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D Fitzpatrick

Publications and source records attributed to D Fitzpatrick.

At least 91 records · Page 5Linked to original sources
PubMed1985

Pharmacokinetics and plasma-concentration-effect relationships of prenalterol in cardiac failure.

Prenalterol was administered as an intravenous infusion at three incremental rates (60, 120 and 240 nmol/min) to five patients with severe cardiac failure. Haemodynamic, hormonal and metabolic variables were measured at the same time as plasma prenalterol concentrations, and the pharmacokinetics of the drug were studied by following plasma concentrations and urinary excretion during and after the infusion. Concentration-dependent increases in cardiac index, stroke index and stroke work index were observed without increases in arterial pressure, heart rate or myocardial oxygen demand. The reninangiotensin-aldosterone system was stimulated, although the extent of stimulation varied among patients. No strong correlations were found between the logarithm of the plasma prenalterol concentration and effect. Plasma clearance of the drug was lower in cardiac patients than in normal volunteers, but a large decrease in renal clearance was partially balanced by an increase in nonrenal clearance. Over the observed range of concentrations, no deviation from linearity was evident, and plasma concentrations of about 150 nmol/l were effective in improving cardiac function without significant side-effects.

Adrenergic beta-Agonists↗
PubMed1985

Immunocytochemical localization of contractile and contraction associated proteins in the spiral ligament of the cochlea.

Most of the extracellular fibers of the spiral ligament are associated with a distinct band of 'anchoring' cells which occur at the boundary between the spiral ligament and the otic capsule. These cells are characterized by parallel arrays of intracellular filaments which, along with the extracellular fibers, insert into electron dense, conical adhesion plaques. The intracellular filaments show a close morphological resemblance to the 'stress fibers' of cultured fibroblasts (Henson et al., 1984). In the present study we have demonstrated by immunofluorescence techniques that the anchoring cells, unlike adjacent cells of the spiral ligament, contain a complement of proteins that is typically associated with stress fibers and with contractile systems. In addition to actin, the cells contain myosin, tropomyosin, alpha-actinin and talin. These results lend further support to the hypothesis that the anchoring cells have the capacity to create and/or maintain tension on the spiral ligament-basilar membrane complex and to influence the mechanical properties of the basilar membrane.

Actinin↗
PubMed1985

Intrinsic connections of macaque striate cortex: afferent and efferent connections of lamina 4C.

We have studied the intrinsic organization of macaque striate cortex by tracing the pattern of horseradish peroxidase (HRP)-labeled axons and cell bodies produced by microinjections of HRP into single cortical laminae. Both anterograde and retrograde transport results were used to examine: (1) the pattern of projections from lamina 4C to the superficial layers; (2) the projection from lamina 4C to deeper cortical layers; and (3) the projections to lamina 4C from other cortical laminae. Laminae 4C alpha and 4C beta differ in their pattern of projections to the superficial layers of striate cortex. Axons from neurons in lamina 4C beta ascend through lamina 4B without giving off collaterals and terminate in lamina 4A and in the base of lamina 3. By contrast, axons from neurons in lamina 4C alpha terminate in lamina 4B and less densely in the 4A/3B region. The projection from lamina 4C beta to lamina 4A is particularly dense and is distributed in a patchy fashion immediately above each injection site. The projection from lamina 4C beta to lamina 3B appears less dense and more widespread; we estimate that individual 4C beta axons may spread laterally for more than 400 micron. Furthermore, the pattern of HRP-labeled cell bodies in lamina 4C beta following injections into laminae 4A and 3B provides evidence for a subdivision within 4C beta. These injections always produce a large number of labeled neurons in the upper part of lamina 4C beta, whereas the lower portion contains few labeled neurons that are located immediately under the center of the injection site. Both lamina 4C alpha and lamina 4C beta also contribute less dense projections to the deeper layers of cortex. Lamina 4C beta projects mainly to lamina 6, whereas lamina 4C alpha contributes axon terminals to both lamina 5A and lamina 6. Neurons in lamina 6 provide the bulk of the intracortical projections to lamina 4C. The axons of these neurons are fine in caliber and have a delicate side-spine morphology that is quite distinct from lateral geniculate axon arbors. Neurons in lamina 5A also project onto lamina 4C, but the projections of these neurons appear concentrated in lamina 4C alpha. These results confirm or refine many conclusions about intrinsic connections of striate cortex drawn from Golgi material and suggest new patterns of connections not suspected from previous work.

Afferent Pathways↗
PubMed1985

Intrinsic connections of macaque striate cortex: axonal projections of cells outside lamina 4C.

We have exploited a technique for making small injections of horseradish peroxidase into single cortical laminae in order to study axonal projections in macaque striate cortex. In the preceding paper (Fitzpatrick, D., J. S. Lund, and G. G. Blasdel (1985) J. Neurosci. 5: 3329-3349) we examined the projections of cells in lamina 4C--cells that receive most of their input from the lateral geniculate nucleus. The present paper deals with the projections of neurons that lie outside of lamina 4C. Among our findings are several projections that previously had not been described in the monkey. These include: a strong and precise (point-to-point) projection from lamina 4B to lamina 2/3A, a reciprocal projection from 2/3A back to 4B, a definite projection from lamina 4B to 5B, as well as a prominent input to lamina 6 from 5B. In many cases, we find it possible to trace the flow of visual information through several "circuits" in striate cortex that have, as their output, projections to extrastriate cortex or to the brainstem. Our results offer additional insights in this regard since we are able, in many cases, to compare the lateral spreads of particular projections. These vary and can be separated into at least three categories: those that terminate in a precise, point-to-point, fashion, those that spread widely, and those that terminate in a laterally periodic fashion. In several cases we find evidence for a correlation between specific patterns of projection and known physiological differences between the topographies of laminae that are connected. In cases where two laminae possess similar topographies (for example, where both contain orderly maps for orientation) their interconnections appear precise, with little diffuse spread. In cases where two laminae are characterized by strikingly different topographies (where, for example, one contains an orderly map for orientation and the other a precise map for retinotopic position, but no specificity for orientation), the connections appear more diffuse.

Animals↗
PubMed1984

GABAergic neurons of mammalian cerebral cortex: widespread subclass defined by somatostatin content.

GABAergic neurons are found in all layers of cerebral cortex and display many types of non-pyramidal morphology. Most are intensely immunoreactive for neuron-specific enolase, suggesting a high rate of metabolic activity. The molecular layer and subcortical white matter are strikingly enriched in GABAergic cell bodies compared to other cortical layers. In rat, cat and monkey, many GABAergic neurons in the subcortical white matter and certain cortical layers are also immunoreactive for the neuropeptide somatostatin. Somatostatin content may define a widespread subclass of GABAergic neurons in mammalian cerebral cortex. Some may be similar in function to reticular neurons of thalamus.

Animals↗
PubMed1984

Glutamic acid decarboxylase-containing neurons in the dorsal column nuclei of the cat.

The retrograde transport of horseradish peroxidase (HRP) and immunocytochemistry for glutamic acid decarboxylase (GAD) have been employed to examine whether local circuit neurons (LCNs) exist in the dorsal column nuclei (DCN) and whether these neurons may be GABA-ergic. Observations focused on the dorsal part of the middle cuneate nucleus (MCd), since this region has been previously shown to contain projecting neurons whose axons terminate almost exclusively in the contralateral thalamus. After large injections of HRP in the nucleus ventralis posterolateralis and surrounding structures of the feline thalamus, the majority of neurons in MCd are labeled. These represent about 89% of the neurons in MCd as counted in 40-microns frozen sections, and about 69% as counted in plastic-embedded, 2.5-microns-thick section. Unlabeled by the same injections are some medium to large neurons at the dorsal rim of MCd, and many characteristically small (mean = +/- 250 microns2) neurons at the periphery of the cell clusters formed by thalamic-projecting neurons. These small neurons represent 10-12% of the neuronal population of MCd, as counted in 40-microns-thick frozen sections, and about 30%, as counted in plastic-embedded, 2.5-microns-thick sections. Neurons in this size range are also unlabeled after injection of retrograde tracer in the pretectal area, inferior and superior colliculi, inferior olivary complex, and/or spinal cord. These injections, however, result in the labeling of neurons along the dorsal rim of MCd and/or in other regions of the cuneate nucleus. In adult, colchicine-treated cats, the use of anti-GAD serum reveals a population of labeled neurons uniformly distributed throughout the DCN. In MCd, these are small (mean = +/- 235 microns2) neurons mainly intercalated between cell clusters, and represent about 25% of the neuronal population of this nuclear subdivision as counted in plastic-embedded, 2.5-microns-thick sections. Labeled processes densely infiltrate the cell clusters, and labeled varicosities appear to cover the soma and dendrites of unlabeled neurons. At the electron-microscopic level, most labeled profiles contain vesicles and correspond to F boutons usually involved in "axoaxonic" contacts with terminals of dorsal root afferent and presynaptic to dendrites. Other vesicle-containing, GAD-positive endings seem to correspond to the P boutons described by Ellis and Rustioni (1981) and are believed to be, at least in part, of dendritic origin. It is suggested that GAD-positive neurons are GABA-ergic LCNs and that these can mediate both pre- and postsynaptic inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

The laminar organization of the lateral geniculate body and the striate cortex in the tree shrew (Tupaia glis).

The organization of geniculostriate projections in Tupaia was studied using three separate methods, anterograde transport from the lateral geniculate, retrograde transport from the striate cortex, and reconstruction of single geniculostriate axons. The results show that each layer of the lateral geniculate body has a unique pattern of projections to the striate cortex, and each pattern consists of a major and a minor target. The two ipsilateral layers project to thin subtiers of layer IV: the major target of geniculate layer 1 is the top of IVa; the major target of geniculate layer 5 is the base of IVb. The minor target of layer 1 is the major target of layer 5. Two of the contralateral layers can be matched to the ipsilateral layers. Layers 1 and 2 are a matched pair and project to IVa; layers 4 and 5 are a matched pair and project to IVb. Thus, projections of a matched pair overlap. The remaining two contralateral layers, 3 and 6, project chiefly to cortical layer III. Layer 3 projects to layers IIIb and I and seems to be the counterpart of the parvocellular C layers in the cat and the intercalated layers in primates. Layer 6 projects to the base of IIIc in a zone contiguous with IVa. This contiguity raises the issue of whether the base of IIIc might actually be a part of layer IV. If this were the case, the two tiers of layer IV which are separated by a conspicuous cleft might be considered two subdivisions of layer IVb.

Afferent Pathways↗
PubMed1984

Physiological organization of layer 4 in macaque striate cortex.

Numerous highly angled electrode penetrations through the opercular region of macaque striate cortex reveal that layers 4A, 4C alpha, and 4C beta--the primary input sublaminae for axons from the lateral geniculate nucleus (LGN)--are retinotopically organized on a fine scale and populated mostly by monocularly driven cells having small receptive fields and lacking orientation selectivity. Layer 4B, which does not receive a direct thalamic input, contains orientationally selective cells, and many of these are also direction selective. To a significant degree the response properties of cells in layers 4C alpha and 4C beta reflect the response properties of their respective afferent inputs, from the magno- and parvocellular laminae of the LGN. Accordingly, cells in layer 4C alpha have lower contrast thresholds and larger minimum response fields than do the cells in layer 4C beta. In contrast to this clear-cut separation, the cells of layer 4A (whose major source of direct LGN input arises from the parvocellular layers) exhibit both high and low contrast thresholds. With regard to the precision of retinotopic mapping that is seen in lamina 4C, it is noteworthy that there is substantial overlap among the minimum response fields of neighboring neurons. Due to a larger mean receptive field size, this overlap is greater in layer 4C alpha than it is in 4C beta. In either sublamina, however, the minimum cortical distance that separates different and nonoverlapping parts of the visual field corresponds closely--within a factor of 2--to the known arborizational spreads of single geniculate afferents.

Animals↗
PubMed1984

Glutamic acid decarboxylase-immunoreactive neurons and terminals in the lateral geniculate nucleus of the cat.

We have examined the distribution of neurons and terminals that are immunoreactive for glutamic acid decarboxylase (GAD), the synthesizing enzyme for the inhibitory neurotransmitter gamma-aminobutyric acid within the lateral geniculate nucleus of the cat. We estimate that GAD-positive neurons constitute approximately one-fourth of the neurons in all layers of the lateral geniculate nucleus and in the medial interlaminar nucleus (MIN). In addition, almost all of the neurons within the perigeniculate nucleus are GAD-positive. The mean size of GAD-positive cell bodies is significantly smaller than the mean size of unlabeled neurons in all subdivisions of the lateral geniculate nucleus. GAD-positive neurons have thick primary dendrites which are associated with thin lightly immunoreactive processes that give rise to clusters of GAD-positive terminals. Clusters of GAD-positive terminals are prominent in lamina A, A1, magnocellular C, and MIN but are rare in the parvocellular C laminae. Within the A laminae, GAD immunoreactivity is found within vesicle-containing profiles of the synaptic glomerulus lying postsynaptic to optic axon terminals and presynaptic to unlabeled dendritic profiles. GAD-positive neurons in the A laminae are distinguished from other small to medium-sized neurons by their failure to label following injections of HRP into visual cortex and by their lack of cytoplasmic laminated body. These results support the idea that GAD-positive neurons constitute a distinct population of neurons in the lateral geniculate nucleus of the cat; a population which has a number of features in common with previous descriptions of presumed local circuit neurons based on Golgi staining.

Animals↗
PubMed1983

Improved visualization of neurons labeled with horseradish peroxidase: silver-intensification of the pyrocatechol/p-phenylenediamine reaction product.

A silver intensification procedure suitable for use with pyrocatechol/p-phenylenediamine (PC-PPD) product of the horseradish peroxidase (HRP) reaction is described. Qualitative and quantitative results from retrogradely labeled neurons in the cat cortex after thalamic injection of HRP demonstrate an increase of the intensity of labeling and in the number of darkly labeled cells after the intensification procedure. In both the non-intensified and the intensified PC-PPD reacted tissue the sensitivity was comparable to that of TMB-treated material. The ratio of lightly to darkly labeled neurons was very similar in intensified PC-PPD and TMB material, suggesting that the lightly labeled cells may have fewer terminals present at the level of the injected target.

Animals↗
PubMed1983

Haemodynamic, hormonal, and electrolyte effects of enalapril in heart failure.

Enalapril, the new converting enzyme inhibitor, was administered to eight patients with heart failure (NYHA Functional Class II to IV) during standardised and intensive haemodynamic, hormone, and electrolyte monitoring. The first dose (5 mg) of enalapril induced a fall in plasma angiotensin II and noradrenaline levels, and prolonged decrements in systemic vascular resistance, arterial pressure, heart rate, and right heart pressures. Maximum haemodynamic effects were evident four to eight hours after the first dose, with return to baseline by 24 hours. Plasma angiotensin II levels, however, were still suppressed at 24 hours. The magnitude of haemodynamic response was related closely to baseline (pre-enalapril) activity of the renin-angiotensin system and the sympathetic system. Enalapril treatment over three days induced a positive cumulative balance of sodium and potassium, and a small increase in plasma potassium. Urine aldosterone excretion decreased in a stepwise fashion. Continued enalapril administration for four to eight weeks resulted in improved clinical status (NYHA Functional Class) and exercise tolerance in patients who initially were most severely incapacitated, but little change was observed in healthier subjects. We conclude that in heart failure, enalapril is a long acting converting enzyme inhibitor with clear cut beneficial haemodynamic effects in the short term. Long term controlled studies of enalapril in heart failure are warranted.

Aged↗
PubMed1983

Hemodynamic, hormonal and electrolyte responses to prenalterol infusion in heart failure.

The hemodynamic, hormonal and electrolyte effects of prenalterol, a synthetic selective beta 1 agonist, were studied in six patients with New York Heart Association functional class II and III heart failure. Prenalterol was infused incrementally at 60, 120 and 240 nmol/min, each rate for 24 hours, producing steady-state plasma prenalterol levels of 52 +/- 3, 121 +/- 6 and 194 +/- 9 nmol/1, respectively (mean +/- SEM). Hemodynamic and hormonal measurements were performed before, during and after prenalterol administration under conditions of constant body posture and a regulated intake of dietary sodium and potassium. Prenalterol induced a statistically significant increase in cardiac index (from 2.6 +/- 0.2 to 3.1 +/- 0.3 1/min/m2), with parallel increases in stroke index (from 28 +/- 2 to 34 +/- 2 ml/beat/m2). Forearm blood flow measurements increased (from 2.9 +/- 0.5 to 4.1 +/- 0.6 ml/min/100 g), while calculated systemic vascular resistance fell, as did pulmonary capillary wedge pressure (from 13.7 +/- 1.6 to 10.5 +/- 1.7 mm Hg). The drug did not alter heart rate, arterial pressure, right heart pressures or the frequency of ventricular premature beats. Prenalterol increased plasma renin activity (from 2.9 +/- 0.8 to 6.6 +/- 1.8 nmol/1/hour), angiotensin II (from 59 +/- 12 to 89 +/- 22 pmol/1), urinary aldosterone excretion (from 41 +/- 10 to 78 +/- 34 nmol/day) and plasma insulin (from 10.6 +/- 2.2 to 19.8 +/- 3.9 mU/1). Circulating catecholamines, cortisol, glucose, glucagon or pancreatic polypeptide did not change. Dose-response studies in five patients showed dose-dependent increments in hemodynamic variables, while hormonal changes plateaued at the second dose level. We conclude that prenalterol infusion augments myocardial contractility, reduces systemic vascular resistance, and stimulates insulin release and the renin-angiotensin-aldosterone system.

Dose-Response Relationship, Drug↗
PubMed1983

Acute haemodynamic, hormonal and electrolyte effects and short-term clinical response to enalapril in heart failure.

To define the short-term haemodynamic, hormonal and electrolyte effects of enalapril in chronic heart failure, we administered it to nine patients. The first dose (5 mg) induced a gradual reduction in plasma angiotensin II, systemic vascular resistance, arterial pressure, heart rate and right heart pressures, the maximum effects occurring within 4-8 h. Angiotensin II levels were still suppressed 24 h after the initial dose, but haemodynamic indices had returned almost to control values by this time. Dose-related increases in cardiac index and plasma renin, and decreases in angiotensin II, systemic vascular resistance and urine aldosterone excretion were seen with 5, 10 and 20 mg enalapril. Cumulative balances for sodium and potassium were positive, plasma potassium increased and plasma antidiuretic hormone fell. After 4-8 weeks of enalapril therapy, clinical status and exercise tolerance improved in the patients who were most severely restricted initially. Enalapril may be useful in the treatment of chronic heart failure.

Aged↗
PubMed1983

The laminar organization of the lateral geniculate body and the striate cortex in the squirrel monkey (Saimiri sciureus).

The organization of the projection from the lateral geniculate body to the striate cortex in the squirrel monkey has been re-examined using the anterograde and retrograde transport of horseradish peroxidase (HRP) and wheat germ agglutinin conjugated to HRP. The results confirm earlier findings that the projections of the magnocellular and parvocellular layers of the lateral geniculate body terminate in separate sublaminae of layer IV of striate cortex; a more superficial projection of the parvocellular layers to a narrow strip at the base of layer III (IVA in Brodmann's terminology) has also been confirmed. In addition to these well characterized pathways, our results show that the projections of the lateral geniculate body terminate in more superficial levels of layer III and sparsely in layer I of striate cortex. The projections to the upper portion of layer III terminate in distinct patches which coincide precisely with patches of cytochrome oxidase activity previously identified in this zone. The projections to the patches originate primarily from small, pale-staining cells of the "intercalated layers" which surround the magnocellular layers of the lateral geniculate body. A comparison of the organization of the geniculo-cortical projections in the squirrel monkey with that of the cat, Galago, and Tupaia suggests that, despite marked species differences in the laminar organization of the lateral geniculate body and striate cortex, there are striking similarities in the pathway which terminates in the most superficial layers of striate cortex.

Afferent Pathways↗
PubMed1983

Glutamic acid decarboxylase-immunoreactive neurons and horseradish peroxidase-labeled projection neurons in the ventral posterior nucleus of the cat and Galago senegalensis.

Immunocytochemical methods were used to identify neurons in the ventral posterior nucleus of the cat and Galago senegalensis that contain glutamic acid decarboxylase (GAD), the synthetic enzyme for the inhibitory neurotransmitter, GABA. In both species GAD-immunoreactive neurons make up about 30% of the total neurons in the ventral posterior nucleus and form a distinct class of small cells. After cortical injections of horseradish peroxidase (HRP), GAD-immunoreactive cells are not labeled with HRP and may, therefore, be GABAergic local circuit neurons. Comparison of the dendritic morphology of GAD-immunoreactive neurons with that of HRP-filled projection neurons reveals that the morphology of the GAD-containing neurons is distinct and, in particular, that the GAD-immunoreactive neurons display fewer primary dendrites. The relay neurons, in turn, can be divided into classes based on dendritic morphology and cell body size.

Animals↗
PubMed1981

Influence of dietary histidine on tissue histamine concentration, histidine decarboxylase and histamine methyltransferase activity in the rat.

Three-week-old male rats were fed for two weeks diets supplying inadequate, adequate, or excess amounts of histidine. After the 2-week feeding of the experimental diets, the rats were killed. Brain, gastrocnemius muscle, kidney and stomach were removed and analyzed for histamine and free-histidine as well as for the degradative enzyme, HMT, and the histamine-synthesizing enzyme HDC. The following results were obtained: As the levels of dietary histidine increased, (1) tissue concentrations of free-histidine and of histamine increased in all the tissues analyzed. (2) The increase of histamine was greatest in brain and stomach (5- and 4-fold, respectively), but less in kidney and muscle (2-fold). (3) HDC activity was not detected in muscle, but doubled from the lowest to the highest histidine intake in brain and increased almost 6-fold between the lowest and the highest histidine levels in stomach. (4) Kidney HDC decreased from the lowest to the two higher levels of dietary histidine. (5) HMT activity increased nominally in brain and not significantly in kidney; none was detected in either muscle or stomach. (6) Brain and kidney, tissues with considerable HMT activity, had almost no histamine. The increases in tissue histamine concentrations observed in the tissues analyzed generally reflected the changes and magnitudes of enzyme activities for HMT and HDC. The results in the rat differ in important ways from those previously observed in chickens as follows: (1) Histamine concentrations as a function in dietary histidine decreased in the chick. (2) Both HDC and HMT activities were present in chick muscle tissue. (3) HDC activity in chick stomach decreased sharply as a function of dietary histidine.

Animals↗