Binocular Integration in the Primate Primary Visual Cortex.

Our brains devote substantial resources to creating a singular, coherent view from the two images in our eyes. Both anatomical and functional studies have established that the underlying fusion of monocular signals into a combined binocular response starts within the first synapses downstream from our eyes. Long-standing consensus held that the two eyes' signals remain largely segregated until they are combined by neurons in the upper layers of the primary visual cortex. However, new experimental data challenge this classic model, suggesting that there are pronounced earlier interactions between the two eyes' streams of activation. In this article, we review the literature and detail how these findings can be functionally interpreted in context with previously established psychophysical models of binocular vision.

Dispersal alters soil microbial community response to drought.

Microbial communities will experience novel climates in the future. Dispersal is now recognized as a driver of microbial diversity and function, but our understanding of how dispersal influences responses to novel climates is limited. We experimentally tested how the exclusion of aerially dispersed fungi and bacteria altered the compositional and functional response of soil microbial communities to drought. We manipulated dispersal and drought by collecting aerially deposited microbes after precipitation events and subjecting soil mesocosms to either filter-sterilized rain (no dispersal) or unfiltered rain (dispersal) and to either drought (25% ambient) or ambient rainfall for 6 months. We characterized community composition by sequencing 16S and ITS rRNA regions and function using community-level physiological profiles. Treatments without dispersal had lower soil microbial biomass and metabolic diversity but higher bacterial and fungal species richness. Dispersal also altered soil community response to drought; drought had a stronger effect on bacterial (but not fungal) community composition, and induced greater functional loss, when dispersal was present. Surprisingly, neither immigrants nor drought-tolerant taxa had higher abundance in dispersal treatments. We show experimentally that natural aerial dispersal rate alters soil microbial responses to disturbance. Changes in dispersal rates should be considered when predicting microbial responses to climate change.

Single-center experience of percutaneous abdominal aortic aneurysm repair with local anesthesia and conscious sedation: technique and results.

AIM: Totally percutaneous endovascular abdominal aortic aneurysm repair (PEVAR) by using the "Preclose" technique has been previously described. We retrospectively analyzed data, collected prospectively at our institution, regarding PEVAR via femoral artery access with local anesthesia and conscious sedation. METHODS: Between January 2001 and May 2009, 1150 patients underwent PEVAR in the endovascular suite of the cardiac catheterization laboratory at our institution. Of those procedures, 915 (79%) were performed with local anesthesia and conscious sedation. RESULTS: The majority of patients were male (87%). Their mean age was 72±10 years, and 98% had a risk status of American Society of Anesthesiologists class III or IV. The PEVAR involved bilateral percutaneous femoral access with 12F to 24F sheaths (depending on the stent-graft system). The mean total procedure time was 149 minutes. Percutaneous closure of the arterial access sites with the Prostar XL was successful in 1727 (94.3%) of the 1830 femoral arteries in which PEVAR was attempted, whereas 103 femoral arteries (5.6%) required surgical repair because adequate hemostasis was not attained at the access site. There were no procedural deaths, but 6 patients (0.6%) died within 30 days of the procedure: 3 died of intestinal ischemia, 1 of stroke, 1 of refractory ventricular arrhythmia, and 1 of worsening renal failure. Mean length of hospital stay was 1.3±2 days. CONCLUSION: PEVAR with local anesthesia and intravenous sedation is safe and feasible and should be considered for patients for whom general anesthesia poses a high risk.

Catheter aspiration thrombectomy during carotid stenting is safe and potentially efficacious: a pilot retrospective study.

AIM: Despite distal embolic protection (DEP) during carotid artery stenting (CAS), there is still an appreciable risk of stroke, especially in symptomatic patients and octogenerians. The mechanism of embolic events is possibly related to microembolization of debris remaining on or forming on stent struts. We evaluated the safety of using aspiration thrombectomy after CAS. METHODS: Between August 2006 and July 2010, 80 symptomatic and asymptomatic patients with severe carotid artery stenosis (>80%) underwent CAS utilizing DEP. After completion of CAS and before removal of DEP, an aspiration catheter was passed through the CAS segment. Both extracted volume and the DEP were visually examined. The primary endpoint was stroke and death at 30 days. These patients were divided into two groups, Group 1 (N=7) comprised those who had aspiration thrombectomy to treat no-flow or an acute neurologic change that occurred during CAS. Group 2 (N=73) comprised patients that underwent prophylactic aspiration thrombectomy. Outcomes were then compared to a control group (N=925) who had CAS with DEP, but without aspiration thrombectomy. RESULTS: Moderate to large amounts of debris were extracted from the CAS segment in the majority of thrombectomy patients (90%). There was one death (1%) and one stroke (1%) in the thrombectomy groups, while the control group had 3.0% rate of death and stroke (P=0.83). CONCLUSION: Aspiration thrombectomy recovers large to moderate amounts of debris and is safe and does not increase adverse periprocedural events. A large scale, randomized trial with magnetic resonance imaging (MRI) is needed to further investigate our findings.

Phenotypic diversity and expression of GABAergic inhibitory interneurons during postnatal development in lumbar spinal cord of glutamic acid decarboxylase 67-green fluorescent protein mice.

The synthesis enzyme glutamic acid decarboxylase (GAD65 or GAD67) identifies neurons as GABAergic. Recent studies have characterized the physiological properties of spinal cord GABAergic interneurons using lines of GAD67-green fluorescent protein (GFP) transgenic mice. A more complete characterization of their phenotype is required to better understand the role of this population of inhibitory neurons in spinal cord function. Here, we characterize the distribution of lumbar spinal cord GAD67-GFP neurons at postnatal days (P) 0, 7, and 14, and adult based on their co-expression with GABA and determine the molecular phenotype of GAD67-GFP neurons at P14 based on the expression of various neuropeptides, calcium binding proteins, and other markers. At all ages >67% of GFP(+) neurons were also GABA(+). With increasing age; (i) GFP(+) and GABA(+) cell numbers declined, (ii) ventral horn GFP(+) and GABA(+) neurons vanished, and (iii) somatic labeling was reduced while terminal labeling increased. At P14, vasoactive intestinal peptide and bombesin were expressed in approximately 63% and approximately 35% of GFP(+) cells, respectively. Somatostatin was found in a small number of neurons, whereas calcitonin gene-related peptide never co-localized with GFP. Moderate co-expression was found for all the Ca(2+) binding proteins examined. Notably, most laminae I-II parvalbumin(+) neurons were also GFP(+). Neurogranin, a protein kinase C substrate, was found in approximately 1/2 of GFP(+) cells. Lastly, while only 7% of GFP(+) cells contain nitric oxide synthase (NOS), these cells represent a large fraction of all NOS(+) cells. We conclude that GAD67-GFP neurons represent the majority of spinal GABAergic neurons and that mouse dorsal horn GAD67-GFP(+) neurons comprise a phenotypically diverse population.

Psychiatric symptoms during interferon treatment for hepatitis C: experiences from a tertiary care hepatology centre.

BACKGROUND: Most research on the psychiatric symptoms of peginterferon/ribavirin for the treatment of hepatitis C comes from VA centres and clinical trials with rigid entry criteria that often excluded patients with markers of mental health and substance use disturbance (MH/SUD). The findings from these lines of research may not be generalizable to patients treated under standard of care in a tertiary care setting. AIM: To investigate the incidence and outcomes of psychiatric symptoms in patients treated under standard of care protocol, not enrolled in clinical trials. METHODS: This is a retrospective analysis of 215 patients who underwent therapy from 2002 to 2006 at a university-based tertiary care centre. Survival curves explored the relationship between history of MH/SUD and the development of psychiatric symptoms on treatment. RESULTS: The cumulative history of MH/SUD was 67%. Of these, 39% had taken psychotropic medications previously, and 80% continued on them during therapy. On therapy, 46% developed depressive symptoms, 19% and 46% endorsed anxiety and irritability respectively. Cumulatively, 64% of patients indicated mood disturbance on therapy. Most symptoms developed between weeks 2 and 18, and rarely after week 20. Of those who developed mood symptoms, 66% required an intervention. Treatment discontinuation was infrequent. CONCLUSIONS: This large observational study provides important insights into the incidence and course of psychiatric symptoms in an unselected sample of patients treated in a tertiary care setting. Patients had higher rates of MH/SUD comorbidity, psychotropic medication use and exhibit higher rates of mood disturbance on therapy compared with previous reports, although a majority completed the prescribed treatment regimen.

Alternative cerebrospinal fluid tests to diagnose neurosyphilis in HIV-infected individuals.

OBJECTIVE: To identify alternatives to the CSF-Venereal Disease Research Laboratory (VDRL) test for the diagnosis of neurosyphilis in HIV-infected individuals. METHODS: CSF fluorescent treponemal antibody (FTA) reactivity and % CSF lymphocytes that were B cells in fresh and frozen samples were determined for 47 HIV-infected cases with syphilis and 26 HIV-infected controls. As for serum, CSF fluorescent treponemal antibody reactivity > or =2+ was considered positive. Based on the results in controls and cases with normal CSF measures, cut-offs for elevated CSF B cells were proposed to be > or =9% in fresh and > or =20% in frozen samples. Neurosyphilis was defined as a reactive CSF-VDRL. RESULTS: CSF-FTA-ABS (absorbed) and CSF-FTA (unabsorbed and undiluted) were 100% sensitive for the diagnosis of neurosyphilis. Elevated % CSF B cells in fresh and cryopreserved samples was specific (100%) but not sensitive (40 and 43%) in post hoc analyses. The results of CSF-FTA and assessment of % CSF B cells together allowed 16% of cases with pleocytosis but nonreactive CSF-VDRL to be diagnosed with neurosyphilis and 26% to be diagnosed as not having neurosyphilis. CONCLUSION: When the CSF-VDRL is nonreactive, CSF-FTA and % CSF B cells may help exclude or establish the diagnosis of neurosyphilis.

Unusual case of AneuRx stent-graft failure two years after AAA exclusion.

PURPOSE: To present a case of type-III endoleak due to separation of modular components and suture breakage after abdominal aortic aneurysm (AAA) repair with the AneuRx stent-graft. CASE REPORT: A 58-year-old man with a 78-mm AAA underwent successful aneurysm exclusion with an AneuRx stent-graft in 1998. Because the bifurcated component migrated during deployment, an additional aortic cuff was deployed to extend the stent-graft proximally to just below the renal arteries. On routine evaluation with computed tomography at 2 years postimplantation, a type-III endoleak with anterior displacement of the stent-graft was discovered. Angiography revealed separation of the aortic cuff from the stent-graft body. The aneurysm, which had decreased to 70 mm at 6 months, had enlarged to 80 mm in diameter. The patient underwent surgical AAA repair with removal of the stent-graft. Macroscopic examination showed suture breakage and separation of the stent rings and the graft material. CONCLUSIONS: This late complication of the AneuRx endograft underscores the need for frequent imaging surveillance in all patients undergoing endoluminal AAA repair.

Outcomes following extracranial carotid artery stenting in high-risk patients.

BACKGROUND: Carotid artery angioplasty and stenting has become a viable alternative to carotid endarterectomy (CEA), especially for patients considered at high risk for post-operative complications. This study investigated the feasibility, safety and long-term outcome of carotid artery stenting (CAS) in high-risk patients. METHODS: From July 1995 to November 2000, sixty-two consecutive patients considered to be at high risk for post-operative complications of CEA were followed prospectively after undergoing extracranial CAS procedures. RESULTS: Sixty-two patients [37 men (60%) and 25 women (40%)] underwent a total of 69 CAS procedures. The mean age was 67 +/- 9 years (range, 32-89 years). Comorbid conditions included hypertension in 95% and severe coronary artery disease in 58%. Sixteen patients (26%) had a previous ipsilateral CEA, twenty-one percent had a history of neck radiation and 32% had a history of significant contralateral carotid artery disease. Fifty-two patients (84%) were symptomatic. All 69 CAS procedures were technically successful. The major post-operative complications were two minor strokes (2.8%), one major stroke (1.4%) and one fatal major stroke (1.4%). The mean length of follow-up was 17 months (range, 4 months to 5.6 years). Two patients (2.8%) have suffered ipsilateral neurologic events following CAS. Long-term follow-up revealed restenosis at 6 months in 4 patients (5.7%). CONCLUSIONS: Carotid artery angioplasty and stenting is safe and feasible. This procedure produces satisfactory outcomes in patients who are at high risk for post-operative complications of CEA.

Hippocampal tyrosine kinase A receptors are restricted primarily to presynaptic vesicle clusters.

Adult septohippocampal cholinergic neurons are dependent on trophic support for normal functioning and survival; these effects are largely mediated by the tyrosine kinase A receptor (TrkA), which binds its ligand, nerve growth factor (NGF), with high affinity. To determine the subcellular localization of TrkA within septohippocampal terminal fields, two rabbit polyclonal antisera to the extracellular domain of TrkA were localized immunocytochemically in rat dentate gyrus by light and electron microscopy. By light microscopy, TrkA immunoreactivity was found mostly in fine, varicose fibers primarily in the hilus and, to a lesser extent, in the granule cell and molecular layers. By electron microscopy, the central and infragranular regions of the hilus contained the highest densities of TrkA-immunoreactive profiles. Most TrkA-labeled profiles were axons (31% of 3,473), axon terminals (20%), and glia (38%); fewer were dendrites (6%), dendritic spines (5%), and granule cell and interneuron somata (<1%). TrkA immunolabeling in axons and axon terminals was discrete, often concentrated in patches of small synaptic vesicles that were adjacent to somatic and dendritic profiles. TrkA-labeled terminals formed both asymmetric and symmetric synapses, primarily with dendritic shafts and spines. TrkA-immunoreactive glial profiles frequently apposed terminals contacting dendritic spines. The findings that presynaptic profiles contain TrkA immunolabeling in sites of vesicle accumulation suggest that NGF binding to TrkA may influence transmitter release. The presence of TrkA immunoreactivity in somata, dendrites, and glia further suggests that cells within the dentate gyrus may take up NGF.

Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury.

Recent studies suggest that the injured adult spinal cord responds to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) with enhanced neuron survival and axon regeneration. Potential neurotrophin sources and cellular localization in spinal cord are largely undefined. We examined glial BDNF localization in normal cord and its temporospatial distribution after injury in vivo. We used dual immunolabeling for BDNF and glial fibrillary acidic protein (GFAP) in astrocytes, adenomatous polyposis coli tumor suppressor protein (APC) for oligodendrocytes or type III CDH receptor (OX42) for microglia/macrophages. In normal cord, small subsets of astrocytes and microglia/macrophages and most oligodendrocytes exhibited BDNF-immunoreactivity. Following injury, the number of BDNF-immunopositive astrocytes and microglia/macrophages increased dramatically at the injury site over time. Most oligodendrocytes contained BDNF 1 day and 1 week following injury, but APC-positive cells were largely absent at the injury site 6 weeks postinjury. Glial BDNF-immunolabeling was also examined 10 and 20 mm from the wound. Ten millimeters from the lesion, astrocyte and microglia/macrophage BDNF-immunolabeling resembled that at the injury at all times examined. Twenty millimeters from injury, BDNF localization in all three glial subtypes resembled controls, regardless of time postlesion. Our findings suggest that in normal adult cord, astrocytes, oligodendrocytes, and microglia/macrophages play roles in local trophin availability and in trophin-mediated injury and healing responses directly within and surrounding the wound site.

Personal and professional beliefs and practices regarding herbal medicine among the full time faculty of the newark-based schools of the university of medicine and dentistry of new jersey.

Background: The use of alternative and herbal medicine is increasing among the general population in the United States. The use of herbal medicine by health care professionals has not been documented. Health care professionals tend to base personal and professional practices on scientific research and facts. This population interacts with the public and with health care students. Therefore, personal and professional practices will impact these audiences. Methods: A survey was distributed to all faculty members of the University of Medicine and Dentistry of New Jersey via interoffice mail. A total of 904 surveys were sent. Statistical analyses included descriptive analysis of personal and professional practice regarding herbal medicine and chi(2) analysis of the relationship between personal and professional practices regarding herbal medicine. Significance was set at alpha <.05. Results: The overall response rate was 51%. Approximately one-third (29.6%, n = 134) of the population reported personal use of herbal medicine, 22.1% (n = 42) of the population who provide patient care recommend herbal medicine, 9.4% (n = 36) of those involved in teaching include herbal medicine in coursework, and 1.1% of the population were involved in research on herbs. Respondents who use herbal medicine were more likely to recommend herbs to patients (p <.0001); likewise, users of herbal medicine were more likely to teach students about herbal medicine (p =.001). Conclusions: The results support the hypothesis that personal beliefs and practices do impact professional practices within the clinical and academic settings of the university.

Safety and efficacy of elective carotid artery stenting in high-risk patients.

OBJECTIVES: We sought to evaluate the safety and efficacy of carotid artery stenting (CAS) in high risk patients. BACKGROUND: Carotid endarterectomy (CE) has been shown to be more effective than medical therapy, but it has limitations. Carotid artery stenting may be a reasonable alternative, particularly in high-risk patients. METHODS: We prospectively evaluated the safety and efficacy of CAS in 170 consecutive patients who underwent the procedure in 192 carotid arteries. Of the patients enrolled, 129 (76%) would have been excluded from the major trials of CE and 54 (32%) were referred by vascular surgeons. This series represents a very high-risk group that included patients with unstable angina, previous ipsilateral CE, contralateral carotid artery occlusion and other severe comorbid illnesses. Only 25 (24%) of 104 symptomatic patients would have met the North American Symptomatic Carotid Endarterectomy Trial (NASCET) entry criteria. The patients' mean age was 73 +/- 8 years (95 confidence interval [CI] 57 to 89), and 42 patients (25%) were > or = 80 years old. Patients had an independent neurologic examination before and after the procedure. RESULTS: The procedural success rate was 99%, including 73 patients who had a coronary intervention. Mean carotid artery stenosis was 78 +/- 10% before (95 CI 58 to 98) and 2 +/- 3% after the procedure (95 CI -4 to 8). During the initial hospital period and 30 days after CAS, there was one major and two category 2 minor strokes, as well as two category 1 minor strokes (total 30-day stroke rate was 2.9% for treated patients or 2.6% for treated arteries). There were no myocardial infarctions or deaths during or within 30 days of CAS. None of the NASCET-eligible patients had a stroke. At a mean follow-up of 19 +/- 11 months, three patients (2%) had asymptomatic restenosis. No other major strokes or neurologic deaths occurred. CONCLUSIONS: Carotid artery stenting is feasible, can be performed even in high-risk patients and is associated with a low restenosis rate.

Parathyroid hormone-related protein as a growth regulator of prostate carcinoma.

Parathyroid hormone-related protein (PTHrP) is produced by prostate carcinoma cells and tumors, but little is known of its role in prostate carcinogenesis. The goal of this study was to evaluate PTHrP expression in the regulation of prostate carcinoma growth using human and animal models. PTHrP expression was assessed in prostate cancer cell lines in vitro. Seven of nine cell lines produced PTHrP, and increased expression was seen during cell proliferation. The MatLyLu rat prostate carcinoma model was used to determine the effects of PTHrP overexpression on prostate tumor growth. PTHrP overexpression did not alter proliferation of the cells in vitro. However, when PTHrP-overexpressing cells were injected into rat hind limbs, primary tumor growth and tumor size were significantly enhanced as compared with control cells. To evaluate PTHrP in human prostate carcinoma patients, immunohistochemistry was performed on metastatic bone lesions. Immunolocalization of PTHrP protein was found in the cytoplasm and nucleus of cancer cells in the bone microenvironment. Because nuclear localization of PTHrP has been associated with an inhibition of apoptosis, the ability of full-length PTHrP to protect prostate cancer cells from apoptotic stimuli was examined. Cells transfected with full-length PTHrP showed significantly increased cell survival after exposure to apoptotic agents as compared with cells producing no PTHrP (plasmid control) or cells transfected with PTHrP lacking its nuclear localization signal. To determine the mechanism of action of PTHrP in prostate cancer cells, the parathyroid hormone/PTHrP receptor status of the cells was determined. These cell lines did not demonstrate parathyroid hormone/PTHrP receptor-mediated binding of iodinated PTHrP or steady-state receptor message by Northern blot analysis, but they did have a detectable receptor message by reverse transcription-PCR analysis. In summary, PTHrP is expressed in many prostate cancer cell lines in vitro and in metastatic bone lesions in vivo. PTHrP expression positively influences primary tumor size in vivo and protects cells from apoptotic stimuli. These data suggest that PTHrP plays an important role in the promotion of prostate tumor establishment and/or progression.

Cholinergic septal afferent terminals preferentially contact neuropeptide Y-containing interneurons compared to parvalbumin-containing interneurons in the rat dentate gyrus.

Septal cholinergic neurons may affect hippocampal memory encoding and retrieval by differentially targeting parvalbumin (PARV)-containing basket cells and neuropeptide Y (NPY) interneurons. Thus, the cellular associations of cholinergic efferents, identified by the low-affinity, p75 neurotrophin receptor (p75(NTR)), with interneurons containing either PARV or NPY in the hilus of the rat dentate gyrus were examined in single sections using dual labeling immunoelectron microscopy. Most profiles immunoreactive (IR) for PARV and NPY were perikaryal and dendritic and found within the infragranular and central hilar regions, respectively, whereas most profiles with p75(NTR)-labeling were unmyelinated axons and axon terminals. Although PARV-labeled profiles were more numerous, p75(NTR)-labeled axons and terminals contacted few PARV-IR profiles compared to NPY-labeled profiles (2% of 561 for PARV vs 12% of 433 for NPY). Moreover, structures targeted by p75(NTR)-IR axon terminals varied depending on the presence of PARV or NPY immunoreactivity. p75(NTR)-IR terminals primarily contacted PARV-IR dendrites (87%) compared to somata (13%); however, they contacted more NPY-IR somata (57%) than dendrites (43%). p75(NTR)-labeled terminals formed exclusively symmetric (inhibitory-type) synapses with PARV-IR somata and dendrites; however, they formed mostly symmetric but also asymmetric (excitatory-type) synapses with NPY-IR somata and dendrites. These results suggest that septal cholinergic efferents in the dentate gyrus: (1) preferentially innervate NPY-containing interneurons compared to PARV-containing basket cells; and (2) may provide a more powerful (i.e., somatic contacts), yet functionally diverse (i.e., asymmetric and symmetric synapses), modulation of NPY-containing interneurons. Moreover, they provide evidence that neurochemical subsets of hippocampal interneurons can be distinguished by afferent input.

Skeletal metastasis of prostate adenocarcinoma in rats: morphometric analysis and role of parathyroid hormone-related protein.

BACKGROUND: Prostate cancer frequently metastasizes to bone, where it induces osteoblastic lesions. Parathyroid hormone-related protein (PTHrP), a product of normal and neoplastic prostate cells, may promote growth and bone metastasis of certain types of cancer. In this study, we investigated the: 1) pathogenesis and morphology of bone metastases in the MATLyLu rat prostate adenocarcinoma model, and 2) effect of PTHrP overexpression on tumor growth and incidence of bone metastasis. METHODS: MATLyLu cells were stably transfected with a PTHrP expression vector or control plasmid. PTHrP expression was determined in vitro by immunoradiometric assay and Northern blot analysis. MATLyLu cells were injected into the left ventricle of Copenhagen rats to induce bone metastases. Histology and radiography were used to quantify the size and number of bone metastases. Serum alkaline phosphatase isoenzyme concentrations and histomorphometric analysis were used to evaluate bone formation and resorption. RESULTS: All rats developed osteolytic metastases in long bones and vertebrae. There was no evidence of increased intramedullary bone formation. PTHrP overexpression by MATLyLu cells was not associated with any difference in the incidence of bone metastasis, size of metastatic foci or tumor-cell proliferation. CONCLUSIONS: The MATLyLu intracardiac injection model of prostate carcinoma is an aggressive tumor model with a high incidence of osteolytic skeletal metastases, and is not altered by increased PTHrP production by neoplastic prostate epithelial cells.

p75NTR immunoreactivity in the rat dentate gyrus is mostly within presynaptic profiles but is also found in some astrocytic and postsynaptic profiles.

To localize neurotrophin binding sites within the rat dentate gyrus, the distribution of low-affinity p75 neurotrophin receptor (p75NTR) immunoreactivity (IR) was examined by using antiserum raised against the cytoplasmic domain of the receptor. Semiquantitative electron microscopic examination of p75NTR-labeled sections showed that most p75NTR-labeled profiles were axons and axon terminals (72% from a total of 3,975); p75NTR-IR was observed throughout the extent of these structures and was not limited to the plasmalemmal surface. Axons and axon terminals containing p75NTR-IR were distributed in approximately equal proportions across the hilus, infragranular zone, and the inner, middle, and outer molecular layers; significantly fewer p75NTR-labeled profiles were observed in the granule cell layer. Axon terminals containing p75NTR-IR, which made synapses (296 of 552), formed equal proportions of symmetric and asymmetric synapses, primarily with the shafts and spines of dendrites. The remainder of the p75NTR-labeled terminals apposed unlabeled somata and dendrites without forming synapses in the single sections analyzed. In addition, p75NTR-IR was contained within some astrocytes (17.5% of 3,975) and dendritic shafts (3%) and spines (5%). Within dendritic spines, p75NTR-IR was most often associated with the plasmalemmal surface near postsynaptic densities; in dendritic shafts, p75NTR labeling was associated with microfilaments distant from the plasmalemma. Most p75NTR-labeled dendritic profiles were located in the molecular layer, and some originated from granule cells. Moreover, in some granule cell somata (<1% of 3,975), p75NTR-IR was associated with endosomes. The primary localization of p75NTR-IR to presynaptic structures in the dentate gyrus, presumably arising from medial septal/diagonal band neurons, agrees with previous reports. However, p75NTR-IR within some astrocytes, somata, and dendritic structures suggests that this receptor may also be involved in controlling local neurotrophin levels and possibly modulating the viability of local hippocampal cell populations.

Procedural results and early clinical outcome of percutaneous transluminal myocardial revascularization.

A substantial number of patients present with medically refractory angina who are not candidates for angioplasty or bypass surgery. The creation of channels between the myocardium and the ventricular blood pool has been performed after thoracotomy with excellent relief of symptoms but has been associated with high perioperative mortality. We investigated the safety of a nonoperative, percutaneous technique for channel creation. Twenty-seven patients with angina and coronary anatomy not amenable to revascularization with coronary angioplasty or bypass surgery underwent percutaneous transluminal myocardial revascularization (PTMR). Energy from a Holmium:yttrium-aluminum-garnet (YAG) laser was directed through a fiber enclosed in a catheter to the ventricular myocardium creating channels between the blood pool and the myocardium. On average, 17 +/- 4 channels were formed per patient. There were no procedure-related deaths, episodes of tamponade, or other complications except for an increase in creatine phosphokinase in 1 patient. Immediately after the procedure, there was no worsening of regional wall motion function in any patient, but rather improvement in some. All patients were discharged alive after a hospital stay of 1.8 +/- 1.5 days. Mean Canadian Cardiovascular Society functional class declined from 3.6 +/- 0.5 before the procedure to 0.65 +/- 0.8 at 30 days after the procedure (p < 0.01). For 12 patients eligible for 6-month follow-up, mean functional class was 0.94 +/- 0.97. At 6-month stress testing, 9 of these 12 had no electrocardiographic evidence of ischemia. Thus, PTMR can be performed safely in the cardiac catheterization laboratory with a complication rate lower than that reported in surgical series and with excellent near-term symptomatic relief. The long-term effect of PTMR on mortality and relief of angina as well as its safety and effectiveness compared with the surgical approach remains to be defined.

The plasminogen activator inhibitor-2 gene is not required for normal murine development or survival.

Plasminogen activator inhibitor-2 (PAI-2), a member of the serpin gene family, is thought to serve as a primary regulator of plasminogen activation in the extravascular compartment. High levels of PAI-2 are found in keratinocytes, monocytes, and the human trophoblast, the latter suggesting a role in placental maintenance or embryo development. The primarily intracellular distribution of PAI-2 also may indicate a unique regulatory role in a protease-dependent cellular process such as apoptosis. To examine the potential functions of PAI-2 in vivo, we generated PAI-2-deficient mice by gene targeting in embryonic stem cells. Homozygous PAI-2-deficient mice exhibited normal development, survival, and fertility and were also indistinguishable from normal controls in response to a bacterial infectious challenge or endotoxin infusion. No differences in monocyte recruitment into the peritoneum were observed after thioglycollate injection. Epidermal wound healing was equivalent among PAI-2 -/- null and control mice. Finally, crossing PAI-2 -/- with PAI-1 -/- mice to generate animals deficient in both plasminogen activator inhibitors failed to uncover an overlap in function between these two related proteins.

Septocingulate and septohippocampal cholinergic pathways: involvement in working/episodic memory.

The contribution of the septohippocampal cholinergic pathway to performance of a working/episodic memory task was compared to that of the septocingulate cholinergic path. The septocingulate and septohippocampal cholinergic pathways were selectively destroyed in male Sprague-Dawley rats using site-specific injections of the anti-neuronal immunotoxin 192-IgG saporin into either the hippocampus or the cingulate cortex. 192-IgG-saporin selectively destroys cholinergic neurons and terminals that express the p75 neurotrophin receptor. Following extensive pre-operative training, working memory was assessed using a delayed nonmatch to sample eight arm radial maze task, with delays of 1, 4 and 8 h. The group with lesions of the septohippocampal cholinergic pathway displayed performance deficits on this task which were not related to length of delay. In contrast, the group with lesions of the septocingulate cholinergic pathway did display delay-dependent deficits which were observed at the 4- and 8-h delays, but not at the 1-h delay. These data suggest that the septocingulate cholinergic pathway is critically involved in working/episodic memory but that the septohippocampal cholinergic pathway is either not contributing to working/episodic memory per se or it is involved only at shorter delays.