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PubMed2021

RNA-seq Analysis of Peri-Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice.

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri-implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone-implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone-implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri-implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri-implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

AGING↗
PubMed2001

Effect of cholesterol content in activation of the classical versus the alternative pathway of rat complement system induced by hydrogenated egg phosphatidylcholine-based liposomes.

Liposomes composed of hydrogenated egg phosphatidylcholine (HEPC) and cholesterol (CHOL) were found to activate the rat complement (C) system in a CHOL content-dependent manner. Liposomes containing 22 or 33 mol% CHOL activated the C system in a Ca(2+)-dependent manner, suggesting that C activation occurred via the classical pathway. Liposomes containing 44 mol% CHOL activated the C system in a Ca(2+) independent manner, suggesting that C activation occurred via the alternative pathway. The CHOL content appeared to dictate the pathway by which the C system was activated. This C activation was inhibited by removal of serum component(s), which adsorb to the liposomes. Activation of the alternative pathway, induced by the liposomes, was reduced by the depletion of IgG and IgM, whereas the classical pathway activation was reduced by the depletion of IgG, but not IgM. In addition, the removal of adsorbed serum component(s) by treatment with 44 mol% CHOL-containing liposomes decreased serum IgG and IgM levels that adsorb to the same liposomes, whereas the removal of adsorbed serum component(s) by treatment with 22 mol% CHOL-containing liposomes only slightly decreased serum IgG levels, which adsorbs to the same liposomes. Collectively, both IgG and IgM, which are specifically adsorbed to the liposomes in a CHOL-content dependent manner, were responsible for C activation via the alternative pathway induced by the 44 mol% CHOL containing liposomes. IgG alone would be partially responsible for C activation via the classical pathway induced by 22 or 33 mol% CHOL-containing liposomes. The discovery of this unique C-activating property of liposomes will be of value in attempts to decipher the underlying mechanism of C activation by providing a useful model membrane system.

Animals↗
PubMed2002

Critical pathways for management of patients with acute coronary syndromes: an assessment by the National Heart Attack Alert Program.

BACKGROUND: The use of critical pathways for a variety of clinical conditions has grown rapidly in recent years, particularly pathways for patients with acute coronary syndromes (ACS). However, no systematic review exists regarding the value of critical pathways in this setting. METHODS: The National Heart Attack Alert Program established a Working Group to review the utility of critical pathways on quality of care and outcomes for patients with ACS. A literature search of MEDLINE, cardiology textbooks, and cited references in any article identified was conducted regarding the use of critical pathways for patients with ACS. RESULTS: Several areas for improving the care of patients with ACS through the application of critical pathways were identified: increasing the use of guideline-recommended medications, targeting use of cardiac procedures and other cardiac testing, and reducing the length of stay in hospitals and intensive care units. Initial studies have shown promising results in improving quality of care and reducing costs. No large studies designed to demonstrate an improvement in mortality or morbidity were identified in this literature review. CONCLUSIONS: Critical pathways offer the potential to improve the care of patients with ACS while reducing the cost of care. Their use should improve the process and cost-effectiveness of care, but further research in this field is needed to determine whether these changes in the process of care will translate into improved clinical outcomes.

Acute Disease↗
PubMed2025

MEIS1 knockdown upregulates WNT signaling pathway genes in esophageal squamous cell carcinoma.

BACKGROUND: The transcription factor MEIS1 belongs to the 3-amino acid loop extension (TALE) family of homeodomain proteins which plays various functions in normal and tumor cell progression. The canonical WNT/β-catenin pathway governs a plethora of biological processes including cell proliferation, differentiation, and tumor development. In the present study, the effect of MEIS1 gene silencing was assessed on WNT pathway genes in esophageal squamous cell carcinoma (ESCC) cells. MATERIALS AND METHODS: Along with the packaging plasmids, the pLKO.1-MEIS1 plasmid was cotransfected into HEK293T to generate lentiviral particles, followed by transduction of a semi-confluent KYSE-30 cell culture. After total RNA extraction and cDNA synthesis, comparative real-time PCR was applied to assess the efficiency of MEIS1 knockdown and the expression of genes related to the WNT signaling pathway. RESULTS: The results revealed effective downregulation of MEIS1 in KYSE-30 cells. Interestingly, MEIS1 silencing led to a substantial overexpression of WNT pathway key components while the expression of negative regulators of this pathway was substantially decreased. CONCLUSIONS: Our data suggest that MEIS1 gene probably induces WNT/β-catenin pathway deactivation in ESCC cells. Consequently, the inverse correlation of MEIS1 expression and WNT signaling pathway activation may introduce a new molecular linkage through ESCC progression and aggressiveness.

Humans↗
PubMed2006

The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion.

Complement is an important mediator of the injuries observed after skeletal muscle ischemia and subsequent reperfusion. Although the classical pathway had been assumed to be the major pathway of activation leading to injury, the mannose-binding lectin (MBL) pathway might also play a contributing role. In this study, we found that MBL-deficient mice had significant protection after skeletal muscle reperfusion injury compared with wild-type, classical pathway-specific C1q-deficient mice, or MBL-deficient mice reconstituted with recombinant human MBL. MBL-deficient mice, however, were not protected from permeability edema or secondary lung injury after ischemia-reperfusion. These data indicate that blockade of the classical pathway alone (C1q) is protective against permeability edema and remote pulmonary injury but not protective against histologic muscle injury. In contrast, blocking the MBL pathway alone protects against histological injury but is not protective against permeability edema or lung injury. Thus, the activation of both pathways is likely responsible for the full spectrum of injuries observed after skeletal muscle reperfusion injury.

Animals↗
PubMed1999

IgG and complement-mediated tissue damage in the absence of C2: evidence of a functionally active C2-bypass pathway in a guinea pig model.

In vitro complement-mediated lysis of heavily sensitized sheep erythrocytes by C4-deficient (C4D) guinea pig and C2-deficient (C2D) human sera was demonstrated some years ago. It was postulated that these "complement-bypass" pathways resulted from activation of C1 and components of the alternative pathway. We used normal, C2D, and C4D guinea pigs in a Forssman shock model to test the in vivo relevance of the C2- and C4-bypass pathways of complement activation. High concentrations of both anti-Forssman Ab and C2D or C4D guinea pig serum induced efficient lysis of sheep erythrocytes in vitro. The most efficient lysis was observed when IgG Ab and C2D guinea pig serum were used. Blocking either the classical pathway (treatments with EGTA-Mg2+ or soluble recombinant complement receptor type 1 (sCR1)) or the alternative pathway (treatment with heating at 50 degrees C, sCR1, or soluble recombinant CR1 lacking the first of the four long homologous repeat sequences (sCR1[desLHR-A])) inhibited lysis; both pathways were required for lysis of sheep erythrocytes by C2D and C4D guinea pig sera. i.v. injection of anti-Forssman Ab in normal guinea pigs resulted in rapid death from pulmonary shock, whereas C4D guinea pigs had no adverse effect. Surprisingly, C2D guinea pigs either died in a delayed fashion or had a sublethal reaction. sCR1 treatment prevented Forssman shock in both normal and C2D guinea pigs, whereas sCR1[desLHR-A] prevented Forssman shock only in C2D animals. Our results suggest that the C2-bypass pathway occurs in vivo to produce tissue damage. Activation of complement in the absence of C2 appears to be far more efficient than in the absence of C4.

Anaphylaxis↗
PubMedDate not supplied

Inhibition of the classical and alternative pathways of the human complement system by glycosaminoglycan polysulfate.

Glycosaminoglycan polysulfate (GAGPS) concentration-dependently inhibited the activation of the classical and alternative pathways of the human complement system in vitro. Concentrations of > or = 0.2 mg/ml GAGPS prevented the cleavage of C4 by human aggregated gammaglobulin as evidence of inhibition of the classical pathway. At concentrations of > or = 0.15 mg/ml a concentration-dependent inhibition of the cleavage of factor B, the major step in the activation of the alternative pathway, was seen in the presence of inulin. Concentrations < 0.05 mg/ml did not have a measurable effect on either pathway. The lysis of sheep red blood cells, which is mediated largely by the classical pathway, was significantly inhibited at 3.84 mg/ml GAGPS, with a mean inhibition of 45.7%. On the other hand, the same concentration of GAGPS almost completely inhibited the lysis of rabbit red blood cells, which is mediated by the alternative pathway of complement. Our results suggest that the inhibition by GAGPS is an early event in the activation of complement, occurring before the assembly of the C3 convertases of either pathway. The possible use of this drug in acute life-threatening situations where complement is thought to have a pathogenic role is discussed.

Animals↗
PubMed1995

Cardioprotective effects of selective inhibition of the two complement activation pathways in myocardial ischemia and reperfusion injury.

The complement (C) system-mediated neutrophil activation, adhesion to the coronary endothelium and accumulation into cardiac tissue are key steps in the pathogenesis of myocardial ischemia-reperfusion (MI/R) injury. We examined the differential role of the classical and the alternative complement pathway in MI/R injury in vivo. Rats were subjected to 20 min of myocardial ischemia followed by 24 h of reperfusion. Either a classical pathway inhibitor [C1 esterase inhibitor (C1-INH) (15 mg/kg)] or an alternative pathway inhibitor soluble complement receptor 1 (sCR1)[des-LHR-A](15 mg/kg) or their vehicle were administered intravenously 1 min prior to reperfusion, and myocardial necrosis (creatine kinase loss) and neutrophil accumulation, cardiac myeloperoxidase activity, were examined. C1-INH significantly attenuated cardiac creatine kinase loss compared to MI/R rats given only vehicle (p < 0.05) 24 h after reperfusion. An alternative pathway inhibitor, sCR1 [des-LHR-A] attenuated myocardial injury to a lesser extent, although it was not significantly different from the value for C1-INH or vehicle. Besides cardiac myeloperoxidase activity, the ischemic cardiac tissue was significantly attenuated by both C1-INH and sCR1[desLHR-A] (p < 0.05 vs. vehicle). Both the classical and alternative pathways may contribute to MI/R injury via a neutrophil-dependent mechanism in vivo. Selective inhibition of the classical pathway of complement activation seems to be slightly more effective in limiting necrotic MI/R injury than the selective alternative pathway inhibition in this 24 h model of reperfusion injury, but equal doses of each inhibitor attenuated neutrophil accumulation.

Animals↗
PubMed2006

Effect of a clinical pathway to reduce hospitalizations in nursing home residents with pneumonia: a randomized controlled trial.

CONTEXT: Nursing home residents with pneumonia are frequently hospitalized. Such transfers may be associated with multiple hazards of hospitalization as well as economic costs. OBJECTIVE: To assess whether using a clinical pathway for on-site treatment of pneumonia and other lower respiratory tract infections in nursing homes could reduce hospital admissions, related complications, and costs. DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized controlled trial of 680 residents aged 65 years or older in 22 nursing homes in Hamilton, Ontario, Canada. Nursing homes began enrollment between January 2, 2001, and April 18, 2002, with the last resident follow-up occurring July 4, 2005. Residents were eligible if they met a standardized definition of lower respiratory tract infection. INTERVENTIONS: Treatment in nursing homes according to a clinical pathway, which included use of oral antimicrobials, portable chest radiographs, oxygen saturation monitoring, rehydration, and close monitoring by a research nurse, or usual care. MAIN OUTCOME MEASURES: Hospital admissions, length of hospital stay, mortality, health-related quality of life, functional status, and cost. RESULTS: Thirty-four (10%) of 327 residents in the clinical pathway group were hospitalized compared with 76 (22%) of 353 residents in the usual care group. Adjusting for clustering of residents in nursing homes, the weighted mean reduction in hospitalizations was 12% (95% confidence interval [CI], 5%-18%; P = .001). The mean number of hospital days per resident was 0.79 in the clinical pathway group vs 1.74 in the usual care group, with a weighted mean difference of 0.95 days per resident (95% CI, 0.34-1.55 days; P = .004). The mortality rate was 8% (24 deaths) in the clinical pathway group vs 9% (32 deaths) in the usual care group, with a weighted mean difference of 2.9% (95% CI, -2.0% to 7.9%; P = .23). There were no significant differences between the groups in health-related quality of life or functional status. The clinical pathway resulted in an overall cost savings of US 1016 dollars per resident (95% CI, 207 dollars-1824 dollars) treated. CONCLUSION: Treating residents of nursing homes with pneumonia and other lower respiratory tract infections with a clinical pathway can result in comparable clinical outcomes, while reducing hospitalizations and health care costs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00157612.

Aged↗
PubMed1998

Synaptic and neurochemical characterization of parallel pathways to the cytochrome oxidase blobs of primate visual cortex.

The primary visual cortex (V1) of primates is unique in that it is both the recipient of visual signals, arriving via parallel pathways (magnocellular [M], parvocellular [P], and koniocellular [K]) from the thalamus, and the source of several output streams to higher order visual areas. Within this scheme, output compartments of V1, such as the cytochrome oxidase (CO) rich blobs in cortical layer III, synthesize new output pathways appropriate for the next steps in visual analysis. Our chief aim in this study was to examine and compare the synaptic arrangements and neurochemistry of elements involving direct lateral geniculate nucleus (LGN) input from the K pathway with those involving indirect LGN input from the M and P pathways arriving from cortical layer IV. Geniculocortical K axons were labeled via iontophoretic injections of wheat germ agglutinin-horseradish peroxidase into the LGN and intracortical layer IV axons (indirect P and M pathways to the CO-blobs) were labeled by iontophoretic injections of Phaseolus vulgaris leucoagglutinin into layer IV. The neurochemical content of both pre- and postsynaptic profiles was identified by postembedding immunocytochemistry for gamma-amino butyric acid (GABA) and glutamate. Sizes of pre- and postsynaptic elements were quantified by using an image analysis system, BioQuant IV. Our chief finding is that K LGN axons and layer IV axons (indirect input from M and P pathways) exhibit different synaptic relationships to CO blob cells. Specifically, our results show that within the CO blobs: 1) all K cell axons contain glutamate, and the vast majority of layer IV axons contain glutamate with only 5% containing GABA; 2) K axons terminate mainly on dendritic spines of glutamatergic cells, while layer IV axons terminate mainly on dendritic shafts of glutamatergic cells; 3) K axons have larger boutons and contact larger postsynaptic dendrites, which suggests that they synapse closer to the cell body within the CO blobs than do layer IV axons. Taken together, these results suggest that each input pathway to the CO blobs uses a different strategy to contribute to the processing of visual information within these compartments.

Animals↗
PubMed1997

Functional organization of forebrain pathways for song production and perception.

This article reviews the organization of the forebrain nuclei of the avian song system. Particular emphasis is placed on recent physiologic recordings from awake behaving adult birds while they sing, call, and listen to broadcasts of acoustic stimuli. The neurons in the descending motor pathway (HVc and RA) are organized in a hierarchical arrangement of temporal units of song production, with HVc neurons representing syllables and RA neurons representing notes. The nuclei Uva and NIf, which are afferent to HVc, may help organize syllables into larger units of vocalization. HVc and RA are also active during production of all calls. The patterns of activity associated with calls differ between learned calls and those that are innately specified, and give insight into the interactions between the forebrain and midbrain during calling, as well as into the evolutionary origins of the song system. Neurons in Area X, the first part of the anterior forebrain pathway leading from HVc to RA, are also active during singing. Many HVc neurons are also auditory, exhibiting selectivity for learned acoustic parameters of the individual bird's own song (BOS). Similar auditory responses are also observed in RA and Area X in anesthetized birds. In contrast to HVc, however, auditory responses in RA are very weak or absent in awake birds under our experimental paradigm, but are uncovered when birds are anesthetized. Thus, the roles of both pathways beyond HVc in adult birds is under review. In particular, theories hypothesizing a role for the descending motor pathway (RA and below) in adult song perception do not appear to obtain. The data also suggest that the anterior forebrain pathway has a greater motor role than previously considered. We suggest that a major role of the anterior forebrain pathway is to resolve the timing mismatch between motor program readout and sensory feedback, thereby facilitating motor programming during birdsong learning. Pathways afferent to HVc may participate more in sensory acquisition and sensorimotor learning during song development than is commonly assumed.

Animals↗
PubMed2004

Critical pathways in the emergency department improve treatment modalities for patients with ST-elevation myocardial infarction in a European hospital.

BACKGROUND: The use of protocols for patients with ST-elevation myocardial infarction (MI) is growing, but no definite conclusion regarding the value of critical pathways in Europe has been drawn. HYPOTHESIS: The aim of this study was to investigate the impact of critical pathway on processes of care and outcome for patients presenting to the emergency department (ED) of a large urban European hospital because of possible ST-elevation MI. METHODS: Critical pathways for management of acute chest pain at our ED were developed in 1998 and have been revised every year. Accordingly, the records of all patients referred in 1997 to the ED because of chest pain (before pathway implementation) and in 2001 (after last pathway revision) were reviewed. An ST-elevation MI was diagnosed at ED in 520 of 5,066 (10.3%) patients with chest pain in 1997, and in 452 of 4,843 (9.3%) patients with chest pain in 2001. Patients were managed according to the ED cardiologists' decisions in 1997, whereas they entered the pathways for ST-elevation MI in 2001, with predefined criteria for diagnosis, thrombolysis, percutaneous coronary intervention, and admission to the coronary care unit. RESULTS: Comparison of treatment modalities disclosed that more patients were given thrombolysis in 1997 (49 vs. 16%, p<0.05), whereas in 2001 more patients were sent to primary angioplasty (63 vs. 11%, p<0.05). Also in 2001, patients more often received aspirin (90 vs. 61%, p<0.05) and intravenous beta blockers (60 vs. 35%, p<0.05) soon after arrival at the ED. Comparison between 1997 and 2001 revealed that admission rates to the coronary care unit (69 vs. 78%, NS) and cardiac wards were similar (19 vs. 10%, NS). Conversely, compared with 1997, patients hospitalized in 2001 had a shorter length of stay (12 +/- 5 vs. 18 +/- 6 days, p<0.05), as well as fewer major adverse coronary events (21 vs. 30%, p<0.05) and lower all-cause in-hospital mortality (12 vs. 20%, p<0.05). The quality of care indicators improved with time, as door-to-electrocardiogram interval (10 +/- 6 vs. 19 +/- 9 min, p<0.05), door-to-needle time (25 +/- 10 vs. 35 +/- 10 min, p<0.05), and door-to-balloon interval (70 +/- 15 vs. 99 +/- 20 min, p<0.05) were shorter in 2001 than in 1997. CONCLUSIONS: A critical pathway for ST-elevation MI at the ED increases the use of evidence-based treatment strategies and improves outcome and quality of care of patients presenting to a European hospital because of acute chest pain.

Adult↗
PubMed2001

Development of the visual pathway is disrupted in mice with a targeted disruption of the calcium channel beta(3)-subunit gene.

Refinement of the retinal pathways to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN) is mediated by nitric oxide (NO). Long-term depression (LTD) can also be induced in SC and LGN during the time at which these pathways are refined, and this LTD is partially dependent on NO and L-type Ca(2+) channel function. In an effort to determine whether NO-mediated pathway refinement is also mediated by Ca(2+) channel function, we have examined the refinement of the retinocollicular and retinogeniculate pathways in mice which lack the gene for the Ca(2+) channel beta(3) subunit (CCKO) and which have significantly reduced L-type Ca(2+) currents. Injections of the anterograde tracer cholera toxin subunit B/HRP were made into one eye of these knockout animals and in wild-type mice ages postnatal day (P) 13, P19, and P26. After 48 hours, mice were perfused and sections processed by using tetramethylbenzidine histochemistry. Labeling distribution in some animals was analyzed quantitatively. Obvious differences in the distribution of the ipsilateral retinocollicular pathway were observed at P15, with the pathway being more exuberant in CCKO mice. This difference was statistically significant. More subtle differences were seen at P21 and P28. Obvious differences were also seen in the contralateral retinogeniculate pathway which in CCKO mice filled most of the domain normally occupied by ipsilateral eye fibers. This difference was also statistically significant. We conclude that reduction in L-type Ca(2+) currents has an effect on axonal refinement similar to that which occurs in NO knockout mice, which supports the possibility that L-type Ca(2+) channel-dependent LTD mediates NO-dependent axonal refinement.

Aging↗
PubMed1981

Cells of origin of pathways descending to the spinal cord in two chondrichthyans, the shark Scyliorhinus canicula and the ray Raja clavata.

The cells of origin of pathways descending to the spinal cord in the shark Scyliorhinus canicula and in the ray Raja clavata have been demonstrated by using the horseradish peroxidase (HRP) technique. Following HRP injections in the spinal cord of Scyliorhinus (fourth to sixth segment) and of Raja (15th to 20th segment) labeled neurons could be identified in the rhombencephalon, the mesencephalon, and in the diencephalon. Cells of origin of diencephalic nuclei, which project to the spinal cord, were observed in the nucleus periventricularis hypothalami and in the thalamus ventralis pars medialis which can in this respect be considered hypothalamic. Descending pathways from mesencephalic structures originate from the interstitial nucleus of the fasciculus longitudinalis medialis, the tectum mesencephali, the nucleus intercollicularis, the tectotegmental junction zone, and from diffusely arranged tegmental neurons. A contralateral rubrospinal pathway could be recognized in Raja, but not in Scyliorhinus. Rhombencephalic cells of origin of pathways descending to the spinal cord were found in all parts of the reticular formation, i.e., the nucleus raphes inferior, the nucleus reticularis inferior, medius, superior, and isthmi, in two vestibular nuclei, and in three nuclei, which have been tentatively indicated as nucleus B, F, and G. Furthermore cells of origin of descending pathways have been found in the nucleus tractus descendens nervi trigemini, in the nucleus funiculi lateralis, and in the nucleus tractus solitarii. The descending pathways of the two species studied have been compared with those of other vertebrates. It is concluded that the basic pattern in the organization of descending pathways to the spinal cord, as proposed by ten Donkelaar ('76) for terrestrial vertebrates, also holds for cartilaginous fishes.

Animals↗
PubMed1995

Topographic organization of a forebrain pathway involved with vocal learning in zebra finches.

A serial pathway from a thalamic nucleus (DLM; the medial portion of the dorsolateral nucleus of the anterior thalamus) to a cortical region (lMAN; the lateral magnocellular nucleus of the anterior neostriatum) to a motor-cortical region (RA; the robust nucleus of the archistriatum) is necessary for vocal production during song learning in juvenile zebra finches but not for the recitation of a song already learned by adults. To obtain new information about the possible function of the DLM-->lMAN-->RA pathway in vocal learning, we used anterograde and retrograde tract-tracing techniques (pressure injections of DiI and DiA) to map the pattern of axonal connections between these brain regions in adult male zebra finches. Results revealed two topographically organized pathways that traverse the songbird forebrain in parallel. An oval-shaped dorsal/lateral portion of DLM projects solely to the central core of lMAN (lMANcore), whereas a crescent-shaped region, including ventral and medial DLM, projects exclusively to a parvicellular shell that encircles lMANcore (lMANshell). In turn, lMANshell neurons project solely to an arc-shaped region of dorsal archistriatum just lateral to RA (Ad; archistriatum, pars dorsalis), whereas lMANcore neurons project exclusively to RA. We also identified crossed and reciprocal pathways between lMANcore/shell and the lateral portion of the ventral archistriatum, which may contribute to interhemispheric coordination of vocal behavior. A robust topographic organization was observed in the axonal projections from dorsal/lateral-DLM-->lMANcore-->RA and from ventral/medial-DLM-->lMANshell-->Ad, raising the question of what is being mapped within these two forebrain pathways. Because RA projection neurons are organized myotopically with respect to the major vocal (syringeal) muscles (D.S. Vicario, 1991, J. Comp. Neurol. 309:486-494), one possibility is that a mapping of vocal/expiratory musculature is preserved "upstream" within these pathways. Similarly, the presence of song-selective auditory neurons in DLM, lMAN, and RA (A.J. Doupe and M. Konishi, 1991, Soc. Neurosci. Abstr. 18:527) suggests that these pathways might subserve some form of auditory or auditory-motor mapping.

Aging↗
PubMed2006

Pathway specificity of dendritic spine morphology in identified synapses onto rat hippocampal CA1 neurons in organotypic slices.

The output of the hippocampus is largely determined by interaction of the three excitatory pathways that impinge on CA1 pyramidal neurons. These synapses, formed by axons of: (1) CA3 pyramidal neurons; (2) neurons of the entorhinal cortex (EC); and (3) neighboring CA1 neurons, are all potentially plastic. Here, we take advantage of the accessibility of the organotypic slice preparation to identify the type of spines with which each of these pathways forms synapses, at different developmental stages. Recent reports have shown that morphology of dendritic spines is activity-dependent with large mushroom spines being thought to represent stronger synaptic connections than thin or stubby spines. Although in a wide range of preparations, mushroom spines represent only 15% of spines across the whole dendritic tree, we find that this proportion is highly pathway specific. Thus in organotypic slices, the axons of CA3 neurons form synapses with mushroom spines on CA1 neurons in approximately 50% of cases, whereas this spine type is rare (<10%) in either of the other two pathways. This high proportion of mushroom spines only occurs after spontaneous excitatory activity in the CA1 cells increases over the second week in vitro. Previous studies suggest that pathway specificity also occurs in vivo. In tissue fixed in vivo, it is the synapses of distal apical dendrites thought to be formed by axons originating in the EC that are richer in mushroom spines. Hence, contrary to previous suggestions, the proportion of mushroom spines is clearly not an intrinsic property of the pathway but rather a characteristic dependent on the environment. We suggest that this is most likely a result of the previous activity of the synapses. The fact that, despite the large differences in pathway specificity between preparations, the overall proportion of different spine types remains unchanged, suggests a strong influence of homeostasis across the network.

Animals↗
PubMed2001

Impact of a pediatric asthma clinical pathway on hospital cost and length of stay.

This study sought to determine if a clinical pathway developed and executed by specialists in pediatric asthma would reduce hospital costs and length of stay (LOS). The study design was a retrospective, nonrandomized, controlled trial. Subjects were children aged 2-18 years (N = 1,004) with a history of recurrent wheezing, hospitalized with a diagnosis of acute asthma exacerbation between 1995-1998 at the New York Hospital-Weill Cornell Medical Center and treated via the pathway, as well as a control group of 206 children ages 2-18 hospitalized for acute asthma exacerbation in 1994, the year prior to pathway implementation. Patients were treated via the pathway under the supervision of an asthma specialist. The pathway provided guidelines for: 1) frequency of patient assessment; 2) bronchodilator usage; 3) corticosteroid use; 4) laboratory evaluation; 5) vital signs, oxygen saturation, and peak flow measurements; 6) chest x-rays; 7) social work intervention; and 8) discharge planning. The main outcome measures were hospital length of stay, cost per hospitalization, nursing, medication, laboratory and radiology costs, and relapse rate. Total charges for admission and average LOS for 1995-1998 were calculated, and compared with 1994, the year preceding implementation of the pathway. LOS decreased from 4.2 days to 2.7 days (P < 0.0001). The annual total charges for pediatric asthma admissions decreased from 2 million dollars to 1.4 million dollars (P < 0.005). Nursing and laboratory costs showed a statistically significant decrease. Follow-up study at 8 months showed a readmission rate of 0.02%. The implementation of a pediatric asthma clinical pathway, directed by specialists, resulted in significantly decreased length of stay and overall cost, without an increased rate of readmission.

Adolescent↗
PubMed1979

The location of LH-RH neurons in the rat hypothalamus and their pathways to the median eminence. Experimental immunohistochemistry and radioimmunoassay.

The location of the perikarya of LH-RH neurons in the rat hypothalamus and their pathways to the median eminence were studied by immunohistochemistry and radioimmunoassay after placing stereotaxic electrolytic lesions in several parts of the hypothalamus. The principal location of the cell somata was found to be in the ventral part of the medial preoptic area; their pathways were classified into a main baso-lateral pathway and an accessory descending pathway branching off from the former. The main pathway was found to cross in the vicinity of the corresponding neuronal perikarya. The central median eminence and the dorsal and ventral walls of the tubero-infundibular sulcus of the caudal part of the median eminence are innervated mainly by the baso-lateral pathway. On the other hand, the rostral and most caudal protions of the median eminence are innervated principally by the descending pathway and have a subsidiary dual innervation. The projection of LH-RH neurons to the OVLT is believed to originate from perikarya adjacent to this circumventricular organ.

Animals↗