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Urgency of operation in infracardiac total anomalous pulmonary venous connection.

BACKGROUND: Because the tendency for pulmonary venous obstruction in the infracardiac type of total anomalous pulmonary venous connection may be partially dependent on the connection of the descending vein to the portal vein, the inferior vena cava, or one of their tributary vessels, we reviewed our surgical experience with various subtypes of infracardiac total anomalous pulmonary venous connection. METHODS: The urgency of operation in 4 neonates with infracardiac total anomalous pulmonary venous connection was reviewed. RESULTS: Two patients with pulmonary venous obstruction in whom the descending vein connected to the portal vein were operated on immediately with successful outcome. One patient who had become critically ill after the ductus venosus had closed died before operation could be undertaken. One patient in whom the descending vein connected to the left hepatic vein was operated on electively with successful outcome. CONCLUSIONS: In hemodynamically stable patients with no clinical or echocardiographic signs of pulmonary venous obstruction, some form of differentiation with regard to urgency of operation may be appropriate. When the descending vein connects to the inferior vena cava or a hepatic vein, the operation may be performed on a semi-elective basis. In contrast, when the descending vein connects to the portal vein or the ductus venosus, operation should generally not be delayed because of the high likelihood of obstruction.

Emergencies↗

Mechanisms involved in development of retinotectal connections: roles of Eph receptor tyrosine kinases, NMDA receptors and nitric oxide.

Axons of retinal ganglion cells exhibit a specific pattern of connections with the brain. Within each visual nucleus in the brain, retinal connections are topographic such that axons from neighboring ganglion cells have neighboring synapses. Research is beginning to shed light on the mechanisms responsible for development of topographic connections in the visual system. Much of this research is focused on the axonal connections of the retina with the tectum. In vivo and in vitro experiments indicate that the pattern of retinotectal connections develops in part due to positional labels carried by the growing retinal axons and by the tectal cells. Evidence suggests that gradients of Eph receptor tyrosine kinases serve as positional labels on the growing retinal axons, and gradients of ligands for these receptors serve as positional labels in the tectum. Blocking expression of EphA3, a receptor tyrosine kinase, in the developing retina resulted in disruption of the topography of the retinotectal connections, further supporting the role of these, molecules. Although positional labels appear to be important, other mechanisms must also be involved. The initial pattern of retinotectal connections lacks the precision seen in the adult. The adult pattern of connections arises during development by activity dependent refinement of a roughly ordered prepattern. The refinement process results in elimination of projections to the wrong side of the brain, to non-visual nuclei and to inappropriate regions within a nucleus. Blocking NMDA receptors during the period of refinement preserved anomalous retinotectal projections, which suggests that elimination of these projections is mediated by NMDA receptors. Furthermore, tectal cells normally express high levels of nitric oxide synthase (NOS) during the period of refinement, and blocking nitric oxide (NO) synthesis also preserved inappropriate projections. Thus, both NMDA receptors and NO appear to be involved in refinement. Blocking NMDA receptor activation reduced NOS activity in tectal cells, which suggests the possibility that NO is the downstream mediator of NMDA function related to refinement. A quantitative comparison of blocking NMDA receptors, NO synthesis or both showed that all three treatments have comparable effects on refinement. This indicates that the role of NMDA receptor activation relative to refinement may be completely mediated through nitric oxide. Quantitative analysis also suggests that other mechanisms not involving NMDA receptors or NO must be involved in refinement. Other mechanisms appear to include cell death.

Animals↗

Pulmonary artery banding and ventricular septal defect enlargement in patients with univentricular atrioventricular connection and the aorta originating from an incomplete ventricle.

BACKGROUND: In patients with univentricular atrioventricular connection and the aorta originating from an incomplete ventricle, subaortic stenosis is generally due to a restrictive ventricular septal defect (RVSD), that may be present at birth or develop after palliative procedures. In particular, a primary role in the genesis of the RVSD has been ascribed to pulmonary artery banding (PAB). The aim of this paper is to analyse the possible risk factors for the development of an RVSD, including PAB, and the results of one of the proposed procedures for treatment of this condition (RVSD enlargement). METHODS: We retrospectively reviewed clinical records and outpatient records of 24 consecutive patients with univentricular atrioventricular connection and the aorta originating from the incomplete ventricle that received their first treatment at our institution from January 1991 to April 2000. The variables age, sex, weight, diagnosis, surgical procedures, associated anomalies, associated surgical procedures, were considered. RESULTS: Four patients (16.7%) had absent left atrioventricular connection, seven (29.7%) had absent right atrioventricular connection and discordant ventriculo-arterial connection, and 13 (54.7%) had double inlet left ventricle and discordant ventriculo-arterial connection. Five patients (20.8%) had associated coarctation or hypoplasia of the aorta, and eight (33.3%) had pulmonary stenosis or atresia. Median age at the first operation was 7.5 days (range: 1-376). Median weight was 3.5 kg (range: 1.9-6.3). Seventeen patients underwent pulmonary artery banding, one underwent a Damus-Kaye-Stansel connection, one received a Glenn shunt and five a modified Blalock-Taussig shunt. Early mortality was 12.5%. The only variable associated with operative mortality was the presence of coarctation or hypoplasia of the aorta (P=0.004). Ten patients (41.6%) developed subaortic stenosis. None of the tested variables, including pulmonary artery banding, was associated with the development of subaortic stenosis. Subaortic stenosis was due to a restrictive VSD in eight patients, six of whom underwent direct VSD enlargement by muscular resection and are well at last follow-up (four complete repairs). None of the procedures was complicated by complete heart block. In two cases subaortic stenosis was treated by a Damus-Kaye-Stansel connection. A single patient died during follow-up, and 11 patients have achieved a complete one-ventricle repair. CONCLUSION: In our experience, pulmonary artery banding was not associated with an increased risk of developing an RVSD. VSD enlargement proved to be safe and effective for treatment of subaortic stenosis due to an RVSD.

Aortic Stenosis, Subvalvular↗

The elusive concept of brain connectivity.

Neurons and neural populations do not function as islands onto themselves. Rather, they interact with other such elements through their afferent and efferent connections in an orchestrated manner so as to enable different sensorimotor and cognitive tasks to be performed. The concept of functional connectivity and the allied notion of effective connectivity were introduced to designate the functional strengths of such interactions. Functional neuroimaging methods, especially PET and fMRI, have been used extensively to evaluate the functional connectivity between different brain regions. After providing a brief historical review of these notions of brain connectivity, I argue that the conceptual formulations of functional and effective connectivity are far from clear. Specifically, the terms functional and effective connectivity are applied to quantities computed on types of functional imaging data (e.g., PET, fMRI, EEG) that vary in spatial, temporal, and other features, using different definitions (even for data of the same modality) and employing different computational algorithms. Until it is understood what each definition means in terms of an underlying neural substrate, comparisons of functional and/or effective connectivity across studies may appear inconsistent and should be performed with great caution.

Brain↗

Display technique using time-dependent scatter diagrams for the study of changing relative timings of three spike trains: evaluation of functional connectivity in a local area of the nervous system.

The relative timings of impulses caused by two neurons can be studied using cross-correlation techniques or the related techniques of the joint peristimulus-time histogram and the time-dependent correlation function. Analysis of the relative timings of several related neurons is important to the study of the dynamics, since we consider functional connectivity to be partially related to the dynamics. Functional connectivity changes of short duration reflect physiological functions rather than changes of synaptic connections. The relative timings of impulses are considered to reflect functional connectivity. Using the joint impulse configuration scatter diagram (JICSD) proposed by Perkel, a time-dependent scatter diagram (TDSD) is calculated to analyze the change of functional connectivity. The JICSD displays the long-time average of relative timings of impulses or the functional connectivity of three interconnected neurons. We generated JICSDs for short durations and we subsequently generated TDSDs by arranging JICSDs in chronological order. The change of a "snowflake pattern" of each JICSD was interpreted in terms of change of the functional connectivity. We propose a method for analyzing the changing functional connectivity among three neurons.

Action Potentials↗

Specificity of cortical synaptic connectivity: emphasis on perspectives gained from quantitative electron microscopy.

This report traces the historical development of concepts regarding the specificity of synaptic connectivity in the cerebral cortex as viewed primarily from the perspective of electron microscopy. The occurrence of stereotypical patterns of connection (e.g., contrasting synaptic patterns on the surfaces of spiny vs. non-spiny neurons, the general consistency with which axonal pathways impinge on and originate within specific cortical areas and layers, triadic synaptic relationships) implies that cortical connectivity is highly structured. The high degree of order characterizing many aspects of cortical organization is mirrored by an equally ordered arrangement of synaptic connections between specific types of neurons. This observation is based on quantitative electron microscopic studies of synapses between identified neurons and from the results of correlative anatomical/electrophysiological investigations. The recognition of recurring synaptic patterns and responses between specific neurons has generated increased support for the notion of specificity of synaptic connections at the expense of randomness, but the role of specificity in cortical function is an unresolved question. At the core of cortical processing lie myriad possibilities for computation provided by the wealth of synaptic connections involving each cortical neuron. Specificity, by limiting possibilities for connection, can impose an order on synaptic interactions even as processes of dynamic selection or synaptic remodeling ensure the constant formation and dissolution of cortical circuits. These operations make maximal use of the richness of cortical synaptic connections to produce a highly flexible system, irrespective of the degree of randomness or specificity that obtains for cortical wiring at any particular time.

Animals↗

Student--teacher connection in clinical nursing education.

BACKGROUND: The trend toward humanistic nursing education has called for a transformed student-teacher relationship that fosters learning and growth of students and teachers. Although such a relationship has been claimed to form the basis for student-teacher connection and to be a positive influence on students' learning outcomes, there is a paucity of research exploring these claims. Neither the nature of student-teacher connection nor the processes by which it occurs have been described. AIMS: A research study was undertaken to explore and describe undergraduate nursing students' experiences of connection within the student-teacher relationship and the effects of student-teacher connection on students' learning experiences in clinical nursing education. RESEARCH DESIGN: The qualitative research approach of interpretive description was chosen for this study. Unstructured interviews and a focus group were used to collect data from eight undergraduate nursing students. Data were analysed using the process of constant comparative analysis, and revealed four interrelated major categories that formed a description of the students' experience of student-teacher connection. FINDINGS: This article presents part of the findings of this study. After describing the nature of student-teacher connection, the discussion focuses on the influence of teachers and other factors on the formation of student-teacher connection. Relevance is given to this discussion by describing the outcomes of connection for students' clinical learning experiences.

Adolescent↗

Myocardial connections between left atrial myocardium and coronary sinus musculature in man.

INTRODUCTION: Anatomic studies have shown that muscle morphologically identical to that of the atrial myocardium consistently surrounds the coronary sinus (CS). The CS musculature is connected to the left atrial (LA) myocardium in a variable fashion, with fewer connections in its distal portion. The aim of this study was to document the presence of connections between the LA myocardium and the CS musculature, using pacing maneuvers in man, and to study their potential association with natural atrial arrhythmia occurrence. METHODS AND RESULTS: Thirty patients (19 men; mean age 50.5 years) underwent electrophysiologic study, during which a decapolar catheter with 2-mm interelectrode spacing every 10 mm was inserted into the CS, with the proximal electrode pair positioned at the ostium. Associated atrial arrhythmias were paroxysmal atrial fibrillation in 5, typical atrial flutter in 13, LA flutter in 1, and other in 11. Baseline S1 and a single extrastimulus were delivered during distal and proximal CS pacing, while recordings were obtained from the four remaining bipoles. During distal CS pacing, double potentials with increasing interpotential interval from proximal to distal CS as a function of extrastimulus prematurity were detected in nine patients, suggesting block in a discrete local pathway distally connecting the CS to the LA and leading to reversion of low LA activation. Local delay in this pathway without complete CS-LA block resulting in LA activation fusion was observed in eight patients. A single nonfractionated potential at the distal CS, even at the shortest attainable S1-S2 coupling interval, which was interpreted as no block within distal CS-LA connection(s), was observed in the other 13 patients. History of atrial fibrillation or atypical atrial flutter was found in 8 of 9 patients with block at the distal CS-LA connection but in only 3 of 13 patients with no CS-LA connection block (P = 0.004). CONCLUSION: The ability to dissociate the LA from the distal CS suggests the presence of discrete connections between these structures in man. This observation appears to be associated with the clinical occurrence of atrial arrhythmias.

Analysis of Variance↗

Connectivity matrix method for analyses of biological networks and its application to atom-level analysis of a model network of carbohydrate metabolism.

An approach for analysis of biological networks is proposed. In this approach, named the connectivity matrix (CM) method, all the connectivities of interest are expressed in a matrix. Then, a variety of analyses are performed on GNU Octave or Matlab. Each node in the network is expressed as a row vector or numeral that carries information defining or characterising the node itself. Information about connectivity itself is also expressed as a row vector or numeral. Thus, connection of node n1 to node n2 through edge e is expressed as [n1, n2, e], a row vector formed by the combination of three row vectors or numerals, where n1, n2 and e indicate two different nodes and one connectivity, respectively. All the connectivities in any given network are expressed as a matrix, CM, each row of which corresponds to one connectivity. Using this CM method, intermetabolite atom-level connectivity is investigated in a model metabolic network composed of the reactions for glycolysis, oxidative decarboxylation of pyruvate, citric acid cycle, pentose phosphate pathway and gluconeogenesis.

Adaptation, Physiological↗

Limited proteolysis of human alpha2-HS glycoprotein/fetuin. Evidence that a chymotryptic activity can release the connecting peptide.

alpha2-HS glycoprotein is a major protein of human plasma whose function is still obscure. A proteolytically processed form of alpha2-HS glycoprotein lacking a segment of 40 amino acid residues bridging its heavy and light chain portions ("connecting peptide") has been described suggesting that this peptide is released by post-translational processing to fulfill biological role(s) of alpha2-HS glycoprotein. To test this hypothesis we investigated how the connecting peptide is released from the parental molecule by limited proteolysis. We developed monoclonal antibodies to various portions of the connecting peptide and its NH2-terminal flanking region which cross-react with the native alpha2-HS glycoprotein. Purified alpha2-HS glycoprotein from human plasma was subjected to limited proteolysis by proteinases including trypsin, chymotrypsin, elastase plasmin, kallikrein, thrombin, and renin. Immunoprint analysis of the proteolytic digests indicated that alpha2-HS glycoprotein is readily cleaved in its connecting peptide region. NH2-terminal amino sequence analysis of the generated fragments demonstrated that a single proteinase, chymotrypsin, cleaves the critical Leu-Leu bond flanking the NH2-terminal portion of the connecting peptide region. Most but not all of the other proteinase cleavage sites map to a short stretch of 9 residues located in the center portion of the connecting peptide region. Immunoprint analysis of plasma samples from patients with sepsis demonstrate that the connecting peptide region is cleaved under pathological conditions. Our results indicate that the connecting peptide and/or fragments thereof are readily releasable from alpha2-HS glycoprotein in vitro and in vivo.

Amino Acid Sequence↗

A novel method for visualizing functional connectivity using principal component analysis.

Functional connectivity is a useful measure of voxel-wise functional magnetic resonance imaging signals that allows for the identification of functionally related brain areas and distributed networks. However, the high dimensionality of functional connectivity makes it difficult to visualize. In most studies, a small percentage of the total functional connectivity is visualized through diagrams that are constructed using individual seed voxels. In the present study describes a new method for visualizing most of the functional connectivity through a single diagram. This method does not rely on seed voxels, but rather employs a reduction of the high-dimensionality of the functional connectivity via a projection onto a three-dimensional color space using principal components analysis. With this new method, most of the information contained in a functional connectivity matrix can be represented through a single color-coded functional connectivity map, thereby facilitating a greater visual appreciation of functional connectivity.

Brain↗

The development of motor control in the rhesus monkey: evidence concerning the role of corticomotoneuronal connections.

Corticospinal fibres terminate in three areas in the spinal grey matter of the rhesus monkey: the nucleus proprius of the dorsal horn, the intermediate zone and directly upon motoneurons, particularly those inervating limb muscles. It was suggested at their earliest discovery that direct corticomotoneuronal (CM) connections might constitute a critical anatomical substrate for the type of fractionated movement exemplified by relatively independent finger movements (RIFM). The present study was undertaken in an attempt to provide further evidence in support of this idea. The evidence is based upon the anatomical finding that few CM connections are present at birth in the monkey, the bulk being formed postnatally to reach an adult density at approximately 8 months of age. There were two experimental approaches: in the first it was argued that if RIFM are dependent upon the presence of CM connections it would be expected that such movements would appear only gradually postnatally, developing in parallel with the development of the connections. In 2 normal monkeys studied from this point of view discrete distal movements did develop only gradually with RIFM reaching an adult level at 7 to 8 months of age. The second experimental appraoch was based upon the fact that pyramidal lesions in newborn animals interrupt corticospinal fibres before CM connections are formed. It was argued that such a situation might provide a better opportunity for other descending pathways to establish the connections necessary for RIFM. Five infant monkeys had bilateral pyramidal tract lesions made from 5 days to 4 weeks after birth and were observed for a period of three years. In the 4 animals in which the lesions were complete, RIFM failed to develop. In the fifth animal, in which the lesions were incomplete, there was development of some degree of RIFM. It was concluded that the development of RIFM is dependent upon fibres passing in the pyramidal tracts and that in infant monkeys, as well as in adults, other descending pathways are unable to form the connections necessary for these movements. The possible contribution to RIFM of the corticospinal fibres arise in the somatosensory cortex and terminate in the dorsal horn was studied by bilateral removal of the arm and leg area of the somatosensory cortex in one animal. Since RIFM were only minimally and transiently altered, it was concluded that such movements are not dependent upon these fibres. The different lines of evidence presented in the study are interpreted as giving further support to the idea that corticomotoneuronal connections constitute an essential anatomical substrate for fractionated movements such as RIFM. Observations were also made of the development of general locomotor activity in normal and pyramidotomized infant monkeys.

Age Factors↗

Functional connectivity in human cortical motor system: a cortico-cortical evoked potential study.

In order to understand the complex functional organization of the motor system, it is essential to know the anatomical and functional connectivity among individual motor areas. Clinically, knowledge of these cortico-cortical connections is important to understand the rapid spread of epileptic discharges through the network underlying ictal motor manifestation. In humans, however, knowledge of neuronal in vivo connectivity has been limited. We recently reported a new method, 'cortico-cortical evoked potential (CCEP)', to electrically track the cortico-cortical connections by stimulating a part of the brain through subdural electrodes and recording the cortical evoked potentials that emanate from a distant region of the cortex via neuronal projections. We applied the CCEP methodology to investigate in vivo cortico-cortical connections between the lateral motor cortex [LMCx; sensorimotor (SM) and lateral premotor areas] and the medial motor cortex [MMCx; supplementary motor area proper (SMA), pre-SMA and foot SM]. Seven patients with intractable partial epilepsy were studied. These patients had chronic implantation of subdural electrodes covering part of the lateral and medial frontal areas. As a part of the routine pre-surgical evaluation, comprehensive cortical mapping was performed by electrical stimulation of the subdural electrodes, and the precise localization of the subdural electrodes was defined by MRI co-registration. Single-pulse electrical stimuli were delivered to MMCx (7 patients) and LMCx (4), and CCEPs time-locked to the stimuli were recorded by averaging electrocorticograms from LMCx and MMCx, respectively. Short-latency CCEPs were observed when stimulating MMCx and recording from LMCx (mean latency: 21.6 ms, range: 9-47 ms) and vice versa when stimulating LMCx and recording from MMCx (mean latency: 29.4 ms, range: 11-57 ms). In terms of the location of these stimulus sites and CCEP responses along the rostrocaudal axis, regression analysis revealed a consistent correlation between the sites of stimulation and maximum CCEP for stimulation of both MMCx and LMCx. Functionally, stimulation of the positive motor areas in MMCx elicited CCEPs at the somatotopically homologous regions in LMCx (71%). The same findings were observed in MMCx (82%) upon stimulation of LMCx. In four subjects in whom bi-directional connectivity was investigated by stimulating both MMCx and LMCx, reciprocality was observed in the majority of connections (78-94%). In conclusion, the present study demonstrated a human motor cortico-cortical network connecting (i) anatomically homologous areas of LMCx and MMCx along the rostrocaudal cognitive-motor gradient; and (ii) somatotopically homologous regions in LMCx and MMCx in a reciprocal manner.

Adolescent↗

Organization of intrinsic connections in owl monkey area MT.

Area MT (middle temporal) is a well-defined visual representation common to all primates, which shows a clear selectivity to the analysis of visual motion. In the present study we examined the architecture of the intrinsic connections in area MT in an attempt to reveal its organizing principles and its potential relationship to the functional domains in area MT. Intrinsic connections were studied by placing small injections of the tracer biocytin in area MT of seven adult owl monkeys (Aotus nancymae). The injections were targeted at well-defined orientation domains revealed using optical imaging of intrinsic signals. The distribution of axons labeled by these injections was related both to the cytochrome oxidase histochemistry and to the layout of functional domains in area MT and surrounding tissue. Tracer injections in the superficial layers of area MT produced a complex network of extrinsic and intrinsic axonal connections. Clear instances of extrinsic connections were observed between area MT proper and the MT crescent situated postero-medially to it. The intrinsic connections were laterally spread and organized in patch-like clusters with an average distance from injection center to the furthest patch of 1.8 +/- 0.55 mm (+/-SD, n = 9). The overall axonal distribution tended to be anisotropic, i.e. the patches were distributed within an elongated ellipse [average anisotropy ratio: 1.86 +/- 0.66 (+/-SD)] and were asymmetrically distributed about either side of the injection site [average asymmetry ratio: 2.3 +/- 0.7 (+/-SD)]. Finally, there was a tendency for the intrinsic connections to connect to functional domains of similar orientation preference in area MT. However, this tendency varied substantially between individual cases. The highly specific nature of MT lateral connections puts clear constraints on models of surround influences in the receptive fields of MT neurons.

Animals↗

The organization and connections of anterior and posterior parietal cortex in titi monkeys: do New World monkeys have an area 2?

We used multiunit electrophysiological recording techniques to examine the topographic organization of somatosensory area 3b and cortex posterior to area 3b, including area 1 and the presumptive area 5, in the New World titi monkey, Callicebus moloch. We also examined the ipsilateral and contralateral connections of these fields, as well as those in a region of cortex that appeared to be similar to both area 7b and the anterior intraparietal area (7b/AIP) described in macaque monkeys. All data were combined with architectonic analysis to generate comprehensive reconstructions. These studies led to several observations. First, area 1 in titi monkeys is not as precisely organized in terms of topographic order and receptive field size as is area 1 in macaque monkeys and a few New World monkeys. Second, cortex caudal to area 1 in titi monkeys is dominated by the representation of the hand and forelimb, and contains neurons that are often responsive to visual stimulation as well as somatic stimulation. This organization is more like area 5 described in macaque monkeys than like area 2. Third, ipsilateral and contralateral cortical connections become more broadly distributed away from area 3b towards the posterior parietal cortex. Specifically, area 3b has a relatively restricted pattern of connectivity with adjacent somatosensory fields 3a, 1, S2 and PV; area 1 has more broadly distributed connections than area 3b; and the presumptive areas 5 and 7b/AIP have highly diverse connections, including connections with motor and premotor cortex, extrastriate visual areas, auditory areas and somatosensory areas of the lateral sulcus. Fourth, the hand representation of the presumptive area 5 has dense callosal connections. Our results, together with previous studies in other primates, suggest that anterior parietal cortex has expanded in some primate lineages, perhaps in relation to manual abilities, and that the region of cortex we term area 5 is involved in integrating somatic inputs with the motor system and across hemispheres. Such connections could form the substrate for intentional reaching, grasping and intermanual transfer of information necessary for bilateral coordination of the hands.

Animals↗

Analysis of the connectional organization of neural systems associated with the hippocampus in rats.

The hippocampus of the rat enjoys a central significance for researchers interested in the neural mechanisms of memory and spatial information processing. Many of the theoretical models advanced to explain function in this system, however, do not reflect the wealth of information on the connectivity of these structures, and employ greatly simplified treatments of its complex connectivity. We were interested in whether a more analytical approach, which begins with analysis of the connectivity of the system, might provide insights complementary to those derived by synthetic models. Accordingly, we collated detailed neuroanatomical information about the connectivity of the hippocampal system in the rat, and analysed the resulting data. Analyses of connectivity based on a variety of different analytical techniques have recently been used to elucidate the global organization of other systems in the macaque and cat, and have given rise to successful predictions. We applied non-metric multidimensional scaling and non-parametric cluster analysis to our summary matrix of connection data. The analyses produced organizational schemes that were consistent with known physiological properties and provided the basis for making tentative predictions of the further structures that may contain 'place' and 'head-direction' cells, which structures we identify. The consistency between the analyses of connectivity and the distribution of physiological properties across the system suggests that functional relationships are constrained by the organization of the connectivity of the system, and so that structure and function are linked at the systems level.

Animals↗

In the biosynthesis of N-glycans in connective tissue of the snail Lymnaea stagnalis of incorporation GlcNAc by beta 2GlcNAc-transferase I is an essential prerequisite for the action of beta 2GlcNAc-transferase II and beta 2Xyl-transferase.

Using a series of relevant substrates, connective tissue of the snail Lymnaea stagnalis was shown to contain beta 1-2 xylosyltransferase (beta 2Xyl-T), beta 1-2 N-acetylglucosaminyltransferase I (beta 2GlcNAc-T I), and beta 1-2 N-acetylglucosaminyltransferase II (beta 2GlcNAc-T II) activities. These enzymes are probably involved in the biosynthesis of the N-linked carbohydrate chains, like those present in hemocyanin. The products formed by incubation of GlcNAc beta 1-2Man alpha 1-6(GlcNAc beta 1-2Man alpha 1-3)Man beta 1-R [where R = -4GlcNAc beta 1-4GlcNAc or O-(CH2)7CH3] with UDP-Xyl and connective tissue microsomes have been purified and characterized by 1H-NMR spectroscopy in conjunction with methylation analysis to be GlcNAc beta 1-2Man alpha 1-6(GlcNAc beta 1-2Man alpha 1-3)(Xyl beta 1-2)Man beta 1-R. Substrate specificity studies focused on connective tissue beta 2Xyl-T show that the minimal structure requirements are fulfilled in GlcNAc beta 1-2Man alpha 1-3Man beta 1-O-(CH2)7CH3. The enzyme activity can therefore be characterized as UDP-Xyl:Glc-NAc beta 1-2Man alpha 1-3Man beta-R (Xyl to Man beta) beta 1-2 xylosyltransferase. In substrate-specificity studies directed to connective tissue beta 2GlcNAc-T I, it could be demonstrated that the enzyme is active towards acceptors having at the minimum a Man alpha 1-3Man beta-R sequence, and that introduction of a beta Xyl residue at C2 of beta Man totally abolishes the enzyme activity. Xylose-containing oligosaccharides are not acceptors for beta 2GlcNAc-T I. In combination with the substrate specificity of beta Xyl-T, this shows that in snail connective tissue beta 2GlcNAc-T I must act before beta 2Xyl-T. The connective tissue beta 2GlcNAc-T II activity follows the earlier established biosynthetic routes. Based on the substrate specificities of the various connective tissue glycosyltransferases known so far, and the structures isolated from L. stagnalis hemocyanin, a partial biosynthetic scheme for N-glycosylation in snail connective tissue is proposed.

Animals↗

Right heart growth after the Bjork connection in tricuspid atresia.

BACKGROUND: Atrioventricular (Bjork) connection used for the correction of tricuspid atresia has become of little more than historical interest. However, the optimal form of management of patients undergoing this repair still requires continued assessment of the long-term outcome. We review our experience with valveless atrioventricular connection focusing on the morphological changes seen in the heart chambers. METHODS: Between October 1978 and March 1986, seven patients with tricuspid atresia having concordant ventriculoarterial connection underwent atrioventricular connection. Configuration of the surgical connection included Dacron extracardiac conduit without valve insertion. End-diastolic volumes were calculated in the respective heart chambers. A group of patients undergoing atriopulmonary connection was used as control subjects. RESULTS: The diminutive right ventricle showed conspicuous growth at 1.1 +/- 1.1 years after the initial repair, with the end-diastolic volume index increasing from 25.0 +/- 8.7% of normal value at a preoperative state to 80.4 +/- 31.1% of normal value postoperatively. Further operation was done in three patients because of the obstructive atrioventricular pathway. At reoperation, reconstruction of the connection with an addition of either atriopulmonary or cavopulmonary anastomosis afforded clinical improvement in our series. CONCLUSIONS: This study suggests that volume load resulting from the widely patent atrioventricular connection combined with backward regurgitation affects the development of young heart muscle of the right ventricle. The optimal choice of surgical strategy should be made at reintervention through recognition of the particular postsurgical anatomy.

Adolescent↗