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Biomedical subjects

L A Anderson

Publications and source records attributed to L A Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1994

A role for non-NMDA excitatory amino acid receptors in regulating the basal activity of rat globus pallidus neurons and their activation by the subthalamic nucleus.

We have investigated the hypothesis that excitatory amino acid (EAA) receptors in the globus pallidus (GP) play a significant role in maintaining the firing rates of GP neurons under basal conditions and following activation of the subthalamic nucleus (STN). Drugs were infused directly into the GP and/or STN while the extracellular single unit activity of Type II GP neurons was recorded in ketamine-anesthetized rats. Local infusions of the EAA agonists NMDA (30-300 pmol/200 nl) or AMPA (0.1-1 pmol/200 nl) elicited increases in the firing rate of GP neurons in a dose-dependent fashion. Infusion of the GABAA receptor antagonist bicuculline methiodide (1-10 pmol/100 nl) into the STN also elicited dose-related increases in the firing rate of GP neurons. Intrapallidal infusion of the non-NMDA (AMPA/kainate) receptor antagonist NBQX (0.1-1.0 nmol) reduced the basal firing rate of GP neurons by 40%. In contrast, the NMDA antagonist MK-801 (0.01-0.1 nmol) produced no significant effect on basal firing rate. Intrapallidal infusion of the non-selective EAA receptor antagonist kynurenic acid or NBQX reversed or blocked the increase in firing rate of GP neurons following bicuculline-induced activation of the STN. Similar treatment with MK-801, however, had no significant effect on this response. These results indicate that tonic stimulation of non-NMDA receptors plays an important role in maintaining the basal activity of GP neurons and in mediating the effects of increased excitatory input from subthalamic afferent neurons.

Animals↗
PubMed1994

The long isoform of the rat thyrotropin-releasing hormone receptor down-regulates Gq proteins.

A cDNA encoding the long isoform of the rat thyrotropin releasing hormone (TRH) receptor was expressed stably in HEK-293 cells. Polymerase chain reaction analysis confirmed expression of mRNA encoding only the long and not the short isoform. Activation of this receptor with TRH caused a large stimulation in production of inositol phosphates but did not produce either activation of basal or inhibition of forskolin-amplified adenylyl cyclase activity. Sustained exposure of these transfected cells to TRH resulted in a substantial reduction in cellular levels of Gq alpha-like immunoreactivity from some 12 to 5 pmol/mg of membrane protein without significant alterations in cellular levels of the alpha subunits of Gs, Gi1, Gi2, Gi3, or Go. Equivalent experiments in GH3 cells also indicated a marked down-regulation of Gq alpha/G11 alpha. Dose-response curves indicated that 20 nM TRH produced half-maximal down-regulation of cellular Gq-like immunoreactivity in the transfected HEK-293 cells and that half-maximal loss was produced within 3-4 h. Separation of the transfected HEK-293 cell membranes in SDS-polyacrylamide gel electrophoresis conditions able to resolve individual members of the Gq family of G-proteins demonstrated the presence of two related G-proteins. Both of the expressed Gq-like G-proteins were observed to be down-regulated in parallel by TRH. The similarity of dose-response curves and time-courses for loss of the two G-proteins indicates that the long isoform of the rat TRH receptor does not functionally select between these two transducer proteins. In GH3 cells both Gq alpha and G11 alpha, which are expressed at similar levels, were observed to be down-regulated equivalently by treatment with TRH.

Adenylyl Cyclases↗
PubMed1994

Interdisciplinary team training in geriatrics: reaching out to small and medium-size communities.

Since 1989, six teams in the state of Michigan have been involved in a team training program designed to promote the development of geriatric services in small to medium-size communities. The program was enthusiastically received by participants, but after 18 months, only half of the teams had implemented clinical services for older adults. Monitoring the progress of the teams over 18 months and analyzing the activities of two teams revealed that financially stable and supportive sponsoring agencies and the community were critical factors in the implementation of interdisciplinary clinical services in geriatrics. Future team training programs trying to promote the development of geriatric services in small to medium-size communities should try to address these issues through community organization interventions.

Community Participation↗
PubMed1994

An update on the cause of abdominal aortic aneurysms.

Historically the most common cause of abdominal aortic aneurysms has been attributed to atherosclerotic degeneration of the vessel wall. However, over the last decade this widely accepted theory has been challenged by a substantial body of research that proposes that atherosclerosis is more likely to be an associated finding rather than an instigating factor. Arguments against an atherosclerotic theory are supported by differences in the characteristics of atherosclerotic occlusive disease and aneurysmal disease. Emerging theories propose that development of abdominal aortic aneurysms involves genetic factors and fundamental structural changes in the aorta. The purpose of this article is to review these emerging theories and discuss their implications on patient treatment.

Aged↗
PubMed1993

High-density genetic map of the BRCA1 region of chromosome 17q12-q21.

To facilitate the positional cloning of the breast-ovarian cancer gene BRCA1, we constructed a high-density genetic map of the 8.3-cM interval between D17S250 and GIP on chromosome 17q12-q21. Markers were mapped by linkage in the CEPH and in extended kindreds in our breast cancer series. The map comprises 33 ordered polymorphisms, including 12 genes and 21 anonymous markers, yielding an average of one polymorphism every 250 kb. Twenty-five of the markers are PCR-based systems. The order of polymorphic genes and markers is cen-D17S250-D17S518-HER2-THRA1-RARA-D17S80 -KRT10-[D17S800-D17S857]-GAS- D17S856-EDH17B-D17S855-D17S859-D17S858-[++ +PPY-D17S78]-D17S183-EPB3-D17S579- D17S509-[D17S508-D17S190 = D17S810]-D17S791-[D17S181 = D17S806]-D17S797- HOX2B-GP3A-[D17S507 = GIP]-qter. BRCA1 lies in the middle of the interval, between THRA1 and D17S183. Markers from this map can be used to determine whether cancer is linked to BRCA1 in families, to evaluate whether tumors have lost heterozygosity at loci in the region, and to identify probes for characterizing chromosomal rearrangements from patients and from tumors.

Alleles↗
PubMed1993

Patient and physician perceptions of their relationship and patient satisfaction: a study of chronic disease management.

This study investigated patient and physician perceptions of their relationship and examined how their perceptions related to patient satisfaction. Data are based on 134 patient-physician interactions. Study participants included 12 physicians (five women and seven men) and 134 male patients with a diagnosis of diabetes mellitus being seen on an outpatient basis. Information on patient and physician demographics, patient's metabolic control and functional status and time spent in the interaction were also collected. Results revealed that patients with lower levels of education were most satisfied and that physicians who viewed the relationship as a patient-physician partnership had more satisfied patients than those who viewed the relationship as physician controlled. Findings also indicated that physicians' gender and number of years in practice were not related to patient satisfaction. Practical implications include: (1) increasing attention to physician's perceptions of his or her relationship with individual patients and (2) exposing newly trained physicians to partnership types of relationships, if future research confirms these findings in chronic disease management.

Attitude of Health Personnel↗
PubMed1993

Pharmacodynamics, pharmacokinetics and faecal persistence of morantel in cattle and goats.

Morantel could not be detected (< 0.05 microgram/ml) in the plasma of cattle or goats following the oral administration of morantel tartrate at a dose rate of 10 mg/kg bodyweight. No morantel was detected in the milk of lactating goats except in one animal where a concentration of 0.092 microgram/ml was detected at 8 h after drug administration. Morantel was highly effective against Cooperia oncophora infections in calves treated 6, 9 or 18 days after infection; however, was highly effective against Ostertagia ostertagi only when treated 18 days after infection. Morantel did not affect the fecundity of adult O. ostertagi surviving treatment 18 days after infection which had similar average numbers of eggs in their uteri (range 13.4 +/- 0.73-16.8 +/- 0.98) as did parasites from control animals (range 12.0 +/- 0.70-13.6 +/- 0.66). Morantel could be detected at a concentration of 96 +/- 4.5 micrograms/g (dry weight) in the faeces of a calf 24 h after treatment with 10 mg/kg bodyweight of morantel tartrate. The concentration of morantel in replicate samples of this faeces exposed to natural atmosphere, but not to soil or soil organisms, declined slowly over the following 322 days. At day 322 after the start of the experiment 8.8 micrograms/g of morantel could be measured in the remaining faecal material. Throughout the faecal degradation study the concentration of morantel in the crusts of the replicate sample pats was lower than the concentration in the core samples.

Animals↗
PubMed1993

THRA1 and D17S183 flank an interval of < 4 cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21.

In order to pinpoint the locale of the gene for early-onset familial breast and ovarian cancer (BRCA1), polymorphisms were developed within the locus for thyroid hormone receptor alpha (THRA1) and for several anonymous sequences at chromosome 17q12-q21. The THRA1 polymorphism is a dinucleotide repeat with 10 alleles and heterozygosity.79. Gene mapping in extended families with inherited, early-onset breast and ovarian cancer indicates that BRCA1 is distal to THRA1 and proximal to D17S183 (SCG43), an interval of < 4 cM. This locale excludes HER2, THRA1, WNT3, HOX2, NGFR, PHB, COLIA1, NME1, and NME2 as candidates for BRCA1 but does not exclude RARA or EDH17B. Resolving the remaining recombination events in these families by new polymorphisms in the THRA1-D17S183 interval will facilitate positional cloning of the breast-ovarian cancer gene on chromosome 17q12-q21.

Adult↗
PubMed1992

Gastric mucosal damage due to aspirin and copper aspirinate assessed by gastric mucosal potential difference changes.

When the gastric mucosa is damaged by antiinflammatory agents, such as aspirin, gastric mucosal potential difference (GPD) decreases and may or may not return to predamage values after the agent is removed. The magnitude and time course of the gastric potential difference changes have been suggested as a measure of mucosal damage. Male Sprague-Dawley rats were fasted, anesthetized, and surgically prepared for measurement of GPD by placement of electrodes in the gastric lumen and spleen. Test mixtures of aspirin, copper aspirinate, copper sulfate, or mixtures of aspirin and copper sulfate were administered by gavage, and subsequent changes in GPD were recorded. The area between the extrapolated control (baseline) GPD and the damage GPD was determined. The product of this area and the maximum change in GPD, the Reizindex (RI), was calculated. Values for all copper (II)-containing systems, including those with no aspirin, were significantly greater than aspirin alone. It was concluded that factors other than mucosal damage may contribute to a reduction in GPD and, therefore, an increase in Reizindex.

Animals↗
PubMed1991

Chromosome 1 Charcot-Marie-Tooth disease (CMT1B) locus in the Fc gamma receptor gene region.

The Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy) loci have been reported to be on at least three chromosomes: 1 (CMT1B, HMSN1B), 17 (CMT1A), and X (CMTX). In this study multipoint linkage analysis of two Duffy-linked families given a combined LOD score of 8.65 to establish that the Duffy-linked CMT1B gene exists in the 18 centimorgan region between the antithrombin III gene and the Duffy/sodium-potassium ATPase loci. The simultaneous segregation of polymorphisms near the CMT1A locus on chromosome 17 excludes linkage to this chromosome region in both families. Polymorphic sites that flank the CMT1B gene have been subchromosomally localized to the proximal chromosome-1 long arm (1q21.2----1q25) by spot blot analysis of sorted chromosomes, polymorphic deletion analysis, in situ hybridization, and multipoint linkage analysis.

Antigens, Differentiation↗
PubMed1990

Linkage of early-onset familial breast cancer to chromosome 17q21.

Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region.

Breast Neoplasms↗
PubMed1990

Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence.

When probes throughout the McArdle disease (myophosphorylase) gene region were used to search for DNA polymorphisms, only an MspI polymorphism was found in 94 enzyme-probe combinations. Along with an insertion/deletion polymorphism more 3' to the gene locus, these polymorphisms will be informative in 75% of at-risk patients. These results contrast strikingly to the six polymorphic sites detected in 15 enzyme-probe combinations in the homologous Her's disease (liver phosphorylase) gene region. This single MspI polymorphic site includes a CpG sequence of known increased mutability suggesting that DNA regions with rare polymorphisms will have most polymorphic sites at sequences with enhanced mutability. Fluorescence in situ hybridization sublocalized this gene to proximal band 11q13, establishing a point of cross-reference between the physical and genetic maps.

Base Sequence↗
PubMed1990

Preparation and purification of soybean lipoxygenase-derived unsaturated hydroperoxy and hydroxy fatty acids and determination of molar absorptivities of hydroxy fatty acids.

A method was developed for the preparation and purification of polyunsaturated hydroperoxy and hydroxy fatty acids from 18:2n-6, 18:3n-6, 18:3n-3, 20:3n-6, 20:3n-3, and 20:4n-6 with soybean lipoxygenase. This method involved incubation of unsaturated fatty acids in Tris-HCl buffer with soybean lipoxygenase and extraction of reaction products on C18 solid-phase columns. The yields of conversion of fatty acid substrate to oxygenated products were in all cases greater than or equal to 95%. C18 solid-phase extracted reaction products were purified by C18 HPLC, yielding 3-4 mg of products with purities of greater than or equal to 98%. Purified polyunsaturated hydroxy fatty acids were characterized by HPLC and mass spectral analysis and showed absorption spectra with maximum absorption occurring between 234.5 and 237.5 nm due to the presence of a conjugated diene function. Polyunsaturated hydroxy fatty acid potassium salts were converted to (4-bromobenzoyl)methyl esters by reaction with 2,4'-dibromoacetophenone in the presence of 18-crown-6. Molar absorptivities for the conjugated diene functions were determined by relating their absorbance to the absorbance contributed by the 4-bromobenzoyl chromophore and its molar absorption intensity of 17.6 X 10(3) (M.cm)-1. The molar absorptivities determined for 13-OH-9,11-18:2, 13-OH-6,9,11-18:3, 13-OH-9,11,15-18:3, 15-OH-11,13-20:2, 15-OH-8,11,13-20:3, 15-OH-11,13,17-20:3, and 15-OH-5,8,11,13-20:4 ranged from 23.2 x 10(3) to 24.6 x 10(3) (M.cm)-1. The molar absorbtivity values of 18.8 x 10(3) and 20.3 x 10(3) (M.cm)-1 determined for commercial, chemically synthesized 12-OH-5,8,10,14-20:4 [12-(S)-hydroxyeicosa-5,8,10,14-tetraenoic acid (12(S)-HETE)] and 5-OH-6,8,11,14-20:4 ((+/-)-5-HETE) were lower than that of soybean lipoxygenase-derived 15-OH-5,8,11,13-20:4 (15-HETE), which exhibited a molar absorptivity of 23.3 x 10(3) (M.cm)-1. The molar absorptivity values determined for 5-, 12-, and 15-HETE are considerably lower than 30.5 x 10(3) (M.cm)-1, which was reported previously.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Intragastric inulin as a measure of mucosal damage caused by aspirin.

In an attempt to find a method of gastric mucosal damage assessment that yields consistent results, the experiments presented here employed the measurement of the movement of inulin out of the gastric contents into the stomach wall and vascular compartment as an estimate of mucosal damage. Anesthetized male Sprague-Dawley rats were functionally nephrectomized and were administered a control or test solution containing 3H-inulin. The test solutions contained one of three doses of aspirin. Blood samples were taken at 15-min intervals over a 90-min exposure period. The stomach was removed from the animal and full-thickness tissue samples taken for measurement of 3H-inulin content. When the gastric mucosa was exposed to the test agents, there was a significantly greater accumulation of inulin in the body and antrum as well as in the plasma when compared to controls. We conclude that intragastric inulin can be employed to estimate gastric mucosal damage.

Animals↗
PubMed1990

Development of the Trust in Physician scale: a measure to assess interpersonal trust in patient-physician relationships.

Trust is widely acknowledged as an essential ingredient in patient-physician relationships. Given a dearth of situation-specific measures designed to quantify patients' trust in their physicians, we set out to develop an instrument to assess a patient's interpersonal trust in his physician. Findings from two studies are reported describing the development and validation of the Trust in Physician scale. Study 1 of 160 participants provided preliminary support for the reliability (Cronbach alpha = .90) and construct validity of the 11-item scale. Study 2, a replication study of 106 participants, supplied further evidence of the reliability and validity of the scale. Cronbach alpha was .85. Trust was significantly related to patients' desires for control in their clinical interactions and subsequent satisfaction with care. Research and clinical applications of the Trust in Physician scale are discussed.

Diabetes Mellitus, Type 2↗
PubMed1989

Optical spectra and kinetics of reactions of prostaglandin H synthase: effects of the substrates 13-hydroperoxyoctadeca-9,11-dienoic acid, arachidonic acid, N,N,N',N'-tetramethyl-p-phenylenediamine, and phenol and of the nonsteroidal anti-inflammatory drugs aspirin, indomethacin, phenylbutazone, and bromfenac.

A combination of cyclooxygenase activity assays, rapid spectrophotometry and pre-steady-state, steady-state, and transient-state kinetics is used to characterize further the properties of prostaglandin H synthase. 13-Hydroperoxyoctadeca-9-11-dienoic acid is used as oxidizing substrate and the effects of the following compounds are examined: arachidonic acid, N,N,N',N'-tetramethyl-p-phenylenediamine, phenol, diethyldithiocarbamate, and the nonsteroidal anti-inflammatory drugs aspirin, indomethacin, phenylbutazone, and Bromfenac. The order of reactivity of four of these substrates, predominantly with compound II of prostaglandin H synthase, is N,N,N',N'-tetramethyl-p-phenylenediamine greater than phenol greater than indomethacin approximately phenylbutazone. Aspirin exhibits no effect. Arachidonic acid causes inactivation. Diethyldithiocarbamate acts as a reducing substrate for the oxidized forms of prostaglandin H synthase. Bromfenac appears to act both as a protective agent and inhibitor.

Animals↗