Search PubMed⌕ Search

Biomedical subjects

J Diamond

Publications and source records attributed to J Diamond.

231 records · Page 13Linked to original sources
PubMed1968

The activation and distribution of GABA and L-glutamate receptors on goldfish Mauthner neurones: an analysis of dendritic remote inhibition.

1. The sensitivity of the membrane of the cell-body and lateral dendrite of the Mauthner neurone to iontophoretically applied GABA and L-glutamic acid has been investigated in goldfish. The cells were afterwards examined histologically. The results, taken together with physiological observations, help to explain some functional properties of dendritic synapses.2. GABA inhibits by increasing the membrane conductance, and has little effect on resting potential. L-Glutamate depolarizes, and its effects could sum with subthreshold excitatory post-synaptic potentials (e.p.s.p.s) to cause impulse firing. Neither substance was effective when released intracellularly, but only when applied to the outside of the membrane.3. Using a roving double-barrelled micropipette to apply brief iontophoretic pulses very close to the cell, and recording from the cell-body, the sensitivity to GABA was found to be uniform over a region extending from the axon-hillock to about half-way along the lateral dendrite; it then appeared to fall progressively as the drug was pipetted further and further out on the dendrite. The sensitivity to L-glutamate however seemed relatively unaffected by varying the site of application.4. In contrast to this, when the recording electrode was inserted into the same region of the cell where the drugs were applied, then the sensitivity to GABA, like that to L-glutamate, was found to be similar everywhere, including the distal part of the lateral dendrite.5. The antidromic spike, which does not actively invade the lateral dendrite, was used as a convenient test signal for detecting electrotonic decrement as well as changes in membrane conductance. The conductance changes due to small doses of GABA applied to the dendrite could be detected only over relatively short distances (tens of microns). But over these same distances very little decrement of potential change took place.6. The concept of dendritic remote inhibition has been put on a firm experimental basis. It occurs in the Mauthner cell, and is shown to be capable of providing a high spatial selectivity of action. The e.p.s.p.s most affected by it are those generated out on the same dendrite, and it follows that many of the e.p.s.p.s produced far out on other dendrites could well be influenced by it, though to a lesser extent. Least affected are large e.p.s.p.s generated in the cell-body and axon-hillock regions. The synaptic grouping provided by the distal parts of dendrites and their associated nerve endings is discussed.7. The results of a theoretical treatment (Appendix) of the effects of a localized membrane resistance change on electrotonic potentials recorded nearer to the source have been applied to results obtained on the Mauthner cell. The experimentally observed properties of the ;remote inhibition' caused by localized GABA application to the lateral dendrite, accord well with those predicted both for an infinitely long uniform cable and for a cable having a closed end at the region of the conductance change. The possible implications of these results for other central neurones are considered.8. Evidence is adduced showing that the synapses responsible for collateral inhibition in the Mauthner cell include at least part of the group of small nerve endings found on the axon-hillock, cell-body, proximal and distal lateral dendrite. (The latter distally-located endings cause dendritic remote inhibition.) All these regions, some of which certainly have excitatory synapses, thus receive an inhibitory input as well, and are sensitive to both GABA and L-glutamate.9. E.p.s.p.s recorded in the cell-body were reduced by about the same amount as was the antidromic spike when GABA was applied there, but considerably more than the spike when the GABA application was to the lateral dendrite near the origin of the e.p.s.p. Even when the recording was made from the affected region of the dendrite, the e.p.s.p. seemed more sensitive to GABA than was the electrotonically conducted spike. This, and other observations, suggests that GABA may act presynaptically on the excitatory endings as well as post-synaptically.10. The detection of effects, and the recognition of site of action, of drugs applied iontophoretically in the central nervous system is discussed on the basis of the present findings.

Action Potentials↗
PubMedDate not supplied

Occupational coronary heart disease among bridge and tunnel officers.

Traffic-control officers employed in New York City tunnels prior to 1981 have been at increased risk of mortality from coronary heart disease. In this study, the authors assessed current coronary heart disease prevalence and evaluated associations between coronary heart disease and occupational factors among New York City bridge and tunnel officers. A clinical cardiovascular disease surveillance and cross-sectional occupational epidemiologic study was conducted. The authors used comprehensive evaluations to identify current and prior incidences of coronary heart disease. Occupational risk factors evaluated included job strain, current and historic exposure to carbon monoxide, and occupational physical inactivity. Current carbon monoxide exposure was assessed via workshift changes in carboxyhemoglobin. Coronary heart disease occurred in 29 (5.5%) of the 526 bridge and tunnel officers examined. Risk of coronary heart disease was associated positively with total years each bridge and tunnel officer work had worked in that capacity (odds ratio = 1.64 for each decade of employment, adjusted for nonoccupational coronary heart disease risk factors). Carboxyhemoglobin levels were low in the subjects, and job strain and physical inactivity were very prevalent. Occupational factors contributed to the risk of coronary heart disease in New York City bridge and tunnel officers. The authors were unable to identify the specific factors that led to the increase in risk described.

Adult↗
PubMedDate not supplied

Determinants of the postfeeding metabolic response of Burmese pythons, Python molurus.

The relatively large meal sizes consumed by sit-and-wait-foraging snake species make them favorable for investigating specific dynamic action, the rise in metabolic rate associated with digestion. Hence, we measured O2 consumption rates (VO2) before and up to 20 d after Burmese pythons (Python molurus) either had only constricted and killed rodent meals or had also been allowed to consume meals ranging in size from 5% to 111% of their body mass. Postprandial VO2 peaked within 2 d at a value that increased with meal size, up to 44 times standard metabolic rate for the largest meals. In addition to being the largest known magnitude of postprandial metabolic response, this also exceeds the factorial increase in VO2 during peak physical activity for all studied animals except perhaps racehorses. Specific dynamic action, calculated from the extra VO2 above standard metabolic rate over the duration of digestion, increased with meal size and equaled 32% of ingested meal energy. The allometric exponent for body mass was 0.68 for standard metabolic rate, 0.90 for peak postprandial VO2, and 1.01 for specific dynamic action. Specific dynamic action is higher, and standard metabolic rate is lower, in sit-and-wait-foraging snake species than in actively foraging snake species. This suggests that sit-and-wait-foraging snakes, which consume large meals at long and unpredictable intervals, reduce standard metabolic rate by allowing the energetically expensive small intestine and other associated organs to atrophy between meals but thereby incur a large specific dynamic action while rebuilding those organs upon feeding.

Animals↗
PubMedDate not supplied

Arterial wall changes in type 2 diabetic subjects.

Arterial ultrasonic appearances using high resolution ultrasound were studied in 97 subjects with Type 2 diabetes and age- and sex-matched controls. The intima-media thickness of both common carotid arteries was measured 2 cm proximal to the bifurcation and the presence or absence of plaque on both common and femoral bifurcations was recorded. The mean intima-media thickness in subjects with diabetes was 0.82 +/- 0.22 mm while in the controls 0.66 +/- 0.13 mm (p < 0.001). Multiple regression in diabetic subjects only showed no correlation between age, sex, body mass index, smoking, duration of diabetes, systolic or diastolic blood pressure, cholesterol, HDL, LDL, triglycerides, HbA1 and the common carotid artery intima-media thickness. Type 2 diabetes is associated with increased intima-media thickness which has been found to be a marker of cardiovascular events in the general population.

Arteriosclerosis↗
PubMedDate not supplied

Distribution of MAP kinase, S6 kinase, and casein kinase II in rat tissues: activation by insulin in spleen.

We examined the distribution of mitogen-activated protein (MAP) kinase, S6 kinase, and casein kinase II (CK-II) in the muscle, spleen, brain, and testes of Wistar rats. It was observed that spleen extracts contained the highest activity of all the kinases. Anion-exchange chromatography of spleen extracts by a MonoQ column resolved a single peak of myelin basic protein phosphotransferase activity that eluted after the usual position of the previously described p42 and p44 MAP kinases. Immunoblotting of the peak fractions with anti-MAP kinase antibody did not detect any immunoreactive bands that coincided with the activity peak, suggesting that the activity may represent a potentially novel MAP kinase. The MonoQ fractionation also resolved a single peak of phosvitin phosphotransferase activity which coincided with the intensity of two immunoreactive bands of 39 and 43 kilodaltons that were detected with antibodies against CK-II. The chromatographic behaviour and immunoblotting data indicate that the phosvitin kinase peak represented CK-II and suggested that the rat spleen CK-II had a molecular structure of alpha alpha ' beta 2. Furthermore, using an intact rat model, we showed that the potentially novel spleen MAP kinase and CK-II were markedly activated following intravenous injection of insulin. The significance of these findings remains to be determined.

Animals↗
PubMedDate not supplied

Activation of cAMP-dependent protein kinase in rat aorta by cAMP analogs is not correlated with relaxation.

The role of cAMP-dependent protein kinase (PKA) in the relaxation of vascular smooth muscle by cAMP analogs was studied. The analog N6,2'-O-dibutyryl-cAMP (dbu-cAMP) reduced KCl- and phenylephrine (PE)-induced tension in rat aortic rings in a dose-dependent fashion (10-100 microM). Conversely, incubation with 8-bromo-cAMP (8Br-cAMP; 10-100 microM) had very little effect on tension. The soluble and particulate PKA activity was determined in the analog-treated, PE-contracted tissue. Interference from extracellular analogs was eliminated by washout of analog prior to homogenization of the tissue for the PKA assay and by the addition of charcoal (10 mg/ml) to the homogenization buffer. The nonrelaxant analog 8Br-cAMP significantly increased the activity ratio of soluble PKA at a concentration of 30 microM and, in the particulate fraction, increased the activity ratio at 30- and 100 microM. Total PKA activity in the soluble fraction was significantly decreased by all concentrations of 8Br-cAMP used (10, 30, 100 microM). The relaxant analog dbu-cAMP had no significant effect at any concentration on catalytically active or total PKA activity levels. The only effect seen, at 30 microM, was an increase in the particulate activity ratio, and this was smaller than that seen with 8Br-cAMP. The basis for the alteration in PKA activity by 8Br-cAMP was a decrease in total soluble PKA activity as opposed to an increase in free catalytic PKA subunit. The fall in total activity was most likely due to adsorption by charcoal of catalytic subunit released from the 8Br-cAMP-activated holoenzyme. Thus, under the conditions used to assay PKA activity in cAMP-analog-treated vascular tissue, a decrease in total PKA activity represents an activation of the enzyme and, in fact, appears to be a better indicator of activation than changes in activity ratios. In either case, activation of soluble and particulate PKA by cAMP analogs did not correlate with relaxation of rat aortic rings.

Animals↗