bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of decomposition models using wood density of Douglas-fir logs
Authors: Means Joseph E. , Cromack Jr Kermit , MacMillan Paul C.
Published: March 2008

Logs of Pseudotsugamenziesii (Mirb.) Franco that had been on the ground for up to 313 years were grouped into five decay classes that ranged from 1, essentially undecayed, to 5, soft and incorporated into the forest floor but still identifiable. The mean residence times on the forest floor were 7, 17, 33, 82, and 219 years for decay classes 1 through 5, respectively. The single-exponential model of litter decomposition was fitted to the density of these logs. The summation-exponential model was constructed by summing single-exponential models fitted to lignin, cellulose, and the acid detergent soluble fraction. Both models gave virtually identical, statistically significant fits to the data. Wood density of these Douglas-fir logs decreased more slowly than that of most species other researchers have studied. The single-exponential model gave mineralization rates (k) of 0.0063 and 0.0070 year−1 when residence time and decay class age (mean residence time of the decay class), respectively, were used as the independent variable. Lignin decayed more slowly than cellulose or the fraction soluble in hot acid detergent, both of which decayed at rates that were not significantly different; thus, the summation-exponential model is recommended when these constituents are of interest.
Factor substitution, technical change, and returns to scale in Canadian forest industries
Authors: Martinello Felice
Published: March 2008

This paper reports estimates of factor substitution, technical change, and returns to scale for three Canadian industries, pulp and paper, sawmills and shingle mills, and logging, using annual data from 1963 to 1982. Each industry's input-demand functions slope down and are inelastic. Factor substitution is not rejected in any of the industries but it is not large. Sawmills and shingle mills show moderate increasing returns to scale, while logging and pulp and paper show very large increasing returns to scale. The technology of the industries is nonhomothetic and cost savings as a result of changes in scale are made mostly on the capital and labour inputs. Technical change is nonneutral, capital using, and labour saving in all industries. Negative technical change is estimated for sawmills and shingle mills and pulp and paper so that all of the productivity gains made over the period of the sample are associated with changes in scale rather than the passage of time. The technical change in all industries is labour saving enough that labour becomes more productive over time, holding everything else constant.
Temporal analysis of breeding structure in jack pine (Pinusbanksiana Lamb.)
Authors: Snyder Thomas P. , Stewart Dale A. , Strickler Ann F.
Published: March 2008

Outcrossing rates for 10 pollination years were estimated for a natural stand of jack pine using allozymic markers at the Mdh-2 and 6-pgd-1 loci. Outcrossing rate estimates showed a general increase with time since pollination. Population fixation index values for the progeny decrease with time since pollination, showing an increasing proportion of heterozygous progeny. These increases parallel those observed for jack pine, lodgepole pine, and alpine ash by other investigators, suggesting selection against inbred progeny may be occurring during the retention of the seed in the serotinous cones. Evaluation of the selection hypothesis by regression of the proportion of heterozygous progeny and of seed germination on year of pollination showed significant linear decreases in germination over a 10-year period for only one of eight trees. This was not accompanied by an increase in the proportion of heterozygous progeny. Apparent deviations from normal Mendelian segregation were noted at the Mdh-2 locus in two trees.
Damage by wildlife, especially small rodents, to North American Pinuscontorta provenances introduced into Sweden
Authors: Hansson Lennart
Published: March 2008

In 20 provenance trials with the North American Pinuscontorta Dougl. introduced into Sweden, 6 were severely damaged by voles, especially Microtusagrestis L., 2 by moose (Alcesalces L.), and 2 by roe deer (Capreoluscapreolus L.). Six trials were abandoned earlier partly because of roe deer damage and one as a result of vole damage. Vole damage was severe in northern Sweden and roe deer damage was severe in southern Sweden. Certain provenances were more severely attacked by voles, moose, or roe deer than others. The three mammals did not show any agreement in their selection. Voles damage southern provenances, or those with long growing seasons, more than northern ones. The differences among provenances declined rapidly in situations of increasing total damage. Selection among provenances for resistance to mammalian attacks may be possible if local or regional attack rates are taken into account.
A leaf area – sapwood area ratio developed to rate loblolly pine tree vigor
Authors: Blanche C. A. , Hodges J. D. , Nebeker T. E.
Published: March 2008

Stem cross-sectional sapwood area was linearly related to leaf area in loblolly pine. A better relationship was obtained using cross-sectional sapwood area taken at crown base than at breast height. The relationship was affected by time of sampling, with time of maximum needle biomass giving the best correlation. Specific leaf area (area in square centimetres per gram dry weight) was variable, but the mean of 95.32 cm2/g is comparable to reported values for other species. The leaf area – sapwood area ratio at breast height varies only slightly among individual trees so that a mean ratio of 0.29 can be utilized to accurately predict leaf area. The ratio between curent-year or previous-year sapwood production and leaf area (grams per square metre of foliage) was used as an indicator of tree vigor. Tree vigor values varied greatly (21 – 180 g/m2), but were normally distributed within this range.
Documentation of red spruce growth decline
Authors: Hornbeck James W. , Smith Robert B.
Published: March 2008

Data from a study of 3001 dominant or codominant red spruces (Picearubens Sarg.) across New England and the Adirondacks showed that their annual growth in basal area increased consistently from 1910–1920 to about 1960. It then fluctuated around a generally declining trend and by the early 1980's was 13 to 40% below its peak. Defoliation by the spruce budworm, climate change, maturation of the forest, and acid deposition are all possible explanations.
NORMAL FORMS FOR ALMOST COMPLEX STRUCTURES
Authors: TONEJC JERNEJ
Published: March 2008

We study the formal normal form of a non-integrable almost complex structure. We do this in terms of the vector fields associated to the almost complex structure. We show that locally such a formal normal form exists and we prove a partial convergence result.
METHOD OF MEAN VALUE OPERATORS FOR RADON TRANSFORMS IN THE SPACE OF MATRICES
Authors: OURNYCHEVA E. , RUBIN B.
Published: March 2008

We extend the Funk–Radon–Helgason inversion method of mean value operators to the Radon transform [Formula: see text] of continuous and Lpfunctions which are integrated over matrix planes in the space of real rectangular matrices. Necessary and sufficient conditions of existence of [Formula: see text] for such f and explicit inversion formulas are obtained. New higher-rank phenomena related to this setting are investigated.
Regulation of Cholinergic Phenotype in Developing Neurons
Authors: Liu Xinhuai , Popescu Ion R. , Denisova Janna V. , Neve Rachael L. , Corriveau Roderick A. , Belousov Andrei B.
Published: March 2008

Specification of neurotransmitter phenotype is critical for neural circuit development and is influenced by intrinsic and extrinsic factors. Recent findings in rat hypothalamus in vitro suggest the role of neurotransmitter glutamate in the regulation of cholinergic phenotype. Here we extended our previous studies on the mechanisms of glutamate-dependent regulation of cholinergic phenotypic properties in hypothalamic neurons. Using immunocytochemistry, electrophysiology, and calcium imaging, we demonstrate that hypothalamic expression of choline acetyltransferase (the cholinergic marker) and responsiveness of neurons to acetylcholine (ACh) receptor agonists increase during chronic administration of an N-methyl-d-aspartate receptor (NMDAR) blocker, MK-801, in developing rats in vivo and genetic and pharmacological inactivation of NMDARs in mouse and rat developing neuronal cultures. In hypothalamic cultures, an inactivation of NMDA receptors also induces ACh-dependent synaptic activity, as do inactivations of PKA, ERK/MAPK, CREB, and NF-κB, which are known to be regulated by NMDA receptors. Interestingly, the increase in cholinergic properties in developing neurons that is induced by NMDAR blockade is prevented by the blockade of ACh receptors, suggesting that function of ACh receptor is required for the cholinergic up-regulation. Using dual recording of monosynaptic excitatory postsynaptic currents, we further demonstrate that chronic inactivation of ionotropic glutamate receptors induces the cholinergic phenotype in a subset of glutamatergic neurons. The phenotypic switch is partial as ACh and glutamate are coreleased. The results suggest that developing neurons may not only coexpress multiple transmitter phenotypes, but can also change the phenotypes following changes in signaling in neuronal circuits.
Discharge Variability of Motor Units in an Intrinsic Muscle of Transplanted Hand
Authors: Farina Dario , Pozzo Marco , Lanzetta Marco , Enoka Roger M.
Published: March 2008

The study analyzed the discharge characteristics of the motor units in an intrinsic muscle of a transplanted hand. Multichannel electromyographic (EMG) recordings were obtained in 11 experimental sessions over 16 mo starting from day 205 after a hand was transplanted in a 35-yr-old man who had lost his right hand 22 yr earlier. The action potentials discharged by single motor units were identified from the surface EMG signals of the abductor digiti minimi muscle in the transplanted hand as the individual performed 60-s maximal and linearly increasing (ramp) contractions. Discharge rate decreased from 27.1 ± 8.4 pulses per second (pps) at the start of the maximal contractions to 17.2 ± 2.9 pps at the end ( P < 0.001) and increased from 17.4 ± 4.3 to 22.1 ± 5.0 pps during the ramp contractions ( P < 0.05). The SD of the interspike interval (ISI) nearly related to the mean ISI with a similar regression slope for the maximal (0.49 ± 0.09) and ramp contractions (0.43 ± 0.10). The coefficient of variation for ISI was higher than values in able-bodied persons and did not change during either the maximal (36.8 ± 10.8%) or the ramp contractions (35.9 ± 7.4%). High-frequency bursts of activity with <20 ms between two and six action potentials occurred during both maximal and ramp contractions. In conclusion, motor neurons that reinnervated a muscle in a transplanted hand discharged action potentials with a high degree of variability that suggested greater synaptic noise during the voluntary contractions.
Ellipticine derivative NSC 338258 represents a potential new antineoplastic agent for the treatment of multiple myeloma
Authors: Tian Erming , Landowski Terry H. , Stephens Owen W. , Yaccoby Shmuel , Barlogie Bart , Shaughnessy John D.
Published: March 2008

High-risk multiple myeloma can be correlated with amplification and overexpression of the cell cycle regulator CKS1B. Herein, we used the COMPARE algorithm to correlate high expression of CKS1B mRNA in the NCI-60 cell line panel with the concentration causing 50% growth inhibition (GI50) of >40,000 synthetic compounds. This led to the identification of NSC 338258 (EPED3), a highly stable, hydrophilic derivative of the plant alkaloid ellipticine. In vitro, this synthetic anticancer compound exhibits dramatic cytotoxic activity against myeloma cells grown in suspension or in coculture with stromal cells. EPED3-induced cell cycle arrest and an apoptotic progression that appear to be a consequence of the instantaneous effect of the drug on cytoplasmic organelles, particularly mitochondria. Disruption of mitochondria and cytoplasmic distribution of cytochrome c initiated the intracellular proteolytic cascade through the intrinsic apoptotic pathway. EPED3 is able to induce apoptosis in myeloma cells with de novo or acquired resistance to commonly administered antimyeloma agents. Collectively, our data suggest that EPED3 targets mitochondrial function to rapidly deplete chemical energy and initiate apoptosis in myeloma cells at nanomolar concentrations while leaving stromal cells unharmed. [Mol Cancer Ther 2008;7(3):500–9]
Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma
Authors: Ding Yan , Boguslawski Elissa A. , Berghuis Bree D. , Young John J. , Zhang Zhongfa , Hardy Kim , Furge Kyle , Kort Eric , Frankel Arthur E. , Hay Rick V. , Resau James H. , Duesbery Nicholas S.
Published: March 2008

We hypothesized that signaling through multiple mitogen-activated protein kinase (MAPK) kinase (MKK) pathways is essential for the growth and vascularization of soft-tissue sarcomas, which are malignant tumors derived from mesenchymal tissues. We tested this using HT-1080, NCI, and Shac fibrosarcoma-derived cell lines and anthrax lethal toxin (LeTx), a bacterial toxin that inactivates MKKs. Western blots confirmed that LeTx treatment reduced the levels of phosphorylated extracellular signal-regulated kinase and p38 MAPK in vitro. Although short treatments with LeTx only modestly affected cell proliferation, sustained treatment markedly reduced cell numbers. LeTx also substantially inhibited the extracellular release of angioproliferative factors including vascular endothelial growth factor, interleukin-8, and basic fibroblast growth factor. Similar results were obtained with cell lines derived from malignant fibrous histiocytomas, leiomyosarcomas, and liposarcomas. In vivo, LeTx decreased MAPK activity and blocked fibrosarcoma growth. Growth inhibition correlated with decreased cellular proliferation and extensive necrosis, and it was accompanied by a decrease in tumor mean vessel density as well as a reduction in serum expression of angioproliferative cytokines. Vital imaging using high-resolution ultrasound enhanced with contrast microbubbles revealed that the effects of LeTx on tumor perfusion were remarkably rapid (<24 h) and resulted in a marked reduction of perfusion within the tumor but not in nontumor tissues. These results are consistent with our initial hypothesis and lead us to propose that MKK inhibition by LeTx is a broadly effective strategy for targeting neovascularization in fibrosarcomas and other similar proliferative lesions. [Mol Cancer Ther 2008;7(3):648–58]
Physiologic Origins of Age-Related β-Amyloid Deposition
Authors: Beach Thomas G.
Published: March 2008

Background: Brain β-amyloid (Aβ) deposition is an extremely common accompaniment of aging in humans and many other mammalian species. We hypothesized that normal physiological changes of aging cause Aβ deposition. Objective: Three normal physiological aging changes were induced in young adult rabbits to determine their effects on brain Aβ concentrations and deposition. The three changes were cortical cholinergic deafferentation, hypercholesterolemia and estrogen deprivation. Methods: Cortical cholinergic deafferentation was achieved through intracerebroventricular immunotoxin injection. Hypercholesterolemia was induced with a 2% cholesterol diet. Estrogen deprivation was modeled with ovariectomy. Results: Cortical cholinergic deafferentation resulted in an 8-fold increase in cortical Aβ42 concentrations and cerebovascular Aβ deposition. Hypercholesterolemia increased cortical Aβ42 4.6-fold while ovariectomy increased cortical Aβ42 1.6-fold. Conclusion: At least three physiological changes of normal aging may underlie age-related brain Aβ accumulation and Alzheimer’s disease.
Processes of β-Amyloid and Intracellular Cytoplasmic Domain Generation by Presenilin/γ-Secretase
Authors: Tagami Shinji , Okochi Masayasu , Fukumori Akio , Jiang Jingwei , Yanagida Kanta , Nakayama Taisuke , Morihara Takashi , Tanaka Toshihisa , Kudo Takashi , Takeda Masatoshi
Published: March 2008

Background/Aims: Following extracellular shedding, transmembrane domains (TMs) of β-amyloid precursor protein (βAPP) and Notch-1 undergo proteolysis by presenilin (PS)/γ-secretase at least at two sites, near the middle of the TM (γ-/S4 cleavage) and at the interface between cytosol and the TM (Ε-/S3 cleavage), releasing Alzheimer disease (AD)-associated β-amyloid (Aβ)/Notch-1β (Nβ) and βAPP intracellular cytoplasmic domain (AICD)/Notch-1 intracellular cytoplasmic domain (NICD). Inhibiting PS/γ-secretase activity is an essential approach to AD treatment, but it also decreases NICD production, which may cause severe side effects. Therefore, it is important to investigate the differences between the cleavages at the two sites. γ-/S4 and Ε-cleavages have diversity, and produce a number of Aβ/Nβ and AICD species. S3 cleavage diversity has been recently identified. It is significant that each cleavage occurs with strict precision, not randomly. Methods: Biochemical analysis of cultured cells was performed to explore the processing mechanisms. Results: Familial AD-associated PS1 mutations as well as a subset of nonsteroidal anti-inflammatory drugs cause similar changes in γ-/S4 cleavage precision, suggesting a common process for these cleavages near the middle of the TM. While the precision of the Ε-cleavage is drastically affected by physiological factors, that of Ε-/S3 cleavage is not. Conclusion: The processes of the two cleavages occurring in different portions of TMs may be diverse, thus representing possible targets for anti-AD therapeutics to selectively reduce Aβ.
Mechanism of Glial Differentiation of Neural Progenitor Cells by Amyloid Precursor Protein
Authors: Sugaya Kiminobu
Published: March 2008

Background: We found that human neural progenitor cells (HNPCs) exposed to high concentrations of amyloid precursor protein (APP) or transplanted into APP transgenic mice (APP23) primarily differentiated into astrocytes, suggesting that pathological alterations of APP processing in Alzheimer’s disease (AD) may prevent neuronal differentiation of HNPCs. Objectives: To investigate the mechanism of APP-induced glial differentiation of HNPCs. Methods: We treat HNPCs with APP and analyze the expression and phosphorylation of signaling molecules using PCR and Western blots. To confirm the involvement of the factors, RNA interference of the signaling molecule is conducted. Results: APP treatment caused inductions of CNTF, gp130 and JAK1 gene expressions, and STAT3 phosphorylation, while silencing of these genes by RNA interference suppressed the glial differentiation of the cells, indicating involvement of the IL-6/gp130 pathway. APP also increased the generation of notch intracellular domain and gene expression of Hes1, indicating that glial differentiation of HNPCs may be mediated by the notch signaling. Conclusion: These results indicate that APP may regulate HNPC differentiation through activation of both the IL-6/gp130 and notch signaling pathway. Although the importance of adult neurogenesis is not clear, glial differentiation of HNPCs may cause problems in maintaining normal brain function and may contribute to the AD pathology.
Preamyloid Lesions and Cerebrovascular Deposits in the Mechanism of Dementia: Lessons from Non-β-Amyloid Cerebral Amyloidosis
Authors: Rostagno Agueda , Ghiso Jorge
Published: March 2008

The importance of amyloid plaques in the pathogenesis of dementia is usually centered on β-amyloid (Aβ) and its role in Alzheimer’s disease (AD). However, since fibrillar plaques correlate poorly with neurodegeneration, challenging their importance in the mechanism(s) of dementia, investigators turned their focus to the importance of soluble oligomers and the role of preamyloid and cerebrovascular deposits. Two non-Aβ cerebral amyloidoses, familial British and Danish dementias (FBD and FDD), share many aspects of AD, including cognitive impairment and the presence of neurofibrillary tangles in limbic areas. The lack of compact plaques in FDD and in many areas in FBD further questions the importance of these lesions in the mechanism of dementia. The main components of the deposits – ABri and ADan – are structurally unrelated to Aβ and yet they all have a high tendency to oligomerize and assemble into amyloid fibrils in vitro and form ion-like channels in lipid membranes. Thus, different amyloid species have the capability to induce similar neuropathological changes, which are neither exclusive for Aβ nor dependent on the presence of compact plaques. These findings reaffirm the notion that non-Aβ amyloidoses constitute alternative models to study the role of preassembled amyloid subunits in neuronal death.
Functional Genomics Dissects Pathomechanisms in Tauopathies: Mitosis Failure and Unfolded Protein Response
Authors: Götz Jürgen , David Della , Hoerndli Frederic , Ke Yazi D. , Schonrock Nicole , Wiesner Andreas , Fath Thomas , Bokhari Laita , Lim Yun-An , Deters Natasha , Ittner Lars M.
Published: March 2008

Background: Alzheimer’s disease (AD) is characterized by β-amyloid (Aβ) peptide-containing plaques and tau-containing neurofibrillary tangles. By intracerebral injection of Aβ42, both pathologies have been combined in P301L tau mutant mice. Furthermore, in cell culture, Aβ42 induces tau aggregation. While both Aβ42 and mutant tau cause neuronal dysfunction, their modes of action are only vaguely understood. Methods: To determine which processes are disrupted by Aβ42 and/or P301L mutant tau, we used transcriptomic and proteomic techniques followed by functional validation and analysis of human AD tissue. Results: Our transcriptomic study in the SH-SY5Y cell culture system revealed that Aβ42 and P301L tau expression independently affect genes controlling the cell cycle and cell proliferation. Proteomics applied to Aβ42-treated P301L tau-expressing SH-SY5Y cells and the amygdala of Aβ42-injected P301L transgenic mice revealed that a significant fraction of proteins altered in both systems belonged to the same functional categories, i.e. stress response and metabolism. Among the proteins identified was valosin-containing protein (VCP), a component of the quality control system during endoplasmic reticulum stress. Mutations in VCP have recently been linked to frontotemporal dementia. Conclusion: Our data support the mitosis failure hypothesis that claims that aberrant cell cycle reentry of postmitotic neurons induces apoptosis. Furthermore, our data underline a role of Aβ42 in the stress response associated with protein folding.
Neuroprotective Properties of Glycosaminoglycans: Potential Treatment for Neurodegenerative Disorders
Authors: Dudas B. , Rose M. , Cornelli U. , Pavlovich A. , Hanin I.
Published: March 2008

Previous studies suggest that proteoglycans and glycosaminoglycans (GAGs) may play an important role in the pathogenesis and/or alleviation of neurodegenerative disorders, including Alzheimer’s disease (AD). Proteoglycans increase the formation of neurofibrillary tangles, and stimulate the aggregation of β-amyloid (Aβ). This effect, on the other hand, is believed to be competitively inhibited by certain GAGs. Over the past few years, we have examined the neuroprotective properties of Neuroparin (C3), a low-molecular-weight GAG (approx. 2.1 kDa), in animal models of lesions characteristic of AD. Neuroparin is composed of 4–10 oligosaccharides, and it is derived from heparin involving depolymerization of heparin by gamma irradiation. In our experiments, Neuroparin protected against cholinergic lesions induced by intracerebroventricular injection of a specific cholinotoxin, AF64A, in rats. Administration of Neuroparin attenuated AF64A-stimulated, low-affinity nerve growth factor receptor-immunoreactive axonal varicosities in the rat septum, and increased arborization of hippocampal CA1 neurons. Neuroparin also reduced the septal caspase 3 immunoreactivity induced by AF64A treatment. Moreover, Neuroparin reduced tau 2 immunoreactivity in the rat hippocampus, stimulated by intra-amygdaloid injection of Aβ25–35. These findings are in good agreement with our previous data indicating a neuroprotective role of GAGs. These results, plus others, all suggest that Neuroparin may possess neuroprotective properties against many of the characteristic neural lesions in AD. Since our pharmacokinetic studies revealed that Neuroparin is capable of crossing the blood-brain barrier, Neuroparin may, conceivably, open an entirely new avenue in the treatment of neurodegenerative disorders. Phase I studies have been completed, and have proven to be extremely supportive in that regard.
Conformationally Altered p53: A Putative Peripheral Marker for Alzheimer’s Disease
Authors: Uberti Daniela , Lanni Cristina , Racchi Marco , Govoni Stefano , Memo Maurizio
Published: March 2008

The identification of biological markers of Alzheimer’s disease (AD) can be extremely useful to improve diagnostic accuracy and/or to monitor the efficacy of putative therapies. In this regard, peripheral cells may be of great importance because of their easy accessibility. After subjects were grouped according to diagnosis, the expression of conformational mutant p53 in blood cells was compared by immunoprecipitation or by a cytofluorimetric assay. One hundred and four patients with AD, 92 age-matched controls, 15 patients with Parkinson’s disease, and 9 with other types of dementia were analyzed. Two independent methods to evaluate the differential expression of a conformational mutant p53 were developed. Mononuclear cells were analyzed by immunoprecipitation or by flow cytometric analysis, following incubation with a conformation-specific p53 antibody, which discriminates unfolded p53 tertiary structure. Mononuclear cells from AD patients express a statistically significantly higher amount of mutant-like p53 compared to mononuclear cells from non-AD subjects, thus supporting the study of conformational mutant p53 as a new putative marker to discriminate AD from non-AD patients. We also observed a strong positive correlation between the expression of p53 and the age of patients. The expression of mutant p53 did not correlate with the duration of illness and the Mini Mental State Examination scores.
The Role of Alpha-Synuclein in Neurodegenerative Diseases: A Potential Target for New Treatment Strategies?
Authors: Windisch M. , Wolf H. , Hutter-Paier B. , Wronski R.
Published: March 2008

α-Synuclein (AS) is the main constituent of Lewy bodies. There is an ongoing discussion if overexpression is already dangerous, or if toxicity is subjected to oligomers, protofibrils or mature aggregates. The facts that the central hydrophobic part of AS is also a constituent of amyloid plaques in Alzheimer’s disease (AD) and that a majority of patients have Lewy bodies and Lewy neurites in specific brain areas raised our interest in the contribution of AS to AD pathogenesis. The N-terminal amino acid sequence 1–15 of β-synuclein (BS) seems to be a natural antiaggregation factor for AS. We synthesized a library with different sequence variations. Several of these peptides displayed neuroprotective activity in tissue culture models of neurodegeneration induced by oxidative stress or β-amyloid 1–42. In spite of the fact that these peptides have a short half-life, a significant in vivo reduction in brain plaque load and improvement of behavior was demonstrated in amyloid precursor protein transgenic mice after intranasal treatment for 2 months. KEGV, the shortest sequence, was also active after intraperitoneal application. The in vitro effects cannot be explained by the antiaggregatory potential, but most likely by interaction of BS derivates with antiapoptotic PI3/Akt or antioxidative pathways. The possibility that BS-derived peptidomimetics act as neuroprotectants and prevent protein misfolding suggests therapeutic usefulness.
M1 Muscarinic Agonists Target Major Hallmarks of Alzheimer’s Disease – The Pivotal Role of Brain M1 Receptors
Authors: Fisher Abraham
Published: March 2008

The M1 muscarinic receptor (M1 mAChR) is a therapeutic target in Alzheimer’s disease (AD) and the M1-selective muscarinic agonists AF102B, AF150(S) and AF267B are cognitive enhancers and potential disease modifiers. Notably, AF267B decreased cerebrospinal fluid β-amyloid (Aβ40 and Aβ42) in rabbits, decreased brain Aβ levels in hypercholesterolemic rabbits and vascular Aβ42 deposition from the cortex in cholinotoxin-treated rabbits. In triple transgenic AD mice, AF267B reduced cognitive deficits and decreased Aβ42 and tau pathologies in the cortex and hippocampus (not amygdala), via M1 mAChR activation of protein kinase C and a disintegrin and metalloproteinase domain 17 (ADAM17 or TACE) and decreased β-site amyloid precursor protein-cleaving enzyme 1 and glycogen synthase kinase 3β, respectively. AF267B is the first reported low-molecular-weight therapy that targets the major AD hallmarks.
Duodenal Levodopa Infusion Improves Quality of Life in Advanced Parkinson’s Disease
Authors: Antonini A. , Mancini F. , Canesi M. , Zangaglia R. , Isaias I.U. , Manfredi L. , Pacchetti C. , Zibetti M. , Natuzzi F. , Lopiano L. , Nappi G. , Pezzoli G.
Published: March 2008

Background: A significant percentage of patients with Parkinson’s disease (PD) continue to experience motor fluctuations and dyskinesias despite the association of dopamine agonists and levodopa with COMT or MAO-B inhibitors. The use of apomorphine infusion is limited by compliance while deep brain stimulation is feasible only for a small number of patients mostly because of age constraints. Objective: To assess prospectively the effectiveness of duodenal levodopa infusion on quality of life as well as motor features in patients with advanced PD. In all but 1 case levodopa infusion was stopped at nighttime. Methods: We report the outcome of 22 PD patients, followed for up to 2 years, who were on continuous duodenal levodopa/carbidopa infusion through percutaneous endoscopic gastrostomy. Results: We found a significant reduction in ‘off’ period duration as well as dyskinesia severity (Unified Parkinson’s Disease Rating Scale part IV, items 33 and 39). There was significant improvement in the 39-item Parkinson’s Disease Quality of Life Questionnaire as well as in the Unified Parkinson’s Disease Rating Scale part II up to the 2-year follow-up. Five patients withdrew: 2 for poor compliance and 3 for adverse events (1 was related to percutaneous endoscopic gastrostomy). Conclusions: These results demonstrate significant clinical improvements in quality of life and activities of daily living consistent with the occurrence of a satisfactory therapeutic response and a reduction in dyskinesia severity.
Depressive Symptoms, Vascular Risk Factors and Mild Cognitive Impairment
Authors: Panza Francesco , D’Introno Alessia , Colacicco Anna M. , Capurso Cristiano , Del Parigi Angelo , Caselli Richard J. , Todarello Orlando , Pellicani Vincenza , Santamato Andrea , Scapicchio Pierluigi , Maggi Stefania , Scafato Emanuele , Gandin Claudia , Capurso Antonio , Solfrizzi Vincenzo
Published: March 2008

Aims: We evaluated the impact of depressive symptoms on the rate of incident mild cognitive impairment (MCI) after a 3.5-year follow-up, and we assessed the interaction between depressive symptoms and vascular risk factors for incident MCI. Methods: A total of 2,963 individuals from a sample of 5,632 65- to 84-year-old subjects were cognitively and functionally evaluated at the 1st and 2nd surveys of the Italian Longitudinal Study on Aging, a prospective cohort study with a 3.5-year follow-up. MCI and dementia were classified using current clinical criteria. Depressive symptoms were measured with the Geriatric Depression Scale. Results: Among the 2,963 participants, 139 prevalent MCI cases were diagnosed at the 1st survey. During the 3.5-year follow-up, 105 new events of MCI were diagnosed. We did not observe any significant association between depressive symptoms and incident MCI (RR = 1.25, 95% CI = 0.85–1.84, χ2 = 1.30, p < 0.25). No sociodemographic variables or vascular risk factors modified the relationship between depressive symptoms and incident MCI. Conclusion: In our population, depressive symptoms were not associated with the rate of incident MCI. Our findings did not support a role of sociodemographic variables or vascular risk factors in the link between depressive symptoms and incident MCI.
Results of Treatment with Ventriculoatrial and Ventriculoperitoneal Shunt in Infantile Nontumoral Hydrocephalus
Authors: Pasqualin Alberto , Mazza Carlo , Da Pian Renato
Published: March 2008

The technique of femoral-cerebral catheterization in infants and children is described, and a series of 1,869 procedures is analyzed for complications. Clinical complications occurred in 12 of 678 or 1.8% of examinations while radiographic complications were discovered in 38 of 1,869 or 1.1% of procedures. The results are compared to a similar retrospective study of a large series (2,184 procedures) of direct puncture/retrograde brachial studies in a similar patient population at the same institution in which there was a 2.6% clinical complication rate and a 4.3% radiographic complication rate. Those factors which predispose to complications, clinical or radiographic, are more pronounced in the younger age groups but affect the direct puncture/retrograde brachial technique to a greater degree. The lower morbidity, greater selectivity and improved comfort make the femoral-cerebral route preferable for neuroangiographic studies in infants and children.
Subarachnoid Hemorrhage in Children
Authors: Sano Keiji , Ueda Yasuichi , Saito Isamu
Published: March 2008

45 cases of subarachnoid hemorrhage in children were surveyed. 73% of the causes were arteriovenous malformations and spontaneous intracerebral hematomata. Arteriovenous malformations in children may grow in size which may be due to the fact that besides the nidus demonstrated by angiography there are surrounding abnormal vascular groups, the reserved nidus. If one fails to extirpate this reserve nidus at the time of surgical excision of the arteriovenous malformation, it may become nidus several years later and may bleed again. The follow-up results of surgery in subarachnoid hemorrhage cases were fairly good.
Cerebrospinal Fluid Antibiotic Concentrations in Ventricular Shunt Infections
Authors: Wilson H.D. , Bean J.R. , James H.E. , Pendley M.M.
Published: March 2008

The concentration of antibiotic in cerebrospinal fluid was measured during treatment of seven children with infected ventricular shunts. Antibiotics were administered via the ventricular shunt or through an external ventricular drain. 53 CSF samples were obtained 7–19 h after antibiotic administration. Wide variation in cerebrospinal fluid antibiotic concentration occurred from patient to patient following either route of administration. For optimal management of shunt infections, we recommend periodic assessment of antibiotic concentration or activity in ventricular fluid and determination of the minimum inhibitory concentration of antibiotic required for each pathogen.
Influence of the Use of a Surgical Isolator on the Rate of Infection in the Treatment of Hydrocephalus
Authors: Hirsch J.F. , Renier D. , Pierre-Kahn A.
Published: March 2008

Two series of patients treated for hydrocephalus (101 original shunt insertions, 81 revisions and 35 reinsertions after infections) have been operated on in the same location, 146 with a surgical isolator (SI), 71 without a SI. Due to temporary poor technical conditions, the use of a SI was decided because, the overall rate of acute postoperative infections had suddenly increased from 9 to 19.7%. Then, although these technical conditionns remained unchanged, the use of the SI immediately reduced the overall rate of acute postoperative infections from 19.7 to 7.4%. In original shunt insertions, this rate decreased from 24.9 to 5.8% and in revisions from 10.7 to 5.5%. In reinsertions after infection, it only fell from 27.2 to 16.6%. With the SI, the rate of peroperative contamination is almost nil. If postoperative contaminations due to wound disruption or scalp necrosis, and shunt reinsertions after infection are not taken into account, the rate of acute postoperative infection is 0.8%. The data presented indicate the efficiency of the SI. This results from elimination by the SI of airborne contamination and errors in aseptic technique. These two factors are probably the main sources of infection in shunt insertions for hydrocephalus.
Immunological Diagnosis of Echinococcosis
Authors: Flórez G. , Sanchez C. , Albala F.
Published: March 2008

Our results with the immunofluorescence technique in the diagnosis of hydatid disease are reported. The sera of 28 patients with surgically proven hydatid disease, of 30 healthy individuals, and of 1 patient with cysticercosis were used. With a diluteion of 1:100 a sensitivity of 96% was obtained in the patients affected by the disease. In the control group all but one of the sera were negative. A brief review of the immunological methods used at present for the diagnosis of echinococcosis is made. The most important problems connected with the immunodiagnosis of this disease are discussed.
Brain Edema in Immature Animals
Authors: Okuma Akio , Yamada Hiromu
Published: March 2008

Applying several procedures to produce brain edema, the authors examined electron microscopically immature rat brains, and the findings were compared with those in adult rat brains. Using Na-fluorescein and ferritin as tracers, the authors also examined the blood brain barrier (BBB) functionally. It was clarified that immature rat brains showed resistance to the brain edema of the vasogenic type in spite of breakdown of the BBB. On the basis of these results the authors discussed on genesis of brain edema of the vasogenic type.
Gangliogliomas in Children
Authors: Garrido Eddy , Becker Laurence F. , Hoffman Harold J. , Hendrick Bruce , Humphreys Robin
Published: March 2008

14 children with central nervous system gangliogliomas are reviewed. The tumors were most frequently located in the cerebral hemisphere and often were cystic and calcified. Total removal was performed in only 1 patient. A well-defined plane of cleavage could not be obtained in the majority of tumors at surgery. All patients are alive on follow-up and only 1 is neurologically disabled. Radiation therapy was given to 4 patients postoperatively. The clinical course of patients given postoperative radiation therapy was not different from that of those who were not irradiated. The histological aspects of the tumors are described.
The Physiopathogenetic Basis for the Angiographic Diagnosis of Bacterial Infections of the Brain and Its Coverings in Children
Authors: Raimondi Anthony J. , Di Rocco Concezio
Published: March 2008

This is a descriptive analysis of the angiographic characteristics of leptomeningeal infections in 36 children and a correlation of these angiographic observations with anatomopathologic changes. Vascular, meningeal and parenchymal changes are described and discussed. In the normal situation, tracer protein particles injected into the subarachnoid space perfuse easily through the extracellular spaces but stop at the outer continuous arachnoidal layer. The parenchymal layer, pia-arachnoid, on the other hand, consists of a uni or pluricellular layer which is regularly crossed by tracer particles. Though the internal carotid, vertebral and basilar arteries have some anatomical characteristics in common with peripheral arteries, they have special anatomical characteristics: thinner tunica media and adventitia, the absence of vasa vasorum and the presence of a fluid cushion (CSF) in which they are bathed. The most striking angiographic observation in leptomeningitis is the transmural extravasation of the contrast medium, primarily in arteries within the depths of the cisterns and sulci, producing ‘halo’ formation. Long after the cerebral circulation time, one may identify contrast media ‘pooling’ within the cisterns and sulci.
Brain Tumors in Childhood
Authors: Yates Allan J. , Becker Laurence E. , Sachs Larry A.
Published: March 2008

A review of the pathology of 689 neuroectodermal tumors occurring over a 30-year period at The Hospital for Sick Children in Toronto has underlined the importance of examining the tissue from each tumor in order to insure consistency and accuracy in histological diagnosis. The age, sex, histology and topographical distribution of this series of tumors is compared with other series and discussed in detail. The high proportion of tumors occurring in early childhood, the striking male preponderance, and the high incidence of astrocytomas, medulloblastomas and ependymomas is emphasized.
Retinal Hemorrhage in the Battered Child
Authors: Eisenbrey Arthur B.
Published: March 2008

The presence of retinal hemorrhage in head-injured children under 3 years of age is believed to be pathognomonic of battering. When a group of battered children was compared to head-injured children due to other causes, the high incidence of retinal hemorrhage in the battered children was contrasted with the absence of retinal hemorrhage produced by other causes of head injury.
Teratocarcinoma of the Brain – A Treatable Disease?
Authors: Marshall L.F. , Rorke Lucy B. , Schut Luis
Published: March 2008

Teratocarcinoma of the brain is a rare teratoid tumor. Less than 100 cases have been previously reported and only 4 were patients with tumors in the lateral ventricular system. At the Children’s Hospital of Philadelphia, 2 patients with teratocarcinoma of the lateral ventricle of the brain have been treated in the past 5 years and both are long-term survivors. A third patient with a recurrence at University Hospital is now receiving chemotherapy. Our experience suggests that a combination of radical surgery, super-voltage radiotherapy and chemotherapy may be successful in controlling these neoplasms. Furthermore, since there is increasing evidence that they have a strong histologic relationship to the embryonal carcinomas that arise in the testes and elsewhere, it appears logical to apply chemotherapeutic strategies to these intracranial neoplasms based on experience with such tumors located in other regions of the body.
Early Surgical Intervention in Posthemorrhagic Hydrocephalus
Authors: Bada Henrietta S. , Salmon James H. , Pearson Donald H.
Published: March 2008

10 premature infants were found to have posthemorrhagic hydrocephalus (PHH) over a 4-year period. All weighed less than 2,500 g. The diagnosis was established by ventricular puncture and ventriculogram. Ventriculo-peritoneal (V-P) shunt placement was done in each infant soon after establishing the diagnosis, while the cerebrospinal fluid (CSF) was bloody. The mean age of infants at surgery was 21.4 days (range 16–33 days). Shunt obstruction occurred in 3 infants and infection in 1. No other complication was observed. All infants improved markedly in the immediate postoperative period, especially respirator-dependent infants. All survived; preliminary follow-up revealed that 3 were severely retarded and 2 mildly retarded; 5 infants were normal. Our preliminary experience with early V-P shunt procedure in the treatment of PHH has been favorable and follow-up appears encouraging.
Histiocytosis ‘X’ of the Central Nervous System
Authors: Iraci Giorgio , Chieco-Bianchi Luigi , Giordano Renzo , Gerosa Massimo
Published: March 2008

The case is presented of a child with early manifestations of Hand-Schüller-Christian disease limited to exophthalmos, and rapid final progression towards a clinical picture dominated by intracranial hypertension and cerebeliar involvement, caused by massive histiocytic infiltration of the cerebellum, combined with discrete subdural deposits of xanthomatous tissue and minor deposits in other parts of the central nervous system and other organs.
Successful Surgical Treatment of Pontine Vascular Malformation in a 3-Year Old
Authors: Sundaresan Narayan , Galicich Joseph , Krol George , Rosen Gerald
Published: March 2008

A 3-year-old male presented with progressive right hemiparesis. Clinical and radiological studies suggested the diagnosis of brain stem glioma. At surgery, a small vascular malformation of the pons was encountered. Although rare, vascular malformations must be considered in the differential diagnosis of brain stem masses.
Subtemporal Decompression for the Slit-Ventricle Syndrome after Shunting in Hydrocephalic Children
Authors: Holness Renn O. , Hoffman Harold J. , Hendrick Bruce
Published: March 2008

During the past 2 years, we have performed subtemporal decompression to deal with recurrent shunt obstruction in 22 hydrocephalic patients with the slit-ventricle syndrome. 13 patients have been followed-up for more than 1 year and 2 others for more than 2 years. The frequency of hospitalization for shunt-revision has been greatly reduced. These results confirm that subtemporal craniectomy is useful in the treatment of patients in whom this syndrome develops.
The Results of Operating upon Cerebral Aneurysms and Angiomas in Children and Adolescents
Authors: Amacher Loren , Drake Charles G. , Hovind Laila
Published: March 2008

Symptomatic angiomas of the brain, brain stem or cerebellum are uncommon in all age groups. They usually present by subarachnoid and intraparenchymatous hemorrhage, but they may act as expanding mass lesions, as causes of ingavescent neurological deficit (?’steal phenomenon’), as epilepticogenic foci, or as a source of relentless headache. We have operated upon 20 patients, 18 years of age or less, with symptomatic angiomas. There has been no surgical mortality, and no patient has been made worse by operation.
Physiopathology and a New Treatment of Chronic Subdural Hematoma in Children
Authors: Gutierrez Francisco A. , McLone David G. , Raimondi Anthony J.
Published: March 2008

Chronic collections of fluid in the subdural spaces may result from trauma or may complicate meningitis. The etiological factor, or factors, which contribute to chronicity of subdural fluid in children remains obscure. We postulate that one possible mechanism is the progressive stretching and narrowing of the cortical veins, bridging the subarachnoid and subdural spaces to enter the superior sagittal sinus. This process ultimately leads to thrombosis of these ‘hanging veins’. Narrowing and angulation of these veins could result in elevated back pressure favoring the formation of a transudate. 16 children who had progressive and persistent collections of xanthochromic fluid in the subdural spaces secondary to trauma or infection who were treated previously either with subdural tap, burr holes, subdural peritoneal shunt, craniotomy, stripping of membranes and/or a combination of these, were treated by lowering and advancing the superior sagittal sinus with its overlying sagittal suture and performing a duraplasty. This new surgical technique is directed to improve venous drainage from the superior anastomotic vein into the superior sagittal sinus. Angiographic follow-up showed that only 2 patients still have evidence of fluid collection: the rest of the patients showed normal arterial phases, the medullary system was minimally filled and all of these showed remarkable improvement of the venous drainage throughout the superficial cortical veins with no evidence of hanging veins. Intellectual development of these children following lowering of the superior sagittal sinus showed that 8 patients (50%) were normal or above normal; 5 patients (31.2%) were retarded and 3 patients (18.7%) were borderline.
Cerebrospinal Fluid Pathways in a Murine Mutant
Authors: McLone David G.
Published: March 2008

The hy-3/hy-3 mouse is a model of congenital hydrocephalus. The development of the subarachnoid space and extracellular space were studied in normal and hydro-cephalic animals. A previous space in the mesenchyme is altered to form the subarachnoid space. Changes in the extracellular space demonstrate that this space is dynamic and acts to compensate for events occurring in the ventricular system. The aqueduct and central spinal canal are also involved in the hydrocephalic process. Change in cerebral vasculature may indicate the processes which lead to irreversibility.