999

Leptin receptor immunoreactivity in sympathetic prevertebral ganglion neurons of mouse and rat.

Prevertebral ganglia, comprising the inferior mesenteric, superior mesenteric and celiac ganglia, contain the cell bodies of sympathetic neurons that regulate gastrointestinal motility, visceral blood flow, secretion and absorption. In the present study, we report the presence of leptin receptor-like immunoreactivity in the superior mesenteric and celiac ganglia of mice and rats. Ganglion neurons were immunopositive for leptin receptor. Confocal microscopy and three-dimensional (3-D) reconstruction of ganglion neurons filled with Lucifer yellow and then immunostained for leptin receptor showed that leptin receptor immunoreactivity was intracellular and that it was present on structures encircling the nucleus. These results raise the possibility that leptin may affect gastrointestinal function by acting on leptin receptors located in prevertebral ganglion neurons.

Animals↗
PubMed1999

Intrinsic vasomotor innervation of blood vessels in human ventrolateral medulla.

Medullae were obtained at autopsy from seven patients with no neurologic disease, and sections were processed for tyrosine hydroxylase (TH), nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), or both. Both TH- and NADPH-d reactive neurons had close anatomical relationship with penetrating blood vessels in the ventrolateral medulla (VLM). Three patterns were identified: 1) processes arising from a neighboring neuron reaching the blood vessel; 2) direct appositions of cell bodies to blood vessels; and 3) fibers coursing parallel to the blood vessels. This intrinsic innervation may provide a mechanism of coupling among local metabolism, sympathetic activity, and blood flow in the VLM.

Aged↗
PubMed1998

Immunohistochemical localization of the angiotensin II type 1 receptor in human hypothalamus and brainstem.

We studied the distribution of the angiotensin II type 1 (AT-1) receptor using a polyclonal rabbit antibody in two human brains. AT-1 receptor immunoreactivity was detected in several hypothalamic nuclei, substantia nigra, locus coeruleus, nucleus tractus solitarius, ventrolateral medulla, pontine nuclei, and inferior olivary nucleus. This provides direct evidence of neuronal localization of the AT-1 receptor in autonomic and motor areas in human brain.

Aged↗
PubMed1998

Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure.

The ventrolateral portion of the intermediate reticular formation of the medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sympathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affected in patients with multiple systems atrophy (MSA) with autonomic failure, we sought to test the hypothesis that catecholaminergic (tyrosine hydroxylase [TH]-positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological disease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% paraformaldehyde at 4 degrees C for 24 hours and cut into 1-cm blocks in the coronal plane from throughout the medulla. Serial 50-microm sections were collected and one section every 300 microm was stained for TH. There was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in the caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was available for study. There was also depletion of TH fibers and sympathetic preganglionic neurons (SPNs) in the 2 MSA cases examined. Thus, depletion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.

Aged↗
PubMed1998

Paroxysmal sympathetic storms ("diencephalic seizures") after severe diffuse axonal head injury.

We describe a patient with a severe traumatic head injury who exhibited paroxysmal sympathetic storms, similar to those described in "diencephalic seizures." No epileptiform activity was evident on electroencephalography, and therapeutic levels of anticonvulsants failed to alter the spells; however, use of morphine sulfate abolished them. The features of this and several previously reported cases refute the primary roles of the diencephalon and seizures in this syndrome. Rather, in the setting of already compromised autonomic neuronal integrity, subtle fluctuations in intraventricular pressure or activation of reflexes triggered from muscle mechanoreceptors or chemoreceptors during episodes of hypertonia are more likely. "Paroxysmal sympathetic storms," a more appropriate descriptive term for these phenomena, should be recognized; thus, unnecessary diagnostic evaluations can be minimized, and appropriate therapy can be initiated.

Adolescent↗
PubMed1998

Dysautonomia in fatal familial insomnia as an indicator of the potential role of the thalamus in autonomic control.

Fatal familial insomnia (FFI) is characterized by insomnia, dysautonomia, disruption of circadian rhythms, and motor dysfunction. The typical neuropathological findings in FFI are severe neuronal depletion in the mediodorsal (MD) and anteroventral nuclei of the thalamus. The interaction between the thalamus and central autonomic control mechanisms is poorly understood. The central autonomic areas include the anterior cingulate and insular cortices; amygdala, paraventricular nucleus, dorsomedial nucleus, and lateral hypothalamic area; periaqueductal gray; parabrachial nucleus; ventrolateral medulla; and nucleus of the solitary tract. Several nuclei of the thalamus have connections with areas of the central autonomic network. The paraventricular nucleus (PVT) projects to the medial prefrontal cortex, and receives multimodal visceral and somatosensory inputs. The MD nucleus is connected with several "limbic" areas involved in autonomic control. The autonomic manifestations of FFI are exaggerated sympathetic activation with preserved parasympathetic drive to the cardiovascular system. This reflects an exaggerated sympathetic drive from supramedullary structures. Bicuculline, administered into the MD, elicits an increase in arterial pressure and heart rate. The medial portion of the MD may share with the PVT a relay function for circuits controlling autonomic responses. MD involvement in FFI suggests a role of the thalamus in central autonomic and other integrative functions.

Autonomic Nervous System↗
PubMed1997

Distribution and relationships of neuropeptide Y and NADPH-diaphorase in human ventrolateral medulla oblongata.

The ventrolateral medulla, including the A1 and C1 catecholamine cell groups, corresponds to the recently defined ventrolateral intermediate reticular zone (IRt) in humans. We sought to determine whether the distribution of neuropeptide Y (NPY) corresponds to that of subpopulations of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactive neurons in human ventrolateral IRt. Medullae obtained from 2 men (ages 69 and 59, no history of neurologic disease, postmortem delay 22 and 5 h, respectively) were processed for NPY, tyrosine hydroxylase (TH) and NADPH-d either alone or combining NADPH-d and NPY or NADPH-d and TH, respectively. Distribution of cells was plotted using computer-aided reconstruction. NPY-reactive neurons were found throughout the rostrocaudal extent of the ventrolateral IRt, particularly at mid-olivary levels. The distribution of NPY immunoreactivity overlapped TH but not NADPH-d reactivity. This indicates that NPY and NADPH-d reactivity may help identify different subpopulations of neurons in human ventrolateral IRt, which may be differentially susceptible to disease.

Aged↗
PubMed1997

Neuropeptide Y innervation of nitric oxide-synthesizing sympathetic preganglionic neurons in humans.

We sought to determine whether neuropeptide Y (NPY) terminals are concentrated in the intermediolateral (IML) cell column and innervate human NADPH-diaphorase (NADPH-d)-reactive sympathetic preganglionic neurons (SPNs). Spinal cords were obtained at autopsy from one man and two women, cut into segments, and immersion fixed in 2% paraformaldehyde for 24 h. The T1, T3, T6 and T8 spinal cord segments were cut serially at 50 microns in the coronal, sagittal and horizontal planes. Alternating consecutive sections were double stained for NADPH-d and NPY or NPY alone. NPY-immunoreactive fibers were identified at all levels analyzed and varicosities appeared to run and cover the NADPH-d processes for long distances. NPY-immunoreactive varicosities were heavily concentrated around the soma and proximal dendrites of NADPH-d SPNs. NPY may exert many possible actions at the level of the IML cell column. Depletion of NPY-containing bulbospinal neurons may contribute to sympathetic failure in disorders such as multiple system atrophy.

Adrenergic Fibers↗
PubMed1997

Chronic constriction model of rat sciatic nerve: nerve blood flow, morphologic and biochemical alterations.

We evaluated the nerve blood flow (NBF), light and electron microscopy, and adrenergic innervation of rat sciatic nerve at 2-45 days after the application of four loose ligatures. Ischemia developed at the lesion edge, creating an endoneurial dam. Calcitonin gene-related peptide, norepinephrine and NBF were increased within the lesion. Morphologic alterations consisted of early endoneurial edema, followed by myelinated fiber degeneration, with relative sparing of small myelinated and unmyelinated nerve fibers, and leukocyte adhesion to microvessels. Axonal degeneration predominated over demyelination. At 45 days, profuse regeneration of small myelinated fibers was seen. The mechanism of lesional sensitization is discussed.

Animals↗
PubMed1996

Organization of NADPH-diaphorase-reactive neurons and catecholaminergic fibers in human intermediolateral cell column.

We studied the distribution of NADPH-d-reactive sympathetic preganglionic neurons (SPNs) and tyrosine hydroxylase (TH) immunoreactive fibers at T1, T4, T8, and T10 of human thoracic cord. NADPH-d-reactive SPNs were present at all segments. TH-immunoreactive fibers were distributed within the NADPH-d neuropil and appeared to contact SPNs. These interactions may be important for normal and pathological control of arterial pressure.

Adrenergic Fibers↗
PubMed1996

Certain cardiovascular indices predict syncope in the postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) represent a patient population with orthostatic intolerance; some are prone to syncope, others are not. The underlying neurocardiovascular mechanisms are not completely understood. The current study was undertaken to assess if certain cardiovascular indices are predictive of syncope in POTS. We compared the response to tilt-up and the Valsalva maneuver in four groups: POTS patients who fainted (POTS-f; n = 11;31 +/- 11 years): POTS patients who did not faint (POTS-nf; n = 9; 29 +/- 9 years); normal controls (NLS; n = 13; 39 +/- 11 years); patients with generalized autonomic failure with orthostatic hypotension and syncope (n = 10; 59 +/- 14 years). Beat-to-beat heart rate (HR), systolic arterial pressure, diastolic arterial pressure (DAP) and pulse pressure (PP) were monitored using Finapres. Cardiac output, stroke volume (SV) and end-diastolic volume (EDV), and calculated total peripheral resistance (TPR) were recorded using thoracic electrical bioimpedance. An autonomic reflex screen which quantitates the distribution and severity of autonomic failure was also done. With the patient supine, all POTS patients (POTS-nf; POTS-f) had increased HR (p < 0.001) and reduced SV/EDV (p < 0.001) when compared with NLS. On tilt-up, POTS-f patients were significantly different from both NLS and POTS-nf patients; the most consistent alteration was a fall instead of an increase in TPR; other changes were a greater reduction in PP, a reduction (instead of an increment) in DAP, and a different pattern of changes during the Valsalva maneuver (excessive early phase II, attenuated or absent late phase II). Our results suggest alpha-adrenergic impairment with increased pooling or hypovolemia in POTS-f patients. We conclude that it is possible to identify the mechanism of syncope in POTS patients, and perhaps other patients with orthostatic intolerance and an excessive liability to syncope.

Adult↗
PubMed1995

Localization and possible interactions of catecholamine-and NADPH-diaphorase neurons in human medullary autonomic regions.

The human medulla contains catecholamine-and NADPH-diaphorase (NADPH-d) neurons in both the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS). There is abundant experimental evidence for the critical role of these areas in control of arterial pressure. We sought to determine the pattern of distribution and topographic relationship between tyrosine hydroxylase (TH)-immunoreactive and NADPH-d-reactive cell groups in normal human VLM and NTS, in view of their potential implications in human autonomic control and involvement in central autonomic disorders. Medullae from three patients with no neurologic disease were obtained at autopsy within 24 h of death. Individual sections, obtained from the rostral and caudal medulla, were stained for TH, NADPH-d or both. We found that: (1) TH-and NADPH-d positive neurons are topographically segregated in the VLM; (2) in the VLM, TH and NADPH-d neurons may coexist within a given area but both markers do not appear to coexist in single neuron; (3) NADPH-d-reactive fibers and processes overlap the distribution of TH neurons within the VLM; and (4) both TH-and NADPH-d-reactive processes appear to innervate intrinsic blood vessels in the VLM and NTS. Thus, there are important topographic relationships between catecholamine and NO-synthesizing neurons in human VLM and perhaps NTS, including innervation of intrinsic blood vessels. This may have important implications in regulation of autonomic reflexes, sympathetic excitatory drive and intrinsic control of cerebral blood flow in humans.

Aged↗
PubMed1995

Prospective evaluation of clinical characteristics of orthostatic hypotension.

OBJECTIVE: To undertake a prospective study of the clinical characteristics of orthostatic intolerant patients referred to the Mayo Autonomic Reflex Laboratory with suspected orthostatic hypotension (OH). DESIGN: Autonomic function tests were performed to quantify the severity of sudomotor, adrenergic, and cardiovagal failure and generate a composite autonomic symptom score (CASS). CASS was related to a symptom score, which was derived from the frequency of orthostatic intolerance and syncope and the standing time until occurrence of symptoms. RESULTS: Three groups were defined by their response to a tilt study: group I, 90 patients with symptomatic OH, mean age, 63.6 years; group II, 60 patients who had symptoms without OH, mean age, 48.9 years; and group III, 5 patients with asymptomatic OH, mean age, 68.0 years. Group I had a significantly higher CASS (P < 0.001) than did those without OH. Further analysis was done on the 90 patients in group I. The most common symptoms were lightheadedness, weakness, impaired cognition, visual blurring, tremulousness, and vertigo. The most common aggravating factors were prolonged standing, exercise, warming, and eating. Most patients (75%) could stand for less than 5 minutes before symptoms occurred. Symptoms regressed significantly with CASS but not with the tilt grade. CONCLUSION: Patients with generalized autonomic failure have a recognizable pattern of symptoms and aggravating factors that relate, albeit imperfectly, to the severity of autonomic failure.

Autonomic Nervous System↗