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Biomedical subjects

G D Block

Publications and source records attributed to G D Block.

69 records · Page 4Linked to original sources

Organophosphate poisoning in office workers.

Five occupants of an office developed symptoms compatible with organophosphate intoxication after application of chlorpyrifos, a moderately toxic pesticide. Recovery of erythrocyte cholinesterase levels occurred during the subsequent three months but followed an exponential distribution rather than the constant rate of recovery most investigators have assumed. This pattern suggests redistribution of the active organophosphate after absorption to a second body compartment with subsequent slow release of the still active substance into the bloodstream.

Adult↗

Cellular analysis of ocular circadian pacemaker coupling in Bulla: role of efferent impulses in phase shifting.

The eyes of Bulla gouldiana, a marine snail, contain circadian oscillators that are coupled to each other. Obvious candidates for the coupling signals are the optic nerve compound action potentials (CAPs) that express the circadian rhythm and lead to efferent impulses in the contralateral optic nerve. In the present experiments, the role of the CAPs as coupling signals was evaluated. We found that, following desynchronization of the two ocular oscillators by phase-delaying one eye with manganese, subsequent phase shifts in the initially unshifted ocular rhythm only occurred during the time that efferent optic nerve signals were present. In addition, in the absence of ocular desynchrony, phase shifts of the ocular rhythm could still be effected by activation of the efferent pathway. The influence of efferent impulses on identified retinal cells was also evaluated. No effect of efferent signals on receptor layer cells was detected, while it was found that efferent impulses generated depolarizations in basal retinal neurons (BRNs), the putative circadian oscillator cells. Depolarization of the BRNs has been shown previously to be involved in the light entrainment pathway. Depolarization appears to be similarly involved in the coupling pathway, since membrane depolarizations that mimicked the efferent-induced postsynaptic potentials likewise generated phase shifts of the ocular rhythm.

Action Potentials↗

Evaluation of the North Carolina Risk Reduction Program for smoking and alcohol.

Seventh grade students in two school systems in rural North Carolina were subjects for a program designed to reduce health risks associated with use/abuse of tobacco and alcohol. One school system was located in the central area of the state, and the other in the western mountains. Both groups were assessed before and after introduction of novel teaching programs dealing with alcohol and tobacco. Knowledge about smoking and alcohol increased in both sites (p less than .05). Attitudes toward alcohol did not change. Attitudes toward smoking eroded in both sites, with attitudes at one site showing a severe erosion (p less than .05). Smoking education in these communities may have conflicted strongly with ambient attitudes toward smoking, eliciting a "boomerang" effect.

Adolescent↗

Analysis of mutual circadian pacemaker coupling between the two eyes of Bulla.

The eyes of Bulla, a marine snail, express a circadian rhythm in the frequency of optic nerve compound action potentials (CAPs). The two ocular pacemakers are mutually coupled, and their interaction can be observed in vitro. The evidence for mutual coupling, as demonstrated in the present experiments, was as follows: (1) When intact Bulla were placed into darkness for up to 72 days, the two pacemakers did not desynchronize. (2) The free-running period of the ocular rhythm in the intact system (24.4 hr) was longer than the free-running period of the rhythm recorded from isolated eyes (23.7 hr). (3) When the two ocular pacemakers were experimentally desynchronized in vitro, resynchronization occurred if the pacemakers were allowed to interact for 48 hr. The coupling signals are most likely the CAPs. These impulses are conducted through the central ganglia and emerge as efferent impulses in the opposite optic nerve. Ocular-derived efferent impulse activity affects spontaneous impulse production in the target eye and alters the waveform of the circadian rhythm. The coupling pathway mediating syncrhonization consists of the two optic nerves, the cerebral ganglia, and the cerebral commissure. The demonstration of coupling in vitro provides a new opportunity for studying the cellular mechanisms underlying mutual pacemaker entrainment.

Action Potentials↗

What is a biological oscillator?

Biological oscillators are amenable to qualitative analysis even before they have been described exhaustively in quantitative terms. Qualitative analysis can identify the elements essential for generating the oscillations and can enhance our understanding of underlying oscillator mechanisms. Two essential elements of a biological oscillator are 1) an inhibitory feedback loop, which includes one or more oscillating variables, and 2) a source of delay in this feedback loop, which allows an oscillating variable to overshoot a steady-state value before the feedback inhibition is fully effective. The analysis of the patterns of interactions and delays observed in biological oscillators is simplified by the translation of variables, interactions, and delays into schematic representations. To illustrate how such translations can be implemented, three biological oscillators are described schematically: 1) the glycolytic oscillator, 2) the bursting of the molluscan neuron, R15, and 3) the oscillations underlying smooth muscle contractions.

Animals↗

Cyclic guanosine 3':5'-monophosphate mimics the effects of light on a circadian pacemaker in the eye of aplysia.

Environmental light regulates the phase of a circadian oscillator in the eye of Aplysia. We are attempting to define the events involved in transmitting light information from the environment to the circadian pacemaking mechanism in the eye. In this paper, we present several lines of evidence that cyclic guanosine 3':5'-monophosphate (cGMP) is involved in the photic entrainment pathway. Light increases the level of cGMP in eyes without having detectable effects on cyclic adenosine 3':5'-monophosphate (cAMP). An analogue of cGMP, 8-bromoguanosine 3':5'-cyclic monophosphate (cGMP), can shift the phase of the circadian rhythm from the eye; the phase response curves for light and for 8-bromo cGMP are indistinguishable. Neither 8-bromo cAMP nor 8-bromo 5'-GMP mimics the effect of light or of 8-bromo cGMP on the rhythm. Light and 8-bromo cGMP appear to use convergent mechanisms for entrainment since the effects of these two treatments are nonadditive. Also, low Na+ solutions antagonize the effects of both treatments. Finally, the kinetics of phase shifting by 8-bromo cGMP are similar to the kinetics of phase shifting by light. In addition to perturbing the circadian rhythm, 8-bromo cGMP increases the frequency of spontaneous optic nerve impulses. The pattern of nerve impulses during 8-bromo cGMP treatment is the same as the pattern of impulses produced by light. The excitatory effect of 8-bromo cGMP, the low Na+ blockade of the effects of 8-bromo cGMP, and the involvement of membrane depolarization in phase shifting by light suggest that depolarization mediates the effect of 8-bromo cGMP on the rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mutual coupling between the ocular circadian pacemakers of Bulla gouldiana.

The ocular circadian pacemakers of Bulla gouldiana were found to be mutually coupled, and their interaction could be observed in an isolated nervous system maintained in vitro. Experimentally induced phase separations between the two ocular pacemakers were reduced when the eyes were allowed to interact for 48 hours. The reduction in phase separation did not occur however when the cerebral commissure was severed, indicating that this neural tract is a critical pathway coupling these two circadian clocks.

Animals↗

Localized illumination of the Aplysia and Bulla eye reveals new relationships between retinal layers.

The cellular organization of the opisthobranch retina is of interest since the eyes of several of these molluscs express circadian rhythms in optic nerve impulse frequency. In a model for retinal organization proposed by Audesirk, photoreceptors make electrical contacts with higher order cells which generate the compound action potential (CAP) recorded in the optic nerve. However, using micro-illumination on selected retinal regions, we now find that cells near the base of the retina are responsible for light transduction leading to CAPs. Illumination of the distal segments of photoreceptors surrounding the lens generates low-amplitude unitary activity in the optic nerve without CAPs. Furthermore, illumination of this region leads to inhibition of spontaneous CAPs or those generated by illumination of the retinal base. This inhibition is blocked by high magnesium-low calcium solutions and thus we conclude that inhibition and a secretory step comprise at least part of the pathway between the photoreceptor layer and neurons giving rise to the CAP.

Animals↗

In vivo recording of the ocular circadian rhythm in Aplysia.

A circadian rhythm in optic nerve impulse frequency was recorded in vivo from unrestrained Aplysia. The mean free-running period (23.9 h) and phase angle for entrainment to light cycles are comparable to values estimated from isolated eyes. The circadian waveform of eyes recorded in vivo is irregular and thus similar to eyes recorded in vitro with the cerebral ganglion attached. However, optic nerve activity recorded in vivo differs from in vitro records in that efferent modulation of afferent impulse patterning is intermittent and is usually associated with the initiation of head or body movements.

Animals↗

A comparison of the effects of feeding sulfur amino acids and protein on urine calcium in man.

It has been suggested that the sulfur amino acids in protein are responsible for the calciuria observed after protein ingestion. This hypothesis was tested by feeding meals containing either 15 g protein (control), 45 g protein (high protein), or 15 g protein plus sulfur amino acids equivalent to those in the high protein diet. Compared to the control, the high protein diet caused an increase in urinary calcium and sulfate and a decrease in the renal reabsorption of calcium. In contrast, the sulfur amino acid supplement had no effect on calcium excretion or reabsorption. Net acid excretion was unaffected by dietary treatment.

Adult↗

Reduction of renal calcium reabsorption in man by consumption of dietary protein.

This experiment was designed to test whether protein consumption reduces the amount of filtered calcium reabsorbed by the kidney. Nine subjects were each fed meals containing 18 g protein and 54 g protein. The intake of energy, sodium, calcium, phosphorus, magnesium and zinc was similar in the two meals. For 4 hours after the meal, measurements were made of serum calcium (total and filterable), serum creatinine, and urinary calcium, creatinine, zinc and nitrogen. Calcium reabsorption was calculated in five clearance periods, as (filterable calcium X GFR) minus urinary calcium. Urinary calcium, zinc and nitrogen were significantly higher between 2 and 4 hours after consumption of the high protein meal. Protein level did not affect urine pH or volume, serum total or filterable calcium & or GFR. The percentage reabsorption of filtered calcium was significantly lower 0.5 hours after the high protein meal, so that at 2.5 hours, reabsorption was 98.0% compared to 98.7% after the lower protein meal. We conclude that protein consumption reduces the amount of calcium reabsorbed by the kidney.

Adult↗

Circadian rhythms.

Circadian rhythms are a ubiquitous adaptation of eukaryotic organisms to the most reliable and predictable of environmental changes, the daily cycles of light and temperature. Prominent daily rhythms in behavior, physiology, hormone levels and biochemistry (including gene expression) are not merely responses to these environmental cycles, however, but embody the organism's ability to keep and tell time. At the core of circadian systems is a mysterious mechanism, located in the brain (actually the suprachiasmatic nucleus of the hypothalamus) of mammals, but present even in unicellular organisms, that functions as a clock. This clock drives circadian rhythms. It is independent of, but remains responsive to, environmental cycles (especially light). The interest in temporal regulation--its organization, mechanism and consequences--unites investigators in diverse disciplines studying otherwise disparate systems. This diversity is reflected in the brief reviews that summarize the presentations at a meeting on circadian rhythms held in New York City on October 31, 1992. The meeting was sponsored by the Fondation pour l'Etude du Système Nerveux (FESN) and followed a larger meeting held 18 months earlier in Geneva, whose proceedings have been published (M. Zatz (Ed.), Report of the Ninth FESN Study Group on 'Circadian Rhythms', Discussions in Neuroscience, Vol. VIII, Nos. 2 + 3, Elsevier, Amsterdam, 1992). Some speakers described progress made in the interim, while others addressed aspects of the field not previously covered.

Aging↗

Cardiovascular tissues contain independent circadian clocks.

Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.

Animals↗