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D Fitzpatrick

Publications and source records attributed to D Fitzpatrick.

At least 55 records · Page 3Linked to original sources
PubMed1996

Specificity in the axonal connections of layer VI neurons in tree shrew striate cortex: evidence for distinct granular and supragranular systems.

Pyramidal neurons in layer VI of striate cortex are the source of descending projections to the lateral geniculate nucleus (LGN) as well as a major source of axon terminals in the layers of striate cortex that receive LGN projections. This study examines how the connections of layer VI neurons are arranged with respect to the functionally distinct classes of neurons that compose their cortical and subcortical targets. By placing injections of biocytin into layer VI of tree shrew striate cortex, we identified two sublayers that differ in their intracortical and thalamic connections. Neurons in the upper part of layer VI, layer VIa, terminate in cortical layer IV, whereas those in the lower part of layer VI, layer VIb, terminate throughout the supragranular layers, layers I-III. The selectivity of layer VI subdivisions for the granular and supragranular layers is also evident in their descending projections. Neurons in layer VIa terminate preferentially in the LGN layers that supply layer IV (LGN layers 1, 2, 4, and 5), whereas neurons in layer VIb terminate in the LGN layers that supply layers I-III (LGN layers 3 and 6) and in the pulvinar nucleus. Additional subclasses of layer VIa neurons were identified based on the restriction of their terminal fields to narrow subtiers within layer IV. By influencing the activity of distinct populations of cortical neurons and the thalamic neurons that supply them, layer VI neurons could exert a powerful influence on the flow of activity in functionally distinct cortical circuits.

Animals↗
PubMed1996

Modification of CAPS-1 for diagnosis of PTSD in Afghan refugees.

A DSM-III-R based instrument for the assessment of posttraumatic stress disorder (PTSD), the Clinician-Administered PTSD Scale (CAPS-1), was modified to accommodate cultural differences and translated into the Afghan languages Pushto and Farsi (Dari) and administered to 30 Afghan refugees living in the United States. The modified CAPS-1 was found to be practical and reliable. Inter-item correlations were calculated on the frequency and intensity scores for the 17 cardinal symptoms and the eight associated features items of the modified CAPS-1. The four reexperiencing items demonstrated significant independence from the avoidance and arousal symptom clusters. However, the avoidance and arousal symptom clusters were not found to be independent cardinal components of PTSD in our participants. The CAPS-1 criteria for diagnosis of PTSD were met by 50% of the subjects evaluated.

Adolescent↗
PubMed1995

Patterns of excitation and inhibition evoked by horizontal connections in visual cortex share a common relationship to orientation columns.

Combined optical imaging and electrophysiological techniques were used to assess directly the functional nature of long-range excitatory and inhibitory synaptic interactions between orientation columns in area 17 of ferret visual cortex. A significant correlation was found between the layout of iso-orientation columns and the pattern of evoked synaptic inputs between cortical sites: the largest-amplitude inhibitory and excitatory synaptic responses were evoked in single neurons when stimulation and recording electrodes were located in orientation columns sharing the same angle preference. Both excitatory and inhibitory synaptic responses decreased in amplitude when stimulation and recording electrodes were located in orientation columns with orthogonal angle preferences. Changing the stimulus intensity altered the balance of evoked excitation and inhibition without changing the columnar specificity of inputs. These results directly demonstrate that horizontal connections modulate both excitatory and inhibitory synaptic interactions between iso-orientation columns.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Therapeutic controversies with use of beta-adrenoceptor blockade in heart failure.

In response to early reports indicating a beneficial adrenoceptor effect of beta blockade, 2 small trials were conducted to investigate the hemodynamic effects of acute and chronic beta-adrenoceptor blockade in patients with congestive cardiomyopathy. Acute beta-blocker therapy with intravenous acebutolol, 25 mg, resulted in a significant decline in cardiac performance, whereas chronic therapy with acebutolol, 200 mg twice daily, resulted in no beneficial effects on exercise tolerance, as reported by the original Swedish investigators. Further, beta-adrenoceptor blockade has been associated with a number of clinical problems: beta blockers tend to interfere with the compensatory mechanisms that support circulation during early or mild heart failure and therefore have little value as routine therapy at that stage of the disorder. Although excessive beta-adrenoceptor blockade may worsen ventricular function by decreasing myocardial contractility, beta blockers appear to have a useful role in patients with moderate heart failure accompanied by tachycardia. Carefully titrated doses of beta blockers in conjunction with afterload-reducing agents may also provide a benefit in patients with rapid heart rates and grossly elevated levels of circulating catecholamines.

Acebutolol↗
PubMed1993

Calcium binding proteins distinguish large and small cells of the ventral posterior and lateral geniculate nuclei of the prosimian galago and the tree shrew (Tupaia belangeri).

Two different cell types were identified in the thalamus of galago and Tupaia by using antibodies to two calcium binding proteins, calbindin and parvalbumin. In each species studied, the lateral geniculate nucleus consists of six layers, two of which have smaller relay cells. Previous studies have shown that the small cell layers receive fibers from the superior colliculus and project to the superficial layers of the striate cortex. These are the only geniculate layers that react to a calbindin antibody but not parvalbumin. The ventral posterior nucleus was included in the study and the results for both nuclei show that calbindin is a marker for thalamic cells that receive small fibers and project to superficial layers of koniocortex.

Animals↗
PubMed1993

Cerebral-evoked potential responses following direct vagal and esophageal electrical stimulation in humans.

Cerebral evoked responses following direct electrical stimulation of the vagus and esophagus were compared in 8 epileptic subjects and with those recorded after esophageal stimulation in 12 healthy nonepileptic controls. Direct vagal stimulation was performed using a left cervical vagal pacemaker, which is used in the treatment of epilepsy. Esophageal stimulation was obtained with the use of an esophageal assembly incorporating two electrodes positioned 5 and 20 cm orad to the lower esophageal sphincter. Evoked potential responses were recorded with the use of 20 scalp electrodes. The evoked potential responses consisted of three distinct negative peaks and were similar with the use of either vagal or esophageal stimulation. The measured conduction velocity of the afferent response was 7.5 m/s in epileptic subjects and 10 m/s in healthy controls, suggesting that afferent conduction is through A delta-fibers rather than slower C afferent fibers. We conclude that the cortical-evoked potential responses following esophageal electrical stimulation are comparable to direct electrical stimulation of the vagus nerve and involve mostly A delta-fibers. This approach provides a method for the assessment of vagal afferent gastrointestinal sensory pathways in health and disease.

Adult↗
PubMed1992

Lateral geniculate projections to the superficial layers of visual cortex in the tree shrew.

Our recent studies of tree shrew striate cortex have focused on the organization of lateral geniculate projections to layer IV and the projections from IV to layer III. Although these pathways play an important role in determining the response properties of layer III neurons, there are additional pathways from the lateral geniculate nucleus (LGN) that terminate directly in layer III. Previous studies provided evidence that these projections originate from layers 6 and 3 of the LGN and terminate in different subdivisions of layer III. In this study we used injections of biocytin to examine the projections of layers 6 and 3 to the cortex in more detail. Consistent with earlier work, we found that LGN layer 6 projects heavily to lower IIIc, while LGN layer 3 terminates densely in layer IIIb and sparsely throughout layers IIIa-I. In addition, we found that neurons in layers 6 and 3 have collateral projections: neurons in LGN layer 6 project to the bottom of layer IVb and sparsely to I-IIIb; neurons in LGN layer 3 project sparsely to layers V and VI and to the middle of IV. These patterns of projections are significant in the light of our studies of the connections from cortical layer IV to layer III. LGN projections to the superficial layers are organized into parallel pathways that exert selective influence over different populations of neurons in layers I-III and on the layer IV neurons that supply them.

Animals↗
PubMed1992

A projection from the parabigeminal nucleus to the pulvinar nucleus in Galago.

A projection from the parabigeminal nucleus (Pbg) to the striate-recipient zone of the pulvinar nucleus in the prosimian Galago was identified by anterograde and retrograde transport methods. In addition to the pulvinar nucleus, Pbg projections were found to terminate in layers 4 and 5 of the dorsal lateral geniculate nucleus and the central lateral nucleus. All three of these structures project to the superficial layers of the striate cortex. Similarities between the Pbg in mammals and the nucleus isthmi in nonmammals in connections and neurochemistry reinforce the idea that these two nuclei are homologous.

Animals↗
PubMed1992

Effects of chronic left vagal stimulation on visceral vagal function in man.

We examined the effects of chronic left vagal electrostimulation on afferent and efferent gastrointestinal vagal function in eight patients. Afferent function was assessed using cortical evoked responses to electrical stimulation of the esophagus and to direct vagal stimulation using the implanted left vagal electrode. Efferent gastrointestinal vagal function was measured by examining the basal, maximal, and sham fed stimulated gastric acid output prior to and with chronic left vagal electrostimulation. Esophageal electrostimulation produced a cortical evoked response consisting of three negative and three positive peaks within 400 msec after stimulation. Prior to vagal electrostimulation the mean conduction velocity of the afferent signal was measured at 8.72 +/- 3.39 m/sec, compatible with A-delta fibers involvement. Basal, maximal, and sham fed acid output were 1.11, 21.87, and 9.37 mmol/hour, respectively. The evoked response to esophageal electrical stimulation was not changed with chronic left vagal electrostimulation. Direct vagal stimulation also produced evoked potentials that were comparable to those obtained with esophageal stimulation. The mean conduction velocity was 6.26 +/- 2.72 m/sec (NS) so that there was no evidence of loss of myelinated fibers with chronic stimulation. No differences were detected in basal (1.29 mmol/h), maximal (21.64 mmol/h), or sham fed stimulated (8.03 mmol/h) acid output, showing that vagal electrostimulation has no effect on either total or vagally mediated acid output, an efferent vagal function. In conclusion, chronic left vagal electrostimulation has no significant adverse effect on gastrointestinal vagal function.

Adult↗
PubMed1992

Evidence of impaired afferent vagal function in patients with diabetes gastroparesis.

Two patients, a 28-year-old male and a 70-year-old female, with chronic insulin dependent diabetes mellitus and evidence of autonomic neuropathy were studied using cortical evoked responses following esophageal balloon and electrical stimulation. Both patients had symptomatic gastroparesis, poor gastric emptying, and reduced gastroduodenal motility including abnormal results of scintigraphy and manometry. There was slowing of afferent vagal conduction but good evoked potential responses were recorded even though one patient could not feel electrical stimulation of either the proximal or distal esophagus. It is improbable that the gastric symptoms are due to an afferent autonomic neuropathy, but symptoms may well be related to impairment of motor vagal pathways. Nevertheless, afferent vagal pathways are involved in severe diabetes mellitus. The clinical significance of this delay in conduction velocity of afferent pathways remains to be established.

Adult↗
PubMed1992

Cellular mechanisms of ventricular failure: myocyte kinetics and geometry with age.

To determine whether heart failure is a consequence of alterations in cardiac cellular performance, myocytes were isolated from Fischer 344 rats at 4, 12, 20, and 29 mo of age and studied mechanically and morphometrically. Left ventricular myocyte length increased by 14.5, 14.4, and 24.0% at 12, 20, and 29 mo when compared with 4-mo-old animals. An 11.4 and 14.2% increase in length was seen for right ventricular myocytes from 4 to 12 mo and from 20 to 29 mo, respectively. Although no change in cell width was seen in either ventricle as a function of age, myocardial cells were more irregular in shape and consistently longer in the left ventricle at 20 and 29 mo. Left myocytes at 29 mo revealed diminished velocities of shortening (31.7%) and relengthening (59.5%). Contraction duration increased due to a 28.9% prolongation of time to peak shortening and a 26.5% increase in time to relengthening, resulting in a 25.8% decrease in myocyte shortening at 29 mo. Similar changes were observed in right ventricular myocytes, but they occurred later in life. Thus the alterations in myocyte geometry and depression in contractile performance seen here are major contributors to the eccentric dilated ventricular chamber and diminished pump function previously documented in the age-related transition from normal cardiac dynamics to left ventricular dysfunction and failure.

Aging↗
PubMed1992

The morphological basis for binocular and ON/OFF convergence in tree shrew striate cortex.

We used retrograde and anterograde transport methods and single-cell reconstructions to examine the projection from layer IV to supragranular layers in the tree shrew's striate cortex. We found that neurons in the ON and OFF subdivisions of layer IV (IVa and IVb, respectively) have overlapping terminal fields throughout layers II and III. Despite their overlap, these projections are organized in a highly stratified, mirror-symmetric fashion that respects the vertical position of neurons within each sublayer. Neurons in the middle of layer IV (lower IVa and upper IVb) project to layers IIIa/b, II, and I; neurons located at the edges of layer IV (upper IVa and lower IVb) project to the lower half of layer IIIc; and neurons in the middle of IVa and the middle of IVb project to upper IIIc. The stratified nature of the projections from layer IV to layer III is reminiscent of the pattern of ipsilateral and contralateral eye inputs to layer IV. Inputs from the ipsilateral eye are limited to the edges of layer IV (upper IVa and lower IVb), while those from the contralateral eye terminate throughout the depth of IVa and IVb. Thus, cells near the edges of layer IV should receive strong input from both eyes, while those in the middle of layer IV should receive mostly contralateral input. Taken together, these results suggest that the projections from layer IV to layer III bring together the information conveyed by the ON and OFF pathways, but do so in a way that matches the ocular dominance characteristics for each pathway.

Animals↗
PubMed1991

Design and synthesis of a mimetic from an antibody complementarity-determining region.

A technique for producing non-peptide compounds (mimetics) of designed specificities was developed that permitted the synthesis of a conformationally restricted molecule that mimicked the binding and functional properties of monoclonal antibody (MAb) 87.92.6, which recognizes the reovirus type 3 cellular receptor. Binding of either MAb 87.92.6, peptide analogs, or 87.1-mimetic to the cellular receptor inhibited cellular proliferation. The mimetic was a synthetic beta-loop structure that mimics the second complementarity-determining region of the MAb. These studies may lead to strategies for the synthetic design of antibody complementarity regions, ligands, and other pharmacologically active agents that are water soluble, resistant to proteolysis, and nonimmunogenic.

Antibodies, Monoclonal↗
PubMed1991

Evidence for separate pathways within the tecto-geniculate projection in the tree shrew.

Two layers (3 and 6) in the dorsal lateral geniculate nucleus (GLd) of the tree shrew (Tupaia belangeri) receive projections from the superficial layers of the superior colliculus. The goal of this study was to determine whether the same or different cells in the superior colliculus give rise to the projections to layers 3 and 6 by following individual axons labeled with biocytin from the superior colliculus to the GLd. The results show that the terminal fields differ in the two layers--those in layer 3 are restricted to a line of projection, whereas those in layer 6 are elongated along the dimension orthogonal to a line of projection. Another important difference between axons that project to GLd layers 3 and 6 is that those that project to layer 6 give off collaterals to the posterior pretectal nucleus, whereas at least some axons that project to layer 3 send a collateral to the ventral lateral geniculate nucleus (GLv). These results suggest that the superior colliculus exerts separate influences on these two GLd layers, both of which project to separate targets above layer IV in the striate cortex. The biocytin method has proved useful by showing the dendritic trees of the superior colliculus cells of origin, the pathways taken by the axons (including the presence of collaterals), and the terminal fields both within and outside the GLd.

Animals↗
PubMed1991

Distribution and morphology of area 17 neurons that project to the cat's extrastriate cortex.

We used intracellular dye injections in lightly fixed cortical slices to examine the distribution and morphology of area 17 neurons that project to extrastriate cortex. Both the projection to the medial bank of the posterior lateral suprasylvian sulcus (PMLS) and the projection to area 18 arise from a number of different morphological types distributed throughout layers 2-6. The majority are found in the superficial layers and include large, medium, and small pyramidal neurons. Some are also found in the deep layers and they include very large, pyramidal neurons as well as some heretofore undescribed, fusiform neurons. The projection to area 18 contains two types not found in the projection to PMLS: spinous stellate neurons in layer 4 and inverted pyramidal neurons in layer 3. Finding that a variety of morphological types contribute projections to a single cortical area raises the possibility that corticocortical projections, like retinogeniculate and geniculocortical projections, comprise multiple parallel pathways with different physiological properties and patterns of termination. Finding that the projection to area 18 contains morphological types that do not project to PMLS indicates that the projections from area 17 are likely to contribute to the functional specialization of extrastriate visual areas.

Animals↗
PubMed1991

Yohimbine and naloxone: effects on male rat sexual behavior.

We evaluated the effects of yohimbine (2 mg/kg) and naloxone (5 mg/kg), separately and in combination, on copulatory behavior in male rats. In Experiment 1, yohimbine evinced decrements in intromission frequency, ejaculation latency, and copulatory efficiency, whereas naloxone administration was followed by an increased ejaculation latency, and the combination of yohimbine plus naloxone was without effect. In Experiment 2, yohimbine evinced decreases in intromission frequency, ejaculation latency, copulatory efficiency in the first, but not subsequent, copulatory series, as well as a decreased latency to sexual exhaustion. Further, treatment with yohimbine alone, naloxone alone, or yohimbine plus naloxone was followed by a reduction in the number of ejaculation prior to sexual exhaustion. Thus, at the doses tested, no synergistic effects were observed for the combination of yohimbine plus naloxone.

Animals↗