Search PubMed⌕ Search

Biomedical subjects

G Lynch

Publications and source records attributed to G Lynch.

At least 379 records · Page 21Linked to original sources
PubMed1985

A new static sampler for airborne total dust in workplaces.

This paper describes the development and laboratory testing of a new static dust sampler for airborne total dust in workplaces. Particular attention is paid to designing the sampling head and entry consistent with the concept of inspirability which in turn defines a biologically-relevant aspiration efficiency. The sampling head has a small cylindrical body and a transverse entry slot with thin protruding lips forming an integral part of a weighable capsule containing a 37 mm filter which collects all of the sampled dust (without introducing errors due to external particle blow-off or internal wall losses). A battery-powered sampling pump provides both air suction at 3 L/min and rigid mounting for the sampling head. The sampling head is rotated continuously through 360 degrees at approximately 1.5 rpm by a simple electric drive, connected to the stationary pump through a rotating seal. Wind tunnel testing of the instrument showed it to display an entry efficiency very close to the inspirability curve of Vincent and Armbruster (now recommended by the ACGIH Technical Committee on Air Sampling Procedures for defining inspirable particulate matter (IPM] for particles of aerodynamic diameter up to 90 micron and for windspeeds in the range of one to three m/sec.

Aerosols↗
PubMed1985

Identification of intracellular factor XIII in human monocytes and macrophages.

Factor XIII is a blood protransglutaminase that is distributed in plasma and platelets. The extracellular and intracellular zymogenic forms differ in that the plasma zymogen contains A and B subunits, while the platelet zymogen has A subunits only. Both zymogens form the same enzyme. Erythrocytes, in contrast, contain a tissue transglutaminase that is distinct from Factor XIII. In this study other bone marrow-derived cells were examined for transglutaminase activity. Criteria that were used to differentiate Factor XIII proteins from erythrocyte transglutaminase included: (a) immunochemical and immunohistochemical identification with monospecific polyclonal and monoclonal antibodies to Factor XIII proteins, (b) requirement for thrombin cleavage to express activity, (c) pattern of fibrin cross-linking catalyzed by the enzyme, and (d) different electrophoretic mobilities in nondenaturing gel systems. By these criteria human peripheral blood monocytes, peritoneal macrophages, and monocytes maintained in culture contain an intracellular protransglutaminase that is the same as platelet Factor XIII. The monocyte-macrophage protein is thrombin-sensitive, and under appropriate conditions there is no enzyme expression without activation of the zymogen. Both the monocyte-macrophage zymogen and enzyme have the same electrophoretic mobilities as platelet Factor XIII zymogen and enzyme. Antibody to A protein reacts with the monocyte-macrophage protein. B protein is not associated with this intracellular zymogen. By immunoperoxidase staining monocyte-macrophage protein seems to be localized in the cytoplasm, similar to the known cytoplasmic distribution of platelet and megakaryocyte Factor XIII. These procedures were also used to study populations of human granulocytes and lymphocytes, and protransglutaminase activity was not observed in these cells.

Acyltransferases↗
PubMed1985

Phase I evaluation and pharmacokinetic study of weekly iv thymidine and 5-FU in patients with advanced colorectal carcinoma.

A phase I study of weekly iv thymidine (TdR) and 5-FU was carried out in patients with advanced colorectal carcinoma using two dosage schedules. Schedule 1 employed a 3-hour infusion of TdR (6-8 g/m2/hour) followed immediately by a bolus of 5-FU (100-200 mg/m2). Schedule 2 used a slightly larger dose of TdR (18 g/m2/hour for 1.5 hours), with 5-FU given 30 minutes after the TdR infusion was started. Myelosuppression was observed erratically at the higher doses of 5-FU. Diarrhea and severe fatigue were seen frequently with Schedule 1. CNS side effects were the dose-limiting effects for both schedules. For long-term use the maximally tolerated 5-FU doses were 100 mg/m2/week for Schedule 1 and 175 mg/m2/week for Schedule 2. In pharmacokinetic studies in five patients, both schedules produced prolonged plasma beta-half-lives of 5-FU (96-189 minutes). Extensive formation of floxuridine was seen with both schedules. It appears likely that CNS toxic effects are characteristic of TdR-containing 5-FU regimens and would limit the therapeutic potential of this approach.

Adult↗
PubMed1984

Inhibitors of lysosomal enzymes: accumulation of lipofuscin-like dense bodies in the brain.

Injections of leupeptin (a thiol proteinase inhibitor) or chloroquine (a general lysosomal enzyme inhibitor) into the brains of young rats induced the formation of lysosome-associated granular aggregates (dense bodies) which closely resembled the ceroid-lipofuscin that accumulates in certain disease states and during aging. The dense material increased in a dose- and time-dependent fashion and was differentially distributed across brain regions and cell types. These observations provide clues to the origins of ceroid-lipofuscin and suggest means for studying the consequences of its accumulation.

Animals↗
PubMed1984

Neurophysiological changes in the in vitro rat hippocampus following chronic lithium administration.

The effect of chronic lithium exposure on the electrophysiological responses of the Schaffer collateral-commissural (SCC) input to the CA1 pyramidal neurons in the in vitro hippocampus was investigated. Experimental animals were intubated intragastrically with lithium carbonate (150 mg/kg) for 3-4 weeks. This treatment produced lithium levels in serum and hippocampus of 0.3-1.3 mM. During the recording period, the hippocampal slice retained a stable lithium concentration of 53% of the initial value. Chronic lithium exposure had a depressive effect on input/output relationships, paired-pulse facilitation and strength of orthodromic inhibition. The antidromic inhibition was virtually intact. No obvious differences were found between control and lithium slices in amplitude, latency or waveforms, of synaptic and antidromic extracellular potentials. These findings are compatible with a major action of lithium on the excitability of SCC axons and synaptic terminals.

Animals↗
PubMed1984

The biochemistry of memory: a new and specific hypothesis.

Recent studies have uncovered a synaptic process with properties required for an intermediate step in memory storage. Calcium rapidly and irreversibly increases the number of receptors for glutamate (a probable neurotransmitter) in forebrain synaptic membranes by activating a proteinase (calpain) that degrades fodrin, a spectrin-like protein. This process provides a means through which physiological activity could produce long-lasting changes in synaptic chemistry and ultrastructure. Since the process is only poorly represented in the brain stem, it is hypothesized to be responsible for those forms of memory localized in the telencephalon.

Animals↗
PubMed1984

Synaptic density and axonal sprouting in rat hippocampus: stability in adulthood and decline in late adulthood.

Synaptic density and axonal sprouting remain stable in the rat dentate gyrus up to 12 months of age. At 18-24 months, an 8-10% loss in synaptic density occurs, and synaptic reinnervation could not be clearly detected at 15 days postlesion, compared to a 40% synaptic recovery in rats lesioned at 6 or 12 months postnatal. Since the amount of synaptic degeneration remaining in the denervated zone was the same at 15 days postlesion in all rats examined, synaptic reinnervation is not primarily dependent on the rate at which degeneration is removed. The results indicate that the decline in the growth response in the rat hippocampus is not a progressive trend from early adulthood into old age, but appears after the midpoint of life.

Aging↗
PubMed1984

The distribution of the commissural-associational afferents of the dentate gyrus after perforant path lesions in one-day-old rats.

Lesions were made in the entorhinal cortex of one-day-old rats and the distribution of the axons in the dentate gyrus molecular layer studied with the Holmes silver stain when the animals reached adulthood. The commissural-associational projections, normally restricted to the inner dendritic zones, spread evenly throughout the molecular layer ipsilateral to the lesion. This pattern of aberrant growth is markedly different from that which occurs after entorhinal lesions placed in 7-day-old rats. The results are discussed in terms of the factors that dictate the topography of developing afferents.

Afferent Pathways↗
PubMed1984

Towards a rational approach to the treatment of peritonitis: an experimental study in rats.

Peritoneal infection progresses through defined stages: contamination, inflammation and abscess formation. An experimental model of established peritonitis without adjuvant in the rat was used to test the effect of various local and systemic agents on survival. There was significant improvement in all treatment groups except those treated with antiseptic lavage using PVP-I and noxythiolin. Intramuscular ampicillin improved survival from 40 to 60 per cent while intramuscular amikacin combined with local irrigation with metronidazole reduced mortality to nil (P less than 0.001). Both cephradine and metronidazole used as peritoneal lavage solutions improved survival (P less than 0.005) when compared with the controls but the difference was not significant when compared with irrigation with Hartmann's solution. Metronidazole given rectally also improved survival from 40 to 60 per cent but this difference was not significant. We conclude that survival in established peritonitis depends upon adequate antibiotic therapy.

Amikacin↗
PubMed1984

A comparative study of L[3H]-glutamate and L[3H]-cysteine sulfinate binding sites in subcellular fractions of rat brain.

A comparative study of the binding of L-cysteine sulfinic acid (CSA) and L-glutamic acid (GLU) to various subcellular fractions of membranes from rat brain was made. Kinetic parameters were determined in all fractions for both types of binding. The effects of membrane preincubation, freezing, and thawing were also examined. The GLU and CSA specific binding levels increased in medium-density (C) and high-density (D) synaptic membranes as compared to the crude mitochondrial/synaptosomal membranes (wP2). Freezing and thawing reduced CSA binding in all tested subcellular fractions. GLU binding is reduced in wP2, C, and D. Binding to the "light" synaptic membranes (B) was not significantly affected, suggesting the presence of two GLU sites. Kinetics of the GLU binding indicated that the temperature-sensitive and -insensitive sites have Kd of 600 nM and 1,100/nM, respectively. Preincubation of fresh membranes conversely affected CSA and GLU binding to the various subcellular fractions, increasing CSA binding in wP2, B, C and decreasing it in D suggesting the existence of distinct sites for GLU and CSA. Preincubation of previously frozen membranes similarly modified CSA and GLU binding except in B fractions. CSA and GLU binding exhibited different pH sensitivities in both fresh and frozen membranes. These results indicate that multiple acid amino acid binding sites exist in membranes and that they can be differentiated according to their sensitivity to temperature. They also suggest the existence of distinct sites for CSA and GLU in fresh membranes, giving further support to the hypothesis that CSA may also serve a neurotransmitter role in the rat central nervous system.

Animals↗
PubMed1984

Leupeptin, a thiol proteinase inhibitor, causes a selective impairment of spatial maze performance in rats.

The effects of chronic intraventricular infusion of leupeptin, a potent inhibitor of thiol proteinases, were tested on ingestive behaviors, escape and avoidance conditioning, and spatial memory in rats. The drug did not detectably influence feeding, drinking, body temperature, or the latency to escape from a mild footshock or inhibitory avoidance behavior. However, rats treated with leupeptin made numerous errors ( reentries ) in an eight-arm spatial maze. These results are interpreted as supporting the hypothesis that calcium-activated thiol proteinases are involved in the formation of certain types of memory.

Animals↗
PubMed1984

Brain fodrin: substrate for calpain I, an endogenous calcium-activated protease.

The calcium-activated thiol-protease calpain I, which is present in cytosolic and membrane preparations from rat brain, was tested for its capacity to degrade the neuronal spectrin-like protein fodrin. In the presence of micromolar calcium concentrations purified calpain I degraded both purified fodrin and the fodrin present in hippocampal and cerebellar membranes. Fodrin was identified as a high molecular weight protein present in brain membranes by the following criteria: (i) comigration on NaDodSO4/polyacrylamide gels with purified fodrin, (ii) reactivity with antibodies to purified fodrin, and (iii) a proteolytic map following calpain activation comparable to that found after calpain-mediated degradation of purified fodrin. The fodrin breakdown was selective in that calpain I did not affect at least 15 other membrane-associated polypeptides. Fodrin degradation by the protease was rapid and was accompanied by the appearance of a lower molecular weight breakdown product. Calpain I had a high affinity for fodrin, with a Km for degradation of about 50 nM. Purified calpain I also degraded purified spectrin and the spectrin present in erythrocyte membranes. Calpain I-mediated degradation of spectrin-like proteins could provide a mechanism by which brief increases in intracellular free calcium levels modify the structure of the submembraneous cytoskeleton and the distribution of cell surface receptors and alter cell shape.

Animals↗
PubMed1984

Hippocampal denervation causes rapid forgetting of olfactory information in rats.

Rats were trained on a succession of two-odor discriminations for a water reward in a modified radial maze. A different odor pair was used each day. After three or four pairs, rats would learn to choose the correct odor in only 3-5 trials. Animals were then subjected to electrolytic lesions in the lateral entorhinal cortex, which is innervated by the lateral olfactory tract, or in the dorsal entorhinal cortex, which is not a target of the olfactory system. Lesions of the first type did not interfere with performance, provided a short interval (30 sec to 2 min) was used between trials. However, the rats were severely impaired when trials were separated by 3-10 min. Dorsal lesions had no effect on olfactory discrimination irrespective of length of delay. In additional experiments, the rats were trained for 10 trials with short inter-trial intervals and then tested 1 hr later with the significance of the cues reversed. Animals with dorsal lesions continued to respond to the formerly correct odor while those with lateral entorhinal damage immediately reversed their response choices. These results provide evidence that lesions to the hippocampal system produce a rapid forgetting syndrome in rats comparable with that reported for humans with temporal lobe damage or dysfunction.

Animals↗
PubMed1984

Classical conditioning of the rabbit eyelid response increases glutamate receptor binding in hippocampal synaptic membranes.

Hippocampal pyramidal neurons exhibit a rapid within-trial increase in firing frequency during classical conditioning of the rabbit eyelid response. It has been proposed that the cellular mechanisms responsible for hippocampal long-term potentiation (LTP) may also mediate this learning-dependent increase in neuronal activity. The induction of LTP in rat hippocampal slices results in an increase in the number of [3H]glutamate-binding sites in the potentiated region. The present study investigates the kinetics of [3H]glutamate binding to hippocampal synaptic membranes after eyelid conditioning in the rabbit. We report that the regional distribution of [3H]glutamate binding across the layers of rabbit hippocampus is compatible with a dendritic localization. The pharmacological and ionic properties of the binding suggest that it is associated with an excitatory amino acid receptor. After eyelid conditioning, the maximal number of hippocampal [3H]glutamate-binding sites is increased in animals receiving paired presentations of the tone conditioned stimulus and corneal air-puff unconditioned stimulus relative to that found in naive or unpaired control animals. These results strengthen the hypothesis that an LTP-like mechanism underlies the increase in hippocampal firing frequency during rabbit eyelid conditioning.

Animals↗
PubMed1983

Rate of synaptic replacement in denervated rat hippocampus declines precipitously from the juvenile period to adulthood.

Synaptic contacts per unit area in the rat dentate gyrus reach adult numbers by the end of the first month after birth and remain constant thereafter. This experiment demonstrated that the rate at which synapses were replaced by sprouting after a lesion declined dramatically from 35 to 90 days of age. Thus, the juvenile period of the rat's life is marked by a considerable change in neuronal plasticity. This may be related to age-dependent effects in recovery from brain damage.

Aging↗
PubMed1983

Irreversibility and time course of calcium stimulated [3H]glutamate binding to rat hippocampal membranes.

Previous studies have indicated that calcium ions induce an irreversible increase of [3H]glutamate binding to rat hippocampal membranes. The present study was intended to provide an estimate of the time-course for this effect. The calcium chelator EGTA and the proteinase inhibitor leupeptin were introduced at various times during the incubation of hippocampal membranes with calcium and the binding of [3H]glutamate subsequently assayed. Both compounds totally blocked the calcium-induced increase in binding when added at the beginning of the incubation period but produced progressively less inhibition when added after longer delays. This method indicates that calcium produces its maximal effect between 5 and 10 min of incubation, a time-course compatible with the hypothesis that calcium stimulates a membrane-bound proteinase which results in the unmasking of [3H]glutamate binding sites.

Animals↗