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The morphology and connections of the posterior hypothalamus in the cynomolgus monkey (Macaca fascicularis). II. Efferent connections.

The efferent connections of the posterior hypothalamus have been analyzed autoradiographically in a series of eight cynomolgus monkey (Macaca fascicularis) brains with injections of 3H-amino acids in different regions of the mamillary complex and the surrounding areas. The medial mamillary nucleus was found to project through the mamillothalamic tract to the ipsilateral anteroventral, anteromedial, and interanteromedial nuclei, and by way of the mamillotegmental tract principally to the deep tegmental nucleus (of Gudden). It also appears to contribute fibers to the medial forebrain bundle, some of which reach as far rostrally as the medial septal nucleus. The lateral mamillary nucleus projects through the mamillothalamic tract bilaterally upon the anterodorsal nuclei of the thalamus, and through the mamillotegmental system to the dorsal tegmental nucleus; it also appears to contribute fibers to the medial forebrain bundle. The supramamillary area has extensive ascending and descending connections that are distributed with the medial forebrain bundle to the hypothalamus and rostral midbrain; in addition, it gives rise to an unusually well-defined projection to field CA2 of the hippocampus and to a narrow zone overlying the outer part of the granule cell layer and the adjoining part of the molecular layer of the dentate gyrus. We have not been able to distinguish the connections of the posterior hypothalamic nucleus from those of the caudal part of the lateral hypothalamic area: they both appear to contribute substantially to the ascending components of the medial forebrain bundle, and through its descending projection to the tegmental fields of the midbrain, the nucleus centralis superior of the raphe complex, the locus coeruleus, and the central gray as far caudally as the facial nerve. Their further projections to the spinal cord were not examined. Viewed broadly, and in the light of previous work, our observations confirm, once again, the constancy of the connections of the hypothalamus in the mammalian brain, and the pivotal position that the posterior hypothalamus occupies in the elaborate system of connections that links the limbic areas of the forebrain with the complex of structures that Nauta has aptly designated the "midbrain limbic region."

Animals↗

Connectivity-behavior analysis reveals that functional connectivity between left BA39 and Broca's area varies with reading ability.

Correlations between temporal fluctuations in MRI signals may reveal functional connectivity between brain regions within individual subjects. Such correlations would be especially useful indices of functional connectivity if they covary with behavioral performance or other subject variables. This study investigated whether such a relationship could be demonstrated in the context of the reading circuit in the brain. The method proved sufficiently powerful to reveal significant correlations between the reading abilities of subjects and the strength of their functional connection between left Brodmann's area 39 and Broca's area during reading. This suggests that the disconnection of the angular gyrus previously reported for dyslexic readers is part of a larger continuum in which poor (but nonimpaired readers) also show reduced connectivity to the region. In addition, it illustrates the potential power of paradigms that examine correlations between behavior and functional brain connections.

Adult↗

Activity in sparsely connected excitatory neural networks: effect of connectivity.

The Nucleus Tractus Solitarius (NTS) of the brainstem contains a neural circuit with only excitatory connections displaying a spontaneous activity involved in the control of respiration. A model of a network with random connections is presented and is used to investigate a possible mechanism of spontaneous activity generation consisting of the amplification of a low-background activity by the excitatory connections. First, the steady states of the network model and its ability to amplify the activity are studied. Then, a low-background activity is introduced, and dynamics of simulated networks are examined. Low-tonic, slow-phasic and fast-tonic activities are successively observed when the mean number K of connections per neuron increases. The transition between the two first types of activity is progressive whereas the transition from slow-phasic to fast-tonic activity is sharp. Simulation results show that activities of low frequency can be obtained with the proposed mechanism of spontaneous activity generation only if the network connectivity is low.

Journal Article↗

Comparison of in vivo activities of 5'-connected and 3'-connected cis-acting ribozymes: selection of intracellularly active ribozymes using the gene for dihydrofolate reductase (DHFR) as a selective marker in Escherichia coli.

If ribozymes are to be exploited in vivo, it is necessary to select ribozymes that are functional in the intracellular environment. Ribozymes selected in the intracellular environment should retain their function in vivo as well as in vitro. We have devised a novel system for selection of active ribozymes from pools of active and inactive ribozymes using the gene for dihydrofolate reductase (DHFR) as a selective marker. In our first attempt, a sequence encoding either an active or an inactive ribozyme was connected upstream of the gene for DHFR. Each plasmid was designed such that, when the ribozyme was active, the ribozyme would cleave the target site and, as a result, the rate of production of DHFR would be high enough to endow resistance to trimethoprim (TMP). However, a critical defect may be associated with introduction of a ribozyme upstream of the DHFR gene because, during actual screening for active ribozymes on the 5' side from a pool of random sequences, there is the danger of selecting sequences that are not related to the activity of ribozymes. Indeed, some upstream linker sequences affected the level of expression of the DHFR protein and, as a result, the resistance of Escherichia coli to TMP. Therefore, we newly constructed a 3'-connected ribozyme system, and activities in vivo of 5'-connected and 3'-connected ribozymes were compared. We found that the cleavage efficiencies in vivo were nearly identical for the two types of ribozyme, 24% for the 5'-side ribozyme and 23% for the 3'-side ribozyme, indicating that polysomes did not seem to inhibit the action of the 3'-connected ribozyme. In both cases, when cells were transformed with a 1 : 1 mixture of active and inactive ribozyme-coding plasmids, it was mainly the cells that harbored the active ribozyme that survived in the presence of TMP.

Base Sequence↗

Connective tissue components of the normal and fibrotic liver. I. Structure, local distribution and metabolism of connective tissue components in the normal liver and changes in chronic liver diseases.

The first part of this review describes the chemistry, the occurrence and the metabolism of extracellular connective tissue components in the liver. The normal liver contains typical connective tissue proteins (collagens, structural glycoproteins and proteoglycans) not only in vessel walls, perivascular areas and in the capsule, but they occur also in small amounts in the parenchyma, mainly in the space of Disse along the sinusoidal walls. The "interstitial" collagens type I and III represent the major amount of collagen in the normal as well as in fibrotic liver, showing a relative increase of type III in fibrosis. Basement membrane collagens type IV and V as well as the cysteine-rich collagenous components "7 S collagen" and "short chain collagen" have been shown to occur in extracts prepared after limited pepsin digestion. In the normal liver, basement membrane collagen can hardly be detected within the parenchyma by immunofluorescence microscopy; increased occurrence, however, can be shown along the sinusoids even in early stages of chronic liver diseases. The glycoprotein fibronectin was shown to be distributed very similarly to collagens type I and III, whereas the basement membrane specific glycoprotein laminin is restricted to vessel walls and the epithelial layer of bile ductuli in the normal liver but is also found in the parenchyma in fibrosis. Occurrence of proteoglycans is increased in fibrosis: a change in the composition of glycosaminoglycans from mainly heparan sulfate in the normal to dermatan- and chondroitin sulfate in the fibrotic liver was observed. It is not yet clear which cell type is mainly responsible for increased connective tissue synthesis in fibrosis. The occurrence of cells resembling smooth muscle cells ("myofibroblasts") in connective tissue septa of fibrotic livers and the fact that similar cells which actively synthesize collagen grow from explants of fibrotic livers may indicate the significance of this cell type in the process of liver fibrosis.

Basement Membrane↗

Connective tissue activation. XXVIII. A connective tissue activating peptide from human urine.

A protein factor in human urine which has the ability to activate connective tissue cells has been identified and partially purified; it appears to be different from epidermal growth factor and IgG. This urinary connective tissue activating factor (CTAP-U) is nondialyzable, labile to protease, stable to thiols, heat, and acid, and has an acidic isoelectric point. Purified preparations of CTAP-U have biologic activities that cause human connective tissue cells to synthesize incremental amounts of 14C-hyaluronic acid, 35S-proteoglycans, and 3H-DNA in vitro. The cell spectrum responsive to this substance includes human synovial cells, human chondrocytes, and skin fibroblasts. CTAP-U does not react with antisera to connective tissue activating peptide-III or to antibodies against IgG or its Fc and Fab fragments. Furthermore, CTAP-U does not cross-react in a radioreceptor assay for insulin, basic somatomedin, or epidermal growth factor-urogastrone. Utilizing standardized isolation conditions, CTAP-U preparations with these properties have been isolated from the urine of 6 normal individuals.

Cartilage↗

Reduced parahippocampal connectivity produces schizophrenia-like memory deficits in simulated neural circuits with reduced parahippocampal connectivity.

CONTEXT: Episodic memory impairments are well characterized in schizophrenia, but their neural origin is unclear. OBJECTIVE: To determine whether the episodic memory impairments in schizophrenia may originate from reduced parahippocampal connectivity. DESIGN: Experimental in silico model. SETTING: Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands. INTERVENTIONS: A new, in silico medial temporal lobe model that simulates normal performance on a variety of episodic memory tasks was devised. The effects of reducing parahippocampal connectivity in the model (from perirhinal and parahippocampal cortex to entorhinal cortex and from entorhinal cortex to hippocampus) were evaluated and compared with findings in schizophrenic patients. Alternative in silico neuropathologies, increased noise and loss of hippocampal neurons, were also evaluated. RESULTS: In the model, parahippocampal processing subserves integration of different cortical inputs to the hippocampus and feature extraction during recall. Reduced connectivity in this area resulted in a pattern of deficits that closely mimicked the impairments in schizophrenia, including a mild recognition impairment and a more severe impairment in free recall. Furthermore, the schizophrenic model was not differentially sensitive to interference, also consistent with behavioral data. Notably, neither increased noise levels nor a reduction of hippocampal nodes in the model reproduced this characteristic memory profile. CONCLUSIONS: Taken together, these findings highlight the importance of parahippocampal neuropathology in schizophrenia, demonstrating that reduced connectivity in this region may underlie episodic memory problems associated with the disorder.

Entorhinal Cortex↗

Repair of combined total anomalous pulmonary venous connection and anomalous systemic connection in early infancy.

A simple intraatrial reconstruction can be utilized in infants to simultaneously correct both the systemic and pulmonary venous returns. Two infants with polysplenia syndrome treated in the first months of life are presented. One had levocardia and combined total anomalous pulmonary venous connection (type II-Cardiac) and anomalous systemic venous connection. The other had dextrocardia L-loop, L-normal great arteries, and combined total anomalous pulmonary venous connection (type II-Cardiac) and anomalous systemic venous connection. The posterior position of the systemic atrioventricular valve and systemic ventricle in both patients allowed the use of this reconstructive technique. The extensive size and transverse position of this patch when used in the infant may require both continued postoperative controlled ventilation until it stiffens and prolonged attention to postoperative cardiac care until adaptation of the infant heart to the new atria can occur. Early restudy and reoperation should be performed if signs of stenosis develop.

Dextrocardia↗

Instantaneous subaortic outflow obstruction after volume reduction in hearts with univentricular atrioventricular connection and discordant ventriculoarterial connection.

OBJECTIVE: To study the phenomenon of potential subaortic outflow obstruction after surgical volume unloading of the heart in patients with univentricular atrioventricular connection, discordant ventriculoarterial connection, and bulboventricular foramen (BVF)-dependent systemic flow. MATERIAL AND METHODS: Intraoperative transesophageal echocardiography was used in five patients with tricuspid atresia (N = 3) or double-inlet left ventricle (N = 2) with rudimentary right ventricle and BVF who were scheduled to undergo a bidirectional cavopulmonary anastomosis (N = 3) or completion of the Fontan procedure after previous banding of the pulmonary artery (N = 2). The BVF diameter was measured in two orthogonal views, and the area was calculated by using the formula for an ellipse. Left ventricular posterior wall thickness and left ventricular internal diameter were also measured. Intraoperative prerepair and postrepair gradients across the BVF were measured by echocardiography. RESULTS: Volume unloading of the left ventricle resulted in instantaneous contraction of left ventricular size (decrease of median left ventricular internal diameter from 38 to 34 mm and increase of median left ventricular posterior wall thickness from 5 to 7 mm), decrease of median BVF area index (from 1.82 to 1.55 cm2/m2), and development of a median gradient of 60 mm Hg across the BVF. At a mean follow-up of 19.6 months, all patients were clinically well and had no echocardiographic evidence of BVF obstruction. CONCLUSION: In hearts with univentricular atrioventricular connection, discordant ventriculoarterial connection, and BVF-dependent systemic flow, a decrease in ventricular volume is associated with an instantaneous alteration in ventricular geometry, diminution in BVF size, and potential for subaortic outflow obstruction. Intraoperative transesophageal echocardiography is of paramount importance in excluding development of subaortic outflow obstruction in this setting.

Anastomosis, Surgical↗

Conversion of the atriopulmonary Fontan connection to a total cavopulmonary connection.

Right atrial-to-pulmonary artery anastomosis (modified Fontan-Kreutzer operation) often results in substantial enlargement of the right atrium over time. Massive right atrial dilatation can cause loss of laminar flow, stasis, compression of the right pulmonary veins posteriorly, and leftward shift of the atrial septum. Some patients may develop arrhythmias related to atrial distension and multiple suture lines. Chronic elevation of the central venous pressure may cause liver dysfunction and/or protein-losing enteropathy in some patients. Some patients with atriopulmonary Fontan connections who develop a decline in functional status may benefit from conversion to a total cavopulmonary connection. Patients with significant ventricular dysfunction can usually only be treated by cardiac transplantation. However, other problems may be successfully managed by revision of the atriopulmonary Fontan connection to a total cavopulmonary anastomosis. Conversion to a total cavopulmonary connection should improve cardiac output by restoring laminar flow, by relieving compression of the right pulmonary veins, and by alleviating the leftward displacement of the atrial septum. Copyright 1998 by W.B. Saunders Company

Journal Article↗

Enumeration of four-connected three-dimensional nets. III. Conversion of edges of three-connected two-dimensional nets into saw chains.

A three-repeat saw (s) chain has each vertical edge separated by a tooth composed of two tilted edges zig and zag. Some horizontal (h) edges from a parallel stack of three-connected two-dimensional (2D) nets can be converted into an s chain. Each resulting four-connected vertex in the three-dimensional (3D) net may be part of either one, two or three s chains. The first type of (h,s)* 3D net is related by a sigma-type mirror plane to a (h,z)* net listed in paper II [Han & Smith (1998). Acta Cryst. A55, 342-359]. The second type does not have an (h,z)* relative. Using the same three-connected 2D nets as in paper II, 174 four-connected 3D nets were selected from the first two types, including six in known structures: 'nepheline hydrate' (International Zeolite Association Structure Commission code JBW), AlPO(4)-12-TAMU (ATT), offretite (OFF), Linde Type L (LTL), SUZ-4 (SZF) and ZSM-10 (ZST). The third type with three back-to-back s chains is represented by edingtonite (EDI), and systematic enumeration is in progress. The geometrical and topological properties of the 3D nets are given. Idealized unit-cell data and atomic coordinates for tetrahedral bonding were obtained for 40 selected 3D nets by distance-least-squares (DLS) refinement.

Journal Article↗

Intrinsic Organization and Connectivity of Intrastriatal Striatal Transplants in Rats as Revealed by DARPP-32 Immunohistochemistry: Specificity of Connections with the Lesioned Host Brain.

Intrastriatal grafts of tissue obtained from the striatal or neocortical primordia of rat fetuses have been studied with respect to their intrinsic organization and connectivity using antibodies to DARPP-32 in combination with acetylcholinesterase (AChE) histochemistry, tyrosine hydroxylase (TH) immunocytochemistry, and anterograde and retrograde axonal tracing techniques. The striatal grafts were characterized by distinct patches of DARPP-32-immunoreactive neurons, which were identical to the densely AChE-positive patches stained in adjacent sections from the same specimens. The non-patch areas possessed only few DARPP-32-positive neurons and contained only sparse AChE-positive fibres. The cortical grafts, by contrast, contained no neurons with clear-cut DARPP-32-positivity and they exhibited a sparse, evenly distributed AChE fibre network, similar to that seen in the non-patch areas of the striatal grafts. The host dopaminergic afferents, as revealed by TH immunostaining, had grown selectively into the DARPP-32-positive patches in the striatal grafts, where they formed a dense terminal network around the DARPP-32-positive cell bodies. The non-patch areas, as well as the cortical grafts, received only sparse TH innervation. By contrast, the host cortical afferents, labelled by Phaseolus vulgaris leucoagglutinin from the host frontal cortex, were seen to extend into both the patch and non-patch areas of the striatal grafts. Transplant neurons projecting into the host brain were labelled by Fluoro-Gold injections into the ipsilateral host globus pallidus. These injections labelled large numbers of medium-sized neurons within the striatal grafts and the vast majority of them (over 85%) were confined to the DARPP-32-positive patches. Similar Fluoro-Gold injections labelled only few graft neurons in the cortical grafts. The results indicate that the striatal grafts are composed of a mixture of striatal and non-striatal tissue, and that the striatal graft compartment selectively establishes afferent and efferent connections with the host nigro-pallidal system. These graft connections demonstrate a remarkable specificity in the formation of graft - host connectivity. The results, moreover, suggest that developmental properties of the grafted striatal primordium are retained and expressed in the implanted cell suspension, and that the neuronal systems of the lesioned adult host brain, at least to some extent, remain responsive to growth regulating mechanisms normally operating during ontogenetic development.

Journal Article↗

The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.

To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created the first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules, together with pattern-matching software to mine these data. We demonstrate that this "Connectivity Map" resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. These results indicate the feasibility of the approach and suggest the value of a large-scale community Connectivity Map project.

Alzheimer Disease↗

Influence of synaptic identity on single-Ia-afferent connectivity and EPSP amplitude in the adult cat: homonymous versus heteronymous connections.

1. This study makes use of the pattern of synaptic connections between motoneurons and Ia afferents of triceps surae muscles in the cat to test the relative importance of synaptic identity, neuronal size, and neuronal topography as determinants of Ia-afferent connectivity and excitatory postsynaptic potential (EPSP) amplitude. 2. The synaptic actions of single-Ia medial gastrocnemius (MG) afferents were measured by intracellular recording in MG and lateral gastrocnemius (LG) motoneurons. The spike-triggered averaging technique was used to measure EPSPs generated by homonymous or heteronymous Ia afferents and motoneurons, i.e., neurons supplying the same or different muscles, respectively. In agreement with earlier studies, the pooled sample showed that the number of functional connections and the size of EPSPs were both significantly greater for homonymous than for heteronymous neurons. 3. Afferent conduction velocity, motoneuron conduction velocity, rheobase current, and position of the motoneuron relative to the spinal cord afferent entry were all correlated with EPSP amplitude, but the amplitude difference between homonymous and heteronymous connections remained significant after the statistical removal analysis of covariance (ANCOVA) of the contribution of these variables. Stepwise multiple-regression analysis showed that synaptic identity explained the greatest fraction of the variance in EPSP amplitude (9%), with significant but smaller fractions accounted for by rheobase current or motoneuron conduction velocity. 4. In a separate experiment, the monosynaptic affects from both homonymous and heteronymous single-Ia afferents were examined in each of 88 MG or LG motoneurons. The single-Ia afferents used in this portion of the study were sampled from both MG and LG muscles and selected for similar conduction velocities and spinal cord entry points.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Modification of the Fontan procedure. Superior vena cava to left pulmonary artery connection and inferior vena cava to right pulmonary artery connection with adjustable atrial septal defect.

BACKGROUND: A modification of the Fontan procedure with unidirectional cavopulmonary connection is described in which the superior vena cava (SVC) is connected to the left pulmonary artery (PA) and the inferior vena cava (IVC) is connected to the right PA via a lateral tunnel with a snare-controlled, adjustable atrial septal defect (ASD). This allows matching of the SVC and IVC flows with the lung of appropriate size. The obligatory left Glenn shunt provides an adequate arterial oxygen saturation, and the elevation in SVC pressure is well tolerated. The adjustable ASD allows selective decompression of the IVC that maintains cardiac output and reduces fluid accumulation in the serous cavities. METHODS AND RESULTS: Since March 1992, we have performed this procedure in 18 patients. There were 17 children and 1 adult. Median age was 3 years and 9 months (range, 13 months to 36 years). Six patients had been staged with a previous bidirectional Glenn shunt. Preoperative cardiac catheterization revealed a PA pressure of 13 +/- 2 mm Hg and a transpulmonary gradient of 5 +/- 3 mm Hg. Ventricular function was satisfactory in all patients. At the completion of bypass, the pressures in the SVC and IVC were 16 +/- 4 mm Hg and 10 +/- 3 mm Hg, respectively (P < .01). The left atrial pressure was 6.0 +/- 3.0 mm Hg and the arterial O2 saturation on 100% oxygen was 93 +/- 3%. There was one death as a result of intractable atrial arrhythmias. The remaining 17 patients had a mean hospital stay of 9.7 days (6 to 18 days). The length of pleural drainage was 7 +/- 3 days. The ASD was adjusted in 11 patients before discharge. Oxygen saturation at discharge was 85.4 +/- 4%. Nine patients had repeat catheterization. The ASD was completely closed in 6 patients, an average of 2.5 months after surgery (range, 3 weeks to 5 months). After ASD closure, the arterial oxygen saturation was 96 +/- 3%, and the SVC and IVC pressures were both 13 +/- 3 mm Hg. CONCLUSIONS: The Fontan procedure with unidirectional cavopulmonary connection and adjustable ASD has several advantages that may reduce mortality and morbidity for the high-risk Fontan candidate.

Adolescent↗

Mechanics of the implant-abutment connection: an 8-degree taper compared to a butt joint connection.

This paper presents aa comparison between the 8-degree Morse Taper and the butt joint aa connections between an implant and an abutment. Three-dimensional, non-linear finite element models were created to compare the 2 connection principles under equal conditions. The loading configuration was thereby modeled according to a test setup actually used for the dynamic long-term testing of dental implants as required for regulatory purposes. The results give insight into the mechanics involved in each type of connection and are compared to actual findings with the testing machine. The comparison indicates the superior mechanics of conical abutment connections and helps to explain their significantly better long-term stability in the clinical application.

Dental Abutments↗

Double connections in total anomalous pulmonary venous connection.

Three infants who underwent operation for total anomalous pulmonary venous connection had unobstructed drainage of all the pulmonary veins to both the coronary sinus and left vertical vein. In one patient the anatomy was demonstrated preoperatively and complete correction accomplished without difficulty, but in two patients the second connection was discovered only at postoperative reinvestigation. Arbitrary classification of total anomalous pulmonary venous connection into cardiac, supracardiac, infracardiac, and mixed types does not lend itself to description of such lesions and may obscure their clinical importance. For these less common variants of total anomalous pulmonary venous connection, a more detailed and precise definition of morphology facilitates accurate surgical repair.

Cardiac Catheterization↗

How important is tumour shape? Quantification of the epithelial-connective tissue interface in oral lesions using local connected fractal dimension analysis.

Quantification of the local complexity of the epithelial-connective tissue interface (ECTI) in normal mucosa, epithelial dysplasia, and squamous cell carcinoma of the floor of the mouth was investigated by estimating the local connected fractal dimension in tissue profiles from histological sections. The use of certain parameters of the distribution of the local connected fractal dimensions of the ECTI classifies the cases belonging to these three histopathological diagnoses with 85 per cent accuracy by means of linear discriminant analysis. The values of the local fractal dimension were also used to produce colour-coded dimensional images of the ECTI, to highlight locations with higher irregularity that may correlate with locally invasive 'higher-risk' areas.

Carcinoma, Squamous Cell↗