Search PubMed⌕ Search

Biomedical subjects

W H Frey

Publications and source records attributed to W H Frey.

At least 37 records · Page 2Linked to original sources
PubMed1997

Inhibition of antagonist binding to human brain muscarinic receptor by vanadium compounds.

Metavanadate, orthovanadate, and pervanadate all inhibited [3H]QNB antagonist binding to the human brain muscarinic acetylcholine receptor (mAChR) in the presence of glutathione, with the order of decreasing potency and the concentration required for 50% inhibition (I[50]) being: pervanadate (95 microM) > orthovanadate (132 microM) > metavanadate (452 microM). Omission of glutathione decreased the inhibition of the vanadium compounds 2-6-fold. Preincubating the vanadium compounds with the mAChR in the presence of glutathione at 37 degrees for 1 h markedly decreased the I(50) values as follows: pervanadate (13 microM) > orthovanadate (46 microM) > metavanadate (118 microM). Inhibition by the vanadium compounds was blocked by EDTA, Mn2+, and Trolox, a water-soluble vitamin E analog. Vanadium use in treating diabetes is discussed regarding its inhibition of mAChR function.

Glutathione↗
PubMed1996

Endogenous Alzheimer's brain factor and oxidized glutathione inhibit antagonist binding to the muscarinic receptor.

An endogenous inhibitor (< 3,500 Da) of antagonist binding to the muscarinic acetylcholine receptor has been extracted from Alzheimer's disease (AD) brain with trifluoracetic acid. Oxidized glutathione, (GSSG) has also been found to inhibit antagonist binding to the receptor. However, in its reduced form, glutathione (GSH) like other reducing agents, markedly enhances the inhibitory effect of both GSSG and the endogenous AD inhibitor. EDTA and the free radical scavengers Mn(2+) and Trolox, a vitamin E analog, block the action of the endogenous AD inhibitor but not of GSSG in the presence of GSH. Further, while GSSG inhibition is reversible, the action of the endogenous AD inhibitor is irreversible, consistent with a free radical mechanism. The enhancement of endogenous AD inhibitor activity by GSH suggested that GSH may be involved in formation of the free radical generated by the inhibitor. The glutathione thiyl radical is shown to inhibit antagonist binding to the receptor and is, therefore, a good candidate for the free radical formed by the endogenous AD inhibitor. The ability of Trolox to block the reduction in muscarinic receptor binding caused by the endogenous AD inhibitor is encouraging and suggests that free radical scavengers, such as vitamin E, may have a potential therapeutic role in AD by protecting the integrity of the muscarinic receptor.

Alzheimer Disease↗
PubMed1996

Latino, Asian, and black segregation in U.S. metropolitan areas: are multiethnic metros different?

This study examines 1990 residential segregation levels and 1980-1990 changes in segregation for Latinos, Asians, and blacks in U.S. metropolitan areas. It also evaluates the effect of emerging multiethnic metropolitan area contexts for these segregation patterns. While black segregation levels are still well above those for Latinos and Asians, there is some trend toward convergence over the decade. More than half of the areas increased their Latino segregation levels over the 1980s, and almost three-fourths increased their Asian segregation levels. In contrast, black segregation levels decreased in 88% of metropolitan areas. Multiethnic metropolitan area context is shown to be important for internal segregation dynamics. Black segregation levels are lower, and were more likely to decline in multiethnic metropolitan areas and when other minority groups grew faster than blacks. Latino segregation was also more likely to decline in such areas, and declines in both Latino and Asian segregation were greater when other minority groups were growing. These findings point up the potential for greater mixed-race and mixed-ethnicity coresidence in the neighborhoods of multiethnic metropolitan areas.

Adult↗
PubMed1995

Quantitative analysis of the olfactory pathway for drug delivery to the brain.

Following intranasal administration to rats, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) concentrated in the olfactory nerve and glomerular layers of the olfactory bulb resulting in a mean olfactory bulb concentration of 140 nM. A negligible amount of label was detected in the olfactory bulb following intravenous administration of WGA-HRP or intranasal administration of unconjugated HRP. This is the first quantitative assessment of intraneuronal transport of a protein into the brain using the olfactory route.

Administration, Intranasal↗
PubMed1995

Immigration impacts on internal migration of the poor: 1990 census evidence for U.S. states.

"This article presents newly-available migration data from the 1990 U.S. census to assess immigration and internal migration components as they affect state poverty populations. New immigrant waves are heavily focused on only a few 'port-of-entry' states. It is suggested that these immigrants have begun to impact upon internal migration into and out of these 'high immigration states', and have also altered the national system of internal migration patterns. This article addresses three questions: How do the magnitudes of poverty population out-migration from high immigration states compare with those of other states? Is this out-migration selective on particular social and demographic groups? Is immigration a significant determinant of internal migration of the poor population? The results of this analysis are consistent with the view that recent, focused immigration is associated with out-migration among a state's poor longer-term residents."

Americas↗
PubMed1995

Elderly demographic profiles of U.S. states: impacts of "new elderly births," migration, and immigration.

Many policy analysts take a narrow view toward assessing demographic change of state elderly populations by focusing only on the migration component. This article examines how 1990 state elderly populations have been affected by "new elderly births" (a state's population ages 55-59 in 1985 which survived to ages 60-64 in 1990) as well as by migration components, over the 1985-90 period. It utilizes 1990 Census migration tabulations of the residence 5-years-ago question, along with demographic decomposition analysis. During this period, elderly births exerted a greater impact than migration on elderly gains and demographic compositions for all states. Migration from abroad is also important for state Latino and Asian elderly populations.

Aged↗
PubMed1995

Changing urban populations: regional restructuring, racial polarization, and poverty concentration.

This study examines the changing profile of the urban United States, with particular reference to the impact of immigration, suburbanization, and growing diversity associated with increased racial and income polarization. "This overview provides a backdrop by focusing on the forces that shape key demographic trends across broad regions and in metropolitan areas and then shows how these trends have led to disparities in growth and decline, racial polarization, and poverty concentration."

Americas↗
PubMed1995

Validation of the NINCDS-ADRDA criteria regarding gait in the clinical diagnosis of Alzheimer disease. A clinicopathologic study.

The NINCDS-ADRDA criteria for the clinical diagnosis of probable Alzheimer disease (AD) state that "gait disturbances at the onset or very early in the course of the illness make the diagnosis of Alzheimer disease uncertain or unlikely," yet there have been few studies documenting the validity of the statement. We therefore reviewed all cases of pure autopsy-proven AD in the Ramsey Brain Bank to determine how frequently an abnormal gait was noted at time of presentation. Any reported gait disturbance was considered an abnormal gait. Only cases for which medical records were available documenting the patient's presentation for dementia were included. Cases were excluded if any other pathology was present that may have contributed to the patient's dementia or to a gait disorder, if neuroleptic medication had been used, or if there was a preexisting gait disorder. Clinical dementia severity at time of presentation was graded as mild, moderate, or severe per DSM-IIIR criteria. Of the 95 cases that met study criteria, none of the 36 patients with mild dementia were reported to have had an abnormal gait. Sixteen percent of the patients with moderate and 32% with severe dementia had gait abnormalities reported. This study confirms the statement regarding gait in the NINCDS-ADRDA criteria.

Age of Onset↗
PubMed1994

Inhibitor of antagonist binding to the muscarinic receptor is elevated in Alzheimer's brain.

The 100,000 x g supernatant fraction of human brain contains endogenous inhibitors of antagonist binding to the muscarinic receptor. Significantly greater inhibition was observed with Alzheimer's than non-demented control supernatant fractions. Low molecular weight inhibitor was separated from larger inhibitor species by membrane dialysis (3,500 dalton cut-off). The activity of low molecular weight inhibitor was greatly increased by sulfhydryl reducing agents. While the low molecular weight inhibitor was stable to heat, acid and base for short time periods (< 20 min), it was inactivated by acid hydrolysis (50% loss after 16 h, 100% loss after 96 h). The low molecular weight inhibitor activity is elevated approximately three-fold in Alzheimer's brain. The low molecular weight inhibitor from Alzheimer's brain was found to be a non-competitive inhibitor. This is the first report of endogenous inhibitors in human brain of ligand binding to the muscarinic receptor and of increased inhibitor activity in Alzheimer's disease.

Aged↗
PubMed1994

Two cases of acute anti-GM1 antibody elevations in response to exogenous GM1 without neurological symptoms.

During a study evaluating GM1 ganglioside as a possible treatment for Alzheimer's disease, two patients suffered immune responses that appeared to be limited to localized inflammation at the sites of the intramuscular GM1 injections. We determined that one patient's anti-GM1 IgM antibody titer rose from 1:400 to 1:3200 and her anti-GM1 IgG titer from < 1:50 to 1:400,000 during the immune response. The second patient's titer rose from < 1:50 to 1:3200 IgM and from 1:3200 to 1:400,000 IgG. These findings document that patients may experience acute rises in their anti-GM1 antibody levels in response to GM1 and that such rises may not necessarily cause significant acute clinical neuronal injury.

Aged↗
PubMed1994

Transforming growth factor beta in Alzheimer's disease.

Alzheimer's disease (AD) has been hypothesized to be an inflammatory condition. We hypothesized that anti-inflammatory cytokines, such as transforming growth factor beta (TGF-beta), counteract the inflammatory process. In the present study, we found that TGF-beta levels were elevated in both cerebrospinal fluid and serum samples obtained from AD patients < 6 h after death. Serum TGF-beta levels were also markedly elevated before death. These results suggest that elevated TGF-beta levels in AD may represent a protective host response to immunologically mediated neuronal injury.

Aged↗
PubMed1994

Serum cytokine levels in patients with Alzheimer's disease.

Alzheimer's disease (AD) has been proposed to be an inflammatory disorder. In a recent study, markedly elevated levels of the anti-inflammatory cytokine transforming growth factor beta (TGF-beta) in the serum and cerebrospinal fluid of patients with advanced AD suggested a potential predictive value of this cytokine in patients with AD. In the present prospective study, we tested the hypothesis that the levels of TGF-beta in serum would be increased in patients with AD and could thereby serve as a diagnostic marker. We found that serum TGF-beta levels but not proinflammatory cytokine levels were significantly (P < 0.05) elevated in patients with AD (n = 22) in comparison with the levels in their healthy spousal controls. Also, serum TGF-beta levels were positively correlated (r = 0.45; P < 0.05) with disease severity. Nevertheless, the elevation in serum TGF-beta levels in patients with Ad was modest, and considerable overlap with the control values suggests that the diagnostic usefulness of this cytokine for AD is limited.

Aged↗
PubMed1993

Silica-ELISA method improves detection and quantitation of minor glycolipid components in lipid mixtures and of other antigens.

This paper describes a new type of ELISA plate in which the reaction wells have been coated with silica gel. ELISA using these prototype silica-ELISA plates is markedly more sensitive for glycolipid antigens in lipid mixtures than ELISA using polystyrene plates without silica. Silica-ELISA plates also improve the analysis of certain protein and carbohydrate antigens. This technology may be of considerable benefit in the analysis of minor lipids and other antigens from human brain, cerebrospinal fluid or blood.

Animals↗
PubMed1993

Pick's disease versus Alzheimer's disease: a comparison of clinical characteristics.

The clinical recognition of Pick's disease depends on its differentiation from Alzheimer's disease (AD). To identify distinguishing clinical features, we reviewed the clinical records of 21 patients with pathologically confirmed Pick's disease and matched them by sex, age of onset, and duration of dementia with 42 patients having pathologically confirmed AD. In the absence of temporal or frontal lobar atrophy on CTs, all the Pick patients and none of the AD patients had three of five clinical features: presenile onset (before age 65), an initial personality change, hyperorality, disinhibition, and roaming behavior. In addition, the Pick patients had a tendency toward reiterative and other speech disturbances. These findings suggest that Pick patients are potentially distinguishable from AD patients on the basis of clinical manifestations.

Adult↗
PubMed1992

Altered aspartate in Alzheimer neurofibrillary tangles.

Normal protein-bound L-aspartyl/L-asparaginyl residues may undergo post-translational modification by racemization to D-aspartate, or by isomerization to the L-isoaspartyl form in which the peptide chain links through the beta carboxyl group of the residue. Based on preliminary results reported here, proteins associated with Alzheimer neurofibrillary tangle preparations contain a significantly greater number of these modified aspartyl residues than the unaffected proteins from the surrounding gray matter or in comparable preparations from normal brains.

Aged↗
PubMed1992

Racemized D-aspartate in Alzheimer neurofibrillary tangles.

Normal protein-bound L-aspartyl/L-asparaginyl residues may undergo posttranslational modification by racemization to D-aspartate. Based on preliminary results reported here, proteins associated with Alzheimer neurofibrillary tangle preparations contain a greater number of these racemized D-aspartyl residues than the unaffected proteins from the surrounding gray matter or in comparable preparations from normal brains.

Alzheimer Disease↗