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Biomedical subjects

L Leach

Publications and source records attributed to L Leach.

At least 19 recordsLinked to original sources
PubMed1998

Clustering and switching on verbal fluency tests in Alzheimer's and Parkinson's disease.

Two components of verbal fluency performance--clustering (i.e., generating words within subcategories) and switching (i.e., shifting between subcategories)--were examined in patients with dementia of the Alzheimer type (DAT), patients with dementia with Parkinson's disease (DPD), nondemented patients with Parkinson's disease (NPD), and demographically matched controls. The DAT and DPD groups were impaired in the number of words generated on both phonemic and semantic fluency. The DAT group produced smaller clusters on both tasks and switched less often on semantic fluency than controls. The DPD group switched less often on both tasks and produced smaller clusters on phonemic fluency than controls. The NPD group was not impaired on any fluency variable. Thus, the total number of words generated on phonemic and semantic fluency did not discriminate the dementia groups from their respective control groups, but measures of clustering and switching did. This differential pattern of performance provides evidence for the potential usefulness of measures of switching and clustering in the assessment of dementia.

Aged↗
PubMed1998

On the nature and pattern of neurocognitive function in major depressive disorder.

An effect size analysis of neurocognitive function in patients with major depressive disorder using meta-analytic principles was conducted. The results from 726 patients with depression and 795 healthy normal controls revealed that depression had the largest effect on measures of encoding and retrieval from episodic memory. Intermediate effect sizes were recorded on tests of psychomotor speed and tests that require sustained attention. Minimal effect sizes were found on tests of semantic memory, primary memory, and working memory. Moreover, major depressive disorder is accompanied by dysfunction of effortful encoding of information along with an accompanying inefficiency of retrieving poorly encoded information from declarative memory.

Cognition Disorders↗
PubMed1997

Perceptual priming of proper names in young and older normal adults and a patient with prosopanomia.

The purpose of this study was to determine if normal participants and a patient with prosopanomia can be perceptually primed for proper names. To this end, 2 experiments were conducted. In Experiment 1, normative data were collected on 4 proper-name priming tasks. The variables of levels of processing at encoding and age were manipulated. Robust priming results were obtained that were not influenced by either of these variables. The results of Experiment 2 indicated that prosopanomic patient N.G. demonstrated normal repetition priming, despite her marked impairment in deliberate retrieval of person and city names. These results are interpreted in terms of a dissociation between explicit and implicit memory for proper names and suggest that the deficit in prosopanomia only involves deliberate access to the name; access to presemantic representations of the visual word form remains intact.

Adult↗
PubMed1996

The effect of carbohydrate ingestion on the motor skill proficiency of soccer players.

This study examined the effects of ingesting a glucose-polymer (GP) solution on the motor skill proficiencies of association football (soccer) players from two teams playing during two matches in a cool environment. Fifteen minutes before each match and at halftime, players from both teams ingested 5 ml/kg of either placebo or a 6.9% GP solution. GP ingestion did not improve tackling, heading, dribbling, or shooting ability. On the contrary, the mean of successful tackles was lower with GP ingestion than with placebo. The success rate for heading, dribbling, and shooting also tended to be lower in the GP than in the placebo condition. In contrast, success in passing and ball control was similar in the two conditions. Improvements in passing and ball control may have been related to a decrease in the intensity of play in the second half of the game. These data indicate that there are no measurable benefits of GP ingestion for the motor skill proficiencies of soccer players during games played in a cool environment.

Administration, Oral↗
PubMed1995

Effect of histamine on endothelial permeability and structure and adhesion molecules of the paracellular junctions of perfused human placental microvessels.

The microvessels of the human placenta resemble those of skeletal muscle, both in endothelial cell junctional organization and in the single passage extraction of radiolabeled tracers. Addition of histamine (100 microM) to the fetal perfusate in an isolated term lobule resulted in a rapid and sustained rise (40-80%) over a 30-min perfusion period in the single circulation extraction values of 57Co-labeled cyanocobalamin and of 51Cr-labeled EDTA, but not of 22Na. Extraction values for 125I-albumin were not increased in histamine-perfused vessels nor was any focal leakage of label observed in serial cryostat sections of lobules perfused with rhodamine-conjugated albumin. There was no electron microscopic evidence of transendothelial channels in the microvascular bed; no gaps were seen at the paracellular cleft regions or in neighboring cytoplasm in any microvessels. Tilting of sections on a goniometric stage showed a significant increase in the separation between adjoining endothelial membrane leaflets at tight junctional regions (from 4.1 to 6.1 nm) although the dimensions of the wide zones remained unchanged. Placental microvessels contain the endothelial adhesion molecules PECAM-1 and VE-cadherin in the wide regions of paracellular clefts: PECAM-1 is also localized on the luminal membrane. Histamine-stimulated microvessels showed an altered staining pattern for both of these molecules, at the expense of the cleft regions. These changes in adhesion molecule distribution and tight junctional membrane separation may be parts of a series of events which leads to increased permeability during inflammatory events.

Antigens, CD↗
PubMed1995

Actin cytoskeletal isoforms in human endothelial cells in vitro: alteration with cell passage.

The microfilamentous actin component of the cytoskeleton is crucial to endothelial angiogenesis and vascular permeability. Differences in actin cytoskeletal profiles in cultured human endothelial cells were explored: when first isolated, both primary human umbilical vein endothelial cells (HUVEC) and primary human placental microvascular endothelial cells (HPMEC) expressed F-actin, but not beta-actin or alpha-smooth muscle actin. A similar endothelial actin profile was observed in cryo-sections of freshly delivered term umbilical cord and placenta. In subsequent cell culture, although the actin cytoskeleton of HUVEC remained unchanged, the actin profiles of HPMEC altered after the second passage with the induction of alpha-smooth muscle actin expression, which was intercellularly heterogeneous and increased to 20% at P4. This behaviour occurred in HPMEC monolayers cultured on a variety of extracellular matrices. Comparisons with a spontaneously immortalized human microvascular cell-line, HGTEN 21, revealed that in prolonged passage, both alpha-smooth muscle actin and beta-actin were expressed, whereas HPMEC at P4 showed a lower level of beta-actin expression. Therefore, in comparison with large vessels, microvascular cells are more likely to dedifferentiate. This may reflect the ability of microvascular cells to remodel according to changing requirements for new vessel formation. In conclusion, passage of human microvascular endothelial cells, but not of larger vessel endothelial cells, alters the expression of actin isoforms. This may be important in relation to comparisons of in vitro and in vivo vascular permeability; higher passage microvascular endothelial cells should thus be used with caution in such studies.

Actins↗
PubMed1995

Advances in understanding permeability in fetal capillaries of the human placenta: a review of organization of the endothelial paracellular clefts and their junctional complexes.

A review is presented of the evidence that the capillaries of the fetal-placental circulations of man and the guinea-pig are typical members of class of continuous non-brain capillaries. Their permeability is similar to that of muscle capillaries, and there is much evidence that the main permeation route for hydrophilic solutes in capillaries of this class is through the paracellular clefts of the endothelium. The properties of this paracellular route are based on discontinuous tight junctions which may serve to restrict the fraction of the paracellular cleft available to solutes, and on a molecular sieve which may be based on arrays of adhesion molecules in the zonula adhaerens of the junctional complex. The characteristics of this paracellular route and of overall microvascular permeability in these types of placenta make it clear that fetal capillaries form a significant component of the total transplacental permeability restriction.

Animals↗
PubMed1994

Isolation of endothelial cells from human term placental villi using immunomagnetic beads.

Chorionic villi excised from freshly delivered human term placentae and small endothelial cell aggregates were released from them by the sequential use of collagenase and trypsin. The endothelial cells were further isolated by rosetting with magnetic polystyrene beads which were coated with QB END/40, the endothelial-specific monoclonal antibody (mAb) to thrombomodulin. Cell rosettes were plated on gelatin coated Petri dishes. The cells initially grew as discrete colonies but reached confluence within 7 days. The monolayers were sub-cultured five times, and grew to confluence each time. All the cells were immunoreactive to the endothelial markers von Willebrand factor, QB-End/40 and Ulex europaeus-1 lectin. They did not show immunoreactivity to trophoblast markers (mAbs ED341 and ED235). The isolated cells could also incorporate acetylated low-density lipoprotein. Most of the cells possessed an elongated morphology, though some were slightly spread and polygonal in shape. The cell monolayers did not resemble the typical cobblestone appearance of endothelial cells isolated from large vessels. Ultrastructurally, most of the cells resembled placental microvascular cells in shape and frequency of caveolae; undifferentiated cell-cell contacts and extracellular matrix material was observed. Human placental microvascular endothelial cells may offer an in vitro model which complements the use of the perfused term placental lobule in studies of microvascular permeability.

Endothelium, Vascular↗
PubMed1994

Intact primary memory in mild to moderate Alzheimer disease: indices from the California Verbal Learning Test.

The California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) was administered to patients with mild to moderate Alzheimer disease (AD) (Group AD; n = 13) and to a control group of normal older adults (Group NC; n = 13) matched on age and education. Two measures were used to determine whether primary memory (PM) is impaired in early AD. One measure, considered a relatively "pure" measure of PM, is based on the procedure developed by Tulving and Colotla (1970) which considers an item to be recalled from PM if no more than six items intervene between its presentation and recall. The other measure is the more commonly used recall from recency. No significant difference between the AD and NC Groups was found, both on the Tulving and Colotla measure, as well as on the recall from recency measure of PM. A significant difference was obtained on two measures of secondary memory (SM), namely, Tulving and Colotla's measure and recall from the primacy and middle regions of the list of words. In comparison to NC, and AD patients showed little evidence of learning over the five trials, and poor retention even over short delays. In addition, the patients with AD showed deficits in clustering words by taxonomic category at recall. We conclude that impairment in PM cannot be used as a diagnostic marker of AD in the early stages of the disease process.

Aged↗
PubMed1993

Permeability of the fetal villous microvasculature in the isolated perfused term human placenta.

1. Capillary permeability-surface area (PS) products for the low molecular weight radioactive tracers, 22Na, 51Cr-EDTA (relative molecular mass 357) and 57Co-cyanocobalamin (relative molecular mass 1353) were measured in the fetal circulation of isolated dually perfused lobules of normal term human placentae using the single circulation, multiple-tracer dilution technique. 2. In lobules perfused with M199 medium, containing dextran and 5 g l-1 bovine albumin, the extractions of all three tracers decreased as the flow was increased over the range of 2-8 ml min-1, and PS products for 51Cr-EDTA and 57Co-cyanocobalamin, but not for 22Na, reached constant values at flows above 0.1 ml min-1 g-1. 3. Flow-independent PS products in the presence of albumin were 0.025 +/- 0.002 ml min-1 g-1 (mean +/- S.E.M., n = 25) for 57Co-cyanocobalamin and 0.057 +/- 0.003 ml min-1 g-1 (n = 25) for 51Cr-EDTA. The ratio of PS values (51Cr-EDTA/57Co-cyanocobalamin) was 2.28, while the ratio of the corresponding free diffusion coefficients was 1.79, indicating substantial restriction to the diffusion of the 57Co-cyanocobalamin. 4. In another series of lobules perfused in the absence of albumin, extraction values for all three test tracers were constant over the same flow range. Values at high flow rates were therefore about twice those measured in the presence of albumin, and PS products for all three tracers failed to reach diffusion-limited values. 6. Lobules perfused with and without albumin were fixed using a glutaraldehyde fixative containing 1% Alcian Blue dye. An ultrastructural examination of the endothelium showed no significant changes in cell or cleft morphology, or in the glycocalyx, in the absence of albumin which might account for the observed permeability change. 7. These data are the first physiological measurements specifically characterizing fetal microvascular permeability in the human placenta. The results suggest that permeability resembles that found in skeletal muscle and, as such, the endothelium presents a significant barrier to the diffusion of large solutes. The observed 'protein effect' indicates that albumin can interact with elements of the solute pathway to increase its restrictiveness.

Alcian Blue↗
PubMed1993

Immunoelectron characterisation of the inter-endothelial junctions of human term placenta.

The molecular constituents of the paracellular clefts in human placental microvessels were investigated using antibodies against PECAM-1, pan-cadherin, A-CAM (N-cadherin), cadherin-5 and two types of integrins (those recognised by antibodies to the beta 1 chain and alpha v beta 3). Ultrastructural localisation of these molecules in ultrathin frozen sections of human term placentae was attempted using colloidal gold immunocytochemistry, after establishing their presence by indirect immunofluorescence. At the light microscopical level, the endothelial paracellular clefts were found to be immunoreactive to the antibodies against PECAM-1, cadherin-5 and pan-cadherin, but not the integrins. The latter showed diffuse distribution in the endothelium and in the abluminal interstitial space. PECAM-1 and pan-cadherin were also seen in the cytoplasm and luminal surface of the endothelium. Immunoelectron studies revealed that the cadherins and PECAM-1 were present in the wide regions of the paracellular clefts, but not in tight junctional regions. Using immunocytochemistry, these wide junctional areas were found to be associated with the cytoskeletal linking molecules vinculin and alpha-actinin. These regions may therefore contain adherens-type junctions. Cadherin-5, localised by two different monoclonal antibodies, 7B4 and TEA, was the only antigen which was cleft-specific, the others also being seen in the cytoplasm of the microvascular endothelium. Cadherin-5 and pan-cadherin were co-localised in the same wide junction, but were usually seen to occupy different microdomains of, and different wide zones of, the same cleft. The cell adhesion molecules localised in the paracellular wide junctions of the human placental microvessels may play a role in maintaining the intercellular spacing between endothelial cells, and may be part of a paracellular "fibre matrix" with permeability-restricting properties.

Actinin↗
PubMed1992

Fine structure of the paracellular junctions of terminal villous capillaries in the perfused human placenta.

Selected lobules of human term placentae were extracorporeally perfused for a recovery period of 20 min, fixed by perfusion and mordanted with ferrocyanide prior to processing for transmission electron microscopy. The lateral membranes of the endothelial cells of the terminal villous capillaries were found to be separated by paracellular clefts of mean width 15.6 nm. At tight junctional regions (1-4 sites per cleft) the two membranes approached each other more closely and frequently appeared to fuse. However, tilting of the sections in the electron microscope stage showed that the membranes were separated by a gap of mean width 4.1 nm in at least 94% of tight junctional profiles. When individual tight junctions were studied by a combination of serial sectioning and goniometric tilting, they were seen to widen abruptly within a distance of three to seven consecutive thin sections, indicating they were not continuous throughout the axial length of the capillaries. The wide regions of the clefts usually showed linkers, strands of glycocalyx-like material spanning the gap. Linkers may contribute to cell adhesion and possibly form part of a filter within the tortuous paracellular pathway provided by the discontinuous network of tight junctional strands. Human term placental capillaries appear to resemble closely other continuous non-brain capillaries.

Capillaries↗
PubMed1991

Immunocytochemical and labelled tracer approaches to uptake and intracellular routing of immunoglobulin-G (IgG) in the human placenta.

Isolated lobules of freshly delivered human term placenta were (a) subjected to an indirect immunoelectron ultracryo method in which the immunoreactivity of endogenous Immunoglobulin-G (IgG) to rabbit anti-human IgG antibody was localized with protein-A-colloidal gold and (b) extracorporeally perfused and human IgG molecules complexed to horseradish peroxidase (HRP) added to the maternal perfusate and the uptake of IgG-HRP over different perfusion durations visualized ultrastructurally by using diaminobenzidine cytochemistry. Immunoreactivity to anti-human IgG antibody was localized all along the apical plasmalemma, in apical coated and uncoated vesicles, in apical and juxtanuclear multivesicular bodies, and in basal vesicles of the syncytiotrophoblast layer of the placenta. The stroma separating the syncytiotrophoblast from the foetal endothelium as well as vesicles within the endothelium were immunoreactive. No immunoreactivity was localized in paracellular clefts of endothelia. A similar distribution of exogenous IgG-HRP was observed for the perfused placentae. When bovine IgG-HRP or HRP alone were used as control tracers no uptake was seen for the former whilst the latter was observed only in early endosomal vesicles of the syncytiotrophoblast. The pattern of localization visualized in both studies is consistent with receptor-mediated uptake of IgG by the syncytiotrophoblast and a vesicular transport of IgG across the foetal endothelium.

Female↗
PubMed1990

Uptake and intracellular routing of peroxidase-conjugated immunoglobulin-G by the perfused human placenta.

Selected lobules of term human placenta were extracorporeally perfused and human immunoglobulin-G complexed to horseradish peroxidase (IgG-HRP) was added to the maternal perfusate. After different durations of perfusion IgG-HRP was visualised by use of diamino-benzidine cytochemistry. Within the first 10 min of perfusion IgG-HRP was found bound to microvilli and coated pits of the syncytiotrophoblast; internalisation into coated vesicles and tubulo-vesicular bodies was also observed. Subsequently, IgG-HRP was found in multivesicular bodies and by 30 min appeared in basal vesicles, the frequency of the latter event increasing with time. No routing of IgG-HRP into Golgi regions or lysosomes could be detected. by 60 min IgG-HRP was found in a few caveolae of fetal endothelium of both terminal and intermediate villi. IgG-HRP was not found in intercellular clefts of the endothelium. The pattern of uptake and routing observed suggests a receptor-mediated transcytosis of IgG-HRP across the syncytiotrophoblast and a transcellular pathway through the endothelium.

Animals↗
PubMed1990

Cytomegalovirus infection in women attending a sexually transmitted disease clinic.

To evaluate prospectively the relationship between current and past sexual practices and seroprevalence of cytomegalovirus (CMV) in adult women, 1481 women (1101 white, 301 black, 79 other) attending a sexually transmitted disease clinic underwent a standardized interview and genital examination. CMV seroprevalence was higher in black (78%) than in white (59%) women. In logistic regression models that adjusted for age and years of education, CMV seropositivity in white women was associated with younger sexual debut (P = .001), more lifetime sex partners (P = .025), recent new partner(s) (P = .003), and parity (P = .002), and was inversely associated with use of barrier contraception (P = .006). In black women, after adjustment for demographic characteristics, CMV antibody was associated with greater numbers of recent sex partners (P = .007), new sex partners (P = .04), and with cervical infection with Chlamydia trachomatis (P = .05). This study confirms that sexual activity is an important determinant of CMV infection in both white and black women; however, the relative contributions of sexual and nonsexual transmission of CMV apparently vary and require further investigation.

Adolescent↗
PubMed1989

Immunogold localisation of endogenous immunoglobulin-G in ultrathin frozen sections of the human placenta.

Endogenous immunoglobulin-G was localised in ultrathin frozen sections of human term placenta by use of an indirect immuno electron-histochemical methodology. Immunoreactivity of endogenous IgG to rabbit anti-human immunoglobulin-G antibody was visualised by use of protein-A--colloidal gold complex. Gold marked the syncytiotrophoblast in both coated and uncoated regions of the apical plasmalemma, in vesicles and multivesicular bodies, and in vesicles near the basal plasmalemma. Immunoreactivity was also seen in the interstitial space between the trophoblast and the fetal endothelial layer as well as in various types of vesicles within the endothelial cells. No immunoreactivity was seen in the intercellular clefts of the endothelium. The pattern of localisation observed is consistent with receptor-mediated uptake of immunoglobulin-G into the syncytiotrophoblast of the human placenta followed by release into the interstitial space and then vesicular transport through the endothelium.

Female↗
PubMed1988

Cognitive deficits in olivopontocerebellar atrophy: implications for the cholinergic hypothesis of Alzheimer's dementia.

A cerebral cortical cholinergic reduction in dominantly inherited olivopontocerebellar atrophy (OPCA) was recently described. Although the magnitude of the cholinergic reduction was similar to that observed in Alzheimer's disease (AD), none of the OPCA patients was reported to have been demented. We now describe a comprehensive neuropsychological assessment of 11 patients from one of the OPCA pedigrees which we examined biochemically. Detailed neuropsychological testing disclosed previously unrecognized deficits in verbal and nonverbal intelligence, memory, and frontal system function which were positively correlated with the severity of cerebellar ataxia. However, our OPCA patients appeared to be at most only mildly disabled by their cognitive impairment and scored within or close to the normal range on a simple mental status screening examination. This, as well as an absence of any aphasia, apraxia, or agnosia, contrasts with the profile and severity observed in advanced AD dementia, characterized by a similar cortical cholinergic deficit. This finding also suggests that cholinergic reduction may explain only part of the pathophysiology underlying the dementia of AD.

Adult↗