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Biomedical subjects

L Lee

Publications and source records attributed to L Lee.

At least 91 records · Page 5Linked to original sources
PubMed2000

Cerebral correlates of psychotic symptoms in Alzheimer's disease.

BACKGROUND: Psychotic symptoms are produced by distributed neuronal dysfunction. Abnormalities of reality testing and false inference implicate frontal lobe abnormalities. OBJECTIVES: To identify the functional imaging profile of patients with Alzheimer's disease manifesting psychotic symptoms as measured by single photon emission computed tomography (SPECT). METHODS: Twenty patients with Alzheimer's disease who had SPECT and clinical evaluations were divided into two equal groups with similar mini mental status examination (MMSE), age, sex, and the range of behaviours documented by the neuropsychiatric inventory (NPI), except delusions and hallucinations. SPECT studies, registered to a probabilistic anatomical atlas, were normalised across the combined group mean intensity level, and subjected to a voxel by voxel subtraction of the non-psychotic minus psychotic groups. Subvolume thresholding (SVT) corrected random lobar noise to produce a three dimensional functional significance map. RESULTS: The significance map showed lower regional perfusion in the right and left dorsolateral frontal, left anterior cingulate, and left ventral striatal regions along with the left pulvinar and dorsolateral parietal cortex, in the psychotic versus non-psychotic group. CONCLUSION: Patients with Alzheimer's disease who manifest psychosis may have disproportionate dysfunction of frontal lobes and related subcortical and parietal structures.

Alzheimer Disease↗
PubMed2000

Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation.

We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in alpha-galactosidase A (alpha-gal A) knockout mice, a model of Fabry disease. C57BL/6 mice treated twice daily for 3 days with D-threo-1-ethylendioxyphenyl-2-palmitoylamino-3-pyrrolidi no-propanol (D-t-EtDO-P4) showed a concentration-dependent decrement in glucosylceramide levels in kidney, liver, and spleen. A single intraperitoneal injection of D-t-EtDO-P4 resulted in a 55% reduction in renal glucosylceramide, consistent with rapid renal glucosylceramide metabolism. A concentration-dependent decrement in renal and hepatic globotriaosylceramide levels was observed in alpha-Gal A(-) males treated for 4 weeks with D-t-EtDO-P4. When 8-week-old alpha-Gal A(-) males were treated for 8 weeks with 10 mg/kg twice daily, renal globotriaosylceramide fell to below starting levels, consistent with an alpha-galactosidase A-independent salvage pathway for globotriaosylceramide degradation. Complications observed with another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, including weight loss and acellularity of lymphatic organs, were not observed with D-t-EtDO-P4. These data suggest that Fabry disease may be amenable to substrate deprivation therapy.

1-Deoxynojirimycin↗
PubMed2000

Orbital and dorsolateral frontal perfusion defect associated with behavioral response to cholinesterase inhibitor therapy in Alzheimer's disease.

The authors retrospectively explored the behavioral and functional imaging profile of Alzheimer's disease (AD) patients who respond to cholinesterase inhibitor therapy by using the Neuropsychiatric Inventory (NPI) and baseline [99mTc]HMPAO SPECT. Thirty AD patients were divided into three groups (Responders, Nonresponders, and Unchanged) based on their behavioral response to donepezil. Responders had significantly (P < or = 0.01) more pretreatment irritability, disinhibition (P < or = 0.05), and euphoria (P = 0.05) than Nonresponders and significantly lower lateral orbital frontal (P < 0.00001) and dorsolateral frontal (P < or = 0.0005) perfusion bilaterally. A pretreatment orbitofrontal syndrome may predict behavioral response to cholinesterase inhibitor therapy in AD.

Aged↗
PubMed2000

Inhibition of cholesteryl ester transfer protein by substituted dithiobisnicotinic acid dimethyl ester: involvement Of a critical cysteine.

SC-71952, a substituted analog of dithiobisnicotinic acid dimethyl ester, was identified as a potent inhibitor of cholesteryl ester transfer protein (CETP). When tested in an in vitro assay, the concentration of SC-71952 required for half-maximal inhibition was 1 microm. The potency of SC-71952 was enhanced 200-fold by preincubation of the inhibitor with CETP, and was decreased 50-fold by treatment with dithiothreitol. Analogs of SC-71952 that did not contain a disulfide linkage were less potent, did not display time dependency, and were not affected by dithiothreitol treatment. Kinetic and biochemical characterization of the inhibitory process of CETP by SC-71952 suggested that the inhibitor initially binds rapidly and reversibly to a hydrophobic site on CETP. With time, the bound inhibitor irreversibly inactivates CETP, presumably by reacting with one of the free cysteines of CETP. Liquid chromatography/mass spectroscopy (LC/MS) analyses of tryptic digests of untreated or SC-71952-inactivated CETP was used to identify which cysteine(s) were potentially involved in the time-dependent, irreversible component of inactivation by the inhibitor. One disulfide bond, Cys143-Cys184, was unaffected by treatment with the inhibitor. Inactivation of CETP by SC-71952 correlated with a progressive decrease in the abundance of free Cys-13 and Cys-333. Conversion of Cys-13 to alanine had no effect on the rapid reversible component of inactivation by SC-71952. However, it abolished the time-dependent enhancement in potency seen with the inhibitor when using wild-type CETP. These data indicate that Cys-13 is critical for the irreversible inactivation of CETP by SC-71952 and provides support for the structural model that places Cys-13 near the neutral lipid-binding site of CETP.

Amino Acid Substitution↗
PubMed2000

Improving health-based payment for Medicaid beneficiaries: CDPS.

This article describes the Chronic Illness and Disability Payment System (CDPS), a diagnostic classification system that Medicaid programs can use to make health-based capitated payments for TANF and disabled Medicaid beneficiaries. The authors describe the diversity of diagnoses and different burdens of illness among disabled and AFDC Medicaid beneficiaries. Claims from seven States are analyzed, and payment weights are provided that States can use when adjusting HMO payments. The authors also compare the taxonomy and statistical performance of CDPS to other leading diagnostic classification systems and find that the new model performs better in a number of respects.

Adult↗
PubMed1999

Secondary structure and fold homology of the ArsC protein from the Escherichia coli arsenic resistance plasmid R773.

Resistance to several toxic anions in Escherichia coli is conferred by the ars operon carried on plasmid R773. The gene products of this operon catalyze extrusion of antimonials and arsenicals from cells. In this paper, we report the determination of the overall fold for ArsC, a 16 kDa protein of the ars operon involved in the reduction of arsenate to arsenite, using multidimensional, multinuclear NMR. The protein is found to contain large regions of extensive mobility, particularly in the active site. A model fold, computed on the basis of a preliminary set of NOEs, was found to be structurally homologous to E. coli glutaredoxin, thiol transferases, and glutathione S-transferase. Some kinship to the structure of low molecular weight tyrosine phosphatases, based on rough topological similarity but more so on the basis of a common anion-binding-loop motif H-CX(n)R, was also detected. Although functional, secondary, and tertiary structural homology is observed with these molecules, no significant homology in primary structure was detected. The mobilities of the active site of ArsC and of other enzymes are discussed.

Adenosine Triphosphatases↗
PubMed1999

Improved inhibitors of glucosylceramide synthase.

Previous work has led to the identification of inhibitors of glucosylceramide synthase, the enzyme catalyzing the first glycosylation step in the synthesis of glucosylceramide-based glycosphingolipids. These inhibitors have two identified sites of action: the inhibition of glucosylceramide synthase, resulting in the depletion of cellular glycosphingolipids, and the inhibition of 1-O-acylceramide synthase, resulting in the elevation of cell ceramide levels. A new series of glucosylceramide synthase inhibitors based on substitutions in the phenyl ring of a parent compound, 1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4), was made. For substitutions of single functional groups, the potency of these inhibitors in blocking glucosylceramide synthase was primarily dependent upon the hydrophobic and electronic properties of the substituents. An exponential relationship was found between the IC50 of each inhibitor and the sum of derived hydrophobic (pi) and electronic (sigma) parameters. This relationship demonstrated that substitutions that increased the electron-donating characteristics and decreased the lipophilic characteristics of the homologues enhanced the potency of these compounds in blocking glucosylceramide formation. A novel compound was subsequently designed and observed to be even more active in blocking glucosylceramide formation. This compound, D-threo-4'-hydroxy-P4, inhibited glucosylceramide synthase at an IC50 of 90 nM. In addition, a series of dioxane substitutions was designed and tested. These included 3',4'-methylenedioxyphenyl-, 3',4'-ethylenedioxyphenyl-, and 3'4'-trimethylenedioxyphenyl-substituted homologues. D-threo-3', 4'-Ethylenedioxy-P4-inhibited glucosylceramide synthase was comparably active to the p-hydroxy homologue. 4'-Hydroxy-P4 and ethylenedioxy-P4 blocked glucosylceramide synthase activity at concentrations that had little effect on 1-O-acylceramide synthase activity. These novel inhibitors resulted in the inhibition of glycosphingolipid synthesis in cultured cells at concentrations that did not significantly raise intracellular ceramide levels or inhibit cell growth.

Cells, Cultured↗
PubMed1999

Control of mitotic spindle position by the Saccharomyces cerevisiae formin Bni1p.

Alignment of the mitotic spindle with the axis of cell division is an essential process in Saccharomyces cerevisiae that is mediated by interactions between cytoplasmic microtubules and the cell cortex. We found that a cortical protein, the yeast formin Bni1p, was required for spindle orientation. Two striking abnormalities were observed in bni1Delta cells. First, the initial movement of the spindle pole body (SPB) toward the emerging bud was defective. This phenotype is similar to that previously observed in cells lacking the kinesin Kip3p and, in fact, BNI1 and KIP3 were found to be in the same genetic pathway. Second, abnormal pulling interactions between microtubules and the cortex appeared to cause preanaphase spindles in bni1Delta cells to transit back and forth between the mother and the bud. We therefore propose that Bni1p may localize or alter the function of cortical microtubule-binding sites in the bud. Additionally, we present evidence that other bipolar bud site determinants together with cortical actin are also required for spindle orientation.

Actins↗
PubMed1999

Novel mutations in African American patients with glycogen storage disease Type II. Mutations in brief no. 209. Online.

The infantile form of GSD II (an inherited deficiency of the lysosomal enzyme, acid alpha-glucosidase, Pompe disease) is a severe and invariably fatal disease characterized by a rapidly progressive generalized hypotonia, hepatomegaly, and cardiomegaly. We have recently demonstrated that African American patients share a common nonsense R854X mutation in exon 18 (Becker et al., 1998). Two other mutations, D645E and M519V, have been identified in individual African American patients (Hermans et al., 1993a; Huie et al., 1994a). We describe here three novel mutations in this population group: a missense W481R in exon 10, a deletion of a T1441 in exon 10, and a splicing defect at the 5' donor site of intron 8 (IVS g+la) . The splicing defect is shared by two unrelated patients and it is linked to intragenic polymorphic sites identical to those found in patients bearing the common R854X mutation.

Amino Acid Substitution↗
PubMed1999

A study to find the optimal orientation of the breast for the cranio caudal view, for screening purposes.

AIM: It is generally accepted that the cranio-caudal (CC) view cannot image the whole breast. The aim of this study was to investigate whether emphasis should be put on imaging the medial or lateral aspect of the breast when performing the CC view. METHOD: The mammograms of all cancers arising within a screened population were reviewed. These included 120 screen detected cancers and 41 interval cancers. Two mammographers individually assessed the CC view to ascertain if the cancer would have been excluded from the film if the patient had been rotated to emphasis the medial or lateral aspect of the breast. A radiologist acted as arbitrator in cases of discordance. RESULTS: No cancers were excluded from the reviewed images, however five would be excluded by 5 degrees lateral rotation and eight by 10 degrees lateral rotation. Four would be excluded by 5 degrees medial rotation and two by 10 degrees medial rotation. CONCLUSION: The optimal position of the breast for the CC view is with the breast straight, i.e. with the nipple pointing towards the edge of the film. More cancers would have been missed off the film if over emphasis had been given to imaging either the medial or lateral aspect of the breast.

Breast Neoplasms↗
PubMed1999

Consistency of acoustic and aerodynamic measures of voice production over 28 days under various testing conditions.

The value of any measure of voice production is dependent on its repeatability over time. The purpose of the present study was to determine the consistency of selected acoustic and aerodynamic measures of voice production over 28 days, under various test/retest conditions. Three groups of healthy young adult females sustained three vowels at comfortable, high, and low pitch levels. Subjects in Group 1 chose their own intensity levels, but matched the fundamental frequencies produced at Test 1 during Test 2. Group 2 controlled intensity levels during both tests, but fundamental frequency was free to vary. Group 3 controlled both intensity and fundamental frequency. Measures of fundamental frequency, jitter, maximum phonation time, phonation volume, and flow rate were compared. Subjects who matched both fundamental frequency and intensity showed repeatable, consistent results for all measures during both tests. Controlling intensity but not fundamental frequency resulted in statistically significant differences in fundamental frequency at comfortable and high pitches, but there was minimal effect on other variables. Controlling fundamental frequency but not intensity led to the most inconsistency between tests, affecting both acoustic and aerodynamic measures. Results underscore the need to control the conditions under which measures are obtained.

Adult↗
PubMed1999

Fluoroscopic landmarks for optimal visualization of the proximal renal arteries.

PURPOSE: To accurately determine the in vivo orientation of the origin of the renal arteries from the aorta relative to a fluoroscopic bony landmark for optimal diagnostic arteriography and renal artery stent placement. MATERIALS AND METHODS: One hundred sixty abdominal computed tomography (CT) scans of patients in eight age groups (20-90 years) were reviewed to determine the angle of the origins of the renal arteries from the aorta relative to the long axis of the L-1 spinous process (L1SP). RESULTS: The right renal artery arises ventrally at an angle of 30 degrees (standard deviation [SD] = 15 degrees) from a plane orthogonal to the long axis of the L1SP. The left renal artery arises dorsally at an angle of 7 degrees (SD = 13 degrees) relative to the same plane. CONCLUSIONS: The optimal initial angle for angiographic evaluation of the origin of the renal artery and for renal artery stent placement is 30 degrees left anterior oblique (LAO) relative to the L1SP for the right renal artery and 7 degrees LAO for the left renal artery. Unfortunately, there is variability in the angle of the renal artery origins from the aorta which cannot be controlled for using this technique. In some patients, additional views will be necessary to optimally depict the origins of the renal arteries.

Adult↗
PubMed1999

Optimum dental radiography in bone marrow transplant patients.

OBJECTIVE: The purpose of this study was to establish an optimum radiographic examination regimen for patients undergoing bone marrow transplantation. Two radiographic examinations were compared: the panoramic radiograph and the full mouth series of radiographs. STUDY DESIGN: A prospective analysis of 65 consecutive patients undergoing bone marrow transplantation was undertaken. All patients were examined through use of both panoramic and full mouth series intraoral radiographs, including bitewings. Significant findings were recorded and compared by means of paired t test analysis for parametric data, such as caries, periapical inflammation and subgingival calculus, and by means of McNemar's test for nonparametric data, such as the presence or absence of severe periodontal disease. RESULTS: Acquired findings, such as caries, periodontal disease, and clinically significant faulty restorations, were detected more frequently from the full mouth series (P < .05). There was no significant difference in the detection of periapical pathosis. In 8 of 65 patients, clinically significant information, such as evidence of impacted wisdom teeth, neoplasms, and multiple myeloma, was better detected from the panoramic radiographs. CONCLUSIONS: The results suggest a combination of both modalities as the optimum means of radiologic survey in this "high-risk" patient population.

Adolescent↗
PubMed1999

The effects of specific antibody fragments on the 'irreversible' neurotoxicity induced by Brown snake (Pseudonaja) venom.

Brown snake (Pseudonaja) venom has been reported to produce 'irreversible' post synaptic neurotoxicity (Harris & Maltin, 1981; Barnett et al., 1980). A murine phrenic nerve/diaphragm preparation was used to study the neurotoxic effects of this venom and pre- and post-synaptic components were distinguished by varying the temperature and frequency of nerve stimulation. There were no myotoxic effects and the neurotoxicity proved irreversible by washing alone. The effects of a new Fab based ovine antivenom have been investigated and proved able to produce a complete, rapid (< 1 h) reversal of the neurotoxicity induced by Brown snake venom. A reversal was also possible when the antivenom addition was delayed for a further 60 min. We believe that this is the first time such a reversal has been shown.

Animals↗
PubMed1999

Determination of the breakpoint of the common alpha-thalassaemia deletion in Filipinos in Hawaii.

The region of the crossover causing the Filipino type of alpha thalassaemia has been determined by examining similarity between the regions which had been indicated as involved in the crossover points by restriction mapping, using the published alpha-globin region DNA sequence. The crossover point was found in 21 base pairs between two Alu sequences using PCR primers flanking these Alu sequences. A simple PCR multiplex assay has been devised to detect heterozygotes and homozygotes.

Base Sequence↗
PubMed1999

Focus groups.

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England↗
PubMed1999

Meeting the training needs of community-based service personnel in Africa through video-based training courses. Leonard Cheshire Foundation International.

PURPOSE: This paper describes the development of a new training model: namely one which is local and open to everyone; in which people learn through seeing and doing; with the focus on information that is practical and relevant to them. A package of video and workbooks enables the courses to be presented by local tutors who have taken part in a training workshop to prepare them for the task. METHOD: This model was applied to an eight unit course on working with children who have cerebral palsy. It was presented in 13 locations by 19 tutors in four southern African countries to over 150 participants within a 6 month period. A developmental approach was adopted which involved working with partners to identify training needs, develop and field test the video course. Tutors and participants evaluated the course separately using quantitative and qualitative methods. RESULTS: Overall tutors and participants rated the course positively. They identified elements which they found particularly useful along with those which were considered less useful. Course results and outcomes are discussed. CONCLUSIONS: The findings indicated that the training model was effective and five further courses have been developed about disability issues. These are described in the Appendix.

Allied Health Personnel↗