Showing papers by "Saint Louis University published in 1990"

The Pain Disability Index: psychometric properties

Abstract: This paper reports two studies of chronic pain patients (n = 444) relevant to the psychometric properties of the Pain Disability Index (PDI), a self-report instrument that has been used to assess the degree to which chronic pain interferes with various daily activities. In the first study, patients with high PDI scores reported more psychological distress (P less than 0.001), more severe pain characteristics (P less than 0.001), and more restriction of activities (P less than 0.001) than patients with low PDI scores, findings supportive of the construct validity of the measure. Further, a multiple regression showed that a linear combination of 9 variables predicted PDI scores (R = 0.74): time spent in bed, psychosomatic symptoms, stopping activities because of pain, work status, pain duration, usual pain intensity, quality of life, pain extent, and education. This study also showed differences for age and gender on disability. The second study involved 46 patients who had undergone inpatient treatment for their pain conditions. The study revealed modest test-retest reliability for the instrument. It also showed the PDI to be associated with the levels of pain behavior exhibited by these patients. The findings of both studies generally support the reliability and validity of the PDI as a brief measure of pain-related disability. Questions regarding its test-retest reliability and lack of association with certain pain behaviors are discussed, as are suggestions for future research.

Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster.

Abstract: We report here that a point mutation in the gene which encodes the heterochromatin-specific nonhistone chromosomal protein HP-1 in Drosophila melanogaster is associated with dominant suppression of position-effect variegation. The mutation, a G-to-A transition at the first nucleotide of the last intron, causes missplicing of the HP-1 mRNA. This suggests that heterochromatin-specific proteins play a central role in the gene suppression associated with heterochromatic position effects.

Two transpallidal pathways originating in the rat nucleus accumbens.

Abstract: The striatopallidal projection originating in the nucleus accumbens was investigated by using anterograde transport of PHA-L in combination with peptide immunohistochemistry in order to localize the injection sites and transported lectin with respect to neurochemically defined subterritories in the nucleus accumbens and subcommissural ventral pallidum. The results reported here supplement our previous observations, which indicated that the subcommissural ventral pallidum of the rat comprises two immunohistochemically defined subterritories (Zahm and Heimer, '88: J. Comp. Neurol., 272:516-535) which give rise to dichotomous downstream projection systems (Zahm, '89: Neuroscience, 30:33-50). The present data indicate that the neurotensin immunoreactivity-rich ventromedial district of ventral pallidum receives its accumbal input almost exclusively from the shell district of the nucleus accumbens. The accumbal core, alternatively, projects to the dorsolateral ventral pallidal subterritory that lacks appreciable neurotensin immunoreactivity and in many other respects more resembles the adjoining striatopallidal components of the caudate-putamen. In addition to direct topographic relationships in the frontal plane among the accumbal injection sites and ventral pallidal terminations, it was observed that more caudally placed core injections resulted in patches of striatopallidal terminations that were more caudally located in ventral pallidum. Shell injections, in contrast, produced columns of terminations that extended continuously from the rostralmost level that they appeared to the caudal end of ventromedial ventral pallidum. The accumbal shell, its exclusive projection to the ventromedial subterritory in the subcommissural ventral pallidum, and the previously reported, almost exclusive projection of that pallidal subdistrict to the mesencephalic ventral tegmental area are discussed in terms of a number of other neurochemical and hodological features that serve to distinguish them sufficiently to suggest that they represent a uniquely specialized part of the basal ganglia.

A Comparison between Heparin and Low-Dose Aspirin as Adjunctive Therapy with Tissue Plasminogen Activator for Acute Myocardial Infarction

Abstract: Background. We report the results of the Heparin—Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction. Methods. Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay. Results. At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients ass...

Insulin-like Growth Factor Receptor Expression and Function in Human Breast Cancer

Abstract: The insulin-like growth factors IGF-I and IGF-II are potent mitogens for several breast tumor cell lines in culture. Additionally, both IGF-I and IGF-II mRNAs are easily detected in the majority of breast tumor specimens examined, while no breast cancer epithelial cell lines we have studied express authentic IGF-I mRNA, and few lines express IGF-II mRNA. Although receptors for insulin, IGF-I, and IGF-II have been described, there is significant cross-reactivity between the various receptors and ligands in the insulin/insulin-like growth factor family, and it is not clear which receptor or receptors are responsible for the biological effects of these growth factors in this system. Using an RNase protection assay, we examined breast tumor specimens and breast cancer epithelial cell lines for expression of mRNA encoding the type I and type II IGF receptors as well as the insulin receptor. Virtually all of the specimens examined expressed mRNA for all three receptors. We then examined estrogen-dependent MCF-7 cells for the mitogenic effects of IGF-I and II in the presence of antibodies to both the type I and type II receptors. alpha IR-3, a monoclonal antibody which blocks the type I receptor, abolished the mitogenic effects of both IGF-I and IGF-II. It did not, however, block the mitogenic effects of insulin. We conclude that type I and type II IGF receptors are ubiquitously expressed in breast cancer, and our experiments with MCF-7 cells suggest the mitogenic effects of both IGF-I and IGF-II are mediated via the type I IGF receptor.

Cultured normal human hepatocytes do not synthesize lipoprotein-associated coagulation inhibitor: evidence that endothelium is the principal site of its synthesis.

Abstract: Human plasma contains a factor Xa-dependent inhibitor of tissue factor/factor VIIa complex termed lipoprotein-associated coagulation inhibitor (LACI). The present study examines the site(s) of LACI synthesis. In this study, cultured hepatocytes isolated from normal human liver were found to be essentially negative in LACI mRNA as revealed by Northern blot analysis using a full-length LACI cDNA as probe. The conditioned media from these cultures were also essentially negative for LACI activity. Similarly, poly(A)+ RNA obtained from normal human liver did not contain detectable LACI mRNA. In contrast, cultured human umbilical vein endothelial cells and human lung tissue (rich in endothelium) both contained abundant amounts of LACI mRNA. Moreover, erythrocyte lysates and culture media from normal monocytes, lymphocytes, or neutrophils did not contain measurable LACI activity; these cells were also negative for LACI mRNA. Platelets, however, contained LACI activity. The likely source of platelet LACI is the megakaryocyte cell since a megakaryocyte cell line (MEG-01) was found to contain LACI mRNA and to secrete small amounts of LACI activity. Additionally, human vascular smooth muscle cells and lung fibroblasts were also found to synthesize only small amounts of LACI. From these observations, we conclude that normal liver does not synthesize LACI and that endothelium is the principal source of plasma LACI. The undegraded LACI synthesized by endothelial cells had a molecular weight of approximately 41,000.

Disorders of attention and activity level in a referral population

Abstract: Of 614 children referred for an evaluation of hyperactivity and inattention, the 422 (68.7%) who qualified for a diagnosis of attention deficit disorder (ADD) were compared with the 192 (31.3%) who did not. The children with ADD had significantly higher full-scale IQ scores, verbal scores, and parental educational levels. They also had a significantly higher incidence of specific learning disabilities (73.7%). The absence of hyperactivity in children with ADD further exaggerated the differences in learning disability between the two groups. Cognitive limitation, severe parental psychopathology, and child neglect/abuse were significantly higher in the group without ADD. The two groups did not differ in the incidence of parental or child depressive symptomatology, motor diagnoses, language disorders, conduct disorders, and psychosomatic complaints. That only 29 children in whom ADD was absent (4.7% of all referrals) had been given a trial of stimulant medication does not support the presence of a major abuse of such drugs in the community.

Involvement of myosin light-chain kinase in endothelial cell retraction.

Abstract: Permeabilized bovine pulmonary artery endothelial cell monolayers were used to investigate the mechanism of endothelial cell retraction. Postconfluent endothelial cells permeabilized with saponin retracted upon exposure to ATP and Ca2+. Retraction was accompanied by thiophosphorylation of 19,000-Da myosin light chains when adenosine 5'-[gamma-[35S]thio]triphosphate was included in the medium. Both retraction and thiophosphorylation of myosin light chains exhibited a graded quantitative dependence on Ca2+. When permeabilized monolayers were extracted in buffer D containing 100 mM KCl and 30 mM MgCl2 for 30 min, the cells failed to retract upon exposure to ATP and Ca2+, and no thiophosphorylation of myosin light chains occurred. The ability both to retract and to thiophosphorylate myosin light chains was restored by the addition to the permeabilized, extracted cells of myosin light-chain kinase and calmodulin together but not by either alone. These studies indicate that endothelial cell retraction, as does smooth muscle contraction, depends on myosin light-chain kinase phosphorylation of myosin light chains.

Cannabinoid receptors and modulation of cyclic AMP accumulation in the rat brain.

Abstract: The mechanism by which cannabinoid compounds produce their effects in the rat brain was evaluated in this investigation. Cannabinoid receptors, quantitated by [3H]CP-55,940 binding, were found in greatest abundance in the rat cortex, cerebellum, hippocampus, and striatum, with smaller but significant binding also found in the hypothalamus, brainstem, and spinal cord. Using rat brain slice preparations, we evaluated the effect of desacetyllevonantradol on basal and forskolin-stimulated cyclic AMP accumulation in the regions exhibiting the greatest cannabinoid receptor density. Desacetyllevonantradol (10 microM) reduced cyclic AMP levels in the hippocampus, frontal cortex, and striatum. In the cerebellum, however, the response to desacetyllevonantradol was biphasic with cyclic AMP accumulation being decreased at lower and increased at higher concentrations. Desacetyllevonantradol reduced cyclic AMP accumulation in isoproterenol-stimulated slices in the cortex and cerebellum, but not in the hippocampus. Cells that responded to vasoactive intestinal peptide with an increase in cyclic AMP accumulation in the hippocampus and cortex also responded to desacetyllevonantradol. The modulation of cyclic AMP accumulation by desacetyllevonantradol could be attenuated following stereotaxic implantation of pertussis toxin, supporting the involvement of a G protein in the cannabinoid response in the brain. However, other actions of cannabinoid compounds may also affect the cyclic AMP levels in brain slice preparations.

Application of fluorescence energy transfer and polarization to monitor Escherichia coli cAMP receptor protein and lac promoter interaction

Abstract: A fluorescence method was developed to study DNA-protein interactions in solution. A 32-base-pair (bp) DNA fragment of the lac promoter containing the primary binding site for Escherichia coli cAMP receptor protein (CRP) was chemically synthesized and labeled specifically at the 5' end with fluorescent probe. Binding of cAMP receptor protein to this fragment can be conveniently followed by measuring changes in polarization of fluorescence of the labeled DNA or by measuring fluorescence energy transfer from protein tryptophan residues to the DNA label. Formation of protein-DNA complex was monitored as a function of cAMP concentration. Various equilibrium constants can be resolved to characterize the binding of cAMP to CRP and the subsequent binding of CRP-cAMP and CRP-(cAMP)2 to DNA. These binding studies showed that the two ligated forms of CRP have significantly different affinities for specific-site DNA. These results show that, in principle, the fluorescence technique can yield thermodynamically valid equilibrium constants under essentially any solution conditions. This technique also has the potential of providing information regarding the structure of protein-DNA complexes.

Prevalence and clinical implications of atrial spontaneous contrast in patients undergoing transesophageal echocardiography.

Abstract: The prevalence of atrial spontaneous contrast was evaluated in 150 consecutive patients undergoing transesophageal echocardiography. Spontaneous contrast was observed in 29 patients (19%). It was seen in the left atrium in 24 patients, in the right atrium in 4 patients and in both atria in 1 patient. Spontaneous atrial contrast was not seen in the absence of an associated cardiac abnormality. Univariate analysis showed a significant relation between the presence of spontaneous contrast and significant mitral regurgitation (p less than 0.05), the presence of mitral valve prostheses (p less than 0.001), atrial fibrillation (p less than 0.0001) and left atrial size (p less than 0.001). Multivariate analysis showed that the presence of atrial fibrillation, prosthetic mitral valve and atrial size were independent factors for the presence of spontaneous contrast. However, of the 29 patients with spontaneous contrast, 13 (45%) were in sinus rhythm and in only 4 (16%) was the left atrial size greater than 60 mm. Left atrial thrombus was detected in 9 of the 150 patients. Although spontaneous contrast was noted in 5 (55%) patients with left atrial thrombus and in only 20 (14%) patients without left atrial thrombus (p less than 0.001), none of the 3 patients who had right atrial thrombus had spontaneous contrast in that chamber. Overall, 7 (58%) of the 12 patients with right or left atrial thrombi had no evidence of spontaneous contrast. Multivariate analysis showed that atrial fibrillation was the only independent clinical predictor of left atrial thrombus. Thus, spontaneous echocardiographic contrast is a common phenomenon observed in approximately 20% of the patients undergoing transesophageal echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

The interview in the admission process.

Abstract: Significant demographic, legal, and educational developments during the last ten years have led medical schools to review critically their selection procedures. A critical component of this review is the selection interview, since it is an integral part of most admission processes; however, some question its value. Interviews serve four purposes: information gathering, decision making, verification of application data, and recruitment. The first and last of these merit special attention. The interview enables an admission committee to gather information about a candidate that would be difficult or impossible to obtain by any other means yet is readily evaluated in an interview. Given the recent decline in numbers of applicants to and interest in medical school, many schools are paying closer attention to the interview as a powerful recruiting tool. Interviews can be unstructured, semistructured, or structured. Structuring involves analyzing what makes a medical student successful, standardizing the questions for all applicants, providing sample answers for evaluating responses, and using panel interviews (several interviewers simultaneously with one applicant). Reliability and validity of results increase with the degree of structuring. Studies of interviewers show that they are often biased in terms of the rating tendencies (for instance, leniency or severity) and in terms of an applicant's sex, race, appearance, similarity to the interviewer, and contrast to other applicants). Training interviewers may reduce such bias. Admission committees should weigh the purposes of interviewing differently for various types of candidates, develop structured or semistructured interviews focusing on nonacademic criteria, and train the interviewers.

MR imaging of tumor and tumorlike lesions of bone and soft tissue.

Abstract: This review examines the role of MR imaging in the diagnosis and staging of tumors and tumorlike lesions of bone and soft tissue. For tumors of bone, the plain radiograph is not only the least expensive diagnostic test but is the most reliable predictor of the histologic nature of a given lesion. Consequently, it should be the first procedure performed and serve as the basis for determining the next step in the patient's evaluation. MR imaging is the examination of choice for staging bone tumors. CT is preferred to MR imaging only when the characteristics of the lesion are inadequately defined on plain radiographs, as may occur in flat bones. Although MR imaging is of limited value in predicting the histology of bone tumors, it is a useful tool for distinguishing round-cell tumors and metastases from stress fractures and medullary infarcts in symptomatic patients with normal radiographs. For depiction of soft-tissue masses, MR imaging is unrivaled. The histologic nature of a soft-tissue mass may, in some instances, be predicted on the basis of its MR appearance and multicentricity. Biopsy of bone and soft-tissue tumors should follow and not precede MR imaging. MR imaging reliably shows change in tumor volume after radiation or chemotherapy. It is less reliable in predicting the amount of tumor necrosis.

A twin study of the effects of the Vietnam War on posttraumatic stress disorder.

Abstract: This study evaluates the impact of military service during the Vietnam era (1965 to 1975) on posttraumatic stress disorder using a sample of 2092 male-male, monozygotic, veteran twin pairs. Data were collected in 1987 using mail and telephone interviews. In 715 monozygotic twin pairs who were discordant for military service in southeast Asia (SEA), posttraumatic stress disorder was found to be strongly associated with military service in SEA. The prevalence of posttraumatic stress disorder was 16.8% in twins who served in SEA compared with 5.0% in co-twins who did not serve in SEA. There was a ninefold increase in the prevalence of posttraumatic stress disorder (95% confidence interval, 4.8 to 17.6), comparing twins who experienced high levels of combat with their co-twin who did not serve in SEA. Our results demonstrate that nearly 15 years following the end of the Vietnam War, there remains a substantially increased prevalence of posttraumatic stress disorder among veterans who served in SEA. ( JAMA . 1990;263:1227-1232)

Rapid identification of the course of anomalous coronary arteries in adults: the "dot and eye" method.

Abstract: It is often difficult to delineate the true course of anomalous coronary arteries by angiography because it only provides a 2-dimensional view of a complex 3-dimensional structure. The purpose of this study was to confirm morphologically the radiographic appearance of anomalous coronary arteries and to construct a protocol for rapid determination of their true course. Twenty-one adults who had anomalous origin of coronary arteries without other evidence of congenital heart disease were reviewed. Using an anatomically correct model of the heart, solder wire was placed in the pathologically described anomalous positions and radiographed. With this model the pathologically described courses could be easily recognized and separated radiographically. These courses were confirmed in the operating room in 2 patients and a rare anomaly of posterior origin of a coronary artery was also confirmed by autopsy.

Altered angioarchitecture in selected areas of brains with Alzheimer's disease.

Abstract: It was the aim of this study to determine, qualitatively and quantitatively, alterations in the blood vessels of brains removed postmortem from patients with Alzheimer's disease (AD), and to compare these findings with the appearance of cerebral blood vessels in a group of individuals without brain disorders. Celloidin sections of brain tissue from four cerebral areas, pre-frontal (Brodmann's area 9), basal forebrain, sensorimotor, and hippocampus, were subjected to an alkaline phosphatase reaction to facilitate the evaluation of the vascular distribution. The vascular density in five sections was determined by counting the number of vascular intersections with a microscopic test grid of 100 squares; ten fields per section were examined in this manner. Analysis of 16 AD and 6 control brains, showed that there was a striking and statistically significant reduction in the vascular net density specifically in the basal forebrain region and the hippocampus of AD brains. In addition, vessels in the AD brains exhibited extensive topographical changes, such as kinking and looping. These results indicate that modifications in vascular density are present in AD brains with a marked regional specificity.

A murine model of mucopolysaccharidosis VII. Gross and microscopic findings in beta-glucuronidase-deficient mice.

Abstract: This report describes the clinical and pathologic alterations found in mice that have a recessively inherited, essentially complete deficiency of the lysosomal enzyme beta-glucuronidase. Affected animals have a shortened life span and are dysmorphic and dwarfed. Abnormal gait and decreased joint mobility correlate with glycosaminoglycan accumulation in articular tissue and cartilaginous and bony lesions result in extensive skeletal deformation. In these enzyme-deficient animals, lysosomes, distended by fine fibrillar and granular storage material, are particularly prominent in the macrophage system but also occur in other tissues including the skeletal and central nervous systems. The clinical and pathologic abnormalities in these mutant mice closely parallel those identified in humans with mucopolysaccharidoses (MPS). Therefore, these mice provide a well-defined genetic system for the analysis of the pathophysiology of mucopolysaccharidosis type VII, which has many features in common with the other MPS. The mutant mice provide an attractive animal model to test potential therapies for lysosomal storage disease.

Nicotinic acetylcholine receptor subtypes in human frontal cortex: changes in Alzheimer's disease.

Abstract: Molecular genetic and pharmacological studies have suggested that several subtypes of nicotinic acetylcholine receptors exist in the mammalian and avian brain. Combining 3H-(-)-nicotine, 125I-alpha-bungarotoxin, and 125I-kappa-bungarotoxin as ligands, we report here the first evidence for the existence in human frontal cortex of at least three different subtypes of nicotinic receptors. Autoradiographic analysis shows that specific 125I-kappa-bungarotoxin binding sites are concentrated mainly in several cortical layers. We also show that kappa-bungarotoxin, but not alpha-bungarotoxin decreases the evoked release of 3H-acetylcholine in rat cortical slices, indicating a likely presynaptic localization for some of the alpha-bungarotoxin-insensitive kappa-bungarotoxin sites in mammalian brain. The brains of patients with Alzheimer's disease show marked decreases in Bmax values for low-affinity 125I-kappa-bungarotoxin sites and both high- and low-affinity 3H-nicotine sites, whereas 125I-alpha-bungarotoxin sites are not significantly different in number from age-matched control brains. We conclude that Alzheimer's disease does not affect all subtypes of nicotinic receptors in the frontal cortex to the same extent.

A Back-Projection Method For Imaging Large-Scale Lateral Variations of Lg Coda Q With Application to Continental Africa

Abstract: SUMMARY A new method is developed which uses back-projection tomography to regionalize large-scale lateral variations of coda Q for Lg waves which have traversed long continental paths. Successful use of this method requires precise and stable single-trace measurements of Lg coda Q (Xie & Nuttli 1988). the method converges rapidly and requires minimal computer storage. It also allows quantitative estimation of resolution and error in imaging lateral variations of coda Q. the spatial resolution of this method is limited by the uneven spatial coverage of the data base, by our limited knowledge of Lg coda generation, and by the trade-off between the stability and the spatial resolution of the coda Q inversion. the method is applied to a large set of digital Lg coda data from Africa, where large-scale lateral variations of Lg coda Q are found to correlate well with major tectonic features. Most of Africa is stable, and like other stable regions, has relatively high coda Q values. the lowest values of coda Q are associated with the African rift system. Other regions of low-Q values include the Atlas mountains and Cape Fold Belt, regions of Mesozoic and younger deformation. the lateral variation of frequency dependence of Lg coda Q correlates, in most regions, with that of Q at 1 Hz. Our analysis of the spatial resolution of this method indicates that the resolving power of Lg coda Q imaging is comparable to that of velocity tomography using long-period surface waves. Using empirical approaches, we estimate that uncertainties in Lg coda Q and its power-law frequency dependence parameter are less than about 60 and about 0.2, respectively, for most of Africa.

Comparison of Biomaterials for Facial Bone Augmentation

Abstract: • We compared the gross behavior of and microscopic response to implant materials currently in clinical use for facial bone augmentation at different sites in dogs. Materials evaluated include porous polytetrafluoroethylene carbon (Proplast), large-pore high-density polyethylene (Medpor), solid medical-grade silicone rubber (Silastic), polyamide mesh (Supra-mid), and autogenous rib bone. The subjects were 12 mixed-breed dogs and the materials were implanted directly on bone with periosteum removed at one of three sites in the dog's face (malar eminence, nasal dorsum, and chin). Animals were killed 3 months after surgery and stability of the implants was graded by manual manipulation. Blocks of tissue, including the study materials and underlying bone, were examined microscopically after sectioning. Stability results are tabulated and histologic appearance is described by site for each material evaluated. These data demonstrate marked variability of stability and cellular response depending on the site of implantation. From these data one may conclude that the site of implantation and implant movement are essential factors in determining the nature of the tissue response and fate of an implant. Solid and porous alloplastic materials show an acceptable tissue response, but neither demonstrates the ability to consistently provide an implant that is stable on underlying bone. ( Arch Otolaryngol Head Neck Surg . 1990;116:551-556)

Development and lesion induced reorganization of the cortical representation of the rat's body surface as revealed by immunocytochemistry for serotonin.

Abstract: Immunocytochemistry with an antiserum directed against serotonin (5-HT) was used to assess the development of the representation of the body surface in the rat's primary somatosensory cortex (S-I). Within 1 hour of birth (P-O), 5-HT-positive fibers were present in the marginal zone, the cortical plate, and developing layers V and VI. Immunoreactivity in the marginal zone consisted of a thin band of coarse fibers oriented parallel to the pia. Only a small number of isolated fibers were visible in the cortical plate. A denser network of both coarse and fine fibers could be seen in presumptive layers V and VI. By the first hour of P-I, 5-HT-positive axons in the deeper cortical plate were organized into a crude representation of the rat's body surface. At this age, aggregates of fibers corresponding to the head, lower jaw, trunk, and forepaw could be clearly distinguished. These regions of dense 5-HT immunoreactivity consisted primarily of fine caliber axons that had invaded the lower part of the cortical plate. Dense aggregates of fine caliber axons were also visible in developing layers V and VI. Coarse 5-HT-positive fibers were visible in all layers, but they did not appear to contribute to the pattern that corresponded to the body surface. By the first hour of P-2, the map of the body surface in S-I was more refined and a row-related organization of 5-HT-immunoreactive fibers was visible in the portion of the cortex representing the vibrissa pad. The laminar distributions of coarse and fine caliber serotoninergic axons at this age were essentially the same as on P-I. By P-2.5 (60 hours after birth), patches of 5-HT-positive fibers corresponding to individual vibrissa follicles were clearly evident. These consisted of dense aggregates of fine caliber axons that were centered in presumptive layer IV, but which also extended above and below this lamina. Over the next 3 days, the pattern continued to mature. By P-4, dense 5-HT labelling was also visible in the secondary somatosensory cortex (S-II). By the beginning of P-5, clusters of fibers corresponding to more rostral facial hairs and individual digits within the forepaw representation could also be discerned. By P-12, the differential distribution of 5-HT fibers in S-I was no longer visible. Thus, immunocytochemistry for serotonin showed a representation in S-I homeomorphic with the body surface prior to the age at which it can be discerned with other methods thought to reveal thalamocortical axons. Transection of the infraorbital nerve (ION) on the day of birth altered the organization of the vibrissal representation in the contralateral cortex from the earliest age at which it could be detected by 5-HT immunocytochemistry in normal animals. However, the departure from the normal organization was gradual. Row-related organization was clearly visible in the cortices of rats sacrificed on P-3, but not in those of rats that were killed on P-5. These results suggested that the organization of the 5-HT innervation of the cortex may be guided by thalamic afferents and further that some aspects of this guidance persist, albeit temporarily, after ION transection on P-0. The 5-HT immunoreactivity that we observed in the developing somatosensory cortex was not contained in thalamocortical axons. Unilateral electrocautery of the ventrobasal thalamus on P-4 did not reduce the density or alter the pattern of the 5-HT innervation of the cortex in rats that were examined on P-6.

Intersubnuclear connections within the rat trigeminal brainstem complex.

Abstract: Prior intracellular recording and labeling experiments have documented local-circuit and projection neurons in the spinal trigeminal (V) nucleus with axons that arborize in more rostral and caudal spinal trigeminal subnuclei and nucleus principalis. Anterograde tracing studies were therefore carried out to assess the origin, extent, distribution, and morphology of such intersubnuclear axons in the rat trigeminal brainstem nuclear complex (TBNC). Phaseolus vulgaris leucoagglutinin (PHA-L) was used as the anterograde marker because of its high sensitivity and the morphological detail provided. Injections restricted to TBNC subnucleus caudalis resulted in dense terminal labeling in each of the more rostral ipsilateral subnuclei. Subnucleus interpolaris projected ipsilaterally and heavily to magnocellular portions of subnucleus caudalis, as well as subnucleus oralis and nucleus principalis. Nucleus principalis, on the other hand, had only a sparse projection to each of the caudal ipsilateral subnuclei. Intersubnuclear axons most frequently traveled in the deep bundles within the TBNC, the V spinal tract, and the reticular formation. They gave rise to a number of circumscribed, highly branched arbors with many boutons of the terminal and en passant types. Retrograde single- or multiple-labeling experiments assessed the cells giving rise to TBNC intersubnuclear collaterals. Horseradish peroxidase (HRP) and/or fluorescent tracer injections into the thalamus, colliculus, cerebellum, nucleus principalis, and/or subnucleus caudalis revealed large numbers of neurons in subnuclei caudalis, interpolaris, and oralis projecting to the region of nucleus principalis. Cells projecting to more caudal spinal trigeminal regions were most numerous in subnuclei interpolaris and oralis. Some cells in lamina V of subnucleus caudalis and in subnuclei interpolaris and oralis projected to thalamus and/or colliculus, as well as other TBNC subnuclei. Such collateral projections were rare in nucleus principalis and more superficial laminae of subnucleus caudalis. TBNC cells labeled by cerebellar injections were not double-labeled by tracer injections into the thalamus, colliculus, or TBNC. These findings lend generality to currently available data obtained with intracellular recording and HRP labeling methods, and suggest that most intersubnuclear axons originate in TBNC local-circuit neurons, though some originate in cells that project to midbrain and/or diencephalon.