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P Adams

Publications and source records attributed to P Adams.

At least 55 records · Page 3Linked to original sources
PubMed1998

Mutational analysis of trans-membrane helices M3, M4, M5 and M7 of the fast-twitch Ca2+-ATPase.

Mutational analysis of trans-membrane helices M3, M4, M5 and M7 of the Ca2+-ATPase revealed a novel phenotypic variant, M4 [Y295A (the one-letter symbols are used for amino acid residues throughout)], displaying an increased affinity for Pi and decreased affinity for MgATP, while retaining the ability to translocate Ca2+ ions across the endoplasmic reticulum membrane. The properties of this mutant suggest that the E1-E2 equilibrium is shifted towards E2, and indicate a key role for this aromatic residue (Y295) at the end of trans-membrane helix M4. A mutant containing three amino acid residue substitutions at the end of the seventh trans-membrane helix, M7 (F834A, F835A, T837F), showed a complete loss of ATPase activity and a reduced ability to phosphorylate with Pi, although MgATP-initiated phosphorylation was unaffected. The observation that single mutations in this cluster of residues had no effect on Ca2+ transport suggests that correct anchoring of the helix at the lipid-water interface by these aromatic residues is important in the functioning of the ATPase. Mutation of polar residues in helix M3 did not affect inhibition of the ATPase by thapsigargin, thapsivillosin A or t-butyl hydroquinone, suggesting that hydrogen-bonding partners for the essential -OH groups on these inhibitors lie elsewhere in the ATPase.

Adenosine Triphosphatases↗
PubMed1998

Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis.

BACKGROUND & AIMS: The diagnosis of hemochromatosis is now possible for C282Y homozygous patients using noninvasive molecular genetic tests. The aim of this study was to define noninvasive factors predictive of severe fibrosis (bridging fibrosis or cirrhosis) to avoid unnecessary liver biopsies in such patients. METHODS: Clinical and biological data were recorded at the time of diagnosis in 197 French C282Y homozygous patients, 52 (26%) of whom had severe fibrosis. Variables significantly linked to severe fibrosis using univariate analysis were entered into a multivariate stepwise analysis. These variables were combined to obtain a simple index allowing for prediction of severe fibrosis. RESULTS: Serum ferritin, hepatomegaly, and serum aspartate aminotransferase were selected using multivariate analysis. Their combination applied to the 96 patients with ferritin level of </=1000 microgram/L, normal aspartate aminotransferase values, and absence of hepatomegaly showed that no severe fibrosis was encountered in this subgroup of patients. The results were validated in 113 C282Y homozygous patients in Canada with a good reproducibility of negative prediction but a poor reproducibility of the positive prediction of severe fibrosis. CONCLUSIONS: In C282Y homozygous patients, the diagnosis of severe fibrosis relies on liver biopsy, but absence of severe fibrosis can be accurately predicted in most patients on the basis of simple clinical and biochemical variables.

Adult↗
PubMed1998

Characterization of human recombinant neuronal nicotinic acetylcholine receptor subunit combinations alpha2beta4, alpha3beta4 and alpha4beta4 stably expressed in HEK293 cells.

Human embryonic kidney (HEK293) cells were transfected with cDNA encoding the human beta4 neuronal nicotinic acetylcholine (ACh) receptor subunit in pairwise combination with human alpha2, alpha3 or alpha4 subunits. Cell lines A2B4, A3B4.2 and A4B4 were identified that stably express mRNA and protein corresponding to alpha2 and beta4, to alpha3 and beta4 and to alpha4 and beta4 subunits, respectively. Specific binding of [3H]epibatidine was detected in A2B4, A3B4.2 and A4B4 cells with Kd (mean +/- S.D. in pM) values of 42 +/- 10, 230 +/- 12 and 187 +/- 29 and with Bmax (fmol/mg protein) values of 1104 +/- 338, 2010 +/- 184 and 3683 +/- 1450, respectively. Whole-cell patch-clamp recordings in each cell line demonstrated that (-)nicotine (Nic), ACh, cytisine (Cyt) and 1, 1-dimethyl-4-phenylpiperazinium iodide (DMPP) elicit transient inward currents. The current-voltage (I-V) relation of these currents showed strong inward rectification. Pharmacological characterization of agonist-induced elevations of intracellular free Ca++ concentration revealed a distinct rank order of agonist potency for each subunit combination as follows: alpha2beta4, (+)epibatidine (Epi) > Cyt > suberyldicholine (Sub) = Nic = DMPP; alpha3beta4, Epi > DMPP = Cyt = Nic = Sub; alpha4beta4, Epi > Cyt = Sub > Nic > DMPP. The noncompetitive antagonists mecamylamine and d-tubocurarine did not display subtype selectivity. In contrast, the Kb value for the competitive antagonist dihydro-beta-erythroidine (DHbetaE) was highest at alpha3beta4 compared with alpha2beta4 or alpha4beta4 receptors. These data illustrate that the A2B4, A3B4.2 and A4B4 stable cell lines are powerful tools for examining the functional and pharmacological properties of human alpha2beta4, alpha3beta4 and alpha4beta4 neuronal nicotinic receptors.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed1997

Altered amyloid protein processing in platelets of patients with Alzheimer disease.

BACKGROUND: beta-Amyloid peptide, the core component of neuritic plaques in brain areas in patients with Alzheimer disease (AD), is 1 cleavage product of the beta-amyloid precursor protein (APP) in neurons and platelets. Alternate cleavage products of intact 140- to 150-kd APPs in platelets include nonamyloidogenic 120- to 130-kd and 110-kd isoforms. The possible differential significance of these 2 isoforms, structurally similar to protease nexin II, is unknown. OBJECTIVE: To determine whether the ratio of the 120- to 130-kd APP isoform to the 110-kd APP isoform as processed in platelets correlates with the presence of AD and/or the apolipoprotein E4 (ApoE4) allele, which is a major risk factor for AD. SETTING: The Alzheimer Disease Center at The University of Texas Southwestern Medical Center at Dallas. METHODS: The APP isoforms were quantitated with the use of 2 different Western blot detection methods in platelets from 15 patients with AD and 19 control subjects in whom genotyping of apolipoprotein E was performed. RESULTS: The mean ratio of the 120- to 130-kd APP isoform to the 110-kd APP isoform in the patients with AD was significantly lower than that of the control subjects (5.98 vs 7.64; P = .03 [method 1] and 5.98 vs 7.92; P = .01 [method 2]) after adjusting for age and the increased incidence of ApoE4 in patients with AD. The lower APP ratios were also associated with increased age and with the presence of an ApoE4 allele. CONCLUSIONS: The APP processing in platelets of patients with AD is different from that of control subjects. This difference, largely caused by factors other than the ApoE4 genotype, may reflect chronic platelet activation in patients with AD. The use of these data to estimate "AD risk," by using the APP isoform ratio, indicates an odds ratio of 1.75, suggesting possible utility as an adjunct in the diagnosis of AD. Moreover, these findings may relate to analogous alterations in APP processing that may occur in brain areas affected by AD.

Aged↗
PubMed1997

Panic disorder with smothering symptoms: evidence for increased risk in first-degree relatives.

Klein's (1993: Arch Gen Psychiatry 50:306-317) "false suffocation alarm" theory of spontaneous panic attacks posits that central receptors compare CO2, O2, and lactate levels and trigger panic when an impending "false" state of suffocation is detected. Several investigators have found abnormalities of respiratory physiology in subjects with panic disorder. Twin and family studies have suggested that both panic disorder and tidal volume response to CO2 are inherited. We hypothesized that, if smothering symptoms are a marker for a hypersensitive suffocation detector and if this hypersensitivity is familial, then relatives of panic subjects with smothering symptoms would have higher rates of panic with smothering than relatives of panic subjects without smothering. We conducted a family study involving 104 panic disorder probands and 247 of their interviewed first-degree relatives. Probands and their relatives were interviewed using the Schedule for Affective Disorders and Schizophrenia--Lifetime Version for Anxiety Disorders to determine their panic disorder and smothering symptom status. Relatives of panic probands with smothering symptoms had an almost threefold higher risk for panic and an almost sixfold higher risk for panic with smothering symptoms when compared with relatives of panic probands without smothering. We conclude that panic disorder with smothering symptoms may be a subtype of panic disorder associated with increased familial risk and may be a group of interest to genetic investigators. These findings provide the first empiric evidence from a family study in support of Klein's false suffocation alarm theory of spontaneous panics.

Adult↗
PubMed1997

Falsified or forged medical prescriptions as an indicator of pharmacodependence: a pilot study. Community pharmacists of the Midi-Pyrénées.

OBJECTIVE: While data on drug abuse liability have been determined for selected drugs in experimental studies, there is limited information available about drug abuse in real life. This study presents the results of a simple experimental epidemiologic survey of prescription forgeries in community pharmacies in the Midi-Pyrénées area (southwest France). During four periods (September-October 1991, January-June 1992, September-October 1992 and January-June 1993), resident pharmacy students in several volunteer pharmacies were asked to complete a specific report form for each suspect prescription request. The main criteria used to identify forgeries were: inadequate dosage, multiple use of the prescription form, drafting not in accordance with the rules of prescription or false prescription forms (stolen prescription forms, photocopies). RESULTS: A total of 165 falsified prescriptions were collected. The 305 drugs involved in these forged prescriptions were opiate analgesics, benzodiazepines, amphetamines and minor opiate analgesics. Medications were essentially buprenorphine, flunitrazepam (in 2 mg dosage), phenobarbitone+amphetamine and chlorazepate. CONCLUSION: These results suggest that forged prescriptions can be used as an indicator of potential abuse liability of marketed psychoactive drugs. Although this survey cannot describe the real prevalence of the misuse or abuse of drugs, it constitutes a useful warning epidemiologic system to elicit early observations regarding new misuses of drugs as they are requested at the pharmacy.

Drug Prescriptions↗
PubMed1997

An analysis of valve re-replacement after aortic valve replacement with biologic devices.

Biologic valve re-replacement was examined in a series of 1343 patients who underwent aortic valve replacement at The Prince Charles Hospital, Brisbane, with a cryopreserved or 4 degrees C stored allograft valve or a xenograft valve. A parametric model approach was used to simultaneously model the competing risks of death without re-replacement and re-replacement before death. One hundred eleven patients underwent a first re-replacement for a variety of reasons (69 patients with xenograft valves, 28 patients with 4 degrees C stored allograft valves, and 14 patients with cryopreserved allograft valves). By multivariable analysis younger age at operation was associated with xenograft, 4 degrees C stored allograft, and cryopreserved allograft valve re-replacement. However, this effect was examined in the context of longer survival of younger patients, which increases their exposure to the risk of re-replacement as compared with that in older patients whose decreased survival reduced their probability of requiring valve re-replacement. In patients older than 60 years at the time of aortic valve replacement, the probability of re-replacement (for any reason) before death was similar for xenografts and cryopreserved allograft valves but higher for 4 degrees C stored valves. However, in patients younger than 60 years, the probability of re-replacement at any time during the remainder of the life of the patient was lower with the cryopreserved allograft valve compared with the xenograft valve and 4 degrees C stored allografts.

Adolescent↗
PubMed1997

Liver iron concentration and distribution in chronic hepatitis C before and after interferon treatment.

BACKGROUND: Recent studies have suggested that, in patients with chronic hepatitis C, elevated iron stores are predictive of a poor response to interferon. AIMS: To assess liver iron concentration and distribution before and after interferon treatment in patients with hepatitis C in order to evaluate further the role of iron in the pathogenesis of hepatitis C. PATIENTS: Fifty-five patients with hepatitis C treated with alpha interferon for six months. METHODS: Patients were evaluated for liver iron concentration (normal value < 36 mumol/g), and liver iron distribution before and six months after therapy. RESULTS: At entry: liver iron concentration was elevated in 16/55 patients (29%); iron staining (Perls' staining) was found in 31/55 patients (56%) mainly within Kupffer and endothelial cells. Iron load was significantly higher in patients with the most histological inflammatory activity. Following treatment: liver iron concentration decreased significantly (40 (24) to 30 (17) mumol/g, p = 0.001); this was related to iron depletion in mesenchymal cells. Iron depletion occurred regardless of the response to therapy. Elevated liver iron concentration was not found to be a predictive factor of failure of interferon. CONCLUSION: Although liver iron stores were usually normal or only slightly elevated in patients with chronic hepatitis C, biochemical and histological liver iron content decreased following treatment due to the diminution in mesenchymal iron deposits. Iron depletion was interpreted as both a consequence of the anti-inflammatory effect of treatment and a factor of improvement in liver histology.

Adult↗
PubMed1997

Reclaiming community: an integrative approach to human services.

Taking the community rather than the service system as its starting point, a community-centered approach to service integration seeks to interweave formal and informal systems of care. Working as part of a community--negotiating and building partnerships with families, social networks, and organizations to change problematic patterns and mobilize resources--requires not only collaboration among administrators, but teamwork among front line staff. Team members need to share work, knowledge, and resources, while building collaborative relationships with their counterparts in other organizations, service users, and other residents. Ensuring congruence between new, integrative methods of practice and the way they are introduced and managed may require substantial changes in management behavior. "Resistance" is best understood in this context as feedback to management about its need to change.

Caregivers↗
PubMed1997

Pharmacological characterization of SIB-1765F: a novel cholinergic ion channel agonist.

Nicotine, the prototypical agonist for neuronal nicotinic acetylcholine receptors (NAChR), nonselectively activates NAChR limiting its use in elucidating the function of NAChR subtypes. SIB-1765F is a subtype selective NAChR agonist that displaces [3H]-nicotine binding with an IC50 of 4.6 nM and [3H]-cytisine binding with an IC50 of 12.2 nM which is 2000- to 6000-fold lower than its displacement of [3H]-QNB or [125I]-alpha-bungarotoxin. SIB-1765F did not inhibit human or rat cholinesterases or the uptake of [3H]-DA in synaptosomal preparations. SIB-1765F mimicked (-)-nicotine in stimulating [3H]-DA release from rat striatal and olfactory tubercle slices, with EC50 values of 99.6 and 39.6 microM, respectively. Such stimulation was sensitive to mecamylamine and DH beta E. SIB-1765F also released endogenous DA in the striatum and the nucleus accumbens as measured by in vivo microdialysis. SIB-1765F was less efficacious than (-)-nicotine at stimulating [3H]-NE release from rat hippocampal slices; in contrast, SIB-1765F increased [3H]-NE release from rat thalamic and cortical slices with efficacies approaching those of (-)-nicotine. Similar to (-)-nicotine and (+/-)-epibatidine, subcutaneous administration of SIB-1765F increased the turnover rate of dopamine ex vivo both in the striatum and olfactory tubercles in a mecamylamine-sensitive manner. Because the release of striatal DA and hippocampal NE appears to be regulated by distinct NAChR, differential effects of SIB-1765F on striatal DA and hippocampal NE release supports the NAChR subtype selectivity of SIB-1765F compared to (-)-nicotine. This is further demonstrated by observations showing that SIB-1765F has a higher affinity for h alpha 4 beta 2 NAChR relative to h alpha 4 beta 4 NAChRs in displacing [3H]-epibatidine binding and increasing cytosolic CA+2 concentration in cell lines stably expressing h alpha 4 beta 2 or h alpha 4 beta 4.

Animals↗
PubMed1996

Unipolar relatives in bipolar pedigrees: a search for elusive indicators of underlying bipolarity.

In an effort to identify features indicative of underlying bipolarity within the unipolar relatives of bipolar probands, we compared unipolar relatives of bipolars with unipolar relatives of controls. Using data from the Yale-NIMH Collaborative Study of Depression, we compared a number of demographic and clinical features individually, and then developed a logistic regression model for the differences found. Unipolar relatives of bipolars were generally similar to relatives of controls, but they were older and more likely to suffer from more severe, even psychotic, depression, and somewhat less likely to report a brief transition into their illness. A multiple logistic regression model for observed differences was highly statistically significant, but had limited ability to discriminate effectively between the two groups. These findings suggest that more stringent diagnostic criteria might be beneficial if unipolar relatives are counted as affected in linkage studies of bipolar disorder. The ability of this strategy to improve the "clinical phenotype" is limited, however, and other approaches may be needed to identify features of underlying bipolarity and thus to define "caseness" for unipolar relatives in linkage analyses of bipolar disorder.

Adult↗
PubMed1996

Genetic factors for the development of Alzheimer disease in the Cherokee Indian.

OBJECTIVE: To study the relationship between the genetic degree of Cherokee ancestry, the apolipoprotein E *E4 (APOE*E4) allele type, and the development of Alzheimer disease (AD) in individuals from the Cherokee Nation who reside in northeastern Oklahoma. SETTING: Alzheimer disease center satellite clinic and university departments of neurology, psychiatry, and academic computing. DESIGN: Standardized dementia evaluations based on criteria from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were performed on 26 patients aged 65 years or older to establish a diagnosis of AD. Twenty-six control subjects were recruited and similarly assessed. The APOE allele type determinations were obtained on all patients and control subjects. Appropriate statistical analyses were used to compare the genetic degree of Cherokee ancestry, the APOE allele type, and the development of AD. RESULTS: The data indicated that as the genetic degree of Cherokee Indian ancestry increased, the representation of AD decreased. The 9 patients with AD with a greater than 50% genetic degree of Cherokee ancestry constituted 35% of the group with AD. The 17 remaining patients with AD who were less than 50% Cherokee constituted 65% of the group with AD. In contrast, 17 (65%) of the control subjects were more than 50% Cherokee; only 9 (35%) were less than 50% Cherokee. These percentages of AD were not changed by the *E4 allele. This inverse relationship between the genetic degree of Cherokee ancestry and AD, independent of the APOE*E4 allele status, diminished with increasing age, suggesting an age-related protective effect of being Cherokee. For a decrease of 10% in Cherokee ancestry, the odds of developing AD are estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at age 80 years. CONCLUSIONS: A greater genetic degree of Cherokee ancestry reduces the risk of developing AD and, thus, seems protective. This protective genetic factor is independent of APOE allele type and diminishes with age.

Aged↗
PubMed1996

State versus trait loneliness in elderly New Zealanders.

505 elderly people in Auckland, New Zealand were administered state and trait versions of the Revised UCLA Loneliness Scale, Version 3, and a battery of psychosocial and health measures. The Pearson correlation for scores on the loneliness measures was .86. Neither age nor gender was predictive of state or trait loneliness scores. Less education, insufficient income, and living alone were predictive of state but not trait loneliness. Having experienced the death of a spouse within the past year was predictive of trait but not state loneliness. The predictive variance for all health outcome variables was lower for trait than state loneliness.

Aged↗