Ca(2+) changes induced by different presynaptic nicotinic receptors in separate populations of individual striatal nerve terminals.

Presynaptic nicotinic acetylcholine receptors likely play a modulatory role in the nerve terminal. Using laser-scanning confocal microscopy, we have characterized physiological responses obtained on activation of presynaptic nicotinic receptors by measuring calcium changes in individual nerve terminals (synaptosomes) isolated from the rat corpus striatum. Nicotine (500 nM) induced Ca(2+) changes in a subset (10-25%) of synaptosomes.

Postsynaptic target regulates functional responses induced by 5-HT3 serotonin receptors on axonal varicosities of NG108-15 hybrid neuroblastoma cells.

Rat brain presynaptic 5-HT3 serotonin receptors, members of the ligand-gated ion channel superfamily, induce changes in nerve terminal [Ca2+]i in a manner distinct from that found for somatic 5-HT3 receptors. Here, we assessed the role of postsynaptic target in regulating the nature of presynaptic receptor-induced responses, using the hybrid neuroblastoma cell line NG108-15 as a model neuronal system that expresses 5-HT3 receptors. Using immunocytochemistry, 5-HT3 receptors were found to be present on the presynaptic-like varicosities of differentiated NG108-15 cells, indicating that these receptors possess an inherent ability to localize to potential presynaptic sites.

Frontotemporal dementia with novel tau pathology and a Glu342Val tau mutation.

It is unclear how tau gene mutations cause frontotemporal dementia (FTD) with parkinsonism linked to chromosome 17 (FTDP-17), but those in exon 10 (E10) or the following intron may be pathogenic by altering E10 splicing, perturbing the normal 1:1 ratio of four versus three microtubule-binding repeat tau (4R:3R tau ratio) and forming tau inclusions. We report on a 55-year old woman with frontotemporal dementia and a family history of FTDP-17 in whom we found a novel E12 (Glu342Val) tau gene mutation, prominent frontotemporal neuron loss, intracytoplasmic tau aggregates, paired helical tau filaments, increased 4R tau messenger RNA, increased 4R tau without E2 or E3 inserts, decreased 4R tau with these inserts, and a 4R:3R tau ratio greater than 1 in gray and white matter. Thus, this novel Glu342Val mutation may cause FTDP-17 by unprecedented mechanisms that alter splicing of E2, E3, and E10 to preferentially increase 4R tau without amino terminal inserts and promote aggregation of tau filaments into cytopathic inclusions.

Functional IP3- and ryanodine-sensitive calcium stores in presynaptic varicosities of NG108-15 (rodent neuroblastoma x glioma hybrid) cells.

Presynaptic varicosities of the model neuronal cell line NG108-15, a cholinergic neuroblastoma cell x glioma cell hybrid capable of innervating striated myotubes, were examined for the presence of inositol 1,4,5-trisphosphate (IP3)-sensitive and Ca2+-activated (ryanodine-sensitive) Ca2+ stores using confocal microscopic imaging of Ca2+-sensitive fluorescent dye loaded into the cells. Initial demonstration of the presence of IP3 receptors and ryanodine receptors in the NG108-15 varicosities was obtained using immunocytochemistry. Treatment of NG108-15 cells with bradykinin (0.

Changing Epidemiology of Bacterial Meningitis in the United States.

Bacterial meningitis is an important cause of morbidity and mortality in the United States and throughout the world. Over the past 20 years, there have been significant changes in the epidemiology of bacterial meningitis. The most important change is the decrease in the frequency of Haemophilus influenzae type b as the most common etiologic agent of bacterial meningitis, since the H.

Nicotinic receptors co-localize with 5-HT(3) serotonin receptors on striatal nerve terminals.

Nicotinic acetylcholine receptors and 5-HT(3) serotonin receptors are present on presynaptic nerve terminals in the striatum, where they have been shown to be involved in the regulation of dopamine release. Here, we explored the possibility that both receptor systems function on the same individual nerve terminals in the striatum, as assessed by confocal imaging of synaptosomes. On performing sequential stimulation, nicotine (500 nM) induced changes in [Ca(2+)](i) in most of the synaptosomes ( approximately 80%) that had previously responded to stimulation with the 5-HT(3) receptor agonist m-chlorophenylbiguanide (mCPBG; 100 nM), whereas mCPBG induced [Ca(2+)](i) responses in approximately half of the synaptosomes that showed responses on nicotinic stimulation.

Familial Alzheimer's disease: site of mutation influences clinical phenotype.

Alzheimer's disease (AD) is caused by multiple genetic and/or environmental etiologies. Because differences in the genetically determined pathogenesis may cause differences in the phenotype, we examined age at onset and age at death in 90 subjects with dominantly inherited AD due to different mutations (amyloid precursor protein, presenilin-1, and presenilin-2 genes). We found that among patients with dominantly inherited AD, genetic factors influence both age at onset and age at death.

Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology.

Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz syndrome, is a rare neurodegenerative disorder characterized clinically by Parkinsonism, cognitive impairment, pseudobulbar features, as well as cerebellar ataxia, and neuropathologically by neuronal loss, gliosis, and iron deposition in the globus pallidus, red nucleus, and substantia nigra. The hallmark pathological lesions of NBIA 1 are axonal spheroids, but Lewy body (LB)-like intraneuronal inclusions, glial inclusions, and rare neurofibrillary tangles also occur. Here we show that there is an accumulation of alpha-synuclein (alphaS) in LB-like inclusions, glial inclusions, and spheroids in the brains of three NBIA 1 patients.

Regulation of the expression and phosphorylation of microtubule-associated protein 1B during regeneration of adult dorsal root ganglion neurons.

Microtubule-associated protein 1B is a major constituent of the neuronal cytoskeleton during the early stages of development. This protein and its phosphorylated isoform, microtubule-associated protein 1B-P, defined by the monoclonal antibody 1B-P [Boyne L. J.

High affinity binding between lipoprotein lipase and lipoproteins involves multiple ionic and hydrophobic interactions, does not require enzyme activity, and is modulated by glycosaminoglycans.

Lipoprotein lipase (LPL) physically associates with lipoproteins and hydrolyzes triglycerides. To characterize the binding of LPL to lipoproteins, we studied the binding of low density lipoproteins (LDL), apolipoprotein (apo) B17, and various apoB-FLAG (DYKDDDDK octapeptide) chimeras to purified LPL. LDL bound to LPL with high affinity (K(d) values of 10(-12) m) similar to that observed for the binding of LDL to its receptors and 1D1, a monoclonal antibody to LDL, and was greater than its affinity for microsomal triglyceride transfer protein.

Complications of lower extremity arteriovenous grafts in patients with end-stage renal disease.

Background: More data are needed to assess lower extremity angioaccess sites for hemodialysis.

Methods: We did a retrospective review of 843 consecutive hospital records of upper and lower extremity arteriovenous (AV) fistulas from 1992 to 1996.

Results: Lower extremity grafts accounted for 16% (134/843) of patients in this series.

Atlanto-occipital dislocation: an unusual lethal airbag injury.

Airbag-induced injury fatality is increasing in frequency. We present the case of a 6-year-old passenger who sustained a fatal atlanto-occipital dislocation associated with airbag deployment in a low-speed motor vehicle crash. The current literature regarding airbag fatalities and methods to ameliorate airbag-induced injury are reviewed.

PTSD severity and health perceptions in female victims of sexual assault.

In women with chronic posttraumatic stress disorder (PTSD), poor physical health may be related to their PTSD symptoms through an underlying negative affect or distress that accompanies the disorder, through the PTSD symptoms in general, or specifically through the chronic hyperarousal present in the disorder. The current study examined the relative contribution of these factors to reported physical symptoms in female victims of sexual assault. Seventy-six women with chronic PTSD were assessed, using measures of stressful life events, psychological difficulties, and perceived health.

Rapid correction of aimed movements by summation of force-field primitives.

Spinal circuits form building blocks for movement construction. In the frog, such building blocks have been described as isometric force fields. Microstimulation studies showed that individual force fields can be combined by vector summation.

Nonocclusive mesenteric infarction in hemodialysis patients.

Background: Dialysis patients develop nonocclusive mesenteric ischemia (NOMI) at an increased rate. Previous studies have associated atherosclerosis and hemodialysis-induced hypotension as inciting factors for NOMI development. A retrospective review of 29 of 1,370 longterm hemodialysis patients who developed NOMI from January 1992 to December 1997 was performed.

Pleural fluid cytology of Hodgkin's disease: cytomorphologic features and the value of immunohistochemical studies.

Two cases in which Hodgkin's disease (HD) was cytologically diagnosed in pleural effusions are presented. The presence of Reed-Sternberg (R-S) cells was confirmed by positive staining for both CD15 and CD30, and negative staining for leukocyte common antigen. In addition, the differential diagnosis of HD in effusion cytology is presented, including look-alikes of R-S cells that can potentially lead to an incorrect diagnosis.

Double-blind study of clozapine dose response in chronic schizophrenia.

Objective: This study explored the relative efficacy of three different doses of clozapine.

Method: Fifty patients who met Kane et al.'s criteria for treatment-refractory schizophrenia or schizoaffective disorder were studied.

Diabetes-prone and diabetes-resistant BB rats share a common major diabetes susceptibility locus, iddm4: additional evidence for a "universal autoimmunity locus" on rat chromosome 4.

Diabetes-prone (DP) BB rats develop autoimmune type 1 diabetes spontaneously. At least five loci are linked to disease expression: the major histocompatibility complex (iddm2), two susceptibility loci (iddm4, iddm5), and, possibly, a resistance locus (iddm3). Spontaneous disease also requires homozygosity for lyp/iddm1, which causes lymphopenia.