Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo.
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Retraction Notice↗
Biomedical subjects
K D Anderson
Publications and source records attributed to K D Anderson.
Administration of carbachol into the lateral ventricle and suprachiasmatic nucleus (SCN) produces dose-dependent phase shifts in the circadian rhythm of locomotor activity.
The cholinergic agonist, carbachol, induces phase-dependent shifts in the timing of the circadian rhythm of locomotor activity (CRLA). The effects of carbachol injections into the lateral ventricles of hamsters were compared between circadian times that produce phase delays vs. phase advances in the CRLA. The shape of the dose-response curves and the ED50 for carbachol injections were similar for the two injection times. The second experiment demonstrated the dose-dependence of phase advances produced by carbachol injections into the area of the suprachiasmatic nucleus. These results indicate that carbachol exerts similar dose-dependent actions for both phases advances and phase delays.
Acetylcholine↗
Ultrastructural double-labeling demonstrates synaptic contacts between dopaminergic terminals and substance P-containing striatal neurons in pigeons.
Immunohistochemical studies in rats have demonstrated dopaminergic input onto medium spiny neurons of the striatum. Medium spiny neurons, however, are known to consist of two major neuropeptide-specific types, those containing substance P (SP) and those containing enkephalin. Although both of these types have been shown to receive dopaminergic input onto their perikarya and proximal dendrites, the extent to which both types also receive direct dopaminergic input onto distal dendritic shafts or onto dendritic spines is uncertain. In the present study, we used EM immunohistochemical double-label techniques to examine the synaptic organization of dopaminergic input onto SP+ striatal neurons. We examined the striatum of pigeons, in whom SP+ striatal neurons, including their dendritic shafts and spines, can be readily labeled. Antibodies against tyrosine hydroxylase (TH) were used to identify dopaminergic terminals, which were labeled using silver-intensified immunogold. The SP+ neurons were labeled immunohistochemically using diaminobenzidine. We found that dopaminergic terminals make appositions and form symmetric synapses with the perikarya, dendritic shafts and dendritic spines of SP+ neurons. Thus, nigral dopaminergic neurons provide a monosynaptic input onto SP+ striatal neurons in a manner similar to that described for dopaminergic input onto striatal medium spiny neurons in general.
Animals↗
Preferential loss of striato-external pallidal projection neurons in presymptomatic Huntington's disease.
We have reported previously that striatal projection neurons are differentially affected in the course of Huntington's disease, and in a prior patient report we noted that differential loss of striatal projection neurons occurs also in patients with presymptomatic Huntington's disease. Striatal neurons projecting to the external segment of the globus pallidus or the substantia nigra show evident loss, whereas those projecting to the internal segment of the globus pallidus appear relatively spared at presymptomatic and early stages of symptomatic Huntington's disease. We now report similar findings in a second apparently presymptomatic Huntington's disease allele carrier.
Adult↗
Solitary thyroid nodules in 71 children and adolescents.
Seventy-one children and adolescents with a solitary nodule of the thyroid gland were seen over a 27-year period and all had their nodules removed surgically. All of the patients had preoperative thyroid scintiscans, 55 of which showed a cold nodule. The most common cause of solitary thyroid nodules was follicular adenoma. Fourteen of the 55 cold nodules were malignant (25.5%) while no malignancies were present in warm or hot nodules. Available diagnostic methods for attempting differentiation of benign from malignant solitary nodules are reviewed and recommendations to their clinical management as derived from our experience are presented.
Adolescent↗
A strategy for resection of Wilms' tumor with vena cava or atrial extension.
Resection of a Wilms' tumor that extends into the vena cava or right atrium results in excellent survival when combined with adjuvant therapy. Preoperative identification of the presence of intravascular tumor thrombus and the level of vascular involvement is essential. It facilitates safe surgical resection, with cardiopulmonary bypass immediately available for retrohepatic and atrial tumors. Six patients with intracaval or intracardiac tumor thrombus were treated over a 5-year period with no perioperative deaths. Preoperative chemotherapy was useful in two patients with extensive tumors and pulmonary metastases. Our results using an integrated management plan suggest that an aggressive surgical approach is justified for this extensive variant of Wilms' tumor.
Algorithms↗
Long-term follow-up of children with colon and gastric tube interposition for esophageal atresia.
BACKGROUND: There are two major methods of esophageal substitution for children born with long-gap esophageal atresia. This study was undertaken to see whether one method of substitution emerged as clearly superior to the other. METHODS: Twenty-four UK children who received a colon transposition for esophageal atresia were compared with 15 US children with esophageal atresia who received a gastric tube. The charts of all patients were reviewed. Follow-up data were obtained by questionnaire, and more than 80% of patients were personally evaluated at follow-up clinics. RESULTS: At follow-up US children were 3 1/2 to 18 1/2 years of age; UK children were 7 1/2 to 19 years of age. Most of the children fell at or below the 10th percentile for height and weight, reflecting the tendency for prematurity in infants with esophageal atresia. One half of the children needed to eat slowly and to avoid certain meats. Dysphagia was rare. Older children ate socially with their friends without embarrassment. Early complications were technical; there were few late complications, and no difference was apparent between the two groups. CONCLUSIONS: In subjects who were growing, no difference was noted between the two methods of substitution as far as nutrition, growth, patient acceptability, or complications, early or late. Both groups functioned well and appeared to improve with the passage of time.
Anastomosis, Surgical↗
Immunohistochemical localization of DARPP-32 in striatal projection neurons and striatal interneurons: implications for the localization of D1-like dopamine receptors on different types of striatal neurons.
Immunohistochemical double-label techniques were used to study the localization of DARPP-32, a phosphoprotein that is enriched in neurons possessing members of the D1 subfamily of dopamine receptors, in several different types of striatal neurons in the rat basal ganglia. The vast majority (94.1%) of striatonigral projection neurons (the vast majority of which contain substance P), identified by retrograde labeling with fluorogold, were observed to contain DARPP-32. Similarly, the vast majority of striatopallidal projection neurons (87.7%), identified by immunofluorescence labeling for enkephalin (ENK), were found to label for DARPP-32. In contrast, cholinergic and neuropeptide Y-containing striatal interneurons were never observed to contain DARPP-32. These results suggest that essentially all major types of striatal medium spiny projection neurons may possess members of the D1 subfamily of dopamine receptors, but that striatal local circuit neurons do not possess members of the D1 subfamily of receptors.
Animals↗
Ultrastructural single- and double-label immunohistochemical studies of substance P-containing terminals and dopaminergic neurons in the substantia nigra in pigeons.
The vast majority of striatonigral projection neurons in pigeons contain substance P (SP), and the vast majority of SP-containing fibers terminating in the substantia nigra arise from neurons in the striatum. To help clarify the role of striatonigral projection neurons, we conducted electron microscopic single- and double-label immunohistochemical studies of SP+ terminals and/or dopaminergic neurons (labeled with either anti-dopamine, DA, or anti-tyrosine hydroxylase, TH) in pigeons to determine: (1) the synaptic organization of SP+ terminals, (2) the synaptic organization of TH+ perikarya and/or dendrites, and (3) the synaptic relationship between SP+ terminals and TH+ neurons in the substantia nigra. Tissue single-labeled for SP revealed numerous SP+ terminals contacting thin unlabeled dendrites in the substantia nigra, but few SP+ terminals were observed contacting perikarya or large-diameter dendrites. SP+ terminals contained round, densely packed, clear vesicles, and often contained one or more dense-core vesicles. Synaptic junctions between SP+ terminals and their targets were more often symmetric (86%) than asymmetric. In tissue single-labeled for DA, we observed few terminals contacting DA+ perikarya, whereas terminals contacting DA+ dendrites were more abundant. Terminals contacting DA+ structures comprised at least four different morphologically distinct types based on the morphology of the clear synaptic vesicles and the type of synaptic junction. One type of terminal contained round clear vesicles and made symmetric synapses, and thus resembled the predominant type of SP+ terminal. The second type contained round clear vesicles and made asymmetric synapses, the third type contained medium-size pleomorphic clear vesicles and made symmetric synapses, and the fourth type contained small pleomorphic clear vesicles and made symmetric synapses. The presence of contacts between SP+ terminals and dopaminergic dendrites in the substantia nigra was directly demonstrated in tissue double-labeled for SP (by the peroxidase-antiperoxidase procedure, or PAP, with diaminobenzidine) and TH (by either the silver-intensified immunogold procedure or the PAP procedure with benzidine dihydrochloride). SP+ terminals commonly contacted thin TH+ dendrites in the substantia nigra, but few SP+ terminals contacted large-diameter TH+ dendrites or perikarya. Synapses between SP+ terminals and TH+ neurons were always symmetric. TH+ dendrites also were contacted by terminals not labeled for SP, which were more abundant than were SP+ terminals. Non-TH+ neurons were also contacted by both SP+ terminals and non-SP+ terminals.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Striatonigral projection neurons: a retrograde labeling study of the percentages that contain substance P or enkephalin in pigeons.
Two largely separate populations of neuropeptide-containing striatonigral projection neurons have been distinguished in pigeons, one population whose neurons contain substance P (SP) and dynorphin (DYN) and a second population whose neurons contain enkephalin (ENK) (Reiner, '86a; Anderson and Reiner, '90a). In the present study, we investigated the abundance of these two types of neurons relative to all striatonigral projection neurons by combining retrograde labeling by the fluorescent dye fluorogold with immunofluorescence labeling for SP and ENK. Pigeons received large intranigral injections of fluorogold to retrogradely label the striatonigral projection neurons, and several days later they were treated with colchicine (32 hours before transcardial perfusion). Adjacent series of sections through the basal ganglia were labeled for SP and ENK using immunofluorescence techniques. The tissue was examined using fluorescence microscopy and the percentages of retrogradely labeled neurons containing either SP or ENK were quantified. We found that 85-95% of the fluorogold-labeled striatonigral neurons were SP+, whereas only 1-4% were ENK+. Thus the majority of striatonigral projection neurons in pigeons appear to contain SP, whereas a small percentage contain ENK. Only a small percentage of striatonigral neurons did not contain either. Since striatal projection neurons also contain GABA (Reiner, '86b), the present results suggest that a high percentage of striatonigral projection neurons coexpress SP, DYN and GABA, whereas a small fraction coexpress ENK and GABA. The available data are consistent with the conclusion that this is true in reptilian and mammalian species as well.
Animals↗
Retroviral vector-mediated in vivo expression of low-density-lipoprotein receptors in the Watanabe heritable hyperlipidemic rabbit.
We have achieved in vivo expression of recombinant low-density-lipoprotein (LDL) receptors in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for the human disease familial hypercholesterolemia. A retroviral vector was constructed containing the human LDL receptor cDNA and was used to stably transduce primary skin fibroblasts from WHHL rabbits. The integrity and function of the introduced LDL receptor was established by immunoprecipitation, by a fluorescent LDL binding assay, and by the ability of the transduced cells to suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase activity in response to exogenous cholesterol. Autologous transduced fibroblasts were reimplanted into donor rabbits; in vivo LDL receptor expression and the survival of the transduced cells were analyzed by immunohistochemistry and by LDL binding assays performed on cells recovered from the implants. LDL receptor-bearing cells could be identified on tissue sections and recovered from implants for up to four weeks. Total and LDL cholesterol levels decreased significantly after implantation of the transduced cells; however, control experiments indicated that the decreases were not mediated through the recombinant LDL receptor. While in vivo stable expression of recombinant LDL receptors in Watanabe rabbits is possible, consequent changes in lipid levels must be interpreted with caution. This system of site-specific in vivo expression of recombinant LDL receptors permits further evaluation of the role of LDL receptor-gene replacement in the therapy of hypercholesterolemia.
Animals↗
Accuracy of surgery clerkship performance raters.
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Clinical Clerkship↗
Distribution and relative abundance of neurons in the pigeon forebrain containing somatostatin, neuropeptide Y, or both.
Immunohistochemical studies in several mammalian species and in red-eared turtles have shown that somatostatin (SS) and neuropeptide Y (NPY) co-occur in a substantial proportion of the telencephalic neurons containing either. To explore further the possibility that telencephalic neurons co-containing SS and NPY may be evolutionarily conserved among amniotes, we determined the distribution and co-occurrence of SS and NPY in forebrain neurons in pigeons. Single-label immunohistochemical studies revealed the presence of overlapping populations of SS+ neurons and NPY+ neurons in most of the major subdivisions of the telencephalon. Double-label immunofluorescence studies revealed that in subdivisions of the telencephalon that are comparable to mammalian cortex (i.e., those dorsal and lateral to the basal ganglia), the vast majority of NPY+ neurons were also SS+, whereas a major and regionally variable percentage of the SS+ neurons were not NPY+. In contrast, within the basal telencephalon (including the basal ganglia and several other structures) neurons labeled only for NPY or only SS were more abundant than those containing both neuropeptides. Outside the telencephalon, the only forebrain cell group containing neurons in which SS and NPY were co-localized was in the lateral hypothalamus. A series of double- and triple-label immunohistochemical studies was undertaken to determine the extent of co-occurrence of SS and NPY in striatal neurons and the relationship of these neurons to striatal neurons containing other neuropeptides. In addition, immunohistochemical single- and double-label techniques were employed in conjunction with retrograde-labeling by fluorogold to determine the projections of SS+ and NPY+ striatal neurons. The results indicate that: 1) a population of striatal interneurons containing both SS and NPY exists in pigeons and constitutes approximately the same fraction of all striatal neurons as reported in mammals, 2) neurons containing NPY (but not SS) form a second, larger population of striatal interneurons, 3) neurons containing SS (but not NPY) form a third population of striatal interneurons that is approximately half as abundant as the NPY+ interneuron population, and 4) one-third of the substance P-containing striatonigral projection neurons also contain SS. The existence in pigeons of a major population of neurons containing both SS and NPY throughout the telencephalon, the existence of a population of neurons containing only SS in cortex-equivalent parts of the telencephalon, and the existence of a population of interneurons containing only NPY in the striatum is consistent with findings in mammals and turtles.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
A controlled trial of corticosteroids in children with corrosive injury of the esophagus.
BACKGROUND: It is controversial whether treatment with corticosteroids reduces stricture formation in the esophagus after the ingestion of caustic material. METHODS: We conducted a prospective study over an 18-year period in which 60 children (median age, 2 years) with esophageal injury from the ingestion of caustic material were assigned randomly to treatment either with or without corticosteroids. The corticosteroids were given initially as prednisolon (2 mg per kilogram of body weight per day intravenously) and then as prednisone orally to complete a three-week course. All patients were evaluated by esophagoscopy within 24 hours of the ingestion. Those with moderate or severe esophageal injury had repeat esophagoscopy and barium swallow at follow-up. RESULTS: Esophageal strictures developed in 10 of the 31 children treated with corticosteroids and in 11 of the 29 controls (P not significant). Four children in the steroid group and seven in the control group eventually required esophageal replacement (P not significant). All but 1 of the 21 children with strictures had severe circumferential burns on initial esophagoscopy. CONCLUSIONS: There appears to be no benefit from the use of steroids to treat children who have ingested a caustic substance. The development of esophageal stricture was related only to the severity of the corrosive injury.
Administration, Oral↗
Extensive co-occurrence of substance P and dynorphin in striatal projection neurons: an evolutionarily conserved feature of basal ganglia organization.
A number of different neuroactive substances have been found in striatal projection neurons and in fibers and terminals in their target areas, including substance P (SP), enkephalin (ENK), and dynorphin (DYN). In a preliminary report on birds and reptiles, we have suggested that SP and DYN are to a large extent found in the same striatal projection neurons and that ENK is found in a separate population of striatal projection neurons. In the present study, we have examined this issue in more detail in pigeons and turtles. Further, we have also explored this issue in rats to determine whether this is a phylogenetically conserved feature of basal ganglia organization. Simultaneous immunofluorescence double-labeling procedures were employed to explore the colocalization of SP and DYN, SP and ENK, and ENK and DYN in striatal neurons and in striatal, nigral, and pallidal fibers in pigeons, turtles, and rats. To guard against possible cross-reactivity of DYN and ENK antisera with each others' antigens, separate double-label studies were carried out with several different antisera that were specific for DYN peptides (e.g., dynorphin A 1-17, dynorphin B, leumorphin) or ENK peptides (leucine-enkephalin, metenkephalin-arg6-gly7-leu8, methionine-enkephalin-arg6-phe7). The results showed that SP and DYN co-occur extensively in specific populations of striatal projection neurons, whereas ENK typically is present in different populations of striatal projection neurons. In pigeons, 95-99% of all striatal neurons containing DYN were found to contain SP and vice versa. In contrast, only 1-3% of the SP+ striatal neurons and no DYN neurons contained ENK. Similarly, in turtles, greater than 75% of the SP+ neurons were DYN+ and vice versa, whereas ENK was observed in fewer than 5% of the SP+ neurons and 2% of the DYN+ neurons. Finally, in rats, more than 70% of the SP+ neurons contained DYN and vice versa, but ENK was found in only 5% of the SP+ neurons and in none of the DYN+ perikarya. Fiber double-labeling in the striatum and its target areas (the pallidum and substantia nigra) was also consonant with these observations in pigeons, turtles, and rats. These results, in conjunction with studies in cats by M.-J. Besson, A.M. Graybiel, and B. Quinn (1986; Soc Neurosci. Abs. 12:876) strongly indicate that the co-occurrence of SP and DYN in large numbers of striatonigral and striatopallidal projection neurons in a phylogenetically widespread, and therefore evolutionarily conserved, feature of basal ganglia organization.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Abnormalities of striatal projection neurons and N-methyl-D-aspartate receptors in presymptomatic Huntington's disease.
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Adult↗
Striatal and nigral neuron subpopulations in rigid Huntington's disease: implications for the functional anatomy of chorea and rigidity-akinesia.
Neuropeptide immunohistochemistry was used to test several hypotheses of the anatomical bases of chorea and rigidity-akinesia. To test the hypothesis that elevated concentration of striatal somatostatin causes chorea, we visually compared the density of striatal neurons containing somatostatin and neuropeptide Y in brains affected by choreic or rigid-akinetic Huntington's disease (HD). The density of these neurons was elevated in both rigid-akinetic and choreic HD specimens with an apparently normal total number of these neurons, indicating that elevated somatostatin concentration, by itself, does not lead to chorea. We tested the hypothesis that rigid-akinetic HD results from deficient dopaminergic nigrostriatal neurotransmission by examining tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra. In rigid-akinetic HD brains, there was no obvious reduction of nigral TH-IR neurons, indicating that rigid-akinetic HD is probably not due to loss of nigral dopaminergic neurons. Finally, we also examined the status of striatal projection neurons and found near total loss of all striatal neurons projecting to the lateral globus pallidus, medial globus pallidus, and substantia nigra in brains affected by rigid-akinetic HD in contrast to the preservation of neurons projecting to the medial globus pallidus in choreic HD. These results are consistent with the hypothesis that chorea results from preferential loss of striatal neurons projecting to the lateral globus pallidus and that rigid-akinetic HD is a consequence of the additional loss of striatal neurons projecting to the medial segment of the pallidum.
Adult↗
Extracorporeal membrane oxygenation and congenital diaphragmatic hernia: should any infant be excluded?
Mortality in infants with congenital diaphragmatic hernia (CDH) remains high despite improvements in neonatal and surgical care because many infants develop persistent pulmonary hypertension of the newborn (PPHN) following repair. Since 1984, extracorporeal membrane oxygenation (ECMO) has been used as rescue therapy in all infants (n = 25) with PPHN following CDH repair when conventional management failed, with an overall survival of 60%. Repair was performed in this hospital on 12 infants and in other hospitals in 13 infants transferred for consideration of ECMO after repair. Mortality was the same in the group repaired here and those transferred for ECMO. Although complications were frequent in the surviving group, they were successfully managed with nonoperative or operative therapy. Selective use of ECMO has been advocated in CDH patients based on various predictors of high mortality such as "best" PO2 postrepair less than 100 mm Hg, oxygenation index greater than 40, and ventilation index greater than 1,000 with PCO2 greater than 40. Seven surviving infants following ECMO would have been classified as unsalvageable by at least one parameter if selection criteria based on these parameters had been used. We conclude from this series that current predictors of high mortality in CDH patients are unreliable when ECMO is used. Surgeons caring for infants with CDH should consider the use of ECMO in all infants.
Extracorporeal Membrane Oxygenation↗