bluuebunny/crossref_metadata_2025 huggingface dataset:
Transglutaminase catalyzes differential crosslinking of small heat shock proteins and amyloid‐β
Authors: Boros Sandor , Kamps Bram , Wunderink Lisa , de Bruijn Willem , de Jong Wilfried W. , Boelens Wilbert C.
Published: September 2004

Crosslinking of proteins by tissue transglutaminase (tTG) is enhanced in amyloid (Aβ) deposits characteristic of Alzheimer's disease and sporadic inclusion body myositis. Small heat shock proteins (sHsps) also occur in amyloid deposits. We here report the substrate characteristics for tTG of six sHsps. Hsp27, Hsp20 and HspB8 are both lysine‐ and glutamine‐donors, αB‐crystallin only is a lysine‐donor, HspB2 a glutamine‐donor, and HspB3 no substrate at all. Close interaction of proteins stimulates crosslinking efficiency as crosslinking between different sHsps only takes place within the same heteromeric complex. We also observed that αB‐crystallin, Hsp27 and Hsp20 associate with Aβ in vitro, and can be readily crosslinked by tTG.
Kinetics of interprotein electron transfer between cytochrome c6 and the soluble CuA domain of cyanobacterial cytochrome c oxidase
Authors: Paumann Martina , Feichtinger Markus , Bernroitner Margit , Goldfuhs Judith , Jakopitsch Christa , Furtmüller Paul G. , Regelsberger Günther , Peschek Günter A. , Obinger Christian
Published: September 2004

Cytochrome c
6 is a soluble metalloprotein located in the periplasmic space and the thylakoid lumen of many cyanobacteria and is known to carry electrons from cytochrome b
6
f to photosystem I. The CuA domain of cytochrome c oxidase, the terminal enzyme which catalyzes the four‐electron reduction of molecular oxygen in the respiratory chains of mitochondria and many bacteria, also has a periplasmic location. In order to test whether cytochrome c
6 could also function as a donor for cytochrome c oxidase, we investigated the kinetics of the electron transfer between recombinant cytochrome c
6 (produced in high yield in Escherichia coli by coexpressing the maturation proteins encoded by the ccmA‐H gene cluster) and the recombinant soluble CuA domain (i.e., the donor binding and electron entry site) of subunit II of cytochrome c oxidase from Synechocystis PCC 6803. The forward and the reverse electron transfer reactions were studied by the stopped‐flow technique and yielded apparent bimolecular rate constants of (3.3 ± 0.3) × 105 M−1
s−1 and (3.9 ± 0.1) × 106 M−1
s−1, respectively, in 5 mM potassium phosphate buffer, pH 7, containing 20 mM potassium chloride and 25 °C. This corresponds to an equilibrium constant K
eq of 0.085 in the physiological direction (Δr
G
′0=6.1 kJ/mol). The reduction of the CuA fragment by cytochrome c
6 is almost independent on ionic strength, which is in contrast to the reaction of the CuA domain with horse heart cytochrome c, which decreases with increasing ionic strength. The findings are discussed with respect to the potential role of cytochrome c
6 as mobile electron carrier in both cyanobacterial electron transport pathways.
Effects of systemic and regional taurine on skeletal muscle function following ischaemia–reperfusion injury
Authors: Kingston Ross , Kearns Stephen , Kelly Cathal , Murray Paraic
Published: September 2004

Introduction: Tissues subjected to prolonged ischaemia are paradoxically further damaged when their perfusion is restored. The mechanisms underlying this ischaemia–reperfusion injury are complex, but oxidative attack is a central feature. Among the therapeutic agents used to attenuate ischaemia–reperfusion injury, endogenous agents such as taurine which form part of the native defence mechanism against oxidative damage are of particular interest.

Methods: Using a model of hindlimb ischaemia–reperfusion injury in the rat, taurine solution was administered either into the operated hindlimb, into the systemic circulation, or both. Contraction strengths of gastrocnemius biopsies from the operated and contralateral (control) hindlimbs of each animal were measured.

Results: Fast twitch strength was impaired significantly by ischaemia–reperfusion injury, and taurine injected into the operated limb conferred partial protection. A similar trend was observed for tetany, but protection by taurine was not statistically significant for tetanic contraction strength.

Conclusion: Preservation of fast twitch strength following ischaemia–reperfusion injury by administration of taurine before ischaemia has clinical potential. However, delivery to the affected tissues during ischaemia presents technical difficulties. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Short, Self‐Report Voice Symptom Scales: Psychometric Characteristics of the Voice Handicap Index‐10 and the Vocal Performance Questionnaire
Authors: Deary Ian J. , Webb Alison , Mackenzie Kenneth , Wilson Janet A. , Carding Paul N.
Published: September 2004

OBJECTIVE

Short, self‐report symptom questionnaires are useful in routine clinical situations for assessing the progress of disorders and the influence of interventions. The Voice Handicap Index‐10 (VHI‐10) and Vocal Performance Questionnaire (VPQ) are brief self‐reported assessments of voice pathology, apparently useful in the general voice clinic population. Little is known of the structure or internal consistency of either tool, nor whether they correlate. This study carried out a substantial, systematic evaluation of their performance in the Laryngology office setting.

STUDY DESIGN AND SETTING

330 adult (222 women, 108 men) voice clinic attenders completed the VHI and the VPQ. RESULTS: The VHI‐10 and VPQ each had a large, single principal component, high internal consistency, and were highly correlated (dis‐attenuated r=0.91).

CONCLUSION

The VHI‐10 and the VPQ are similar, short, convenient, internally‐consistent, unidimensional tools.

SIGNIFICANCE

The total VHI‐10 or VPQ score is a good overall indicator of the severity of voice disorders.
Revision Gore‐Tex Medialization Laryngoplasty
Authors: Cohen Jacob T. , Bates Dwight D. , Postma Gregory N.
Published: September 2004

OBJECTIVE

To evaluate the indications, results, and safety of revision Gore‐Tex medialization laryngoplasty (GML).

METHODS

A retrospective chart review of 156 patients that underwent GML procedures between the years 1998–2002. Study population consisted of those patients who required revision surgery for any reason.

RESULTS

Sixteen patients required 22 revision procedures. Indications for revision were divided into 2 groups, complications and glottal closure problems. Complications included extruded or displaced implants (n = 4). The most common glottal closure problem was undercorrection (n = 9). Others included anterior overcorrection (n = 1) and persistent posterior glottal gap (n = 2). Revision procedures included GML (n = 9), injection augmentation (n = 9), endoscopic implant removal (n = 2), and arytenoid adduction (n = 2). In patients with glottal closure problems, the GCI improved in all 10 and the voice rating scale improved in 9.

CONCLUSION

Reasons for revision of GML are variable, the most common being undercorrection. A variety of safe, effective revision techniques are available with a high success rate.
Evaluation of Patients' Preferences for Triamcinolone Acetonide Aqueous, Fluticasone Propionate, and Mometasone Furoate Nasal Sprays in Patients with Allergic Rhinitis
Authors: Stokes Michael , Amorosi Stacey L. , Thompson David , Dupclay Leon , Garcia Jorge , Georges George
Published: September 2004

OBJECTIVE

To compare product attributes, preferences, and expected compliance associated with triamcinolone acetonide aqueous (TAA‐AQ), fluticasone propionate (FP), and mometasone furoate (MF) nasal sprays in patients with allergic rhinitis.

STUDY DESIGN AND SETTING

Data from 2 randomized, double‐blind crossover studies with identical design were pooled (N = 215). Patients completed a 14‐item sensory attributes questionnaire immediately after each product, and stated their preference and expected compliance with a prescription after receiving all products.

RESULTS

Compared with FP and MF, TAA‐AQ was associated with significantly less odor and greater liking of odor (P < 0.001); and less taste, less dryness of nose/throat, less aftertaste, and greater overall liking (P < 0.05). Significantly more patients preferred most a prescription of TAA‐AQ (50.0%) versus FP (25.0%; P < 0.001) and MF (25.0%; P < 0.001), and would “definitely comply” with TAA‐AQ (62.5%) versus FP (49.0%; P < 0.01) and MF (51.0%; P < 0.01).

CONCLUSION

TAA‐AQ was associated with significantly more positive sensory attributes, higher preference, and better expected compliance than FP and MF.

SIGNIFICANCE

Patients' preferences for the sensory attributes of an intranasal corticosteroid may affect adherence to treatment.
Efficacy and Safety of Oral Telithromycin Once Daily for 5 Days Versus Moxifloxacin Once Daily for 10 Days in the Treatment of Acute Bacterial Rhinosinusitis
Authors: Ferguson Berrylin J. , Guzzetta Richard V. , Spector Sheldon L. , Hadley James A.
Published: September 2004

OBJECTIVE

To compare the clinical and bacteriologic efficacy and safety of short‐duration treatment with telithromycin given for 5 days with moxifloxacin given for 10 days in adults with acute bacterial rhinosinusitis (ABRS).

STUDY DESIGN

In this prospective, double‐blind, parallel‐group, randomized, multicenter study, adult patients (N = 349) with ABRS were randomized to oral telithromycin (800 mg once daily for 5 days) or to oral moxifloxacin (400 mg once daily for 10 days) and followed for 31 to 36 days. Clinical outcome was determined by the investigator at the posttherapy/test of cure (TOC) visit. Bacteriologic outcome was determined by comparing cultures taken at the pretreatment visit with cultures obtained at the posttherapy/TOC visit. The primary objective was to demonstrate equivalence of clinical cure rates in the per‐protocol population between treatment groups at the posttherapy/TOC visit.

RESULTS

Clinical success at TOC (primary endpoint) was achieved in 87.4% of patients in the telithromycin group compared with 86.9% for moxifloxacin (per‐protocol patients; 0.5% difference between treatment groups; 95% confidence interval (CI), −8.1, 9.2;P= 0.8930). The bacteriologic success rates were 94.1% and 93.9%, respectively (0.2% difference between treatment groups; 95% CI, −14.2, 14.5;P= 0.9734). Overall treatment‐emergent adverse events for both drugs (mostly gastrointestinal) were mild to moderate in intensity.

CONCLUSION AND SIGNIFICANCE

The clinical and bacteriologic efficacy of telithromycin 800 mg once daily for 5 days was equivalent to that of moxifloxacin 400 mg once daily for 10 days, establishing telithromycin as an important treatment option for ABRS.
Evaluating global ocean carbon models: The importance of realistic physics
Authors: Doney S. C. , Lindsay K. , Caldeira K. , Campin J.‐M. , Drange H. , Dutay J.‐C. , Follows M. , Gao Y. , Gnanadesikan A. , Gruber N. , Ishida A. , Joos F. , Madec G. , Maier‐Reimer E. , Marshall J. C. , Matear R. J. , Monfray P. , Mouchet A. , Najjar R. , Orr J. C. , Plattner G.‐K. , Sarmiento J. , Schlitzer R. , Slater R. , Totterdell I. J. , Weirig M.‐F. , Yamanaka Y. , Yool A.
Published: September 2004

A suite of standard ocean hydrographic and circulation metrics are applied to the equilibrium physical solutions from 13 global carbon models participating in phase 2 of the Ocean Carbon‐cycle Model Intercomparison Project (OCMIP‐2). Model‐data comparisons are presented for sea surface temperature and salinity, seasonal mixed layer depth, meridional heat and freshwater transport, 3‐D hydrographic fields, and meridional overturning. Considerable variation exists among the OCMIP‐2 simulations, with some of the solutions falling noticeably outside available observational constraints. For some cases, model‐model and model‐data differences can be related to variations in surface forcing, subgrid‐scale parameterizations, and model architecture. These errors in the physical metrics point to significant problems in the underlying model representations of ocean transport and dynamics, problems that directly affect the OCMIP predicted ocean tracer and carbon cycle variables (e.g., air‐sea CO2 flux, chlorofluorocarbon and anthropogenic CO2 uptake, and export production). A substantial fraction of the large model‐model ranges in OCMIP‐2 biogeochemical fields (±25–40%) represents the propagation of known errors in model physics. Therefore the model‐model spread likely overstates the uncertainty in our current understanding of the ocean carbon system, particularly for transport‐dominated fields such as the historical uptake of anthropogenic CO2. A full error assessment, however, would need to account for additional sources of uncertainty such as more complex biological‐chemical‐physical interactions, biases arising from poorly resolved or neglected physical processes, and climate change.
A statistical study of the geoeffectiveness of magnetic clouds during high solar activity years
Authors: Zhang Jichun , Liemohn Michael W. , Kozyra Janet U. , Lynch Benjamin J. , Zurbuchen Thomas H.
Published: September 2004

Using the Dst value corrected for the effects of magnetopause currents (Dst*) and solar wind magnetic field and plasma data from 1 January 1998 to 30 April 2002, during elevated solar conditions, we have statistically examined the relationship of 271 storms (Dst* ≤ −30 nT) to 104 magnetic clouds. It is found that most of the magnetic clouds result in geomagnetic storms, but only about 30% of storms are due to magnetic clouds. A storm can be driven by a cloud's various regions or their combinations with dissimilar occurrence percentages. These percentages change as a function of geomagnetic activity levels as well. It is found that the leading field is the most geoeffective region and the sheath region is equally effective at causing magnetic storms during solar maximum (42%) compared to solar minimum (43%) as a percentage of magnetic cloud‐induced storms. The occurrence percentage of intense storms caused by clouds is 72%, which is much higher than the ∼20% occurrence percentage of smaller storms caused by clouds. It is also found that “unipolar Bz” and “bipolar Bz” clouds have different geoeffectiveness percentages, depending on the Bz orientation. The long‐known control of magnetic activity mainly by southward Bz is supported by the results of this study. It is also shown that multistep development storms can result not only from both the combinations of sheath and cloud fields but also from different fields within a cloud. A new name, quasi‐cloud, is proposed for those cloud‐like solar wind structures which show evidence of relatively organized field rotations.
The extracellular matrix geneFrem1is essential for the normal adhesion of the embryonic epidermis
Authors: Smyth Ian , Du Xin , Taylor Martin S. , Justice Monica J. , Beutler Bruce , Jackson Ian J.
Published: September 2004

Fraser syndrome is a rare recessive disorder characterized by cryptophthalmos, syndactyly, renal defects, and a range of other developmental abnormalities. Because of their extensive phenotypic overlap, the mouse blebbing mutants have been considered models of this disorder, and the recent isolation of mutations inFras1in both theblebbedmouse and human Fraser patients confirms this hypothesis. Here we report the identification of mutations in an extracellular matrix geneFras1-related extracellular matrix gene 1(Frem1) in both the classichead blebsmutant and in anN-ethyl-N-nitrosourea-induced allele. We show that inactivation of the gene results in the formation ofin uteroepidermal blisters beneath the lamina densa of the basement membrane and also in renal agenesis.Frem1is expressed widely in the developing embryo in regions of epithelial/mesenchymal interaction and epidermal remodeling. Furthermore,Frem1appears to act as a dermal mediator of basement membrane adhesion, apparently independently of the other known “blebs” proteins Fras1 and Grip1. Unlike bothFras1andGrip1mutants, collagen VI and Fras1 deposition in the basement membrane is normal, indicating that the protein plays an independent role in epidermal differentiation and is required for epidermal adhesion during embryonic development.
Leber congenital amaurosis linked to AIPL1: A mouse model reveals destabilization of cGMP phosphodiesterase
Authors: Ramamurthy Visvanathan , Niemi Gregory A. , Reh Thomas A. , Hurley James B.
Published: September 2004

Leber congenital amaurosis (LCA4) has been linked to mutations in the photoreceptor-specific gene Aryl hydrocarbon interacting protein like 1 (
Aipl1
). To investigate the essential role of AIPL1 in retina, we generated a mouse model of LCA by inactivating the
Aipl1
gene. In
Aipl1
–/–
retinas, the outer nuclear layer develops normally, but rods and cones then quickly degenerate.
Aipl1
–/–
mice have highly disorganized, short, fragmented photoreceptor outer segments and lack both rod and cone electroretinogram responses. Recent biochemical evidence indicates that AIPL1 can enhance protein farnesylation. Our study reveals that rod cGMP phosphodiesterase, a farnesylated protein, is absent and cGMP levels are elevated in AIPL1
–/–
retinas before the onset of degeneration. Our findings demonstrate that AIPL1 enhances the stability of phosphodiesterase and is essential for photoreceptor viability.
Electrical detection of single viruses
Authors: Patolsky Fernando , Zheng Gengfeng , Hayden Oliver , Lakadamyali Melike , Zhuang Xiaowei , Lieber Charles M.
Published: September 2004

We report direct, real-time electrical detection of single virus particles with high selectivity by using nanowire field effect transistors. Measurements made with nanowire arrays modified with antibodies for influenza A showed discrete conductance changes characteristic of binding and unbinding in the presence of influenza A but not paramyxovirus or adenovirus. Simultaneous electrical and optical measurements using fluorescently labeled influenza A were used to demonstrate conclusively that the conductance changes correspond to binding/unbinding of single viruses at the surface of nanowire devices. pH-dependent studies further show that the detection mechanism is caused by a field effect, and that the nanowire devices can be used to determine rapidly isoelectric points and variations in receptor-virus binding kinetics for different conditions. Lastly, studies of nanowire devices modified with antibodies specific for either influenza or adenovirus show that multiple viruses can be selectively detected in parallel. The possibility of large-scale integration of these nanowire devices suggests potential for simultaneous detection of a large number of distinct viral threats at the single virus level.
Matrix Metalloproteinase‐2‐Mediated Inhibition of Na + ‐Dependent Ca2 + Uptake by Superoxide Radicals (O2. ‐ ) in Microsomes of Pulmonary Smooth Muscle
Authors: Mandal Amritlal , Chakraborti Tapati , Das Sudip , Ghosh Biswarup , Ghosh Amarnath , Chakraborti Sajal
Published: September 2004

Treatment of microsomes (preferably enriched with endoplasmic reticulum) isolated from bovine pulmonary artery smooth muscle tissue with the O2. ‐‐generating system (hypoxanthine (HPX) plus xanthine oxidase (XO)), markedly stimulated matrix metalloproteinase‐2 (MMP‐2) activity and also enhanced Ca2 + ATPase activity and ATP‐dependent Ca2 + uptake. Pretreatment with superoxide dismutase (SOD) and tissue inhibitor of metalloproteinase (TIMP‐2) (50 μg ml‐1), preserved the increase in MMP‐2 activity, Ca2 + ATPase activity and also ATP‐dependent Ca2 + uptake in the microsomes. In contrast, Na +‐dependent Ca2 + uptake in the microsomes was found to be inhibited by the O2. ‐‐generating system. Additionally, O2. ‐ ‐induced inhibition of Na + ‐dependent Ca2 + uptake was reversed by SOD and TIMP‐2 (50 μg ml‐1). Electron microscopy revealed that treatment with the O2. ‐‐generating system did not cause any noticeable damage to the microsomes. O2. ‐ ‐induced changes in MMP‐2 activity, ATP‐dependent Ca2 + uptake and Na +‐dependent Ca2 + uptake, were not reversed upon pretreatment of the microsomes with a low dose (5 μg ml‐1) of TIMP‐2 which, on the contrary, reversed MMP‐2 (1 μg ml‐1)‐mediated alteration on these parameters. The inhibition of Na +‐dependent Ca2 + uptake by O2. ‐ and MMP‐2, overpowered the stimulation of ATP‐dependent Ca2 + uptake in the microsomes. Treatment of TIMP‐2 (5 μg ml‐1) with the O2. ‐‐generating system abolished the inhibitory effect of TIMP‐2 (5 μg ml‐1) on MMP‐2 (1 μg ml‐1) (measured by 14C‐gelatin degradation). Overall, the present study suggests that O2. ‐ inactivated TIMP‐2, the ambient inhibitor of MMP‐2, leading to activation of the ambient proteinase, MMP‐2, which subsequently stimulated Ca2 + ATPase activity and ATP‐dependent Ca2 + uptake, but inhibited Na +‐dependent Ca2 + uptake, resulting in a marked decrease in Ca2 + uptake in the smooth muscle microsomes.
IUBMB Life, 56: 267‐276, 2004
Dietary Alpha‐Tocopherol Affects Differential Gene Expression in Rat Testes
Authors: Rota Cristina , Barella Luca , Minihane Anne‐Marie , Stöcklin Elisabeth , Rimbach Gerald
Published: September 2004

Gene‐chip technology was employed to study the effect of dietary vitamin E (VE) on gene expression in rat testes. Male albino rats were fed with either a diet deficient in VE or a standard diet containing VE. Differential gene expression was monitored at five individual time‐points over a period of 14 months with all animals individually profiled. Low VE intake resulted in the consistent up‐regulation of 7‐dehydrocholesterol reductase and GATA binding protein 4, both involved in testosterone synthesis. Cyclin D3, important in cell cycle progression and Wilms tumor 1, related to cancer development, were also up‐regulated in the vitamin E deficient animals. This study demonstrates that low dietary VE intake has long‐term effects on gene expression in the testes. Our data provides insights into the possible molecular mechanisms underlying the beneficial effects of vitamin E on the male reproductive organ.
IUBMB Life, 56: 277‐280, 2004
Protective effect of TAT‐delivered α‐synuclein: relevance of the C‐terminal domain and involvement of HSP70
Authors: Albani Diego , Peverelli Erika , Rametta Raffaela , Batelli Sara , Veschini Lorenzo , Negro Alessandro , Forloni Gianluigi
Published: September 2004

α‐Synuclein (α‐syn) is a 140‐amino acid presinaptic protein whose mutations A30P and A53T have been linked to familiar Parkinson’s disease (PD). Many data suggest that α‐syn aggregation is the key event that triggers α‐syn‐mediated neurotoxicity. Nevertheless, other lines of evidence proposed a protective role of α‐syn against oxidative stress (a major feature of PD), even if the exact mechanism of this protective action and the role of the pathogenetic mutations to this respect have not been elucidated yet. To address these points, we developed an in vitro model of oxidative stress by exposing PC12 cells to hydrogen peroxide (H2O2) (150 µM) for 72 h, and we evaluated α‐syn‐mediated protection delivering increasing amounts of α‐syn (wild type [WT] or mutated) inside cells using the fusion proteins TAT‐α‐syn (WT, A30P, and A53T). We found that nanomolar amounts of TAT‐α‐syn‐mediated protected against oxidative stress and other cellular injuries (6‐hydroxydopamine and serum deprivation), whereas micromolar amounts of the fusion proteins were intrinsically toxic to cells. The protective effect was independent from the presence of the mutations A30P and A53T, but no protection occurred when cells were challenged with the proteasome inhibitors lactacystin and MG132. We verified that the protection mechanism required the presence of the C‐terminal domain of α‐syn, as nanomolar amounts of the C‐terminal truncated fusion protein TAT‐α‐syn (WT[1‐97]) failed in preventing H2O2 toxicity. To further characterize the molecular mechanisms at the basis of α‐syn protection, we investigated the possible involvement of the chaperone protein HSP70 that is widely implicated in neuroprotection. We found that, at nanomolar concentrations, TAT‐α‐syn was able to increase HSP70 protein level, whereas at the micromolar scale, TAT‐α‐syn decreased HSP70 at the protein level. These effects on HSP70 were independent from the presence of α‐syn pathogenetic mutations but required the α‐syn C‐terminal domain. The implications for α‐syn‐mediated neurotoxicity and for PD pathogenesis and progression are discussed.
INGAP peptide improves nerve function and enhances regeneration in streptozotocin‐induced diabetic C57BL/6 mice
Authors: Tam Joseph , Rosenberg Lawrence , Maysinger Dusica
Published: September 2004

INGAP peptide comprises the core active sequence of Islet Neogenesis Associated Protein (INGAP), a pancreatic cytokine that can induce new islet formation and restore euglycemia in diabetic rodents. The ability of INGAP peptide in vitro to enhance nerve growth from sensory ganglia suggests its potential utility in peripheral nerve disorders. In this study, INGAP peptide was administered alone or in combination with insulin to streptozotocin‐induced diabetic mice exhibiting signs of peripheral neuropathy. Following a 2‐wk treatment period, thermal hypoalgesia in diabetic mice was significantly improved in groups that received INGAP peptide, without development of hyperalgesia. Explanted dorsal root ganglia (DRG) from these groups showed enhanced nerve outgrowth and evidence of increased mitochondrial activity. Western blotting experiments revealed attenuation of neurofilament hyperphosphorylation, up‐regulation of β‐tubulin and actin, and increased phosphorylation of the transcription factor STAT3 in DRG. These findings suggest that INGAP peptide can activate some of the signaling pathways implicated in nerve regeneration in sensory ganglia, thereby providing a means of improvement of nociceptive dysfunction in the peripheral nervous system.
CpG motifs in bacterial DNA delay apoptosis of neutrophil granulocytes
Authors: József Levente , Khreiss Tarek , Filep János G.
Published: September 2004

Human neutrophil granulocytes die rapidly, and their survival is contingent upon rescue from programmed cell death by signals from the environment. We now show that a novel signal for delaying neutrophil apoptosis is unmethylated CpG motifs prevalent in bacterial DNA (CpG‐DNA). Human neutrophils express toll‐like receptor 9 that recognizes these motifs. CpG‐DNA, but not mammalian DNA or methylated bacterial DNA, markedly enhanced neutrophil viability by delaying spontaneous apoptosis. Endosomal maturation of CpG‐DNA is prerequisite for these actions and was coupled to concurrent activation of the extracellular signal‐regulated kinase (ERK) and phosphatidylinositol 3‐kinase/Akt signaling pathways, leading to phosphorylation of BAD at Ser112 and Ser136, respectively, and to prevention of decreases in mitochondrial transmembrane potential, cytochrome c release and caspase‐3 activation. Consistently, pharmacological inhibition of either ERK or phosphatidylinositol 3‐kinase partially reversed these actions of CpG‐DNA; however, they did not produce additive inhibition. Furthermore, intravenous injection of CpG‐DNA (200 μg/kg) into rats evoked slight decreases in blood pressure and induced a modest leukocytosis, whereas it effectively suppressed neutrophil apoptosis as assayed ex vivo. Our results indicate that unmethylated CpG motifs in bacterial DNA promote neutrophil survival by suppressing the apoptotic machinery and may therefore contribute to prolongation and amplification of inflammation.
Double Aneurysms at Distal Basilar Artery: Report of Nine Cases
Authors: Tanaka Yuichiro , Hongo Kazuhiro , Nagashima Hisashi , Tada Tsuyoshi , Kobayashi Shigeaki
Published: September 2004

OBJECTIVE

Double aneurysms at the basilar bifurcation and the basilar artery-superior cerebellar artery (BA-SCA) junction have not been well investigated previously. We analyzed nine patients with double basilar aneurysms to evaluate their radiological characteristics and suitable treatment.

METHODS

Between 1978 and 1999, the incidence of double aneurysms was 5.3% in our 169 consecutive surgical cases of distal BA aneurysms. Seven (77.8%) of the nine patients with double aneurysms had associated aneurysms in the anterior circulation. Open surgery was performed in eight patients and coil embolization in one. The patients' radiological findings, choice of treatment, and surgical results were analyzed retrospectively.

RESULTS

The size of the basilar bifurcation aneurysms ranged from 2 to 8 mm (mean, 4.4 ± 2.0 mm), and the size of the BA-SCA aneurysms ranged from 2 to 12 mm (mean, 5.6 ± 3.6 mm). Diagnosis of double basilar aneurysms was difficult when the basilar trunk had twisted or when size differences between the two aneurysms were apparent. The angle between the posterior cerebral artery and SCA appeared to be wider on the same side as the BA-SCA aneurysms (101 ± 42 degrees) than on the opposite side (26 ± 24 degrees). The P1 segment of the posterior cerebral artery originated in an upright direction from the basilar bifurcation between the two basilar aneurysms in seven patients. The pterional approach was used in eight patients; 14 basilar aneurysms were successfully clipped and 2 were wrapped. Nonstraight clips with short blades were used frequently. Coil embolization of double aneurysms was required twice in one patient because the initial angiogram was misinterpreted as a single aneurysm and its bleb.

CONCLUSION

Measurement of the posterior cerebral artery-SCA angle is a simple method to estimate the presence of BA-SCA aneurysms and to differentiate double aneurysms from a bilocular aneurysm at the basilar bifurcation. The pterional approach is suitable for clipping double basilar aneurysms because anterior circulation aneurysms often coexist, and the upstanding P1 segment is an obstacle in the subtemporal approach to the basilar bifurcation aneurysm. Nonstraight clips with short blades are convenient to avoid conflicting clips in the narrow surgical space.
Catastrophic Football Injuries: 1977–1998
Authors: Cantu Robert C. , Mueller Frederick O.
Published: September 2004

THE PRIMARY PURPOSE of this study was to investigate the occurrence of catastrophic football head and spine injuries, in an attempt to reduce their frequency. We analyzed epidemiological and medical data from 1977 through 1998. Catastrophic football injuries are defined as football injuries that result in death, brain or spinal cord injury, or cranial or spinal fracture. All studied cord injuries involved the cervical region. During the period covered by this study, 118 athletes died as a direct result of participation in the skills of football, 200 football players received a permanent cervical cord injury, and 66 sustained a permanent cerebral injury. Most cervical injuries occurred to defensive players during the act of tackling. The axial loading mechanism of spinal cord injury was identified in 27% of tackling injuries. To further reduce catastrophic injuries, players must stop tackling with the head down and using the head as a battering ram; instead, players should use the shoulder for blocking and tackling. Other recommendations for reducing catastrophic injuries are presented.
Sinonasal Undifferentiated Carcinoma: Case Series and Review of the Literature
Authors: Gorelick Judith , Ross Donald , Marentette Lawrence , Blaivas Mila
Published: September 2004

OBJECTIVE AND IMPORTANCE

We report on four cases of sinonasal undifferentiated carcinoma (SNUC), a relatively newly described clinicopathological entity of the nasal cavity and paranasal sinuses. SNUC tends to present with advanced-stage disease, often with intracranial invasion, and requires an aggressive treatment approach that includes surgical resection. A review of the literature identified several reports of SNUC in pathology and otolaryngology journals since its initial description in 1986, but no report has yet appeared in the neurosurgery literature.

CLINICAL PRESENTATION

Four patients presented with various symptoms related to the nose and/or orbit, including one or more of the following: obstruction, epistaxis, decreased visual acuity, diplopia, and pain. All patients were noted to have masses in the nasal cavity or paranasal sinuses, with or without intracranial extension.

INTERVENTION

All four patients underwent multimodal treatment with chemotherapy, radiotherapy (60–65 Gy), and aggressive surgical resection via a combined bifrontal craniotomy and a subcranial approach to the anterior cranial fossa. Three of four patients died as a result of their disease, an average of 15 months after diagnosis. Only one patient remains alive, although with metastatic intracranial disease, at 24 months after diagnosis.

CONCLUSION

SNUC is a rare neoplasm with a poor prognosis despite an aggressive multimodal approach to treatment. On the basis of our experience, we advocate radical resection as part of the initial combined therapy for patients who present with locally advanced, nonmetastatic disease but we suggest reserving surgery for patients with early brain invasion until there has been a radiographically proven central nervous system response to adjuvant therapy.
Hydrocephalus in Coccidioidal Meningitis: Case Report and Review of the Literature
Authors: Romeo June H. , Rice Louis B. , McQuarrie Irvine G.
Published: September 2004

OBJECTIVE AND IMPORTANCE

Coccidioidomycosis was once confined to the southwest United States and northern Mexico. It has become a larger concern because of the concentration of military bases in these areas, the increasing mobility of populations, and the rising population of immunocompromised persons. Outside endemic areas, the diagnosis is rarely considered. Patients with coccidioidomycosis may develop occult basilar meningitis progressing to communicating hydrocephalus and death.

CLINICAL PRESENTATION

A 60-year-old white man presented with a 1-month history of vertigo, falls, and vomiting. Computed tomography of the head revealed mild hydrocephalus. Lumbar puncture results were remarkable for 1065 mg/dl protein; acid-fast bacillus stain, Gram's stain, and culture results were negative. Postgadolinium magnetic resonance imaging demonstrated enhancement of basilar and cervical meninges, suggesting inflammation, and communicating hydrocephalus. For 48 hours, the patient's level of consciousness decreased progressively.

INTERVENTION

A ventriculoperitoneal shunt was placed, and antifungal agents were initiated on an emergent basis.

CONCLUSION

Coccidioidomycosis should be considered in the differential diagnosis of occult basilar meningitis. The diagnosis is established by the discovery of a high (>1:2) titer of complement-fixing antibody in the cerebrospinal fluid. Communicating hydrocephalus is a common complication of untreated coccidioidal meningitis, and it may develop during appropriate treatment (oral fluconazole, 200–400 mg/d, continued indefinitely). Patients with hydrocephalus and evidence of increased intracranial pressure require a shunt.
Liliequist's Membrane Is a Fold of the Arachnoid Mater: Study Using Sheet Plastination and Scanning Electron Microscopy
Authors: Zhang Ming , An Po-Chung
Published: September 2004

OBJECTIVE

The subarachnoid space consists of a number of distinct subarachnoid cisterns. They are separated from each other by trabecular walls, one of which is Liliequist's membrane. The aim of this study was to investigate the anatomic characteristics of Liliequist's membrane.

METHODS

The study used a combined approach, consisting of the modified E12 sheet plastination method for 3 adult cadavers and gross anatomic dissection for 35 cadavers, 2 of which were further examined using scanning electron microscopy.

RESULTS

The results from this study indicate that 1) Liliequist's membrane is an avascular fold of the arachnoid mater that lacks openings and spreads out laterally, being in direct continuity with the arachnoid mater covering the tentorium; 2) the carotid-chiasmatic walls, which separate the chiasmatic cistern and carotid cisterns and had been considered to be parts of Liliequist's membrane, are vascular and incomplete trabecular walls and should not be considered parts of Liliequist's membrane; and, 3) as a fold of the arachnoid mater, Liliequist's membrane is not directly attached to the temporal lobes and oculomotor nerves.

CONCLUSION

Liliequist's membrane is a double-layer fold of the arachnoid mater and has anatomic characteristics different from those of arachnoid trabecular walls.
Near-real-time Guidance Using Intraoperative Magnetic Resonance Imaging for Radical Evacuation of Hypertensive Hematomas in the Basal Ganglia
Authors: Bernays René L. , Kollias Spyros S. , Romanowski Ben , Valavanis Anton , Yonekawa Yasuhiro
Published: September 2004

OBJECTIVE

To report our preliminary clinical experience in treating patients with hypertensive hemorrhage in the basal ganglia using a minimally invasive approach facilitated by intraoperative real-time imaging of an open magnetic resonance imaging (MRI) system and a newly designed cutting suction device.

METHODS

We developed an artifact-free device for use during intraoperative MRI consisting of a guiding base that locks into a burr hole, a side-cutting composite-based cannula connected to a standard aspirator, and a handpiece that allows aspiration strength to be regulated by the surgeon. Thirteen patients with hypertensive bleeding in the basal ganglia were included in the study. Outcome was evaluated by mortality, Glasgow Outcome Scale score, activities of daily living score, and Rankin score at 2 weeks and at a median of 4.2 months after the hemorrhage.

RESULTS

In this group of 13 patients, complete evacuation was achieved in 8 patients (62%) and subtotal evacuation of 75 to 90% of the initial volume in 4 patients (31%); the evacuation was partial in 1 patient (8%). Vascular malformations were preoperatively excluded angiographically. There was no rebleeding during surgery or postoperatively, as demonstrated by immediate postoperative MRI and computed tomography on the 1st postoperative day. Hematomas were evacuated on median Day 4 after the hemorrhage, varying between Day 1 and Day 8; evacuation was performed on Day 21 after the hemorrhage in one patient. Twelve of the 13 patients survived during a median follow-up time of 4.2 months. Neurological function improved in 11 of the 12 patients eligible for assessment. One patient with an additional head injury died 15 days after surgery from pulmonary embolism.

CONCLUSION

This study shows an excellent outcome with regard to mortality and a positive trend regarding neurological outcome for the specific group of patients with hypertensive hematomas in the basal ganglia. This minimally invasive approach is feasible in the open intraoperative MRI in combination with the cutting suction device developed in our institution. Online imaging is extremely helpful for planning, guiding, and real-time monitoring of the procedure.
Radiosurgery for Epilepsy Associated with Cavernous Malformation: Retrospective Study in 49 Patients
Authors: Régis Jean , Bartolomei Fabrice , Kida Yoshihisa , Kobayashi Tatsuya , Vladyka Vilibad , Liscàk Roman , Forster David , Kemeny Andras , Schröttner Oskar , Pendl Gerhard
Published: September 2004

OBJECTIVE

Microsurgical resection of a cavernous malformation (CM) with or without associated cortical resection can provide efficient treatment of drug-resistant associated epilepsy. To explore the potential alternative role of radiosurgery and to evaluate its safety and efficacy for this indication, we conducted a retrospective multicenter study.

METHODS

We retrospectively reviewed the files of patients with long-lasting drug-resistant epilepsy, presumably caused by CM, who were treated by gamma knife (GK) surgery for the control of their epilepsy in five centers (Marseilles, Komaki City, Prague, Graz, and Sheffield). A satisfactory follow-up was available for 49 patients (mean follow-up period, 23.66 ± 13 mo). The mean duration of epilepsy before the GK procedure was 7.5 (±9.3) years. The mean frequency of seizures was 6.9/month (±14). The mean marginal radiation dose was 19.17 Gy ± 4.4 (range, 11.25–36). Among the 49 patients, 17 (35%) had a CM located in or involving a highly functional area.

RESULTS

At the last follow-up examination, 26 patients (53%) were seizure-free (Engel's Class I), including 24 in Class IA (49%) and 2 patients with occasional auras (Class IB, 4%). A highly significant decrease in the number of seizures was achieved in 10 patients (Class IIB, 20%). The remaining 13 patients (26%) showed little or no improvement. The mediotemporal site was associated with a higher risk of failure. One patient bled during the observation period, and another experienced radiation-induced edema with transient aphasia. Postradiosurgery excision was performed in five patients, and a second radiosurgical treatment was carried out in one patient.

CONCLUSION

This series is the first to specifically evaluate the capability of GK surgery to safely and efficiently treat epilepsy associated with CM. Seizure control can be reached when a good electroclinical correlation exists between CM location and epileptogenic zone. Although we do not recommend GK surgery for prevention of bleeding for a CM that has not bled previously, our findings suggest that GK surgery can be proposed for the treatment of epilepsy when the CM is located in a highly functional area.
Neurological Grades of Patients with Poor-grade Subarachnoid Hemorrhage Improve after Short-term Pretreatment
Authors: Suzuki Michiyasu , Otawara Yasunari , Doi Mamoru , Ogasawara Kuniaki , Ogawa Akira
Published: September 2004

OBJECTIVE

Short-term pretreatment of patients with subarachnoid hemorrhage, but without hematomas causing mass effect, who presented in poor neurological condition at admission was evaluated as a protocol for the selection of candidates for radical surgery.

METHODS

One hundred-three patients were pretreated for 12 hours with control of blood pressure and intracranial pressure, using diuretic agents and/or ventricular drainage.

RESULTS

Neurological improvement was observed for 32 of 47 patients in Grade IV at admission and 23 of 56 patients in Grade V (P < 0.01). Hydrocephalus requiring drainage was more common (P < 0.05) and the interval between onset and admission was shorter (P < 0.01) for the improved group. Clipping surgery was performed for all patients in Grade III or better and for patients in Grade IV who were less than 75 years of age and without systemic complications, i.e., 38 of 47 patients in Grade IV and 16 of 56 patients in Grade V at admission. Good outcomes (defined as moderately disabled or better on the Glasgow Outcome Scale) were achieved by 34 of 38 patients in Grade IV and 10 of 16 patients in Grade V (P < 0.01). The proportion of patients in Grade IV after pretreatment was lower for Grade IV (2 of 38 patients) than for Grade V (9 of 16 patients) (P < 0.00001). However, none of the 49 patients who underwent nonsurgical treatment achieved good outcomes.

CONCLUSION

Our protocol may be beneficial for the selection of candidates for radical surgery among patients with subarachnoid hemorrhage but without hematomas who are in poor neurological condition at admission and for the improvement of postoperative outcomes.
Endovascular Treatment of Distally Located Giant Aneurysms
Authors: Ross Ian B. , Weill Alain , Piotin Michel , Moret Jacques
Published: September 2004

OBJECTIVE

Because giant aneurysms (GAs) can be technically difficult to clip, the endovascular approach is becoming increasingly popular. Endovascular treatment of distally located GAs, which often requires parent vessel occlusion, is particularly challenging because limited pathways are available for collateral flow. We aimed to determine the outcomes of endovascular attempts to treat GAs downstream from the circle of Willis.

METHODS

Between 1991 and 1998, 27 patients with 27 distally located very large aneurysms or GAs were evaluated for possible endovascular treatment. Ten underwent selective embolization and 9 were treated with primary parent vessel occlusion, with or without distal bypass. Eight patients could not be treated endovascularly.

RESULTS

Selective embolization resulted in only one cure. Two patients died as a result of subarachnoid hemorrhage during the follow-up period. One coil-treated patient, who underwent subsequent spontaneous parent vessel occlusion, and all nine patients treated primarily with parent vessel occlusion were considered cured after their treatments. Only two patients treated with parent vessel occlusion experienced periprocedural ischemia, which did not result in a major deficit in either case. Of the eight patients who could not be treated endovascularly, one succumbed to surgery, four died while being treated conservatively, and three were lost to follow-up monitoring.

CONCLUSION

Selective aneurysm embolization is usually not curative in these situations. For selected patients, however, endovascular parent vessel occlusion is usually safe and effective in preventing the progression of symptoms and bleeding.
Intraoperative Electrophysiological Monitoring of Oculomotor Nuclei and Their Intramedullary Tracts during Midbrain Tumor Surgery
Authors: Sekiya Tetsuji , Hatayama Toru , Shimamura Norihito , Suzuki Shigeharu
Published: September 2004

OBJECTIVE

During surgery for intrinsic midbrain lesions, we intraoperatively recorded evoked compound muscle action potentials (ECMAPs) from the extraocular muscles and evaluated how this type of intraoperative electrophysiological monitoring could minimize postoperative oculomotor nerve palsy (ptosis and/or diplopia).

METHODS

The ECMAPs were recorded through a spring electrode applied to the extraocular muscle (Method 1, seven cases) or a needle electrode inserted into the superior intraorbital space (Method 2, five cases). The surgeon repeated electrical stimulations whenever tissue of unknown origin was encountered intraoperatively, and this information was used to safely guide surgical resection of the tumors.

RESULTS

Using these monitoring techniques, the response-free areas were resected and the areas from which ECMAP responses were recorded were avoided. For all 12 patients, ECMAPs were successfully recorded from the extraocular muscles. Ten patients did not exhibit any postoperative deterioration of oculomotor nerve function. Two patients exhibited deterioration of oculomotor nerve function immediately after surgery, which resolved within 1 month. Equally robust ECMAPs could be recorded with Method 2, compared with Method 1.

CONCLUSION

Intraoperative ECMAP recordings from the extraocular muscles precisely indicated the locations of the oculomotor nuclei and/or intramedullary oculomotor tracts. Although Method 2 is a more indirect method for recording ECMAPs than is Method 1, Method 2 was equally useful in recording ECMAPs, which seemed to be the summed potentials from the superior rectus muscle and the levator palpebrae superioris muscle. These monitoring techniques are valuable in guiding surgeons to avoid causing inadvertent harm to the oculomotor nuclei and tracts during midbrain surgery, particularly when the neuroanatomic features are distorted by the presence of tumor.