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Biomedical subjects

P M Byrne

Publications and source records attributed to P M Byrne.

At least 19 recordsLinked to original sources
PubMed2002

Evidence for a sustained increase in clonal beta-cell basal intracellular Ca2+ levels after incubation in the presence of newly diagnosed Type-1 diabetic patient sera. Possible role in serum-induced inhibition of insulin secretion.

We have previously reported that newly diagnosed Type-1 diabetic patient sera potently suppressed insulin secretion from a clonal rat pancreatic beta-cell line (BRIN BD11) but did not alter cell viability. Here, we report that apoptosis in BRIN BD11 cells incubated in various sera types (fetal calf serum (FCS), normal human serum and Type-1 diabetic patient) was virtually undetectable. Although low levels of necrosis were detected, these were not significantly different between cells incubated in sera from different sources. ATP levels were reduced by approximately 30% while nitrite production increased twofold from BRIN BD11 cells incubated for 24 h in the presence of Type-1 diabetic patient sera compared with normal human sera. Additionally, ATP levels were reduced by approximately 40% and DNA fragmentation increased by more than 20-fold in BRIN BD11 cells incubated in FCS in the presence of a pro-inflammatory cytokine cocktail (interleukin-1beta, tumour necrosis factor-alpha and interferon-gamma), compared with cells incubated in the absence of cytokines. Nitric oxide production from BRIN BD11 cells was markedly increased (up to 10-fold) irrespective of sera type when the cytokine cocktail was included in the incubation medium. Type-1 diabetic patient sera significantly (P<0.001) raised basal levels of intracellular free Ca(2+ )concentration ([Ca(2+)](i)) in BRIN BD11 cells after a 24-h incubation. The alteration in [Ca(2+)](i) concentration was complement dependent, as removal of the early complement components C1q and C3 resulted in a significant reduction (P<0.01) of sera-induced [Ca(2+)](i )changes. We propose that the mechanism of Type-1 diabetic patient sera-induced inhibition of insulin secretion from clonal beta-cells may involve complement-stimulated elevation of [Ca(2+)](i) which attenuates the nutrient-induced insulin secretory process possibly by desensitizing the cell to further changes in Ca(2+).

Adenosine Triphosphate↗
PubMed2000

Evidence for complement-dependent and -independent inhibition of insulin secretion from clonal beta-cells incubated in the presence of sera of newly diagnosed IDDM patients.

There are conflicting reports on the effect of serum from patients with insulin-dependent diabetes mellitus (IDDM) or normal human serum on beta-cell function and insulin secretion. Here, we report that the sera of newly diagnosed IDDM patients potently suppresses insulin secretion from a clonal rat pancreatic beta-cell line (BRIN-BD11), but do not alter cell viability. Indeed, the viability of the beta-cells was not significantly different between cells cultured in 10% (v/v) IDDM sera, normal human sera, or fetal calf serum after 24, 48 and 72 h. Alanine-stimulated insulin secretion from cells cultured for 24 h in (10% v/v) IDDM patient sera was reduced to 48% of that secreted from cells cultured in (10% v/v) normal human sera. After depletion of the complement components C1q and C3, the inhibition of insulin secretion induced by IDDM patient sera was significantly reversed (no significant difference was observed between cells cultured in complement-depleted IDDM patient sera and cells cultured in normal human sera or complement-depleted normal human sera). The concentration of glutamic acid decarboxylase (GAD) autoantibodies was markedly increased in the sera of six out of nine newly diagnosed IDDM patients in this study, whereas insulin auto-antibodies (IAA) were detected in the sera of three of the nine patients and islet-cell antibodies (ICA) in the sera of five of them. In addition, the concentration of soluble terminal complement complexes (SC5-9) was greater in some of the beta-cell culture media samples after 24 h incubation when the incubation medium was supplemented with IDDM patient sera than when supplementation was with normal human sera. We propose that the mechanism of sera-induced inhibition of insulin secretion from clonal beta-cells may involve complement- and cytokine-stimulated intracellular events that attenuate the metabolite-induced secretory process.

Adolescent↗
PubMed1995

Vitamin D supplementation in the elderly: review of safety and effectiveness of different regimes.

Vitamin D deficiency is common in the elderly, especially in countries where effective sunlight or exposure to sunlight is limited. Two regimes for vitamin D supplementation--low-dose daily oral administration and intermittent high-dose administration--were examined with regard to safety and effectiveness. Eleven papers reporting studies in 449 elderly subjects were reviewed. On low-dose continuous supplementation mean concentration of 25 hydroxyvitamin D (25(OH)D) ranged from 57 to 105 nmol/L compared to 55 to 87 nmol/L following high-dose supplementation. These mean values fall within the physiological range for young adults. Hypercalcemia occurred in only 3 subjects and was associated with a predisposing cause in 2 of 3 subjects. We suggest that low dose continuous supplementation (10 to 20 micrograms daily) is the regime of choice but high-dose intermittent supplementation (2.5 mg six monthly) may be suitable where compliance is poor.

Aged↗
PubMed1994

Temperature changes associated with excitation of the electric organ in the African electric catfish.

By using heat-sensors made from synthetic pyroelectric film, it was shown that excitation of the Malapterurus electric organ brings about first a rapid rise, then a slow fall and finally a very slow rise in the temperature of the organ. Difficulties encountered in determining these rapid temperature changes by the method of employing thermistor probes are pointed out.

Action Potentials↗
PubMed1994

Discontinuous volume transitions induced by calcium-sodium ion exchange in anionic gels and their neurobiological implications.

Discontinuous volume transitions in poly (acrylic acid) gels were studied by determining equilibrium swelling curves of small gel beads immersed in salt solutions containing varying concentrations of Ca2+ and Na+. Reversible contractions of gel membranes associated with Ca(2+)-Na+ exchange were examined using both isometric and isotonic recording devices. A discontinuous change in electric conductance was demonstrated in association with Ca(2+)-Na+ exchange in gel membranes. These experimental findings provide a sound physicochemical basis for elucidating the mechanism of nerve excitation.

Action Potentials↗
PubMed1993

Rapid heat production associated with excitation of electric organs of the electric eel.

By constructing a new type of thermal detector, rapid production of heat was demonstrated during the rising phase of the action potential of the eel electric organs evoked by direct electric stimulation. Following the indirect (synapse-mediated) action potential of the organs, the existence of very large and variable production of heat of unknown origin was revealed.

Action Potentials↗
PubMed1993

The origin of rapid changes in birefringence, light scattering and dye absorbance associated with excitation of nerve fibers.

By comparing the time-courses of rapid optical changes in the garfish olfactory nerve evoked by electric stimulation with those of mechanical changes observed at the site of optical recording, the origin of optical changes in the nerve has been investigated. Based on the finding that the time-course of the birefringence change accurately coincides with that of swelling of the nerve, optical changes are interpreted as being brought about by invasion of water into the superficial layer of the nerve fibers. A close relationship has also been demonstrated between nerve swelling and changes in light scattering and in dye absorbance.

Animals↗
PubMed1992

Rapid structural changes in nerve fibers evoked by electric current pulses.

Using the garfish olfactory nerve, the time-courses of lateral expansion (swelling) and birefringence changes in nerve fibers have been examined at the site of application of electric current pulses. The effects of various chemical agents on these non-electrical signs of rapid structural changes in the nerve fibers have been examined. These studies have shown that a pulse of outwardly-directed current through the superficial layer evokes a fast increase, followed by a slow, gradual increase, in the water-content of the nerve fibers. The full significance of these findings in studies of the process of nerve excitation is discussed.

Animals↗
PubMed1992

Heat production associated with a propagated impulse in bullfrog myelinated nerve fibers.

By using heat-sensors constructed with thin film of polyvinylidene fluoride, it was found possible to detect the heat generated by myelinated fibers in the bullfrog sciatic nerve in association with a propagated impulse. The quantity of heat generated (about 0.4 microcal/g at 4.5 degrees C) is roughly two orders of magnitude smaller than that observed in nerves containing only non-myelinated nerve fibers. The smallness of the heat observed is attributed to the localization of the heat sources at the nodes of Ranvier. The major portion of the heat generated is re-absorbed by the nerve.

Animals↗
PubMed1991

Demonstration of heat production associated with spreading depression in the amphibian retina.

Using thin film of synthetic pyroelectric material, polyvinylidene fluoride, sensitive heat-sensors were constructed for the purpose of detecting heat production associated with the phenomenon of spreading depression in isolated amphibian retinae. Measurements with these sensors revealed the existence of large heat production, which closely follows the electrical sign of spreading depression. Studies of the effects of chemical agents known to affect spreading depression have demonstrated the usefulness of heat measurements.

Animals↗
PubMed1991

Thermal and mechanical responses of the amphibian skin to nerve stimulation.

The isolated calf skin of the toad and bullfrog was found to generate a burst of heat in response to stimulation of the cutaneous nerve. The electric responses of the skin evoked by nerve stimulation invariably lagged behind the heat burst. The generation of a heat burst was followed by a slow mechanical response of the skin. Suppression of these responses by adrenergic blocking agents suggests that heat is produced at the junction between the gland cells and the sympathetic nerve fibers. Large mechanical changes in the skin were observed when noradrenaline was applied to the inner surface of the skin.

Animals↗
PubMed1990

Heat production associated with neuromuscular transmission in the toad nerve-muscle preparation.

The time course of the heat produced by the toad sartorius muscle in response to nerve stimulation was determined by using a new type of heat-sensor with a high time resolution. The records obtained showed the existence of a brief burst of large heat production prior to the onset of the muscle heat associated with contraction. This initial heat-burst was shown to be produced at the motor endplates. The implications of these findings are discussed.

Animals↗
PubMed1989

Rapid mechanical and thermal changes in the garfish olfactory nerve associated with a propagated impulse.

Mechanical and thermal changes associated with a propagated nerve impulse were determined using the garfish olfactory nerve. Production of an action potential was found to be accompanied by swelling of the nerve fibers. The swelling starts nearly at the onset of the action potential and reaches its peak at the peak of the action potential. There is a decrease in the length of the fibers while an impulse travels along the fibers. The time-course of the initial heat was determined at room temperature using heat-sensors with a response-time of 2-3 ms. Positive heat production was found to start and reach its peak nearly simultaneously with the action potential. The rise in temperature of the nerve was shown to be 23 (+/- 4) mu degrees C. In the range between 10 degrees and 20 degrees C, the temperature coefficient of heat production is negative, primarily due to prolongation of the period of positive heat production at low temperatures. The amount of heat absorbed during the negative phase varies widely between 45 and 85% of the heat evolved during the positive phase. It is suggested that both mechanical and thermal changes in the nerve fibers are associated with the release and re-binding of Ca-ions in the nerve associated with action potential production.

Action Potentials↗
PubMed1988

Large mechanical changes in the bullfrog olfactory bulb evoked by afferent fiber stimulation.

The isolated olfactory bulb of the bullfrog responds to olfactory nerve stimulation with large mechanical changes in the bulb. The sequence of these changes represents: (1) swelling of the bulb associated with action potential production in the secondary neurons; (2) shrinkage during powerful inhibition of the secondary neurons; and (3) swelling accompanied by repetitive firing of action potentials in the bulb. The effects of bicuculline and Cl-free Ringer on these mechanical changes were examined. The shrinkage of the bulb is closely related with the inhibitory postsynaptic potentials (IPSPs) in the mitral cells.

Action Potentials↗