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Biomedical subjects

D Shepherd

Publications and source records attributed to D Shepherd.

At least 37 records · Page 2Linked to original sources
PubMed1993

Neuronal growth factor regulation of two different sodium channel types through distinct signal transduction pathways.

Neuronal growth factors regulate the expression of voltage-activated sodium current in differentiating sympathetic neurons and PC12 cells. We show that, in PC12 cells, the NGF- and FGF-induced sodium current results from increased expression of two distinct sodium channel types. Sodium current results from the rapid induction of a novel sodium channel transcript, also found in peripheral neurons, and from the long term induction of brain type II/IIA mRNA. Expression of the type II/IIA sodium channel requires activation of the cyclic AMP-dependent protein kinase (A-kinase), whereas induction of the peripheral neuron type sodium channel occurs through an A-kinase-independent signal transduction pathway. These findings suggest that the two sodium channel types act in concert to ensure the generation of action potentials during neuronal differentiation.

Animals↗
PubMed1992

Embryonic development of synapses on spiking local interneurones in locust.

The development of synapses on an identified population of spiking local interneurones in the thoracic ganglia of embryonic locusts was examined by means of intracellular horseradish peroxidase injection and electron microscopy. In adult locusts, spiking local interneurones of the midline group receive direct inputs onto a ventral field of branches from leg mechanosensory afferents and in turn make output synapses, mainly from a dorsal field of branches, directly upon leg motor neurones, nonspiking local interneurones, and intersegmental interneurones. The aim of this study is to examine the development of these connections. These interneurones are born relatively late in embryogenesis and are not identifiable until approximately 55% of development. At this time (55-60%) only simple filopodial contacts or punctate contacts are evident between the stained interneurones and other neurones. By 65-70% embryogenesis, vesicles are found adjacent to regions where apposed membranes are symmetrically thickened with amorphous electron-dense material. These symmetrical contacts lack distinct presynaptic bar-shaped densities and therefore, are not considered to be synapses. At this stage, the interneurones do not produce action potentials upon intracellular injection of depolarising current. Morphologically identifiable synapses, with vesicles, a presynaptic bar, and relatively little postsynaptic density, are first evident at 70-75%, coincident with the time of arrival of the majority of leg mechanosensory afferents into the central nervous system. At this stage, action potentials and synaptic potentials are also recorded for the first time. The midline spiking interneurones thus become electrically excitable when synapses are first recognisable, at approximately 70% embryogenesis. Most of the synapses found on the interneurones are outputs. The ratio of outputs to inputs on ventral branches is 7.5:1 which contrasts markedly to the adult ratio of 1:2. By 85-90%, output synapses still predominate on the ventral branches, but the ratio of outputs to inputs is reduced to almost 2:1. Dorsal branches have predominantly output synapses throughout embryogenesis. The ratio of dorsal outputs to inputs at 85-90% is 8.5:1 which compares with the adult ratio of 6.5:1. At this stage, action potentials and synaptic activity are always recorded.

Action Potentials↗
PubMed1992

Embryonic development of a population of spiking local interneurones in the locust (Schistocerca gregaria).

We examined the embryonic development of an identified group of thoracic spiking local interneurones in the locust. These interneurones are primary integrators of mechanosensory information from the legs and make inhibitory output connections with motor neurones, nonspiking local interneurones, and intersegmental interneurones. Using intracellular dye injection, we traced the origins of these interneurones and described their morphological development. All of the interneurones in this population are produced by neuroblast NB4-1. The interneurones are produced during the latter stages of the neuroblast lineage and could not be identified before 55% development. Their growth could be divided into three distinct phases: first, a period of initial outgrowth (55-70%) during which the basic skeleton of major neurites is formed; second, a shorter period of rapid growth (70-80%) during which the basic skeleton is elaborated by the addition of many side branches; and third, a period of maturation (80-95%) during which the branches formed during earlier growth appear to be pruned. The possible implications of these results for neural development and synaptogenesis are discussed.

Animals↗
PubMed1992

Hypoxaemia and pain relief after upper abdominal surgery: comparison of i.m. and patient-controlled analgesia.

Forty patients recovering from upper abdominal surgery were allocated randomly to receive i.m. morphine 0.15 mg kg-1 as required or patient-controlled analgesia (PCA), with i.v. morphine 1 mg and a 5-min lock out time. Arterial oxygen saturation (SpO2) was measured continuously the night before and for 24 h immediately after surgery. A significantly greater proportion of patients in the PCA group (nine of 19) rated their analgesia as excellent compared with the i.m. group (two of 20) (P < 0.05). There was no significant difference in the incidence of postoperative hypoxaemia in the two treatment groups. Severe postoperative hypoxaemia (SpO2 < 85% for more than 6 min h-1) was seen in three patients receiving i.m. analgesia and one patient in the PCA group.

Abdomen↗
PubMed1991

Neural repair and glial proliferation: parallels with gliogenesis in insects.

There is a growing recognition, stemming from work with both vertebrates and invertebrates, that the capacity for neuronal regeneration is critically dependent on the local microenvironment. That environment is largely created by the non-neuronal elements of the nervous system, the neuroglia. Therefore an understanding of how glial cells respond to injury is crucial to understanding neuronal regeneration. Here we examine the process of repair in a relatively simple nervous system, that of the insect, in which it is possible to define precisely the cellular events of the repair process. This repair is rapid and well organised; it involves the recruitment of blood cells, the division of endogenous glial elements and, possibly, migration from pre-existing glial pools in adjacent ganglia. There are clear parallels between the events of repair and those of normal glial development. It seems likely that the ability of the insect central nervous system to repair resides in the retention of developmental capacities throughout its life and that damage results in the activation of this potential.

Animals↗
PubMed1989

Leukocytes and mediators in bronchoalveolar lavage during allergen-induced late-phase asthmatic reactions.

We have measured the total and differential cell counts, histamine, leukotriene (LT) B4 and LTC4, immunoglobulins, complement (C3), eosinophil-derived basic proteins, and monocyte complement rosettes in bronchoalveolar lavage (BAL) 6 h after challenge with either antigen or diluent control in seven patients with antigen-induced single early reactions, and seven with dual (early and late phase) reactions. In both groups, the total cell counts in BAL were similar, irrespective of whether they were challenged with antigen or diluent. However, in the late-phase responders (LPR), there were significant increases in lymphocytes, neutrophils, and eosinophils (p less than 0.05), and significant decreases in the percentage of lung mast cells (p less than 0.05). The eosinophil major basic protein and eosinophil-derived neurotoxin increased in four of five subjects with dual responses and in the majority of single early responders (SER). BAL histamine concentrations increased in five of seven patients with dual responses. There were no consistent changes in LTB4 concentrations in either the LPR or the SER between diluent and antigen days, but a small but significant increase in LTC4 was observed in the LPR. Concentrations of IgG, IgA, IgM, IgE, C3, and albumin did not differ significantly. The percentage of monocyte complement rosettes also increased significantly (p less than 0.05) in LPR, but not in SER. These findings support the hypothesis that eosinophils and their products play a role in tissue injury in LPR and that eosinophil infiltration may be associated with macrophage activation.

Adolescent↗
PubMed1988

Synaptic rearrangement during postembryonic development in the cricket.

Synaptic rearrangement during development is a characteristic of the vertebrate nervous system and was thought to distinguish vertebrates from the invertebrates. However, examination of the wind-sensitive cercal sensory system of the cricket demonstrates that some identified synaptic connections systematically decrease in strength as an animal matures, while others increase in strength over the same period. Moreover, a single sensory neuron could increase the strength of its synaptic connection with one interneuron while decreasing the strength of its connection with another interneuron. Thus, rather than being a hallmark of the vertebrate nervous system, synaptic rearrangement is probably characteristic of the development of many if not all nervous systems.

Action Potentials↗
PubMed1986

Competition regulates the efficacy of an identified synapse in crickets.

The efficacy of the synaptic contact between an identified sensory neuron and an identified interneuron in crickets is increased when neighboring afferent synapses are removed early in postembryonic life. The physiological changes are correlated with changes in the structure of the presynaptic neuron's axonal arborizations: When neighboring axons are destroyed, there is a shift of the remaining axonal arbors into deafferented regions and an increase in the number of putative contacts with the postsynaptic neuron. Changes in the structure of the presynaptic neuron also directly affect the probability of formation of this synaptic connection. The connection was found in 67% of the control specimens, but it was present in 100% of the partially deafferented specimens. The results demonstrate that interactions between growing sensory neurons can influence both the probability of synapse formation and the strength of those connections. This is the first case in which the effects of competition on the structure of a single, identified, presynaptic neuron can be directly related to its synaptic efficacy.

Female↗
PubMed1985

Inhibition of GABA uptake potentiates the effects of exogenous GABA on locust skeletal muscle.

Insect skeletal muscle is relatively insensitive to applied GABA, responses are elicited only when relatively high concentrations of GABA are used (greater than 10(-6) M). Pretreatment of the muscle with the GABA uptake inhibitors nipecotic acid, beta-aminobutyric acid or beta-alanine increases the sensitivity of the muscle to GABA by as much as 1000-fold. The evidence suggests the existence of a GABA uptake mechanism in the insect neuromuscular system which could reside in glial cells.

Aminobutyrates↗
PubMed1984

Regulation of natural killer cell activity by anti-I-region monoclonal antibodies.

The effects of a monoclonal antibody directed against immune response gene products on mouse NK activity were examined. In vivo administration of an anti-I-Ak antibody to C3H/He (H-2k) mice modulated their peritoneal cell (PC) and spleen cell (SC) natural killer (NK) activity against YAC-1 lymphoma target cells in vitro. No such effect was observed when BALB/c (H-2d) mice were treated with this antibody. Administration of anti-I-Ak antibody to mice before and after infection with Toxoplasma or treatment with poly(I:C) leads to suppression of NK activity in comparison to NK activity of mice infected with Toxoplasma or injected with poly(I:C) alone. A similar treatment regimen with M5/114 antibody which reacts with I-Ab, I-Ad, I-Ed, and I-Ek molecules resulted in decreased NK activity in B10.D2 (H-2d) but not in B10.BR (H-2k) mice. Serum and cell culture supernatant interferon (IFN) concentrations were not altered as a result of anti-I-Ak treatment. Removal of adherent cells did not restore NK activity of anti-I-Ak-treated Toxoplasma-infected mice to levels obtained with mice infected with Toxoplasma. In contrast, depletion of Ly 2.1+ cells from nylon-wool nonadherent SC of mice treated with anti-I-Ak antibody, before and after infection with Toxoplasma, resulted in restoration of NK activity to the same level as that observed in Toxoplasma-infected mice.

Animals↗
PubMed1984

Self-assessment of specific interpersonal skills of medical undergraduates using immediate feedback through closed-circuit television.

For a 2-week period, fifth-year medical students of the University of Melbourne are attached to a general practice to obtain experience in primary medical care. During this time they also attend a number of seminars in the Department of Community Medicine. In one session of 45 minutes duration, pairs of students are videotaped, each role-playing a diagnostic and a management interview. To determine the value of this session in improving clinical history-taking specific interpersonal skills by self-assessment and discussion, a questionnaire was administered consecutively to three groups, each of twenty-six students. It was found that being videotaped in a role-playing situation was an acceptable procedure to most students. An analysis of the results shows that the method outlined is a practical form of immediate self-assessment, and that the technique could be used to reinforce clinical history-taking, and specific interpersonal skills of students.

Australia↗
PubMed1979

The effect of changes in pH on phosphate and potassium uptake by Monascus rubiginosus ATCC 16367 in submerged shaken culture.

Monascus rubiginosus ATCC 16367 was cultivated aerobically in media containing ammonium and nitrate as nitrogen source. The pH of the medium was adjusted at different times, the pH of the nitrate medium being lowered to the pH of the ammonium medium and the pH of the ammonium medium raised to that of the nitrate. More phosphate was taken up on the nitrate medium, but potassium uptake did not start until 24h. On the ammonium medium, both were taken up in parallel from the beginning, but the amount of phosphate taken up never reached the same level as on nitrate medium. When the pH was adjusted, the uptakes changed, especially on the ammonium medium where a great increase in phosphate uptake was observed. More conidia were formed on the nitrate medium and more pigment on the ammonium medium. When the pH of either media was adjusted, the development of conidia and pigment production changed to that of the other control medium where the pH evolved normally in the direction of the change, regardless of the source of nitrogen. The reasons for the development of conidia on nitrate medium or where the pH is high, and the production of pigment on ammonium medium or at low pH is discussed.

Ascomycota↗
PubMed1978

The effect of pH and amino acids on conidiation and pigment production of Monascus major ATCC 16362 and Monascus rubiginosus ATCC 16367 in submerged shaken culture.

Monascus major ATCC 16362 and Monascus rubiginosus ATCC 16367 were cultivated aerobically on media containing nitrate or ammonium as nitrogen source to which the following modifications were made: (1) pH adjusted to 2.5 before sterilization; (2) addition of yeast extract; (3) addition of amino acids in identical proportions and concentrations to those found in yeast extract; (4) adjustment of pH to 2.5 after addition of amino acids. The addition of amino acids in the form of yeast extract increased mycelium formation and reduced conidiation and pigment production. The addition of an amino acid mixture did not increase mycelium formation to the same extent as yeast extract but increased the number of conidia, while pigment production was reduced, especially when nitrate was the nitrogen source. As the amino acids are taken up after conidial formation has started, it would appear that it is not the amino acids themselves which are directly responsible for the induction of conidiation. The addition of amino acids inhibits nitrate and ammonium uptake suggesting the need for an early intracellular nitrogen limitation to induce conidiation. Lowering the pH inhibits the formation of conidia and increases pigment production; also the effect of amino acid addition is totally annulled. The pH of the medium is all important in regulating the formation of conidia and pigment production. The possible effects of the pH on the uptake of certain medium components is discussed, as well as their possible control of certain metabolic pathways which ultimately determines the availability of intermediates for conidiation and pigment production.

Aerobiosis↗
PubMed1977

The effect of different nitrogen sources on pigment production and sporulation of Monascus species in submerged, shaken culture.

Thirty-nine strains from the genus Monascus were cultivated aerobically to study the relation between nitrogen nutrition and sporulation and pigment production. The effects of yeast extract, nitrate, ammonium, and ammonium nitrate have been compared. During cultivation the pHs of the different media are not the same, resulting in the formation of different coloured pigments. When the source of nitrogen is yeast extract or nitrate the pH is around 6.5 and red pigments are formed, whereas with ammonium or ammonium nitrate the pH is around 2.5 and the pigments are orange. It is proposed that only the orange pigments, monascorubrin and rubropunctatin, are produced biosynthetically and that the other pigments are formed from these by chemical transformations depending on the cultural conditions. The presence of organic nitrogen is optimal for growth and unfavourable for pigment production. Reduced growth and best pigment formation occurs with the three other nitrogen sources. Nitrate stimulates conidiation and sexual reproduction, while ammonium is inhibitory. Pigment production is better when conidiation is reduced. A mechanism is proposed for the control of sporulation and pigment production.

Ascomycota↗
PubMed1975

Sexal reproductive cycle of Monascus in submerged shaken culture.

A strain of Monascus was grown in submerged, shaken culture using a glucose-salts mediumn. The formation of ascospores was studied by microscopic examination of samples taken at regular intervals for 6 days. All the stages of sexual reproduction previously described for Monascus were observed. The unusual feature of the strain studied was that it produced sexual structures and cliestothecia of greatly varying sizes.

Ascomycota↗