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Biomedical subjects

M A Lynch

Publications and source records attributed to M A Lynch.

At least 73 records · Page 4Linked to original sources
PubMed1996

Ageing is associated with changes in glutamate release, protein tyrosine kinase and Ca2+/calmodulin-dependent protein kinase II in rat hippocampus.

We have used synaptosomes prepared from rat hippocampus to investigate the role of protein tyrosine kinase and Ca2+/calmodulin-dependent protein kinase II in modulating glutamate release in young animals and to investigate possible parallel age-related changes in release and kinase activity. We report that depolarization of synaptosomes with 40 mM KCl, which stimulated glutamate release, also significantly increased activity of both kinases, while the protein tyrosine kinase inhibitor, genistein and the Ca2+/calmodulin-dependent protein kinase II inhibitor, KN62 (1-(N,O-bis[5-isoquinolinesulfonyl]-N-methyl-tyrosyl)-4-phenylpiperax ine) decreased K(+)-stimulated, Ca2(+)-dependent release of glutamate. K(+)-stimulated release of glutamate was significantly decreased in hippocampal synaptosomes prepared from aged, compared to young, animals. In parallel with these changes in release, we report an age-related decrease in activities of both protein tyrosine kinase and Ca2+/calmodulin-dependent protein kinase II. We conclude that these kinases play a role in modulating release of glutamate in hippocampus and that the age-related decrease in glutamate release may be partly due to an age-related decrease in kinase activities.

Aging↗
PubMed1996

Interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro.

The effects of the cytokine, interleukin-1 beta (IL-1 beta), and its receptor antagonist IL-1ra, were studied on long-term potentiation in the dentate gyrus of rat hippocampal slices. Field excitatory postsynaptic potentials were recorded extracellularly in the molecular region of the dentate gyrus in response to stimulation of the medial perforant path. Low frequency synaptic transmission was unaffected by IL-1 beta (1 ng/ml), but pre-treatment with IL-1 beta completely blocked induction of long-term potentiation. Co-application of IL-1 beta and IL-1ra (100 ng/ml) attenuated the inhibitory effect of IL-1 beta. In parallel with these findings, we demonstrate that IL-1 beta also inhibited 45Ca influx into the slices. The inhibitory effect of IL-1 beta on induction was mimicked by tumour necrosis factor (TNF; 4.5 ng/ml) and lipopolysaccharide (LPS; 10 micrograms/ml). These results indicate a modulatory role for cytokines in hippocampus and suggest that the inhibitory effect of IL-1 beta on long-term potentiation may relate to its inhibitory effect on calcium channel activity.

Animals↗
PubMed1996

The synergism between metabotropic glutamate receptor activation and arachidonic acid on glutamate release is occluded by induction of long-term potentiation in the dentate gyrus.

In synaptosomes prepared from dentate gyrus, activation of the metabotropic glutamate receptor by the specific agonist, trans-1-amino-cyclopentyl-1,3-dicarboxylate, increases release of glutamate in the presence of a low concentration of arachidonic acid. A similar interaction between trans-1-amino-cyclopentyl-1,3-dicarboxylate and arachidonic acid is observed on inositol phospholipid turnover and on protein kinase C activity. We report here that when long-term potentiation is induced in the dentate gyrus by high frequency tetanic stimulation to the perforant path, the synergism between arachidonic acid and trans-1-amino-cyclopentyl-1,3-dicarboxylate is occluded. The occlusion of the synergistic action between arachidonic acid and trans-1-amino-cyclopentyl-1,3-dicarboxylate on glutamate release extended to occlusion of the effect in inositol phospholipid turnover and protein kinase C activation in synaptosomes prepared from dentate gyrus in which long-term potentiation was induced in vivo. One interpretation of the results presented here is that tetanic stimulation is followed by stimulation of metabotropic glutamate receptors at a time when arachidonic acid concentration in the synaptic region is elevated, and that this interaction triggers the presynaptic changes required for expression of long-term potentiation.

Animals↗
PubMed1995

Failure to thrive and the risk of child abuse: a prospective population survey.

OBJECTIVE: To identify the relative importance of failure to thrive during infancy as a risk factor for later abuse or neglect. DESIGN: Whole population birth cohort (1 January to 31 December 1986) studied prospectively over a four year period. SETTING: An inner city health district in London, England. SUBJECTS: 2609 births, of whom 47 were identified as having non-organic failure to thrive by first birthday. MAIN OUTCOME MEASURES: Registration on Child Protection Register, or subject to investigation of suspected abuse or neglect without registration. RESULTS: 2.5% (64) of birth cohort had been placed on the Child Protection Register during the period 1986-1990, and a further 1.2% (32) had been a cause for concern. The relative risk attributable to non-organic failure to thrive was 4.3 (95% CI 1.65 to 11.94) and exceeded other measured risk factors, including birth weight < 2500 g, 1.96 (95% CI 1.01 to 3.82); gestation < 35 weeks, 3.26 (95% CI 1.32 to 3.75); ordinal position > or = 4, 1.53 (95% CI 0.72 to 3.23). A multiple logistic regression confirmed the independent contribution of non-organic failure to thrive to subsequent poor parenting warranting professional intervention. CONCLUSIONS: Early postnatal non-organic failure to thrive is a risk factor for later serious parenting deficiencies, but previous research has overstated its importance. Within the community studied the nature of subsequent risk was (non-nutritional) neglect, rather than non-accidental injury. More than eight out of 10 cases do not give further cause for concern.

Age Factors↗
PubMed1994

A study of the synergism between metabotropic glutamate receptor activation and arachidonic acid in the rat hippocampus.

We report that activation of the metabotropic glutamate receptor by the specific agonist, trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), increases release of glutamate only in the presence of a low concentration of arachidonic acid (AA). To identify the molecular mechanism underlying this effect, cAMP accumulation, inositol phospholipid metabolism and protein kinase C (PKC) activation were examined in synaptosomes prepared from hippocampus. ACPD increased cAMP accumulation, but this increase was not further enhanced in the presence of AA. ACPD and AA stimulated both inositol phospholipid turnover and PKC activity; a synergistic action was indicated by the additional stimulation in the presence of both agents. The increase in PKC activity, either directly, or indirectly by increased inositol phospholipid turnover, might therefore underlie the enhanced glutamate release.

Animals↗
PubMed1994

Impaired spatial memory in aged rats is associated with alterations in inositol phospholipid metabolism.

WE have investigated changes in inositol phospholipid turnover and membrane arachidonic acid concentration in the dentate gyrus and frontal cortex of animals aged 3-6 months, 14 months or 22 months which were trained in the Morris water maze. Ageing was associated with poorer performances in the behavioural test, characterized by increased variability in retention and acquisition amongst individuals, a decrease in membrane arachidonic acid concentration and increased unstimulated inositol phospholipid metabolism in synaptosomes prepared from frontal cortex and dentate gyrus. Arachidonic acid stimulated inositol phospholipid metabolism in synaptosomes, but in the older groups, stimulation was associated with good performance in the Morris water maze. In slices prepared from frontal cortex, responsiveness of inositol phospholipid metabolism to glutamate was also age- and performance-dependent. The findings highlight a correlation between age, inositol phospholipid metabolism and performance in the Morris water maze.

Aging↗
PubMed1994

Membrane arachidonic acid concentration correlates with age and induction of long-term potentiation in the dentate gyrus in the rat.

We examined the induction and maintenance of long-term potentiation (LTP) in vivo in the dentate gyrus of 4-month-old and 22-month-old urethane-anaesthetized rats. High-frequency stimulation of the perforant path induced an immediate increase in the slope of the population excitatory postsynaptic potential (EPSP), which was sustained in the 4-month-old animals for the duration of the experiment (45 min post-tetanus). In the 22-month-old group, the mean slope of the population EPSP decreased almost to baseline by the end of the experiment. Examination of the individual records indicated that LTP was sustained for the duration of the experiment in half of the 22-month-old animals, while in the others only post-tetanic potentiation was observed. Membrane arachidonic acid concentration was reduced in aged compared with young animals and was lowest in the subgroup of aged animals which failed to sustain LTP. Potassium-stimulated, calcium-dependent release of glutamate was also decreased in aged compared with young animals, but LTP was associated with an increase in glutamate release in the 4-month-old group and 22-month-old subgroup in which LTP was successfully sustained; no change was observed in the 22-month-old group in which LTP was not sustained. The results indicate a correlation between membrane arachidonic acid concentration, glutamate release and ability to sustain LTP in aged animals.

Aging↗
PubMed1994

Increase in synaptic vesicle proteins accompanies long-term potentiation in the dentate gyrus.

Maintenance of long-term potentiation in synapses formed by the perforant path on to granule cells of the dentate gyrus is accompanied by a sustained increase in the extracellular concentration of glutamate, the presumed transmitter at this excitatory hippocampal pathway. Quantal analysis indicates that, at least in the first hour of induction, this reflects an increase in transmitter release rather than a decrease in glutamate uptake, while biochemical studies have suggested that the increase in release persists for several hours. Morphological studies have described early but persistent increases in the spine number and area. Increases in the number of segmented/perforated synapses persisting for at least 1 h after induction of long-term potentiation, have also been reported. These morphological changes suggest both presynaptic and postsynaptic modifications. Increases in synaptic vesicle number and distribution lasting for at least 1 h specifically indicate presynaptic changes. To explore further the role of the presynaptic terminal in long-term potentiation, we have investigated changes in three synaptic vesicle proteins, synapsin, synaptotagmin and synaptophysin, in control tissue and in tissue prepared from potentiated dentate gyrus 45 min and 3 h after induction of long-term potentiation. We found that there was an increase in the concentration of the three proteins 3 h after induction of long-term potentiation. No such increase was observed 45 min after induction or in tissue prepared from animals in which an intraventricular injection of the N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, blocked induction of long-term potentiation.

2-Amino-5-phosphonovalerate↗
PubMed1993

The DistalCAM video camera.

A new endoscopic camera that does not require a viewing rod lens endoscope has been developed. It consists of a 10-mm metal tube and handle containing a distally placed camera chip. The distal chip endoscope is attached to a combined camera light source and processor by a well-protected cable. Due to the distally placed chip and the fact that no glass rod lenses are used, a full-screen image of improved quality and constant lighting is achieved. Elimination of rod lenses and all but one interface in the system minimizes image distortion, color degradation and interface-related loss of illumination. A bright light is provided across the entire screen uniformly, without variation in intensity or color regardless of temporal proximity to target tissues. The system does not require white balancing or focusing since the color and focus range are set, and it uses a cool 40-W light to achieve the same intensity of existing 300-W lamps. The camera system was used successfully in 30 operative laparoscopy procedures.

Electronics, Medical↗
PubMed1993

When the patient is also a lesbian.

Social stigma impedes the delivery of quality health care to women who identify as lesbians. Nurses who are aware of and sensitive to women who are lesbians in their practice are able to increase the caliber of the health care they provide. This article provides examples in which a lesbian sociosexual orientation has an impact on the medical history, differential diagnosis, physical examination, and treatment.

Confidentiality↗
PubMed1992

Domain-specific and cell type-specific localization of two types of cell wall matrix polysaccharides in the clover root tip.

Using immunocytochemical techniques and antibodies that specifically recognize xyloglucan (anti-XG), polygalacturonic acid/rhamnogalacturonan I (anti-PGA/RG-I), and methylesterified pectins (JIM 7), we have shown that these polysaccharides are differentially synthesized and localized during cell development and differentiation in the clover root tip. In cortical cells XG epitopes are present at a threefold greater density in the newly formed cross walls than in the older longitudinal walls, and PGA/RG-I epitopes are detected solely in the expanded middle lamella of cortical cell corners, even after pretreatment of sections with pectinmethylesterase to uncover masked epitopes. These results suggest that in cortical cells XG and PGA/RG-I are differentially localized not only to particular wall domains, but also to particular cell walls. In contrast to their nonoverlapping distribution in cortical cells, XG epitopes and PGA/RG-I epitopes largely colocalize in the epidermal cell walls. The results also demonstrate that the middle lamella of the longitudinal walls shared by epidermal cells and by epidermal and cortical cells constitutes a barrier to the diffusion of cell wall and mucilage molecules. Synthesis of XG and PGA/RG-I epitope-containing polysaccharides also varies during cellular differentiation in the root cap. The differentiation of gravitropic columella cells into mucilage-secreting peripheral cells is marked by a dramatic increase in the synthesis and secretion of molecules containing XG and PGA/RG-I epitopes. In contrast, JIM 7 epitopes are present at abundant levels in columella cell walls, but are not detectable in peripheral cell walls or in secreted mucilage. There were also changes in the cisternal labeling of the Golgi stacks during cellular differentiation in the root tip. Whereas PGA/RG-I epitopes are detected primarily in cis- and medial Golgi cisternae in cortical cells (Moore, P. J., K. M. M. Swords, M. A. Lynch, and L. A. Staehelin. 1991. J. Cell Biol. 112:589-602), they are localized predominantly in the trans-Golgi cisternae and the trans-Golgi network in epidermal and peripheral root cap cells. These observations suggest that during cellular differentiation the plant Golgi apparatus can be both structurally and functionally reorganized.

Antibodies, Monoclonal↗
PubMed1991

Increase in arachidonic acid concentration in a postsynaptic membrane fraction following the induction of long-term potentiation in the dentate gyrus.

We have determined the concentration of free fatty acids in membranes of slices prepared from the dentate gyrus following the induction of long-term potentiation in the anaesthetized rat. Compared to unpotentiated tissue, there was a significant increase in the concentration of free arachidonic acid 2.5 min, 45 min and 3 h after induction of long-term potentiation. There was no corresponding increase in oleic, stearic or palmitic acids. To account for the increase in free arachidonate, the activities of phospholipase A2, phospholipase A1 and phospholipase C were determined at the same three time intervals in control and potentiated tissue. Two-and-a-half minutes after the induction of long-term potentiation, activity of phospholipase A2 was enhanced, while at 45 min, and at 3 h phospholipase C activity was increased. These results suggest that the liberation of free arachidonate is due initially to phospholipase A2 activity, but that at later stages of long-term potentiation, control switches to phospholipase C. Subcellular fractionation experiments revealed an increase in free arachidonate in the postsynaptic density fraction 45 min after induction of long-term potentiation, without significant changes in synaptosomal- or glial-enriched fractions. These results are consistent with the hypothesis that arachidonic acid, released from a postsynaptic site, acts as a trophic retrograde synaptic signal in long-term potentiation in the dentate gyrus.

Animals↗
PubMed1991

Spatial organization of the assembly pathways of glycoproteins and complex polysaccharides in the Golgi apparatus of plants.

The Golgi apparatus of plant cells is the site of assembly of glycoproteins, proteoglycans, and complex polysaccharides, but little is known about how the different assembly pathways are organized within the Golgi stacks. To study these questions we have employed immunocytochemical techniques and antibodies raised against the hydroxyproline-rich cell wall glycoprotein, extensin, and two types of complex polysaccharides, an acidic pectic polysaccharide known as rhamnogalacturonan I (RG-I), and the neutral hemicellulose, xyloglucan (XG). Our micrographs demonstrate that individual Golgi stacks can process simultaneously glycoproteins and complex polysaccharides. O-linked arabinosylation of the hydroxyproline residues of extensin occurs in cis-cisternae, and glycosylated molecules pass through all cisternae before they are packaged into secretory vesicles in the monensin-sensitive, trans-Golgi network. In contrast, in root tip cortical parenchyma cells, the anti-RG-I and the anti-XG antibodies are shown to bind to complementary subsets of Golgi cisternae, and several lines of indirect evidence suggest that these complex polysaccharides may also exit from different cisternae. Thus, RG-I type polysaccharides appear to be synthesized in cis- and medial cisternae, and have the potential to leave from a monensin-insensitive, medial cisternal compartment. The labeling pattern for XG suggests that it is assembled in trans-Golgi cisternae and departs from the monensin-sensitive trans-Golgi network. This physical separation of the synthesis/secretion pathways of major categories of complex polysaccharides may prevent the synthesis of mixed polysaccharides, and provides a means for producing secretory vesicles that can be targeted to different cell wall domains.

Carbohydrate Sequence↗
PubMed1991

Presynaptic changes in long-term potentiation: elevated synaptosomal calcium concentration and basal phosphoinositide turnover in dentate gyrus.

In this report, two changes that occur in the presynaptic terminal following induction of long-term potentiation in the dentate gyrus are examined, and the results demonstrate that the same changes are stimulated by the putative retrograde messenger arachidonic acid. First, there is an increase in the concentration of intracellular calcium in synaptosomes prepared from potentiated tissue compared with control tissue. This effect on intracellular calcium concentration was mimicked in control tissue by treatment of synaptosomes with either arachidonic acid or inositol 1,4,5-trisphosphate in a dose-dependent but nonadditive manner. Second, there is an increase in phosphoinositide turnover in synaptosomes prepared from potentiated tissue compared with control tissue, and this change can also be mimicked in control tissue by exposure of synaptosomes to arachidonic acid. These findings are consistent with the hypothesis that the increase in glutamate release associated with long-term potentiation may be stimulated by arachidonic acid, as a result of an increase in intrasynaptosomal calcium concentration, perhaps occurring as a result of arachidonate-stimulated phosphoinositide metabolism.

Animals↗