Searched for: in-biosketch:true
person:pomarn01
Possible muscarinic supersensitivity in Alzheimer's disease
Pomara N; Deptula D; Singh R
In contrast to the well established presynaptic cholinergic deficits which are associated with Alzheimer's Disease (AD), the functional status of the remaining muscarinic receptors has not received adequate attention. This paper examined the possibility that the presynaptic cholinergic deficits in AD may be accompanied by muscarinic supersensitivity. While the majority of QNB binding studies have failed to find an upregulation of muscarinic receptors in AD patients, most of those studies did not differentiate between presynaptic and postsynaptic receptors. In addition, receptor density and functional response are not necessarily correlated. To determine whether AD is accompanied by alterations in the functional status of central muscarinic receptors, we studied the biological responses to a muscarinic agonist in AD patients and controls. In this pilot study, AD patients demonstrated an increased arecoline-induced HVA response in the CSF. This finding is consistent with the hypothesis that AD is accompanied by muscarinic supersensitivity
PMID: 2690092
ISSN: 0361-7742
CID: 23700
Loss of the cortisol response to naltrexone in Alzheimer's disease
Pomara N; Stanley M; Rhiew HB; Bagne CA; Deptula D; Galloway MP; Tanimoto K; Verebey K; Tamminga CA
The administration of a single dose of the opiate antagonist naltrexone (NT) was accompanied by significant elevations in plasma cortisol in normal elderly subjects; in contrast, the cortisol response to NT was absent in individuals of comparable age with Alzheimer's disease (AD). The differential effect of AD on the cortisol response was not accompanied by a significant group difference in plasma prolactin in response to NT administration. Furthermore, this differential cortisol response to NT was not associated with any evident differences in age, sex ratio, plasma levels of naltrexone or its major metabolite beta-naltrexol, or with differences in measures of nonspecific stress, such as plasma free MHPG, pulse, or blood pressure, between the two groups. The absence of the well-characterized cortisol response to NT in AD, together with other reports of abnormal responses to other pharmacological challenges, suggests that neuroendocrine abnormalities might be an important concomitant and possibly a central contributor to the pathophysiology of Alzheimer's disease
PMID: 3285899
ISSN: 0006-3223
CID: 23701
The effects of diazepam and aging on intrusions
Pomara N; Deptula D; Rubinstein S; Stanley B; Stanley M
PMID: 3212154
ISSN: 0048-5764
CID: 23702
Comparison of methods for analysis of CSF proteins in patients with Alzheimer's disease
Townsend LE; Gilroy J; LeWitt P; Wolfe DE; Pomara N; Weintraub J; Reitz D
Cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and controls was analyzed by one- and two-dimensional gel electrophoresis, electron microscopy, and fluorescence microscopy with thioflavin S staining. In CSF from patients with AD, abnormal proteins were found following two-dimensional gel electrophoresis and silver staining. In CSF samples from most of the AD patients studied, a highly argentophilic material was detected upon silver staining the stacking gel of the one-dimensional gels. Electron microscopy of material eluted from the stacking gel showed fibers of approximately 7-10 nm diameter, with some twisting; properties consistent with paired helical filaments or amyloid. Furthermore, material with the characteristics of amyloid (fiber diameter ranging from 4-10 nm) was found in the CSF sediment. The CSF from AD patients had significantly elevated numbers of yellow fluorescent particles following thioflavin S staining when compared with age-matched, other neurological disease controls. We did not see an increase in autofluorescence, indicating that thioflavin S staining is specific. Our data suggest that AD CSF contains plaque amyloid and possibly proteins from neurofibrillary tangles. The thioflavin S staining method appears to have potential for development as a diagnostic tool
PMID: 3627573
ISSN: 0734-600x
CID: 23703
The cholinergic hypothesis of memory dysfunction in Alzheimer's disease--revisited
Pomara N; Stanley M
PMID: 3726056
ISSN: 0048-5764
CID: 23704
Prospective strategies for cholinergic interventions in Alzheimer's disease
Pomara N; Bagne CA; Stanley M; Yarbrough GG
The cholinergic hypothesis of memory dysfunction has guided most of the recent proposals for treating the primary symptoms of AD. The efficacy of these treatments has been severely limited. This review examines two major lines of evidence which suggest that the cholinergic hypothesis may have to be expanded and revised. The cholinergic hypothesis focuses on pre-synaptic defects. It assumes cholinoceptive neurons would function normally with adequate stimulation. Evidence is not sufficient to support this assumption. In addition, dissociations have been demonstrated between muscarinic receptor number and functional response of cholinoceptive neurons. Various measures are proposed to investigate the functional integrity of muscarinic receptors in AD patients. AD often has been characterized as a disorder produced by generalized cholinergic hypoactivity. Evidence for cortisol hypersecretion, abnormal dexamethasone suppression, and the occurrence of depressive symptoms, motoric dysfunction and sleep abnormalities in AD patients is more consistent with regional cholinergic hyperactivity than generalized hypoactivity. Resolution of these discrepancies could shed new light on the pathophysiology and treatment strategies for AD. Cholinoceptive neurons could be hypersensitive, subsensitive or have unaltered responsivity. These options would have very different treatment implications. New developments in outcome assessment which are capable of discriminating varieties of differential response to treatment can spur treatment development and improve quality of care for patients with complex disorders such as AD
PMID: 3541050
ISSN: 0278-5846
CID: 23705
Electrophoresis and immunoblot of cerebrospinal fluid proteins in spasmodic torticollis
Cullis PA; Townsend L; LeWitt P; Pomara N; Reitz D
Protein patterns of cerebrospinal fluid (CSF) from patients with spasmodic torticollis (ST) were investigated to determine whether abnormalities previously reported could be detected and further identified. CSF was collected from 12 patients with ST and 6 normal controls. The CSF proteins were analyzed using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and silver staining. In 11 of the 12 patients with ST, a CSF protein pattern was observed which differed from that in the controls. The identity of the abnormal proteins was ascertained by blotting and immunostaining with specific antisera to IgG and ceruloplasmin (Cp). CSF from 2 of 12 patients had distinct bands staining for IgG and 7 had abnormal immunostaining for Cp
PMID: 3504243
ISSN: 0885-3185
CID: 23706
Alzheimer's disease: Strategies for treatment and research
Chapter by: Bagne, Curtis A; Pomara, Nunzio; Crook, Thomas; Gershon, Samuel
in: Treatment development strategies for Alzheimer's disease by Crook, Thomas [Eds]
Madison, CT, US: Mark Powley Associates, 1986
pp. 585-638
ISBN: 0-943378-05-2
CID: 4796
Memory performance in individuals with primary degenerative dementia: its similarity to diazepam-induced impairments
Block RI; DeVoe M; Stanley B; Stanley M; Pomara N
Impairments of memory storage and retrieval produced by diazepam (2.5 mg, 5 mg, and 10 mg) in normal elderly individuals were compared to those observed in patients with primary degenerative dementia tested under nondrug conditions. The highest diazepam dose affected retrieval as well as storage processes in Buschke's 'selective reminding' task, producing impairments qualitatively similar to those shown by demented patients. All diazepam doses impaired Buschke task performance in the normal elderly individuals; normal young subjects, in contrast, showed no impairment with a low (2.5 mg) diazepam dose
PMID: 4076305
ISSN: 0361-073x
CID: 23711
Clinical ratings: relationship to objective psychometric assessment in individuals with dementia
Block RI; DeVoe M; Russell M; Pomara N
PMID: 4048333
ISSN: 0033-2941
CID: 23707