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Biomedical subjects

M Migliore

Publications and source records attributed to M Migliore.

35 records · Page 2Linked to original sources

Input-output relations in the entorhinal-hippocampal-entorhinal loop: entorhinal cortex and dentate gyrus.

The pattern of impulse transfer along the entorhinal-hippocampal-entorhinal loop has been analyzed in the guinea pig by field potential analysis. The loop was driven by impulse volleys conducted by presubicular commissural fibers, directly stimulated in the dorsal psalterium, which monosynaptically activated perforant path neurons in the medial entorhinal cortex. Perforant path volleys activated in sequence the dentate gyrus, field CA3, field CA1, subiculum, and entorhinal cortex. Input-output curves were reconstructed from responses simultaneously recorded from different stations along the loop. The entorhinal response to the presubicular volley was found to increase gradually with respect to its input. The population excitatory postsynaptic potential (EPSP) of the dentate gyrus granule cells had a similar behavior. By contrast, the input-output relation between the granule cell population spike and population EPSP was described by a very sleep sigmoid curve. The population spike of CA3 and CA1 pyramidal neurons as well as the response evoked in the entorhinal cortex by the hippocampal output had slightly higher threshold than the granule cell population spike and, like the latter, abruptly reached maximum amplitude. These findings show that the entorhinal-hippocampal-entorhinal loop transforms a linear input in a non-linear, almost all-or-none output and that the dentate gyrus is the critical site where the transformation occurs. Beyond the dentate gyrus, the loop appears very permeant to impulse traffic.

Afferent Pathways↗

A model for long-term potentiation and depression.

A computational model of long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus is presented. The model assumes the existence of retrograde signals, is in good agreement with several experimental data on LTP, LTD, and their pharmacological manipulations, and shows how a simple kinetic scheme can capture the essential characteristics of the processes involved in LTP and LTD. We propose that LTP and LTD could be two different but conceptually similar processes, induced by the same class of retrograde signals, and maintained by two distinct mechanisms. An interpretation of a number of experiments in terms of the molecular processes involved in LTP and LTD induction and maintenance, and the roles of a retrograde signal are presented and discussed.

Animals↗

Diffuse colonic lipomatosis with giant hypertrophy of the epiploic appendices and diverticulosis of the colon. Report of a case and review of the literature.

PURPOSE: A case of diffuse colonic lipomatosis, dolichosigmoid, hypertrophy of the epiploic appendices and diverticulosis of the colon producing constipation, recurrent sub-occlusive episodes with diarrhea and vomiting, and weight loss is reported. METHODS: Careful preoperative assessment of clinical, radiologic, and endoscopic findings suggested the diagnosis. RESULTS: A total colectomy, followed by a lateroterminal ileoproctostomy, gave complete relief from symptoms. CONCLUSIONS: Of the 12 cases of colonic lipomatosis previously reported, only 2 have isolated involvement of the entire organ, but they do not present lipomatosis of the epiploic appendices.

Adult↗

Computer simulations of morphologically reconstructed CA3 hippocampal neurons.

1. We tested several hypotheses with respect to the mechanisms and processes that control the firing characteristics and determine the spatial and temporal dynamics of intracellular Ca2+ in CA3 hippocampal neurons. In particular, we were interested to know 1) whether bursting and nonbursting behavior of CA3 neurons could be accounted for in a morphologically realistic model using a number of the known ionic conductances; 2) whether such a model is robust across different cell morphologies; 3) whether some particular nonuniform distribution of Ca2+ channels is required for bursting; and 4) whether such a model can reproduce the magnitude and spatial distribution of intracellular Ca2+ transients determined from fluorescence imaging studies and can predict reasonable intracellular Ca2+ concentration ([Ca2+]i) distribution for CA3 neurons. 2. For this purpose we have developed a highly detailed model of the distribution and densities of membrane ion channels in hippocampal CA3 bursting and nonbursting pyramidal neurons. This model reproduces both the experimentally observed firing modes and the dynamics of intracellular Ca2+. 3. The kinetics of the membrane ionic conductances are based on available experimental data. This model incorporates a single Na+ channel, three Ca2+ channels (CaN, CaL, and CaT), three Ca(2+)-independent K+ channels (KDR, KA, and KM), two Ca(2+)-dependent K+ channels (KC and KAHP), and intracellular Ca(2+)-related processes such as buffering, pumping, and radial diffusion. 4. To test the robustness of the model, we applied it to six different morphologically accurate reconstructions of CA3 hippocampal pyramidal neurons. In every neuron, Ca2+ channels, Ca(2+)-related processes, and Ca(2+)-dependent K+ channels were uniformly distributed over the entire cell. Ca(2+)-independent K+ channels were placed on the soma and the proximal apical dendrites. For each reconstructed cell we were able to reproduce bursting and nonbursting firing characteristics as well as Ca2+ transients and distributions for both somatic and synaptic stimulations. 5. Our simulation results suggest that CA3 pyramidal cell bursting behavior does not require any special distribution of Ca(2+)-dependent channels and mechanisms. Furthermore, a simple increase in the Ca(2+)-independent K+ conductances is sufficient to change the firing mode of our CA3 neurons from bursting to nonbursting. 6. The model also displays [Ca2+]i transients and distributions that are consistent with fluorescent imaging data. Peak [Ca2+]i distribution for synaptic stimulation of the nonbursting model is broader when compared with somatic stimulation. Somatic stimulation of the bursting model shows a broader distribution in [Ca2+]i when compared with the nonbursting model.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium↗

Pathophysiologic basis for operation on Zenker's diverticulum.

An increased resistance to bolus flow through the upper esophageal sphincter has in the past been considered the main cause of increased pharyngeal contraction and the subsequent development of Zenker's diverticulum (ZD). Our study was designed to elucidate the pathophysiologic characteristics of the swallowing mechanism and its possible role in the development of ZD. Fourteen patients with radiologically proved ZD and a matched control group of healthy volunteers with no gastrointestinal symptoms were investigated with esophageal manometry using the station pull-through technique. Although the mean amplitude of pharyngeal contraction was higher in the ZD group, there was no difference in the duration of contraction. The resting tone of the upper esophageal sphincter zone in patients with ZD was found to be lower than normal, but the closing pressure was higher and its duration longer. Though present in 2 patients, pharyngosphincteric incoordination was not the main feature in the ZD group. Sphincteroesophageal incoordination was noted in 9 patients, however. The mean amplitude of the upper esophageal contraction was higher and the duration longer in the ZD group. There was no upper esophageal peristalsis in 3 patients. An operation for the repair of ZD should therefore be undertaken only after careful interpretation of the manometric features of each patient.

Aged↗

Esophageal carcinoma with airway invasion. Evolution and choices of therapy.

In order to define the evolution of airway invasion by esophageal cancer, we reviewed 53 patients presenting with (group A) or without (group B) tracheoesophageal fistulae. Patients in group A were treated by esophageal bypass (4), esophageal diversion (4), expectant therapy (4), or esophageal prosthesis (1). The median survival was 4 months. Group B patients were treated by esophageal resection (18), esophageal bypass (4), or radiation therapy (13), depending on the extent of local disease. Bronchoscopy was a valuable tool for predicting resectability. Surgical resection, when possible, yielded better palliation. There were 4 long-term survivors in group B.

Adenocarcinoma↗

[Intraoperative esophageal manometry].

The intraoperative esophageal manometry (IEM) has been used to improve results in operative management of gastroesophageal reflux and achalasia. The IEM pointed out the necessity to perform an antireflux procedure with an intraoperative sphincter pressure higher than normal, because the measured postoperative sphincter pressures were one-half the intraoperative values measured after repair. Nevertheless some authors failed to find any correlation between intraoperative and subsequent postoperative sphincter pressure measurements. The Authors, in their experience, achieved the same results with and without IEM in the surgical management of gastroesophageal reflux and achalasia. For this reason The IEM does not seem to be necessary when performing the standard Nissen or Heller procedure. It is probably useful in the surgical treatment of patients with motor disorders or sclerodermia associated with reflux and in patients who have had multiple prior operations for reflux or achalasia.

Adult↗

Early evaluation and therapy for caustic esophageal injury.

Forty-one patients with caustic ingestion were reviewed. Eighty-three percent were children, all of whom suffered accidental injury. Liquid drain cleaner was the agent in 57 percent and was responsible for all esophageal burns. Symptoms and physical findings were unreliable in predicting the extent of injury. Endoscopy was performed in most patients within 36 hours of ingestion and accurately estimated the risk of subsequent esophageal stricture formation. Steroid administration had no influence on the development of strictures. Esophageal strictures developed in 22 percent of the patients. One-third were successfully managed by periodic dilation, whereas the remaining two-thirds required esophagectomy and reconstruction. Early endoscopic evaluation was the best means of assessing the degree of injury after caustic ingestion. Routine steroid administration had no apparent clinical benefit.

Adult↗

Biomolecular-solvent stereodynamic coupling probed by deuteration.

Thermodynamic interpretation of experiments with isotopically perturbed solvent supports the view that solvent stereodynamics is directly relevant to thermodynamic stability of biomolecules. According with the current understanding of the structure of the aqueous solvent, in any stereodynamic configuration of the latter, connectivity pathways are identifiable for their topologic and order properties. Perturbing the solvent by isotopic substitution or, e.g., by addition of co-solvents, can therefore be viewed as reinforcing or otherwise perturbing these topologic structures. This microscopic model readily visualizes thermodynamic interpretation. In conclusion, the topologic stereodynamic structures of connectivity pathways in the solvent, as modified by interaction with solutes, acquire a specific thermodynamic and biological significance, and the problem of thermodynamic and functional stability of biomolecules is seen in its full pertinent phase space.

Deuterium↗

The role of distal dendritic gap junctions in synchronization of mitral cell axonal output.

One of the first and most important stages of odor processing occurs in the glomerular units of the olfactory bulb and most likely involves mitral cell synchronization. Using a detailed model constrained by a number of experimental findings, we show how the intercellular coupling mediated by intraglomerular gap junctions (GJs) in the tuft dendrites could play a major role in sychronization of mitral cell action potential output in spite of their distal dendritic location. The model suggests that the high input resistance and active properties of the fine tuft dendrites are instrumental in generating local spike synchronization and an efficient forward and backpropagation of action potentials between the tuft and the soma. The model also gives insight into the physiological significance of long primary dendrites in mitral cells, and provides evidence against the use of reduced single compartmental models to investigate network properties of cortical pyramidal neurons.

Animals↗

A model of the effects of cognitive load on the subjective estimation and production of time intervals.

How and where the brain calculates elapsing time is not known, and one or more internal pacemakers or others timekeeping systems have been suggested. Experiments have shown that the accuracy in estimating or producing time intervals depends on many factors and, in particular, both on the length of the intervals to be estimated and on the additional, and unrelated, cognitive load required during the task. The psychological 'attentional approach' is able to explain the experimental data in terms of perturbations of a cognitive timer. However, the basic biophysical mechanisms that could be involved at the single neuron level are still not clear. Here we propose a computational model suggesting how the process to focus the attention on a non-temporal task could alter the perception of time intervals as observed in the experiments. The model suggests that an attention-based excitatory and/or inhibitory background synaptic noise, impinging on the pacemaker circuit, could represent both qualitative and quantitative features of the cognitive load. These effects are predicted to be independent of the number, location or specific implementations of the internal timing systems.

Brain↗

Energy efficient modulation of dendritic processing functions.

The voltage dependent ionic conductances and the passive properties of the neural membrane determine how external inputs are processed by the dendritic tree, and define the computational characteristics of neurons. However, what controls these characteristics and how they are implemented at the single neuron level, in such a way that an external input results in the coding of the appropriate output, is essentially unknown. We show here that a slow inactivation of the Na+ channel, involved in the attenuation and/or failure of APs in the dendrites, acts as an active and energy efficient filter of synaptic input, and results in an activity-dependent control of the properties of individual neurons. Thus, the activation or expression of this mechanisms could be an efficient way to selectively modulate the input/output processing properties of dendrites, and could be needed to limit or suppress the onset of a number of pathological brain disorders.

Action Potentials↗

Role of an A-type K+ conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons.

Action potentials elicited in the axon actively back-propagate into the dendritic tree. During this process their amplitudes can be modulated by internal and external factors. We used a compartmental model of a hippocampal CA1 pyramidal neuron to illustrate how this modulation could depend on (1) the properties of an A-type K+ conductance that is expressed at high density in hippocampal dendrites and (2) the relative timing of synaptic activation. The simulations suggest that the time relationship between pre- and postsynaptic activity could help regulate the amplitude of back-propagating action potentials, especially in the distal portion of the dendritic tree.

Action Potentials↗

Dendritic Ih selectively blocks temporal summation of unsynchronized distal inputs in CA1 pyramidal neurons.

The active dendritic conductances shape the input-output properties of many principal neurons in different brain regions, and the various ways in which they regulate neuronal excitability need to be investigated to better understand their functional consequences. Using a realistic model of a hippocampal CA1 pyramidal neuron, we show a major role for the hyperpolarization-activated current, Ih, in regulating the spike probability of a neuron when independent synaptic inputs are activated with different degrees of synchronization and at different distances from the soma. The results allowed us to make the experimentally testable prediction that the Ih in these neurons is needed to reduce neuronal excitability selectively for distal unsynchronized, but not for synchronized, inputs.

Animals↗

[Systemic neoadjuvant chemotherapy in locally advanced gastric carcinoma: phase II study with 5-fluorouracil, epirubicin and etoposide].

Locally advanced gastric adenocarcinomas have a poor prognosis, particularly when the tumours are bulky, located in the cardia or when they present local/regional lymph node involvement. Neoadjuvant chemotherapy for locally advanced gastric cancer is an experimental treatment strategy that may increase resectability and improve survival in patients suffering from an almost uniformly fatal neoplasm. At our institution 11 patients younger than 70 years of age in good physical and mental condition with non-resectable adenocarcinomas of the stomach as determined by endoscopy, computed tomography scans and pathology examinations, were treated with combination chemotherapy [5-fluorouracil (375 mg/m2 i.v. for 5 days, epirubicin (60 mg/m2 i.v. on day 1), etoposide 80 mg/m2 on days 1, 2 and 3, leucovorin 100 mg/m2 for 5 days] every 4 weeks as neoadjuvant chemotherapy. The response to chemotherapy was evaluated after three courses. After three courses, we had one complete response, 8 partial responses or stable disease, and no response in two cases. One patient was still alive 36 months postoperatively. These preliminary results suggest that this protocol is an effective form of neoadjuvant chemotherapy for locally advanced gastric carcinoma.

Adenocarcinoma↗

[Ogilvie's syndrome].

Ogilvie's Syndrome is defined as acute distension of the colon without any mechanical obstruction. We reported two new cases who underwent surgical treatment and the revision of the literature. Four hundred eight-six cases are described until now. The physiopathology is unknown. The diagnosis is done with abdominal x-ray, barium enema must be used with attention. The more frequent symptoms are nausea, vomiting, diarrhea, and abdominal pain. The perforation of the colon is possible with a diameter of 9-12 cm. The mortality was 11.3% in two hundred ninety patients (59.6%) who underwent conservative treatment. In one hundred ninety-six patients who underwent surgical treatment the mortality was 28.5%. The treatment is conservative, medical or endoscopic. The best surgical treatment is the tube cecostomy.

Aged↗