Human Inferior Research Articles

Nicotinic Acetylcholine Receptors in the Rat And Primate Nucleus Tractus Solitarius And On Rat And Human Inferior Vagal (Nodose) Ganglia: Evidence From In Vivo Microdialysis and [ 125I]α-Bungarotoxin Autoradiography

The nucleus tractus solitarius is a key brain centre involved in the regulation of numerous autonomic functions. The present study has employed in vitro autoradiography and in vivo microdialysis to investigate the presence and function of nicotinic acetylcholine receptors located in the medial nucleus tractus solitarius of the rat. Autoradiography using [ 125I]α-bungarotoxin (0.5 nM) enabled visualization of binding sites on sections of rat and monkey brainstem. Specific binding was highest in the medial nucleus tractus solitarius. The presence of binding sites was also apparent on sections of rat nodose ganglia/vagus nerve and human inferior vagal ganglia. Subsequent to unilateral ligation of the vagus nerve in the rat, an accumulation of binding sites was visualized adjacent to the ligature. Unilateral nodose ganglionectomy in the rat caused an approximate 97% reduction in [ 125I]α-bungarotoxin binding site density in the medial nucleus tractus solitarius from 814 ± 183 to 27 ± 2 d.p.m./mm 2. Microdialysis results indicated that local adminstration of nicotine (1 mM) into the nucleus tractus solitarius of the rat resulted in increases of extracellular L-glutamate of 146 ± 9% of basal levels. This effect was not reproducible following a second stimulation and was also blocked by prior and co-administration of the nicotinic acetylcholine receptor antagonist mecamylamine (100 μM). Extracellular levels of L-aspartate exhibited a similar pattern although results were not significant. Taken together, these results are supportive of the presence of a population of [ 25I]α-bungarotoxin binding sites located presynaptically with respect to vagal afferent terminals in the medial nucleus tractus solitarius of the rat. It is possible that these binding sites are the site of action of locally administered nicotine on extracellular levels of L-glutamate, the favoured neurotransmitter at primary baroreceptor afferent fibres. These data are discussed in relation to the functional pharmacology of acetylcholine and nicotinic acetylcholine receptors in this region of the brain.

Prepro-neuropeptide Y mRNA and NPY binding sites in human inferior vagal ganglia.

The inferior vagal ganglia contain the cell bodies of centrally projecting vagal afferent neurones. Using in situ hybridization-histochemistry with a combination of two antisense neuropeptide Y (NPY) oligonucleotides, we have demonstrated that a population of human inferior vagal perikarya express mRNA encoding prepro-NPY, the precursor of NPY. In vitro receptor autoradiography, using both [125I]Bolton Hunter-NPY ([125I]BH-NPY, 15 pM) and [125I]peptide YY ([125I]PYY, 25 pM), enabled visualization of NPY binding sites. Competition binding with NPY (1 microM), PYY (1 microM) and [Leu31,Pro34]NPY (100 nM), suggest that both Y1 and Y2 receptor subtypes are present on human vagal afferent neurones. These observations suggest a potential role for NPY in neuromodulation of vagal transmission in humans.

Neuropeptide Y Y 1 receptors are involved in the vasoconstriction caused by human sympathetic nerve stimulation

Neuropeptide Y, a novel neurotransmitter, interacts with selective membrane receptors to cause vasoconstriction. Frequency- and concentration-dependent isometric contractions were observed in human inferior mesenteric artery and vein mounted rings that were stimulated with either electrical pulses (70 V, 0.5 ms, 2.5–20 Hz) or noradrenaline. The antagonism elicited by 100 nM tetrodotoxin and 1 μM guanethidine confirmed the neuronal and sympathetic origins of the vasomotor response. Incubation with BIBP 3226 (( R)- N 2-(diphenacetyl)- N-(4-hydroxyphenyl)-methyl- d-arginineamide), a selective neuropeptide Y Y 1 receptor antagonist, significantly reduced the vasoconstriction. The incomplete antagonist activity of BIBP 3226 tends to support the hypothesis of sympathetic co-transmission involving neuropeptide Y, adenosine 5′-triphosphate and noradrenaline. These findings were confirmed in parallel studies using rat superior mesenteric artery and vein ring preparations.

Why Can't a Woman Be More Like a Man?

Western biomedical theory supported the idea of human female inferiority. The Aristotelian formulation was: Nature intends to produce the perfect male form with external genitalia; the female with internal genitalia is less than perfect and thus a defect of nature. In the Renaissance, peripubertal virilization in females was interpreted as further evidence that females were "defective" males capable of developing into the more perfect male form.

Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients

Quantitative cytochemistry of cytochrome oxidase (C.O.) was implemented in human brains to measure C.O. activity in the 3 main divisions of the inferior colliculus (IC): central (ICC), dorsal (ICD), and external (ICE). Units of C.O. activity (μmol/min/g tissue wet weight) were quantified in cellular compartments (overall average, neuropil, perikaryon, and dendrites) at the light microscope level using microdensitometry calibrated with C.O. activity standards measured spectrophotometrically. In a non-AD (Alzheimer's disease) control group (mean age = 79.6 ± 3.1 years, postmortem time = 6.9 ± 1.6 h), the ICC and ICD demonstrated higher ( p < 0.008) overall average activities (mean = 183.40 ± 18.7 and 184.98 ± 45.1 units, respectively) relative to the ICE (56.46 ± 15.9 units). Comparison of cellular morphometry (soma and nucleus area, perimeter, and diameter) revealed that the ICC contained cells of significantly larger soma size than in both the ICD and ICE ( p < 0.002). The distribution of soma diameters in the ICC of controls showed a clear bimodality, enabling the typing of the cells into larger and smaller than average soma diameter. Brains from patients with Alzheimer's disease (AD: mean age = 78.3 ± 2.9 years, postmortem time = 6.5 ± 1.3 h) were compared with the non-AD controls. Significant group differences were found only in the large cells of the ICC. The AD large cells showed a decrement in C.O. activity relative to the corresponding controls in overall average activity ( p < 0.032) and in peak activity of neuropil near the soma ( p < 0.012). These findings provide the first quantitative cytochemical data of C.O. activity in humans. They also suggest that cellular alterations in C.O. metabolism in AD affect predominantly specific groups of larger projection neurons while neighboring neurons are spared.

Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex.

The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

GABAA receptor binding in the aging rat inferior colliculus.

The inhibitory neurotransmitter GABA has been shown to be critically involved in shaping neuronal responses to simple and complex acoustic stimuli in the inferior colliculus. Studies in the rat and human inferior colliculus have suggested significant changes in functions related to GABA neurotransmission occur in the aged. These changes include significant decreases in GABA content, GABA release, GABA neurons, glutamate decarboxylase enzymatic activity, and GABAB receptor binding. Such changes within the inferior colliculus may affect the ability of elderly listeners to process complex acoustic signals, particularly in the presence of background noise. The present study was designed to examine the regional distribution and effects of aging on GABAA receptor binding sites in the Fischer 344 rat inferior colliculus using in vitro quantitative receptor autoradiography. [3H]GABA binding to GABAA receptors was significantly reduced in the inferior colliculus of young adult (3 months) and aged (18-26 months) rats when compared to 2-month animals. However, no significant changes were observed after 3 months of age. Single concentrations of tritiated GABAA receptor ligands (muscimol, t-butylbicycloorthobenzoate, and flunitrazepam) revealed no significant age-related changes in receptor binding in the inferior colliculus between 3 and 26 months of age. To characterize further the pharmacology of the GABAA receptor in the inferior colliculus, GABA modulation of the picrotoxin binding site was examined using [3H]t-butylbicycloorthobenzoate. When increasing concentrations of GABA were added to the incubation buffer, a significant decrease in binding was observed in the inferior colliculus of rats in each age group. In aged rats, the dose-response curve was shifted to the left, indicating an increase in the potency of GABA to inhibit [3H]t-butylbicycloorthobenzoate binding. Although no changes in GABAA receptor binding were detected in the inferior colliculus after 3 months of age, a significant alteration in interaction between the GABA and picrotoxin binding sites was observed in the inferior colliculus of aged rats when compared to 3-month-old young adults. This difference appears to reflect an increased sensitivity of the receptor to GABA modulation in aged rats and, thus, may serve as a compensatory mechanism to enhance GABAA receptor function in response to a presynaptic loss of inhibition.

Features of the partially expanded human inferior conjunctival sac: Cygan WF, Benjamin WJ: Acta Ophthalmol 1995;73:555–559

Features of the partially expanded human inferior conjunctival sac: Cygan WF, Benjamin WJ: Acta Ophthalmol 1995;73:555–559

Radioligand binding and autoradiographic visualization of adenosine transport sites in human inferior vagal ganglia and their axonal transport along rat vagal afferent neurons

The present study has employed membrane-binding studies and in vitro autoradiography to demonstrate the presence of adenosine transport sites in human inferior vagal ganglia using [ 3H]nitrobenzylthioinosine ([ 3H]NBMPR), a potent inhibitor of adenosine transport. In addition, [ 3HINBMPR was used to determine whether adenosine transport sites are subject to axonal transport along the rat vagus nerve. Binding of [ 3H]NBMPR to human inferior vagal ganglia membranes was saturable and reversible. Saturation experiments revealed a single class of high affinity-binding sites with a K d of 93.73 ± 23.13 pM and B max of 413.50 ± 50.40 fmol/mg protein. In displacement experiments, the adenosine transport inhibitor dipyridamole was the most potent displacer of [ 3H]NBMPR binding ( K i = 42.7 ± 28.0 nM). Adenosine itself was able to fully displace [ 3H]NBMPR binding with a K i of 115.0 ± 34.0 μM. The A 1/A 2a adenosine receptor agonist 5′-(N-ethylcarboxamido)-adenosine (NECA) was able to fully displace [ 3H]NBMPR binding in only one experiment at a concentration of 100 ,LM, yielding an affinity 1000-fold higher than its affinity for adenosine receptors. All competition curves obtained from displacement experiments displayed monophasic profiles, indicating the presence of a single class of [ 3H]NBMPR binding sites. Incubation of human inferior vagal ganglia sections with [ 3H]NBMPR (0.7 nM) revealed dense binding which appeared to be consistent with the distribution of neuronal cell bodies in this tissue. Following unilateral ligation of the vagus nerve in the rat, acccumulation of [ 3H]NBMPR binding sites occurred both proximal and distal to the vagal ligatures. These results suggest that [ 3H]NBMPR binds with high affinity to a single class of adenosine transport sites, and that these sites are present on vagal afferent neurons in the human and undergo bidirectional axonal transport along the rat vagus nerve.

Morphological variability of smooth muscle cells in human nasal swell bodies

The complex functional behavior of nasal swell bodies is still not completely understood. In the present study the histology of the vessels involved in the swelling mechanism is examined and the ultrastructural appearances described of the different types of smooth muscle cells located in the vascular wall of swell bodies in the human inferior turbinate. Even though the majority of smooth muscle cells of the nasal swell bodies showed a normal, elongated appearance comparable to other smooth muscle cells elsewhere in the body, a variety of cells with atypical shapes could be detected that have not been described previously in vessels of the nasal mucosa. The diameters of the smooth muscle cells in general were strikingly variable. The individual smooth muscle cells were surrounded by a basal lamina that was occasionally disrupted or doubled. Myoblasts were separated by a connective tissue space containing collagen fibrils, mature elastin fibers and bundles of microfibrils. The latter two types of fibers and fibrils occurred mainly in the outer parts of the muscular coat. The endowment of cytoplasmic components was similar in all smooth muscle cells of the vascular wall in the swell bodies. These findings indicate that the specific feature of smooth musculature presumably resides in the unusual morphological variability of the single cells present, as well as in the striking heterogeneity of the arrangement of bundles of these cells in the vascular wall.

Morphometric development of the human fetal auditory system: inferior collicular nucleus

The development of the human inferior collicular nucleus was studied on serial sections of the brains of 9 fetuses at 12–34 weeks of gestation and an adult of 63 years using an electronic planimeter with a computer. Morphometric analysis of the development of the inferior collicular nucleus showed that its development accelerates after 18 weeks of gestation in terms of the columnar volume and length, size of neurons and circularity ratio. Large-sized neurons 2–3 times the area of small-sized neurons appeared after 18 weeks of gestation. The ratio of large neurons to the total ranged between 3 and 6% in the inferior collicular nucleus. The development of the inferior collicular nucleus was similar to that of the ventral cochlear nucleus and the medial superior olivary nucleus.

Features of the partially expanded human inferior conjunctival sac.

Space in the inferior conjunctival sac has not been studied in sufficient detail to allow optimal physical design of conjunctival inserts. We analyzed shape and volume of partially expanded, anesthetized, left inferior conjunctival sacs in 10 young adult subjects by injection of a liquid polysiloxane molding compound. Mean volume, greatest thickness, central thickness, horizontal width, and vertical height of 60 molds were 125.7 microliters (SD = 55), 1.56 mm (SD = 0.69), 1.46 mm (SD = 0.62), 20.7 mm (SD = 2.2), and 8.9 mm (SD = 0.8), respectively. Volumetric and linear dimensions varied between subjects, but certain features were common to all molds: 1) a crescent shape horizontally; 2) a thick inferior horizontal ridge; and 3) a wedge-like shape sagittally. We postulate several advantages of conjunctival inserts with features representative of our molds of conjunctival sacs, e.g. such inserts may be more comfortable, less expelled, larger in volume, and contact more tissue area.

Significant differences The Construction of Knowledge, Objectivity, and Dominance

Abstract The scientific method is a tool for the construction and justification of dominance in the world. The invention of statistics was a major methodological advance in the descriptive sciences causing a shift from descriptive analysis to mathematical analysis. The new methodological techniques were invented by men who were interested in explaining the inheritance of traits in order to support their political ideology of natural human superiority and inferiority. The statistical techniques transformed the scientific method and resulted in a process that constructs knowledge and establishes “significant differences” between the dominant group as the norm and the subordinate group as the “Other.” The five steps in the process that integrates domination into the scientific method and results in the scientific construction the Other are: (a) Naming, (b) Quantification, (c) Statistical Analysis, (d) Reification, and (e) Objectification.

Significant differences: The construction of knowledge, objectivity, and dominance

The scientific method is a tool for the construction and justification of dominance in the world. The invention of statistics was a major methodological advance in the descriptive sciences causing a shift from descriptive analysis to mathematical analysis. The new methodological techniques were invented by men who were interested in explaining the inheritance of traits in order to support their political ideology of natural human superiority and inferiority. The statistical techniques transformed the scientific method and resulted in a process that constructs knowledge and establishes “significant differences” between the dominant group as the norm and the subordinate group as the “Other.” The five steps in the process that integrates domination into the scientific method and results in the scientific construction the Other are: (a) Naming, (b) Quantification, (c) Statistical Analysis, (d) Reification, and (e) Objectification.

Visualization of beta-adrenoceptor binding sites on human inferior vagal ganglia and their axonal transport along the rat vagus nerve

Because of uncertainties regarding the complete antihypertensive mechanism of action of beta-adrenoceptor antagonists, the present study determined whether vagal afferent neurons of humans and rats possess beta-adrenoceptors. Such a location would provide an appropriate target for beta-blockers to modulate neurotransmission of barosensitive neurons, thereby affecting blood pressure. Therefore, in vitro receptor autoradiography of high-affinity beta-adrenoceptor binding sites was performed on slices of human and rat inferior vagal (nodose) ganglia with [125I]-pindolol. Slide-mounted sections of human and rat inferior vagal ganglia were incubated with [125I]-pindolol in the absence or presence of propranolol (10 mumol/l) to define non-specific binding, atenolol (10 mumol/l) to inhibit binding to beta 1-adrenoceptors, or ICI 118551 (3 nmol/l) to inhibit binding to beta 2-adrenoceptors. Unilateral vagal ligation was also performed in the rat to study whether beta-adrenoceptors are subject to axonal transport along the vagus nerve. [125I]-pindolol bound with > 90% specific binding to sections both of human and of rat inferior vagal ganglia. Specific binding occurred over both neuronal perikarya and nerve fibres. In both species the beta 2-adrenoceptor subtype appeared to predominate, as defined by the differential ability of ICI 118551 (beta 2) and atenolol (beta 1) to inhibit the binding of [125I]-pindolol. Furthermore, unilateral vagal ligation in the rat caused an accumulation of specific binding adjacent to the ligature sites. We conclude that human and rat vagal afferent (and efferent) neurons possess beta-adrenoceptors that potentially could explain the mechanism of action of beta-adrenoceptor antagonists in the therapy of hypertension.

Functional comparison between the human inferior epigastric artery and internal mammary artery: Similarities and differences

Although the inferior epigastric artery has been used as an alternative arterial graft for coronary artery bypass grafting, little is known about the contractile and relaxation characteristics of this artery. This study was designed to compare the pharmacologic reactivity of the two arterial conduits—the inferior epigastric artery and the internal mammary artery. Forty-one inferior epigastric artery ring segments from eight patients undergoing coronary grafting and 62 internal mammary artery ring segments were set up in organ baths under physiologic pressure. The contractility was determined from the contraction induced by the depolarizing agent potassium and receptor-mediated vasoconstrictor agents, norepinephrine, U46619, and endothelin-1. Endothelium-dependent relaxation was induced by the calcium ionophore A23187, a non-receptor agonist for endothelium-derived relaxing factor, and acetylcholine, a receptor agonist for endothelium-derived relaxing factor. Glyceryl trinitrate was used to study endothelium-independent relaxation. The maximal response (either contraction or relaxation) and the effective concentration causing 50% of the maximal response for these two arteries were compared. There was no difference ( p > 0.05) either in the maximal contraction force (5.30 ± 0.87 versus 4.76 ± 0.89 gm for potassium, 5.13 ± 0.67 versus 4.47 ± 1.15 gm for norepinephrine, 8.04 ± 1.23 versus 6.23 ± 0.99 gm for U46619, and 4.88 ± 0.69 versus 5.57 ± 0.93 for endothelin-1 ( n = 6 to 10 for each vasoconstrictor) or in the maximal relaxation induced by glyceryl trinitrate (86.46% versus 92.98%, n = 6) or by acetylcholine (20.72% versus 45.51%, Am J Obstet Gynecol n = 5) between the inferior epigastric artery and internal mammary artery. The effective concentration causing half maximal response to all vasoconstrictors and vasodilators was similar between the two arteries ( p > 0.05). However, A23187 induced significantly less relaxation in the inferior epigastric artery (38.42 ± 15.49%, n = 6) than in the internal mammary artery (71.89 ± 7.17%, n = 9, p < 0.05). We conclude that contractility, endothelium-independent relaxation, and receptor-mediated endothelium-dependent relaxation are similar in the inferior epigastric artery and the internal mammary artery. However, the endothelium of this arterial graft has less ability to respond to the non-receptor-mediated endothelium-derived relaxing factor stimulant. The influence of this difference on the prevalence of atherosclerosis and long-term patency rate in the inferior epigastric artery remains to be studied. (J T horac Cardiovasc Surg 1995;109:13-20)

Word recognition in the human inferior temporal lobe.

Studies of primates and of patients with brain lesions have shown that the visual system represents the external world in regions and pathways specialized to compute visual features and attributes. For example, object recognition is performed by a ventral pathway located in the inferior portion of the temporal lobe. We studied visual processing of words and word-like stimuli (letter-strings) by recording field potentials directly from the human inferior temporal lobe. Our results showed that two discrete portions of the fusiform gyrus responded preferentially to letter-strings. A region of the posterior fusiform gyrus responded equally to words and non-words, and was unaffected by the semantic context in which words were presented. In contrast, a region of the anterior fusiform gyrus was sensitive to these stimulus dimensions. These regions were distinct from areas that responded to other types of complex visual stimuli, including faces and coloured patterns, and thus form a functionally specialized stream within the ventral visual pathway.

Visualization of dopamine D2 binding sites on human inferior vagal ganglia.

The present study used in vitro autoradiography to assess whether high affinity D2 binding sites are present on sections of human inferior vagal ganglia, where arterial baroreceptor primary afferent cell bodies are located. Incubation of tissue sections with [125I]NCQ 298 (0.5 nM) revealed dense but non-uniform binding, with a well-defined topography, consistent with the localization of binding sites over cell bodies rather than nerve axons. Coincubation with the D2 antagonist raclopride (10 microM) completely abolished binding of [125I]NCQ 298. Densitometric quantification of autoradiograms estimated 82 +/- 4% specific binding for [125I]NCQ 298 (0.5 nM). These observations indicate the presence of D2 binding sites on sensory ganglia involved in cardiovascular control pathways in the human, and may help to explain some of the documented cardiovascular effects of dopamine.

Functional anatomy of the retro- and suprahepatic portions of the human inferior vena cava and their main affluents.

The arrangement of muscle, collagen and elastic fibers was studied in the retro- and suprahepatic (subdiaphragmatic) portions of the inferior vena cava, the hepatic veins and their main affluents. Distinctive features of the longitudinal and transverse muscle bundles are described. In these portions of the vena cava, both bundle systems are clearly separate and any continuity was observed only at the entrances of the hepatic veins. A musculo-venulolymphatic complex was noted in spurs formed by the vascular junctions. The hepatic veins and their main affluents exhibit an elliptical contour in transverse section, which apparently results from cranial and caudal thickenings of the longitudinal muscle layer. Many of these bundles are in continuity with those of the transverse muscle layer. Terminal elastic tendons were rarely observed in connection with muscle fibers of the inferior vena cava and are not present in the hepatic veins and their main affluents. In terms of form and function, the relatively thin muscular layer has a dilating action on the hepatic venous system because of the external fixed insertion point of the muscle bundles. Such an arrangement and a "polar" disposition of the muscle bundles in the hepatic venous system may assists in "suction" of the blood toward the heart. A sphincteric control of the ostia by means of crossed muscular loops supported by venulo-lymphatic micropads is a possibility.

Comparative evaluation of clinically available inferior vena cava filters with an in vitro physiologic simulation of the vena cava.

A physiologic in vitro model of the human inferior vena cava (IVC) was developed to evaluate the clot-trapping efficiency of various IVC filters. The flow model closely simulates the physical parameters of the human IVC in fluid viscosity, specific gravity, temperature, and pulsatility; blood flow velocity, volume, and inherent turbulence; and vein orientation, wall compliance, and clot composition. Five filters--Greenfield (G), Bird's Nest (BN), Vena Tech (VT), Simon nitinol (SN), and titanium Greenfield (TG)--were compared by using two vena cava and blood clot sizes and horizontal and vertical orientation of the model. Each filter varied significantly in its clot-capturing efficiency, depending on vena cava size and orientation and emboli size. Overall, decreasing rank order in filter clot-trapping efficiency was SN, BN, VT, TG, and G. The in vitro model of the human IVC is an alternative to multicenter clinical trials in evaluating the relative clot-trapping efficiency of various IVC filters.