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L Leach

Publications and source records attributed to L Leach.

53 records · Page 3Linked to original sources
PubMed1988

Immunoblot analysis of the humoral immune response in primary cytomegalovirus infection.

Cytomegalovirus is a common infection in immunologically normal adults. It may cause an asymptomatic infection or may manifest symptomatically as heterophilic-negative mononucleosis. Studies of CMV infection in immunocompromised patients indicate that humoral immune response plays a role in modulating disease severity; however, the effect of antibodies to CMV in modifying disease expression and transmission in immunologically normal individuals has not been well characterized. Using immunoblot technology, we have demonstrated that immune serum from normal adults contains antibodies to at least 15 CMV-associated proteins and that there is strain-to-strain variation in the expression of these immunogens. The kinetics of the immune response were evaluated by using serial sera collected from normal adults after primary CMV infection; analysis of immunoblots of these sera identified one group of antibodies to CMV proteins that arise early and are stable over time, a second group that appear late after infection, and a third group that are variable among patients and over time.

Adult↗
PubMed1987

Immunocytochemical localization of neurosecretory amines and peptides in the free-living nematode, Goodeyus ulmi.

Mammalian antibodies to the neuroamines, serotonin and gamma-amino-butyric acid (GABA) and to the neuropeptides, adrenocorticotrophic hormone (ACTH) and FMRF-amide evoked a response to Goodeyus ulmi, a free-living nematode. Serotonin-like immunoreactivity was found in cell bodies in the nerve ring and in the ventral nerve cord in all developmental stages. Neurons in the vulva, implicated in egg-laying, were immunoreactive to anti-serotonin in G. ulmi females, while in males serotonergic nerve fibres was found in the spicular region. Immunoreactivity to ACTH was also seen to differ depending on the developmental stage of G. ulmi, being present only in the ventral cord from the late L3 stage. Anti-GABA immunoreactivity was localized in two cell bodies near the amphids in all life stages and FMRF-amide immunoreactivity was seen in the nerve ring in all developmental stages. No reactivity was found with antibodies to vasointestinal peptide and somatostatin-14.

Adrenocorticotropic Hormone↗
PubMed1980

Effects of kainic acid lesions in the lateral hypothalamus on behavior and hippocampal and neocortical electroencephalographic (EEG) activity in the rat.

Electrolytic lesions of the lateral hypothalamus (LH) are known to produce severe and chronic behavioral and electrographic abnormalities. In order to assess the effects of damage to LH cells vs damage to fibers of passage in the LH, a comparison was made of the effects of electrolytic lesions and microinjections of the neurotoxin kainic acid (kainate) in the LH. Behavior and neocortical and hippocampal electroencephalographic (EEG) activity were studied before, immediately after, and for 25 days after the lesions were made. Electrolytic-lesioned rats were aphagic and adipsic, showed an absence of normal atropine-resistant EEG activity, and a release of atropine-sensitive EEG activity in the hippocampus and neocortex. Kainic acid-lesioned rats showed some similar behavioral impairments but the kainate lesions produced different EEG abnormalities, including chronic slow-wave and seizure activity in both the neocortex and hippocampus. Following extended recovery hippocampal EEG was normal despite extensive cellular loss in areas CA3 and CA4. Understanding of the differences in EEG between the electrolytic and kainate effects was compounded by widespread cellular damage in areas outside the hypothalamus in the rats with kainate lesions. Thus, the kainate-produced abnormalities precluded a simple analysis of the contribution that cell damage alone makes to LH lesion-induced behavioral and EEG changes.

Animals↗
PubMedDate not supplied

Structure and permeability of human placental microvasculature.

Endothelial paracellular junctions are important structures for the regulation of vascular permeability, junctional organisation being systematically related to the functional properties of the endothelium. Electron microscopic studies, immunocytochemistry, and single-passage permeability measurements have established that the placental microvessels resemble the fairly tight continuous microvessels of skeletal muscle both in structure and permeability. The endothelial paracellular clefts of these microvessels contain two distinct junctional entities which may influence permeability: the tight junction and the adherens junction. These clefts impose a substantial restriction to molecules above RMM 1000 Da and large haemproteins cannot cross the clefts. The 18 nm-wide zones of the clefts possess the transmembrane adhesion molecules PECAM-1 and VE-cadherin, which have been implicated in junctional assembly and permeability. Inflammatory mediators such as histamine and tumour necrosis factor cause a redistribution of these adhesion molecules to non-junctional regions, and histamine (100 microM) causes a rapid and sustained rise in extraction of radio-labeled tracers. Electron microscopy has also revealed possible first indications of tight junctional disassembly. Both the endothelia of larger placental vessels and isolated placental microvascular endothelial cells express cadherins and PECAM-1 and contain an extensive F-actin cytoskeleton, which is implicated in changes of cell shape and junctional assembly/disassembly. Thus, the human placental endothelium, using perfusion techniques and in vitro experiments, offers a valuable model for vascular permeability studies.

Female↗
PubMedDate not supplied

Not trophoblast alone: a review of the contribution of the fetal microvasculature to transplacental exchange.

The fetal microcirculation of the term human placenta offers an interesting microvascular model. A perfused placenta can be used for integrated studies of vascular permeability-structure relationships. The organization of the paracellular pathway in human placental microvessels closely resembles not only that of the guinea-pig placenta, but also that seen in typical continuous non-cerebral capillaries such as those of the myocardium. This uniformity of organization has allowed the development of a model of the organization of endothelial junctional complexes that allows testable predictions about the relationship between junctional organization and microvascular permeability. The key features of this model are: (1) molecular size restriction may be determined by a fibre matrix based on cadherin arrays in the zonula adhaerens. (2) The zonula occludens (tight junction) is discontinuous and so cannot act as a molecular sieve for solutes. It may serve as a shutter that limits the proportion of the paracellular cleft available for permeation. The main implication for placental function is that the human placental microcirculation is relatively tight and is an important restriction to diffusive permeation of the maternal-fetal barrier by large molecules.

Animals↗
PubMedDate not supplied

The use of clock tests in schizophrenia.

Though clock drawing tests are well recognized as measures of cognitive function, there is little data on the performance of patients with schizophrenia. We compared 24 patients with schizophrenia to 24 healthy, age-matched controls on clock drawing, copying, and reading. Patients with schizophrenia performed significantly worse on clock drawing and copying despite the fact that the groups had similar scores on the MMSE. Worse performance was associated with higher scores on the BPRS. Clock drawing and copying may be useful for the assessment of cognition in schizophrenia, and the monitoring of cognitive changes associated with antipsychotic medication.

Adult↗
PubMedDate not supplied

Proliferation, differentiation and apoptosis in villous trophoblast at 13-41 weeks of gestation (including observations on annulate lamellae and nuclear pore complexes).

Ultrastructural, immunochemical, fluorescence and stereological studies were undertaken on human villous trophoblast from 13 weeks of gestation to term. The aim was to describe and quantify morphological changes during proliferation, differentiation and apoptosis in cytotrophoblast and syncytial regions of non-aggregated and aggregated nuclei. Numbers of trophoblast nuclei increased continuously from 13 weeks. In term placentae, intrasyncytial differentiation was characterized ultrastructurally by gradual decreases in nuclear size and packing density accompanied by nucleolar regression, and increasing heterochromatinization, envelope convolution and packing density of nuclear pore complexes. In densely packed areas, nuclear profiles resembled interlocking jigsaw pieces. Occasionally, these 'pre-apoptotic' nuclei were associated with annulate lamellae. Rarely, nuclear changes terminated in apoptosis with a characteristic pattern of condensed peripheral chromatin, a central island of euchromatin, no nucleoli and no discernible nuclear pores. Apoptotic nuclei were seen singly and within dense nuclear aggregations. Similar spatial patterns of nuclei and chromatin were seen in propidium iodide-stained sections at 13-41 weeks. Whilst the relative incidence of intensely fluorescent nuclei remained constant, absolute numbers increased linearly during gestation and correlated positively with the volume of syncytial knots. Nuclei labelled for DNA fragmentation occurred very infrequently and were also found in nuclear clusters as well as singly. We suggest that nuclear differentiation in syncytium has two phases: on entering syncytium, nuclei become committed to a long programmed pre-apoptotic phase which leads to a short apoptotic execution phase. We propose further that clustered nuclei (pre-apoptotic and apoptotic) in syncytial knots probably represent the extrusion component of normal continuous epithelial turnover.

Apoptosis↗
PubMedDate not supplied

Molecular organization of tight and adherens junctions in the human placental vascular tree.

Tight and adherens junctions are major determinants of endothelial integrity. Molecules present therein have been implicated in vascular permeability, stability of junctions, angiogenesis and intracellular signalling. Using immunofluorescence and confocal scanning microscopy, the adherens junctions (AJs) in human placental vessels were found to contain the entire cadherin-catenin complex predicted from in vitro studies. Vascular endothelial cadherin (VE-cadherin) clusters were co-localized with beta-catenin, an important signal transduction ligand, and with alpha-catenin, which is thought to link the complex to the peri-junctional actin. Antibodies to plakoglobin, a molecule shown to be a component of stable adherens junctions, revealed immunoreactivity in clefts of stromal villous vessels, but weak or negative immunoreactivity in intermediate and terminal villi. Tight junctional molecules demonstrated a differential surface expression. Within the same villous tree, arteries, veins and arterioles contained occludin but the exchange vessels in terminal villi were immunonegative. ZO-1, however, was present throughout. Ultrastructurally, there were no differences in frequency, position or dimension of tight junctions in these vessels. They showed a consistent 4 nm separation between outer membrane leaflets regardless of their location in the vascular tree. Occludin is not necessary for formation of tight junctions in the placenta; it may have an accessory role providing stability or added adhesiveness to tight junctions of large vessels. Its absence in terminal villous microvessels, along with the weak plakoglobin immunoreactivity in AJs, suggest that the junctions here are less stable. This may allow the increased plasticity necessary in terminal villi for continual growth, proliferation and solute exchange.

Adult↗
PubMedDate not supplied

Distinct patterns of microvascular endothelial cell morphology are determined by extracellular matrix composition.

Endothelial interactions with the extracellular matrix (ECM) play important roles in angiogenesis but whether specific ECM signals can determine specific cellular morphologies is unclear. The authors compared in vitro ECM-induced morphological responses of the phenotypically distinct human placental microvascular endothelial cells (HPMECs) with large vessel endothelial cells (HUVECs). HPMECs showed distinct patterns of reorganization in response to collagen-I or collagen-IV (monolayer disruption, sprouting, migration) and Matrigel or laminin-A (intussusception, cord formation, tubulogenesis), and an intermediate response to fibrin; whereas HUVECs responded similarly to collagen-1 and Matrigel (elongation, lattice formation, vacuolation) and showed little response to fibrin. Although the extent of collagen and Matrigel responses of HPMECs were increased by serum, acidic or basic fibroblast growth factor (aFGF, bFGF), or vascular endothelial growth factor (VEGF), and varied with matrix protein concentration, the basic patterns were matrix specific, and were independent of fibronectin. The collagen responses correlated with disruption of adherens and tight junctions and the formation of filopodial protrusions. Matrigel responses were associated with up-regulated junctional localization of VE-cadherin, and tubulogenesis developed mainly through paracellular remodeling rather than intracellular vacuolation. Overall, these findings suggest that distinct ECM interactions stimulate specific morphological responses. These signals may regulate morphological behaviour in the angiogenesis cycle, switching endothelial cells between migratory and vasculogenic phenotypes.

Antigens, CD↗
PubMedDate not supplied

Meeting the challenge of cesarean births.

This article presents a perspective aimed at helping nurses achieve family-centered cesarean births that meet the needs of health-care consumers. It begins by discussing the concept of loss as it relates to cesarean births along with the need for parents to receive support in order to achieve acceptance of the experience. Parents' needs to have control over their birthing experience are then reviewed and the choices concerning type of anesthetic and the father's presence during the cesarean delivery are discussed in some detail. The impact of the birthing experience on readiness for discharge and long-term effects are briefly discussed and finally, a list of possible choices and suggestions aimed specifically at helping nurses are also presented.

Anesthesia↗
PubMedDate not supplied

16alpha-bromoepiandrosterone, a dehydroepiandrosterone (DHEA) analogue, inhibits Plasmodium falciparum and Plasmodium berghei growth.

Dehydroepiandrosterone (DHEA) and its analogue, 16alpha-bromoepiandrosterone (alpha-epi-Br), may have activity against viral and parasitic infections, including human immunodeficiency virus (HIV) and Cryptosporidium parvum. Therefore, we evaluated its antimalarial effects on Plasmodium falciparum and Plasmodium berghei. In vitro, chloroquine (CQ)-sensitive and resistant strains of P. falciparum parasitized red blood cells were incubated with escalating doses of alpha-epi-Br or CQ. In vivo, 62 rats were infected with P. berghei and treated with CQ or alpha-epi-Br. At the highest doses tested against a CQ-sensitive strain, parasitemias decreased from 25.4% in the saline control group to 4.3% and 4.8% in the alpha-epi-Br and CQ groups, respectively (P < 0.05). Against two CQ-resistant strains, parasitemias decreased from 22.3-28.8% and 24.8-30% in the CQ and saline groups, respectively, to 2.5-2.7% in the alpha-epi-Br groups (P = 0.003). In vivo, on Day 4, parasitemias decreased from 23% in the saline group to 9-12% and 12% in the in alpha-epi-Br and CQ groups, respectively (P < 0.05). These data demonstrate that alpha-epi-Br shows activity against CQ-sensitive and resistant strains of P. falciparum in vitro. At the doses tested against P. berghei in vivo in rats, alpha-epi-Br is comparable to CQ.

Androsterone↗