Search PubMed⌕ Search

Biomedical subjects

L B Cohen

Publications and source records attributed to L B Cohen.

At least 37 records · Page 2Linked to original sources

Visual stimuli induce waves of electrical activity in turtle cortex.

The computations involved in the processing of a visual scene invariably involve the interactions among neurons throughout all of visual cortex. One hypothesis is that the timing of neuronal activity, as well as the amplitude of activity, provides a means to encode features of objects. The experimental data from studies on cat [Gray, C. M., Konig, P., Engel, A. K. & Singer, W. (1989) Nature (London) 338, 334-337] support a view in which only synchronous (no phase lags) activity carries information about the visual scene. In contrast, theoretical studies suggest, on the one hand, the utility of multiple phases within a population of neurons as a means to encode independent visual features and, on the other hand, the likely existence of timing differences solely on the basis of network dynamics. Here we use widefield imaging in conjunction with voltage-sensitive dyes to record electrical activity from the virtually intact, unanesthetized turtle brain. Our data consist of single-trial measurements. We analyze our data in the frequency domain to isolate coherent events that lie in different frequency bands. Low frequency oscillations (<5 Hz) are seen in both ongoing activity and activity induced by visual stimuli. These oscillations propagate parallel to the afferent input. Higher frequency activity, with spectral peaks near 10 and 20 Hz, is seen solely in response to stimulation. This activity consists of plane waves and spiral-like waves, as well as more complex patterns. The plane waves have an average phase gradient of approximately pi/2 radians/mm and propagate orthogonally to the low frequency waves. Our results show that large-scale differences in neuronal timing are present and persistent during visual processing.

Animals↗

Functions of the LE sensory neurons in Aplysia.

Mechanosensory neurons which innervate the siphon and have their cell bodies in the LE cluster of the abdominal ganglion of Aplysia have revealed many cellular and molecular processes that may play general roles in learning and memory. It was initially suggested that these cells are largely responsible for triggering the gill-withdrawal reflex evoked by weak siphon stimulation, and that most of this effect is mediated by their monosynaptic connections to gill motor neurons. This implied a simple link between plasticity at these synapses and modifications of the reflex during learning. We review more recent studies from several laboratories showing that the LE cells are not activated by very weak tactile stimuli that elicit the gill-withdrawal reflex, and that an unidentified population of siphon sensory neurons has lower mechanosensory thresholds and produces shorter latency responses. Furthermore, the direct connections between LE cells and gill motor neurons make a minor contribution when the reflex is elicited in pinned siphon preparations by light stimuli that weakly activate the LE cells. Because weak mechanical stimulation of the unrestrained siphon causes little or no LE cell activation, it is unlikely that, under natural conditions, sensitization or conditioning of reflex responses elicited by light siphon touch depends upon plasticity of LE cell synapses onto either motor or interneurons. The LE cells appear to function as nociceptors because they are tuned to noxious stimuli and, like mammalian nociceptors, show peripheral sensitization following nociceptive activation. This sensitization and the profound activity-dependent potentiation of LE synapses indicate that LE cell contributions to defensive reflexes should be largest during and after intense activation of the LE cells by noxious stimulation (with the LE cell plasticity contributing to long-lasting memory of peripheral injury). The LE sensory neurons offer special opportunities for direct tests of this and other hypotheses about specific mnemonic functions of fundamental mechanisms of neural plasticity.

Animals↗

The synapse between LE sensory neurons and gill motoneurons makes only a small contribution to the Aplysia gill-withdrawal reflex.

The monosynaptic connection between the mechano-sensory neurons in the LE cluster and gill motoneurons has been extensively studied and used as a model for the gill-withdrawal reflex and its behavioural plasticity. In an attempt to evaluate the contribution of this synapse to the behaviour, we used voltage-sensitive dye recording to determine the number of activated LE neurons and the number of spikes made by each neuron in response to a light touch. In five preparations, light touch activated a median of five sensory cells with a median of 1.6 spikes per cell. From a comparison of the sizes of the motoneuron synaptic potentials elicited by LE spikes and elicited by a light siphon touch, we estimate that the LE sensory neurons contribute approximately 5% of the motoneuron synaptic potential in response to this touch. This result casts doubt on the validity of using this synaptic connection as a model for gill-withdrawal behaviour. Siphon nerve recordings reveal the existence of short-latency, low-threshold neurons that may provide much of the sensory input in response to a light touch.

Animals↗

Pancreatic insufficiency due to antituberculous therapy.

OBJECTIVE: To describe a case of chronic pancreatic insufficiency related to antituberculous therapy. CASE SUMMARY: A 57-year-old man developed rash, fever, and hepatitis (aspartate aminotransferase 369 IU/L, alanine aminotransferase 506 IU/L), 6 weeks after starting isoniazid, rifampin, ethambutol, and pyrazinamide. He also developed severe metabolic acidosis secondary to diabetic ketoacidosis and lactic acidosis (serum bicarbonate 7 mEq/L, glucose 1778 mg/dL, and lactate 4.0 mEq/L). Acute pancreatitis was diagnosed on the basis of a mildly elevated amylase concentration (392 U/L) and radiologic evidence of pancreatic inflammation. He developed pancreatic insufficiency with steatorrhea and an abnormal secretin test. He continues to require pancreatic enzyme replacement and insulin therapy. Rechallenge was not performed. DISCUSSION: Hypersensitivity syndromes have been reported for various drug therapies, including antituberculous agents. Hypersensitivity syndrome reactions are characterized by fever, rash, and internal organ involvement. Rifampin has been reported to cause acute pancreatitis in up to 2.7% of patients. Drug-induced chronic pancreatitis, however, is reported to be extremely rare. This is the first reported case of chronic pancreatic insufficiency occurring in the setting of a hypersensitivity syndrome reaction to antituberculous drugs. CONCLUSIONS: Chronic pancreatic insufficiency should be considered as a possible long-term sequelae of a hypersensitivity syndrome reaction to antituberculous therapy.

Antitubercular Agents↗

Voltage-sensitive dye recording using retrogradely transported dye in the chicken spinal cord: staining and signal characteristics.

We describe a novel method for retrogradely labeling specific neuronal populations using voltage-sensitive dyes. Styryl dyes were injected into the ventral roots of the isolated embryonic chick spinal cord. After waiting several hours, the dye labeled motoneurons and autonomic preganglionic neurons. Neuronal cell bodies, dendrites and axons were labeled; we presume that the dye traveled either by retrograde transport or by diffusion within the membrane of the axon to which the dyes were initially applied. Using either a photodiode array or a photomultiplier, fluorescence changes could be recorded from motoneurons following antidromic or synaptic activation. Several characteristics of the fluorescence changes were measured indicating that the signals did indeed reflect changes in the motoneuron membrane potential. The best labeling and optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12-ANEPEQ. In the great majority of cases these dyes responded with an increase in fluorescence of 1-3% (delta F/F) in response to synaptic or antidromic depolarization of the motoneurons. We anticipate that these techniques should be useful in the mapping of activity patterns and connectivity in neural networks within a defined population of neurons.

Action Potentials↗

Dye screening and signal-to-noise ratio for retrogradely transported voltage-sensitive dyes.

Using a novel method for retrogradely labeling specific neuronal populations, we tested different styryl dyes in attempt to find dyes whose staining would be specific, rapid, and lead to large activity dependent signals. The dyes were injected into the ventral roots of the isolated chick spinal cord from embryos at days E9-E12. The voltage-sensitive dye signals were recorded from synaptically activated motoneurons using a 464 element photodiode array. The best labeling and optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12-ANEPEQ. Over the 24 h period we examined, these dyes bound specifically to the cells with axons in the ventral roots. The dyes responded with an increase in fluorescence of 1-3% (delta F/F) in response to synaptic depolarization of the motoneurons. The signal-to-noise ratio obtained in a single trial from a detector that received light from a 14 x 14 microns2 area of the motoneuron population was about 10:1. Nonetheless, signals on neighboring diodes were similar, suggesting that we were not detecting the activity of individual neurons. Retrograde labeling and optical recording with voltage-sensitive dyes provides a means for monitoring the activity of identified neurons in situations where microelectrode recordings are not feasible.

Animals↗

Effect of feedback from peripheral movements on neuron activity in the aplysia abdominal ganglion.

We have made reasonably comprehensive measurements of action potential activity in the Aplysia californica abdominal ganglion to determine the amount of feedback the central nervous system (CNS) receives from a movement which it initiates. Voltage-sensitive dye measurements of action potential activity of cells in the ganglion were made during the gill-withdrawal reflex elicited by siphon stimulation. We compared recordings in two situations which differed dramatically in the amount the gill moved. In the control sea water, the gill withdrawal was normal; in low-Ca2+, high-Mg2+ sea water, the gill movement was blocked. Both the timing and the number of spikes of the individual neurons were similar in the two situations. Histograms of the summed spike activity versus time and histograms of the number of active neurons versus time in the two conditions were also similar. Finally, two numerical measures of trial-to-trial differences, a paired t-test and a measure we named fractional similarity, did not indicate larger differences between two trials in the different sea waters than two trials in the same sea water. Feedback from sensory neurons activated by the gill movement itself does not make a large contribution to the spike activity in the abdominal ganglion. Apparently the Aplysia CNS issues the command for the withdrawal and does not make adjustments for the magnitude of the actual withdrawal. It may not even receive the information necessary for such adjustments to be made. A second motivation for these experiments was to test whether removing the feedback might simplify the neuronal activity that occurs during the gill-withdrawal reflex. This did not occur.

Abdomen↗

Colorectal cancer: a primary care approach to screening.

The adenomatous polyp is the precursor of most--if not all--colorectal cancers. The average 10 to 12 years that it takes for a polyp to undergo malignant degeneration provides a window of opportunity to identify and remove benign neoplasms, before they become invasive cancers. The incidence of colorectal cancer rises significantly after age 50 and doubles with each successive decade. For screening asymptomatic patients age 50 and older, the fecal occult blood test and flexible sigmoidoscopy are the methods of choice. Recommendations for screening higher-risk individuals are based upon the relative risk of colon cancer in various subgroups, based on family and individual history.

Aged↗

Neuronal activity during different behaviors in Aplysia: a distributed organization?

The active neuronal populations in the Aplysia abdominal ganglion during spontaneous and evoked behaviors were compared with the use of multineuronal optical measurements. In some preparations, more than 90 percent of the neurons activated during the reflex withdrawal of the gill also were activated during respiratory pumping and during small spontaneous gill contractions. Although the same neurons made action potentials in all three behaviors, the activity patterns were different. There was a substantial interaction between the neural substrates underlying evoked and spontaneous behaviors when they were made to occur together. If a gill withdrawal reflex was elicited a few seconds after a respiratory pumping episode, the evoked neuronal activity in most neurons was clearly altered. These results suggest that a distributed organization involving a large number of neurons may be responsible for generating the two behaviors. Different behaviors appear to be generated by altered activities of a single, large distributed network rather than by small dedicated circuits.

Action Potentials↗

A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group.

After polypectomy for adenomatous colorectal polyps, 201 persons were randomized to receive counselling on a diet low in fat (the lesser of 50 g/day or 20% of energy) and high in fibre (50 g/day) (LFHF), or to follow a normal western diet (ND), high in fat and low in fibre. After 12 months of counselling, fat consumption was about 25% of energy in the LFHF group and 33% in the ND group; fibre consumption was 35 g and 16 g respectively. After an average of two years of follow-up, an intention to treat analysis led to a ratio of cumulative incidence rates of 1.2 (95% CL 0.6-2.2) for recurrence of neoplastic polyps, a finding which suggests no significant difference between dietary groups over the period of observation. An exploratory analysis conducted among 142 persons with substantial diet counselling indicated a reduced risk of neoplastic polyp recurrence in women (RR = 0.5), associated with reduced concentrations of faecal bile acids while on the LFHF diet, but indicated an increased risk of recurrence in men (RR = 2.1), associated with increased faecal bile acids. Although a larger study would be needed to rule out the role of chance, these findings of gender-specific associations between diet counselling and both faecal bile acid concentrations and recurrence of colorectal neoplasia are consistent with recently published evidence of differences between genders.

Adenomatous Polyps↗

Distributed aspects of the response to siphon touch in Aplysia: spread of stimulus information and cross-correlation analysis.

We examined two aspects of the response to siphon stimulation in an attempt to test the hypothesis that the Aplysia CNS functions as a distributed system. First, we estimated the number of central neurons that respond to a light touch to the siphon skin. We made voltage-sensitive dye recordings from the abdominal, pleural, pedal, and cerebral ganglia. From these recordings we estimated that 220 abdominal neurons, 110 pleural neurons, and 650 pedal neurons were affected by the light touch. Thus, the information about this mild and localized stimulus is very widely distributed within the Aplysia CNS. This result allows the possibility that the Aplysia CNS functions as a distributed system. If only a small number of neurons had responded to the touch, it would have supported the conclusion that the gill-withdrawal reflex could be generated by a small, dedicated circuit. Second, we searched for correlations between the spike times of the individual abdominal ganglion neurons. Two time scales were examined: a millisecond time scale corresponding to the duration of a fast synaptic potential and a seconds time scale corresponding to the duration of the gill-withdrawal movement. Neuron pairs with highly correlated spike activity on a millisecond time scale must be connected by (or have a common input that uses) relatively powerful, fast, excitatory synapses. We expected that this kind of synaptic interaction would be relatively rare in nervous systems that functioned in a distributed manner. Indeed, only 0.3% of the neuron pairs had correlation coefficients of 0.15 or greater. These correlations accounted for approximately 2% of the action potentials generated in response to siphon stimulation. Thus, large, fast excitatory synaptic interactions appear to be relatively unimportant. This result is consistent with the hypothesis that the abdominal ganglion functions as a distributed system. When the longer time scale was used for the cross-correlograms, a large fraction of the cell pairs had correlated activity because many neurons are activated by the stimulus. It was not possible to interpret the slow correlations in terms of actual synaptic interactions between individual neurons. Our results are consistent with the possibility that the abdominal ganglion functions in a distributed manner. However, this evaluation is indirect and thus only tentative conclusions can be drawn. Evidence from several sources suggests that the neuronal interactions for generating the Aplysia gill-withdrawal reflex are complex.

Animals↗

Consistency in nervous systems: trial-to-trial and animal-to-animal variations in the responses to repeated applications of a sensory stimulus in Aplysia.

What is the internal noise in a nervous system? We studied this question by determining the trial-to-trial consistency of the neuronal response in the abdominal ganglion of Aplysia californica. Because our voltage-sensitive dye recordings detected the spike activity from a large fraction of the neurons in the ganglion, these results provide a reasonably complete characterization of the consistency of the response to a sensory stimulus. The consistency of each neuron was evaluated by the number and timing of spikes in the response. The variability in the spike count was described using the coefficient of variation. The spike count variations follow a Poisson distribution, indicating that most of these variations were the result of a random process. For each neuron the reliability of the response to touch was measured in two ways; both measures indicated a broad distribution of reliabilities within the neuron population. The time of the maximum response also varied substantially in some animals. These timing variations were in part due to random processes and in part due to systematic effects (changes in activity of many neurons that were highly correlated). The time course of the activity of individual neurons was compared with the time course of the gill withdrawal. In some animals the activity of individual neurons was only poorly correlated with the behavior; in contrast, the summed activity of groups of neurons matched the behavior quite well. This implies that the behavioral output of the system may be a distributed combination of the activity of many neurons. The differences between animals were substantially larger than the trial-to-trial differences in one animal. The responses made by different preparations differed along many dimensions.

Action Potentials↗

Nonuniform expression of habituation in the activity of distinct classes of neurons in the Aplysia abdominal ganglion.

Global observations of neuronal response in the Aplysia abdominal ganglion were made during habituation of the gill withdrawal reflex using voltage-sensitive dye recording. This technique makes it possible to measure the spike activity of 30-50% of the 1000 neurons present in the ganglion. Our experiments address the issue of how habituation is expressed in the activity of the population of neurons responding to siphon stimulation. Several classes of neurons exhibited characteristically distinct responses to the stimuli and to habituation training. One class of neurons (group I) responded to the onset and offset of the sensory stimulus although they are probably not primary sensory neurons. They habituate only partially when the behavioral reflex has already habituated completely. Two other classes (groups II and III) both have sustained responses to the touch, but habituate differently. Members of group III habituate completely while those in group II habituate only partially. Another class of neurons are inhibited by the stimulus (group IV). They become less inhibited after habituation. The response of both group I and group IV are new classes of response that have not been previously reported.

Action Potentials↗

A naphthyl analog of the aminostyryl pyridinium class of potentiometric membrane dyes shows consistent sensitivity in a variety of tissue, cell, and model membrane preparations.

The fast potentiometric indicator di-4-ANEPPS is examined in four different preparations: lipid vesicles, red blood cells, squid giant axon, and guinea pig heart. The dye gives consistent potentiometric responses in each of these systems, although some of the detailed behavior varies. In lipid vesicles, the dye displays an increase in fluorescence combined with a red shift of the excitation spectrum upon hyperpolarization. Similar behavior is found in red cells where a dual wavelength radiometric measurement is also demonstrated. The signal-to-noise ratio of the potentiometric fluorescence response is among the best ever recorded on the voltage-clamped squid axon. The dye is shown to be a faithful and persistent monitor of cardiac action potentials with no appreciable loss of signal or deterioration of cardiac activity for periods as long as 2 hr with intermittent illumination every 10 min. These results, together with previously published applications of the dye to a spherical lipid bilayer model and to cells in culture, demonstrate the versatility of di-4-ANEPPS as a fast indicator of membrane potential.

Animals↗

Power and change in health care: challenge for nursing.

This article proposes the need for consideration of status and power issues in nursing research, in theory, and at all levels of nursing education. Including the concept of power in nursing curricula will better prepare nurses to participate in social and political decisions affecting health care. By recognizing the role nurses have played, often in the face of opposition, nursing students will gain a sense of the potential power and strength of nurses. Curricular reform and revision of nursing theories to emphasize the sociopolitical context of nursing may change the socialization of student nurses by stressing autonomy, independence, and confidence. These changes may have a positive impact on recruitment, retention, and on efforts to change the public's perception of nursing.

Clinical Competence↗

Optical methods can be utilized to map the location and activity of putative motor neurons and interneurons during rhythmic patterns of activity in the buccal ganglion of Aplysia.

We sought to develop a map of the locations of neurons that are active during patterned activity in the buccal ganglion of Aplysia using optical techniques. Staining ganglia with a voltage-sensitive absorbance dye (JPW 1124) did not prevent them from generating patterned activity similar to that observed before staining, in response to shock of the esophageal nerve. Absorbance changes were monitored with a 124-element photodiode array, while extracellular electrodes monitored activity of the 6 buccal nerves. Optical and extracellular spikes were grouped with the aid of a template matching program; a total of 120 distinct units were detected in one 15 s recording. Optical signals (83 units) were found in the region of the ganglion containing mainly large neurons. Of these, 13 were detected on both optical and extracellular electrode recordings, suggesting that they might be motor neurons, while 25 of the optically detected neurons appeared not to be correlated with extracellular activity, suggesting that they might be interneurons. It was not possible to determine whether the remaining 45 optically identified units did or did not have correlated nerve activity. The ganglionic locations of putative motor neurons corresponded to the locations of large neurons identified by backfilling nerves of other buccal ganglia, and were consistent with the locations of putative motor neurons found in two other ganglia studied using optical methods. Thus, optical methods have generated a map of the locations and activity patterns of putative motor neurons and interneurons in the buccal ganglion that may be involved in the generation of rhythmic patterns.

Animals↗

Upper gastrointestinal bleeding due to superior mesenteric artery to duodenum fistula: rare complication of metastatic lung carcinoma.

Although metastases from primary carcinoma of the lung to the small intestine appear to be more common than previously suspected, they rarely produce symptoms. Such metastases may present as bowel perforations. Overt gastrointestinal bleeding has been described only as a prelude to perforation. We describe the case of a 55-yr-old man with carcinoma of the lung that had metastasized to the brain and to the third part of the duodenum. The duodenal metastasis presented with massive upper gastrointestinal hemorrhage. The metastasis was seen to be actively bleeding at endoscopy, and a direct fistula from a branch of the superior mesenteric artery to the third part of the duodenum was shown angiographically. Arterial invasion and destruction by tumor was confirmed at postmortem examination. This complication of metastatic carcinoma of the lung has not been previously described in the English literature.

Carcinoma↗