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Biomedical subjects

A Fisher

Publications and source records attributed to A Fisher.

At least 109 records · Page 6Linked to original sources
PubMed1996

Activation of m1 muscarinic acetylcholine receptor regulates tau phosphorylation in transfected PC12 cells.

Hyperphosphorylated tau proteins are the principal fibrous component of the neurofibrillary tangle pathology in Alzheimer's disease. The possibility that tau phosphorylation is controlled by cell surface neurotransmitter receptors was examined in PC12 cells transfected with the gene for the rat m1 muscarinic acetylcholine receptor. Stimulation of m1 receptor in these cells with two acetylcholine agonists, carbachol and AF102B, decreased tau phosphorylation, as indicated by specific tau monoclonal antibodies that recognize phosphorylation-dependent epitopes and by alkaline phosphatase treatment. The muscarinic effect was both time and dose dependent. In addition, a synergistic effect on tau phosphorylation was found between treatments with muscarinic agonists and nerve growth factor. These studies provide the first evidence for a link between the cholinergic signal transduction system and the neuronal cytoskeleton that can be mediated by regulated phosphorylation of tau microtubule-associated protein.

Animals↗
PubMed1996

The mouse Smcx gene exhibits developmental and tissue specific variation in degree of escape from X inactivation.

The Smcx gene is the first known example of a non-pseudoautosomal X-linked gene in mouse that normally escapes X chromosome inactivation. We have analysed the kinetics of escape at different stages of development, and in adult tissues. Our results demonstrate that Smcx exhibits partial escape from X inactivation in embryos, in extraembryonic lineages where paternally imprinted X inactivation occurs and also in adult tissues. The degree of escape in different tissues is highly variable, the level of transcript from the inactive X allele representing between 20% and 70% of the active X allele. Partial escape is also seen in clones derived from haematopoietic stem cells, suggesting that partial repression of the inactive X allele is at the level of individual cells. This contrasts with classical position effect variegation (PEV), where a given gene is either active or silent in a given cell and its clonal derivatives. We discuss the implications of these results with respect to mechanisms of X inactivation and escape.

Alleles↗
PubMed1996

MR imaged neurovascular relationships at the cerebellopontine angle.

Improvements in MR imaging techniques allow visualisation of the anatomy of the cerebellopontine angle (CPA) in increasingly accurate detail, revealing the complex interrelationship of the neurovascular structures in this region. We wished to assess whether vessels and vascular loops intimately associated with cranial nerves VII and VIII, corresponded to any abnormality or symptom pattern, and thus had any clinical significance. The MR scans of 108 patients were retrospectively reviewed and the imaging status of VII, VIII, the vessels, presence of vascular loops and their relationship to the nerves, coded and recorded. The patients' records were independently reviewed and the presence and "sidedness' of asymmetrical hearing loss, tinnitus, vertigo, and the results of caloric and brain stem evoked responses recorded. The vessels were closely associated with VII and VIII in over 30% of this sample with vascular loops imaged in 21% of patients, and clearly imaged entering the IAM in 7% of both right and left CPAs studied. There was no statistically significant relationship demonstrated between the proximity of the vessels, or vascular loops, to the nerves and a symptom, or symptom pattern. These findings should be considered a normal variant on MR scanning.

Adult↗
PubMed1996

Customer perceptions of agency risk communication.

A government agency commissioned a baseline study of how its customers view the agency's risk information. The 70% response rate to a mail survey allows analysis by subgroups representing customers' primary interests. Although this agency traditionally has been responsible for ensuring plant and animal health at the farm gate (or where imported), responses emphasized emerging customer concerns about the environment and human health. Customers think many risk communication activities are important, but that the agency is not especially effective in conducting those activities. Customers are moderately satisfied with much of the risk information they receive, although many have little contact from or interaction with the agency. Customers identified other sources they use, which suggest potentially effective channels for this agency's risk messages. The study provides a baseline for measuring change in the agency's risk communication effectiveness. It also can be a model when other organizations plan their own risk communication evaluations.

Agriculture↗
PubMed1996

Characteristics of psychogeriatric patient visits to a general hospital emergency room.

OBJECTIVE: This study describes psychogeriatric patients who visit the Emergency Room (ER) in a teaching hospital with a comprehensive psychogeriatric service. METHOD: A survey assessing demographic and clinical characteristics was completed for every psychiatric ER patient during a 2-year period. RESULTS: One hundred and seventy-three ER patients aged over 60 (mean age 71.2) were assessed. Fifty-three percent were previously known to the psychogeriatric service. The majority of these previously known psychogeriatric patients who used the ER suffered from mood disorders. The majority of new psychogeriatric patients seen in the ER had an organic brain syndrome (OBS). CONCLUSIONS: Few OBS patients who visited the ER were previously known to the psychogeriatric service, but many new OBS patients accessed the psychogeriatric service via the ER. For patients with mood disorders, particularly if suicidal, the ER was used as part of their service delivery system.

Adult↗
PubMed1996

Routine use of a higher order interpolator and bone algorithm in thoracic CT.

OBJECTIVE: This study was designed to evaluate the utility of the routine use of high spatial frequency algorithms and higher order helical interpolators for imaging lung parenchyma during routine thoracic CT. SUBJECTS AND METHODS: We evaluated 50 consecutive patients undergoing clinically indicated thoracic CT using the same imaging parameters and scanner. The helical volume was reconstructed three separate times using standard and higher order (180 degrees linear with double-sided lobes) interpolators and standard and high spatial frequency (bone) algorithms. The images were photographed and given to five separate readers who were kept unaware of the interpolator and algorithm and who were asked to evaluate simultaneously each patient's three sets of images for best, in-between, and worst images of the lung interstitium, pathology, and normal anatomy. RESULTS: All five readers rated the standard interpolator and algorithm images as the worst (p < .01). All five readers consistently rated the double-sided lobe interpolator and bone algorithm images as the best (p < .01). CONCLUSION: A second reconstruction of routine thoracic helical CT data using higher order helical interpolators and a bone algorithm significantly improves interstitial detail of lung parenchyma and overall visualization of normal anatomy and pathologic processes.

Aged↗
PubMed1996

Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene.

Desmoid tumors are slowly growing fibrous tumors highly resistant to therapy and often fatal. Here, we report hereditary desmoid disease (HDD), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene. In general, one or more members in approximately 10% of the FAP families manifest desmoid tumors. Affected individuals from the HDD kindred are characterized by multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and other congenital features were also observed. We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development.

Adolescent↗
PubMed1996

Five years' experience of an organ donation team in southern Israel.

An account of the work of the organ donation team from 1990 to 1995 in the main hospital serving southern Israel is presented. Organ donor rate averaged 7.5 donors per million population per year, a rate inadequate to provide the number of organs required for transplantation. Family agreement for organ donation was obtained in 30% of potential donors over this 5 year period. The three principal reasons for refusal of consent were based on religious tradition, intra-family disputes, and denial reactions. It is suggested that public education is indispensable in order to improve organ donation rates.

Adolescent↗
PubMed1995

Dehydroepiandrosterone augments M1-muscarinic receptor-stimulated amyloid precursor protein secretion in desensitized PC12M1 cells.

Epidemiologic studies suggest that the age-related decline in dehydroepiandrosterone (DHEA) levels may be associated with Alzheimer's disease (AD). Cholinergic markers also decline with age, and are associated with AD pathology. Activation of m1AChR-transfected PC12 cells (PC12M1) with cholinergic agonists results in secretion of Alzheimer's beta-amyloid precursor protein (APP) which in turn reduces beta-amyloid production. This study examined whether DHEA affects APP processing in m1AChR-transfected PC12 cells. DHEA treatment did not significantly alter basal or m1AChR-stimulated APP secretion. However, DHEA (0.1 microM) significantly diminished the desensitization of APP secretion in cells exposed to carbachol for 24 h. The effect of DHEA on APP processing is probably not related to up-regulation of m1AChR or increased m1AChR-activated phosphoinositide hydrolysis since these parameters did not change following DHEA treatment. These findings imply a possible involvement of DHEA in APP processing. Thus, the age-associated decline in DHEA levels may contribute to decreased APP secretion and a consecutive increase in beta-amyloid deposition, which in turn may play a role in the development of AD.

Amyloid beta-Peptides↗
PubMed1995

Safety and efficacy of thymopentin in zidovudine (AZT)-treated asymptomatic HIV-infected subjects with 200-500 CD4 cells/mm3: a double-blind placebo-controlled trial.

Thymopentin, 50 mg subcutaneously (s.c.) 3 times per week, was evaluated in a double-blind, randomized, placebo-controlled trial of zidovudine (AZT)-treated asymptomatic human immunodeficiency virus (HIV)-infected subjects with 200-500 CD4 cells/mm3 at entry. The 352 subjects were prestratified by prior AZT use into stratum I (235 subjects, > 6 months AZT at entry) and stratum II (117 subjects, < or = 6 months AZT at entry). Clinical end points, CD4 cell counts, serum p24, serum immune complex dissociated (ICD) p24, and safety variables were evaluated through 48 weeks, using an intent-to-treat analysis. The two strata were analyzed individually because they yielded different clinical outcomes, with a statistically significant treatment-by-stratum interaction. In stratum I (mean, 16 months AZT at entry) two AIDS or death events occurred in thymopentin and 10 in placebo recipients (p = 0.024; relative risk (RR) estimate, 4.9 [95% confidence limit (CI), 1.1 to 22.2]). There were three AIDS-related complex (ARC), AIDS, or death events in thymopentin and 18 in placebo recipients [p = 0.001; RR estimate, 5.9 (95% CI, 1.7 to 20.0)]. In stratum II (mean, 3 months AZT at entry), four AIDS or death events occurred in thymopentin and none in placebo recipients (p = 0.11), and four ARC, AIDS, or death events occurred in thymopentin and two in placebo recipients (p = 0.79). The treatment groups did not differ significantly with respect to changes in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities. Thus, AZT-experienced placebo-treated subjects had relatively high progression rates to AIDS or death and to ARC, AIDS, or death, and these rates were reduced by thymopentin treatment. In contrast, placebo-treated subjects with little prior AZT experience had low progression rates; these were not significantly changed by thymopentin treatment. There was no increase in the incidence of adverse reactions with thymopentin.

Adult↗
PubMed1995

NGF-dependent neurotrophic-like effects of AF102B, an M1 muscarinic agonist, in PC12M1 cells.

The non-selective muscarinic agonist oxotremorine induces atropine-sensitive neurite outgrowth in PC12 cells stably transfected with m1 muscarinic receptors. In contrast, AF102B, an M1-selective muscarinic agonist, mediated minimal neurite outgrowth in these cells. In the presence of nerve growth factor (NGF) however, it induced atropine-sensitive neurite outgrowth in almost half the cell population. AF102B mediated phosphoinositide hydrolysis, but unlike carbachol, it did not stimulate cyclic AMP accumulation in these cells. These signals were not affected by NGF, indicating that they were not directly responsible for the cholinergic neurotrophic-like response. Our observations suggest that AF102B may improve neuronal responsiveness to neurotrophic factors, and thus may provide another beneficial aspect for treating Alzheimer's disease.

Animals↗
PubMed1995

Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus.

Most patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin. Insulin resistance precedes the onset of this disease, suggesting that it may be an initial abnormality. Insulin-receptor kinase activity is impaired in muscle, fibroblasts and other tissues of many patients with non-insulin-dependent diabetes mellitus, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase. Here we show that this inhibitor is a membrane glycoprotein, termed PC-1 (refs 10, 11). We find that PC-1 activity is increased in fibroblasts from seven of nine patients with typical non-insulin-dependent diabetes mellitus. In addition, overexpression of PC-1 in transfected cultured cells reduces insulin-stimulated tyrosine kinase activity. These studies raise the possibility that PC-1 has a role in the insulin resistance of non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1995

CA19-9 does not predict cholangiocarcinoma in patients with primary sclerosing cholangitis undergoing liver transplantation.

The results of liver transplantation in patients with cholangiocarcinoma have been poor. It has been suggested that elevated serum CA19-9 levels predict cholangiocarcinoma in patients with primary sclerosing cholangitis. We analyzed the predictive value of CA19-9 antigen as a marker of cholangiocarcinoma in patients with primary sclerosing cholangitis evaluated for liver transplantation. We reviewed the charts of 26 patients with primary sclerosing cholangitis (stage IV) in whom preoperative serum CA19-9 levels were determined; 22 of 26 underwent liver transplant. Explant specimens were serially sectioned and examined for tumor. In 3 of the 26 patients, cholangiocarcinoma was diagnosed during pretransplantation evaluation; exploratory laparotomy on the last patient showed no evidence of cholangiocarcinoma, and this patient is awaiting transplantation. Twelve of the 26 patients had CA19-9 levels more than double the laboratory reference range (0-37 U/mL) (mean 183.1 +/- 103 U/mL, range 77-415 U/mL). Two of the 12 patients with elevated CA19-9 levels had cholangiocarcinoma. Of the 14 patients with normal levels, two had cholangiocarcinoma. No correlation between elevated CA19-9 and bile duct dysplasia was noted. Sensitivity for serum CA19-9 levels more than twice the reference range is 50%, specificity is 54.5%, positive predictive value is 16.6%. An elevated serum CA19-9 level in a patient with stage IV primary sclerosing cholangitis does not reliably predict coexisting cholangiocarcinoma. Persistently high or rising serum CA19-9 levels do not indicate more urgent need for liver transplantation.

Adult↗
PubMed1995

AF150(S): a new functionally selective M1 agonist improves cognitive performance in rats.

This study was aimed at evaluating the ability of a new functionally selective partial M1 agonist, AF150(S), to reverse cognitive impairments in rats. A memory deficits-induced animal model was used that involved AF64A (3 nmol/2 microliters/side) bilaterally injected ICV. AF150(S) was administered PO. The pharmacodynamic profile of the compound was established and its general toxicity was evaluated. Animals were tested on three behavioral tasks: step-through passive avoidance, Morris water maze reference memory paradigm, and radial arm maze working memory paradigm. The sign-free dose of AF150(S) was > 40 mg/kg whereas the LD50 was > 500 mg/kg. In comparison, the effective dose in reversing performance impairments on the various tasks was much lower (0.5-5 mg/kg). The data suggest that AF150(S) possesses potential cognitive enhancement abilities, probably due to a specific increase of cholinergic function.

Animals↗