bluuebunny/crossref_metadata_2025 huggingface dataset:
Lassa virus: Seroepidemiological survey of rodents caught in Ekpoma and environs
Authors: Okoror L E , Esumeh F I , Agbonlahor D E , Umolu P I
Published: February 2005

Of the 876 rodents caught in different parts of Ekpoma, Nigeria, and environs, 218 were Mastomys natalensis, while 658 were other rodents. Of the 218 M. natalensis caught, 102 (46.79%) were positive for complement fixing antibody to Lassa virus.
Clinicopathological study of head and neck cancers in Ilorin, Nigeria
Authors: Ologe F E , Adeniji K A , Segun-Busari S
Published: February 2005

Eighty-nine cases of head and neck cancers were studied over a 5-year period (1997–2001) at the University of Ilorin Teaching Hospital, Nigeria. The most common cancer affecting the head and neck region was carcinoma which constituted 70.8% of all the cases studied. It was followed by the lymphomas and blastomas which accounted for 20.2% and 9%, respectively. The nose/paranasal sinuses were the most common site of primary cancer (18%) followed by thyroid (12.4%), nasopharynx (11.3%) and larynx (4.5%). Other sites include a hypopharynx (3.4%), eye (2.2%), palate (2.2%), tongue (2.2%), skin (1.1%), lip (1.1%), salivary gland (1.1%), oropharynx (1.1%). Cervical lymph node metastasis with unknown primary lesion was seen in 10.1%. The peak age incidence was in the fifth decade of life. The improvement in locoregional control of head and neck cancers over the last decades does not appear to modify the final survival of these patients. It is crucial to understand as accurately as possible the risk factors for these malignancies in order to improve primary prevention.
Feasibility study of serial lumbar puncture and acetazolamide combination in the management of elevated cerebrospinal fluid pressure in AIDS patients with cryptococcal meningitis in Uganda
Authors: Orem J , Tindyebwa L , Twinoweitu O , Mukasa B , Tomberland M , Mbidde E K
Published: February 2005

A feasibility study of serial lumbar puncture and acetazolamide combination in managing raised cerebrospinal fluid pressure was undertaken in 18 patients with AIDS and cryptococcal meningitis in Uganda. There were no adverse events related to the intervention and improvement in minimental status score, performance score, symptoms and a reduction in intracranial opening pressure were observed. This method is therefore feasible in AIDS-associated cryptococcal meningitis in a resource-poor setting given the observed safety and possible effectiveness, a larger study is warranted.
Isolated splenic tuberculosis
Authors: Singh B , Ramdial P K , Royeppen E , Moodley J , Chetty R
Published: February 2005

Tuberculosis isolated to the spleen is a rare clinical entity particularly in the non-HIV-positive patient population. In the four patients described, two presented with thrombocytopenia; in two patients the condition was diagnosed serendipitously at laparotomy undertaken for abdominal trauma.
Valsartan in Chronic Heart Failure
Authors: Ripley Toni L
Published: February 2005

OBJECTIVE:

To evaluate the evidence for valsartan in the treatment of heart failure and determine its need for formulary inclusion.

DATA SOURCES:

OVID and PubMed databases were searched (1983–June 2004) using the key words angiotensin-receptor blocker, heart failure, valsartan, Diovan, and angiotensin-converting enzyme inhibitor. Only English-language literature was selected.

STUDY SELECTION AND DATA EXTRACTION:

Pharmacology and pharmacokinetic evaluations for valsartan were selected. Prospective, randomized clinical trials investigating the use of valsartan and other angiotensin-receptor blockers (ARBs) in chronic heart failure were evaluated.

DATA SYNTHESIS:

Valsartan, a selective antagonist for angiotensin receptor subtype 1, is the first ARB to be approved for use in chronic heart failure. Clinical trial data support valsartan as an alternative to angiotensin-converting enzyme (ACE) inhibitors in ACE inhibitor—intolerant patients with chronic heart failure. Valsartan is generally well tolerated, with renal impairment, elevated serum creatinine and potassium levels, and dizziness being the most common adverse effects; consequently, patients experiencing those adverse events while taking ACE inhibitors are likely to experience them with valsartan. Although further study is needed, differences in effectiveness among races may exist with use of valsartan; however, at this time, valsartan is recommended as an alternative to ACE inhibitors regardless of race. Candesartan and losartan have been studied in similar settings. Candesartan's data support its use in heart failure; however, losartan's data have been less consistent.

CONCLUSIONS:

Valsartan is a safe and effective alternative for heart failure patients intolerant of ACE inhibitors. Valsartan has not been shown to be safe and effective when used in combination with ACE inhibitors.
Potential Drug—Disease Interactions in Frail, Hospitalized Elderly Veterans
Authors: Lindblad Catherine I , Artz Margaret B , Pieper Carl F , Sloane Richard J , Hajjar Emily R , Ruby Christine M , Schmader Kenneth E , Hanlon Joseph T
Published: February 2005

BACKGROUND:

Drugs can improve quality of life for many older people, but they may cause adverse health outcomes (eg, drug—disease interactions) if used inappropriately.

OBJECTIVE:

To determine the prevalence of potential drug—disease interactions as defined by explicit criteria and examine associations between sociodemographic and health status variables and potential drug—disease interactions.

METHODS:

The study design was cross-sectional. We evaluated 397 frail elderly inpatients from the Geriatric Evaluation and Management trial conducted at 11 Veterans Affairs Medical Centers. Drug—disease interactions were defined using explicit criteria from consensus expert panels of geriatricians from the US and Canada.

RESULTS:

Overall, 159 (40.1%) patients had one or more potential drug—disease interaction. The most common potential interactions were calcium-channel blockers and heart failure (12.3%) and β-blockers and diabetes (6.8%). Multivariable logistic regression analyses revealed that age ⩾75 years (adjusted OR 2.43; 95% CI 1.52 to 3.88), being married (adjusted OR 1.77; 95% CI 1.11 to 2.82), comorbidity index defined by Charlson method (adjusted OR 1.19; 95% CI 1.05 to 1.34), and use of multiple prescription drugs (5–8: adjusted OR 4.17; 95% CI 1.96 to 8.88, ⩾9: adjusted OR 9.22; 95% CI 4.26 to 19.95), were significantly (p < 0.05) associated with having one or more potential drug—disease interaction.

CONCLUSIONS:

Potential drug—disease interactions are common in hospitalized elderly patients and are related to specific sociodemographic and health status factors. Further research is needed to examine the relationship between health outcomes and drug—disease interactions.
QTc Prolongation Associated with Combination Therapy of Levofloxacin, Imipramine, and Fluoxetine
Authors: Nykamp Diane L , Blackmon Casey L , Schmidt Paul E , Roberson Andrea G
Published: February 2005

OBJECTIVE:

To report QTc interval prolongation associated with combination therapy including levofloxacin, imipramine, and fluoxetine.

CASE SUMMARY:

A 49-year-old white female presented to the emergency department with fever, aches, and pains for the past 3 days. She was diagnosed and treated for pyelonephritis in the hospital. Therapy included intravenous levofloxacin 500 mg every 24 hours and ceftriaxone 2 g every 24 hours, along with her medications upon admission, including imipramine 50 mg at bedtime and fluoxetine 10 mg/day. She was discharged after 5 days and returned the next day with chest tightness and shortness of breath. Upon the second admission, a 12-lead electrocardiogram showed a QTc interval of 509 msec. Levofloxacin was discontinued and the QTc interval fell to 403 msec. The patient was discharged 3 days later and instructed to consult with her primary care physician about discontinuing imipramine.

DISCUSSION:

This adverse drug reaction is thought to be a pharmacodynamic additive effect among fluoxetine, imipramine, and levofloxacin. Fluoxetine is a potent inhibitor of CYP2D6, and imipramine is metabolized by CYP2D6. Therefore, fluoxetine is able to increase the plasma concentrations of imipramine, leading to QT interval prolongation. Taken with imipramine, levofloxacin can lead to even greater prolongation of the QT interval. Based on the Naranjo probability scale, levofloxacin was possibly associated with cardiac arrhythmias in our patient.

CONCLUSIONS:

The use of levofloxacin alone, or more often in concomitant therapy with other medications that are known to prolong the QT interval, may cause QT interval prolongation; however, additional studies/case reports are needed to validate this conclusion.
Nicotine-Induced Antinociception, Rewarding Effects, and Physical Dependence Are Decreased in Mice Lacking the Preproenkephalin Gene
Authors: Berrendero Fernando , Mendizábal Victoria , Robledo Patricia , Galeote Lola , Bilkei-Gorzo Andras , Zimmer Andreas , Maldonado Rafael
Published: February 2005

It has been shown previously that the endogenous opioid system may be involved in the behavioral effects of nicotine. In the present study, the participation of endogenous enkephalins on nicotine responses has been investigated by using preproenkephalin knock-out mice. Acute nicotine-induced hypolocomotion remained unaffected in these mice. In contrast, antinociception elicited in the tail-immersion and hot-plate tests by acute nicotine administration was reduced in mutant animals. The rewarding properties of nicotine were then investigated using the place-conditioning paradigm. Nicotine induced a conditioned place preference in wild-type animals, but this effect was absent in knock-out mice. Accordingly,in vivomicrodialysis studies revealed that the enhancement in dopamine extracellular levels in the nucleus accumbens induced by nicotine was also reduced in preproenkephalin-deficient mice. Finally, the somatic expression of the nicotine withdrawal syndrome precipitated in nicotine-dependent mice by mecamylamine was significantly attenuated in mutant animals. In summary, the present results indicate that endogenous opioid peptides derived from preproenkephalin are involved in the antinociceptive and rewarding properties of nicotine and participate in the expression of physical nicotine dependence.
Tau Protein Is Cross-Linked by Transglutaminase in P301L Tau Transgenic Mice
Authors: Halverson Robyn A. , Lewis Jada , Frausto Shanti , Hutton Mike , Muma Nancy A.
Published: February 2005

The microtubule-associated protein tau is highly soluble under physiological conditions. However, in tauopathies, tau protein aggregates into insoluble filaments and neurofibrillary tangles (NFTs). The mechanisms underlying the formation of tau filaments and NFTs in tauopathies remain unclear. Several lines of evidence suggest that transglutaminase may cross-link tau into stable, insoluble aggregates, leading to the formation of NFTs in Alzheimer's disease and progressive supranuclear palsy. To further determine the contribution of transglutaminase in the formation of NFTs, we compared the levels of cross-linked tau protein from P301L tau transgenic mice that develop NFTs to four-repeat wild-type (4RWT) tau transgenic and nontransgenic mice that do not develop NFT pathology. Immunoprecipitation and immunoblotting experiments show that transglutaminase cross-links phosphorylated tau in the hindbrain of P301L tau transgenic mice but not in mice overexpressing 4RWT tau and nontransgenic mice. Cross-linked, phosphorylated tau from P301L tau transgenic mice runs as high-molecular mass aggregates on Western blots, similar to cross-linked tau from paired helical filaments of Alzheimer's disease. We also used double-label immunofluorescence to demonstrate colocalization of PHF-1-immunoreactive tau and the transglutaminase-catalyzed cross-link in the hindbrain, spinal cord, and cortex of P301L tau transgenic mice. In the spinal cord, 87% of PHF-1-labeled cells colocalize with the transglutaminase-catalyzed cross-link. Additionally, transglutaminase enzymatic activity is significantly elevated in the spinal cord of P301L tau transgenic mice. These studies further implicate transglutaminase in the formation and/or stabilization of NFT and paired helical filaments and provide a model system to investigate the therapeutic potential of transglutaminase inhibitors in tauopathies.
G-Protein-Coupled Receptor Modulation of Striatal CaV1.3 L-Type Ca2+Channels Is Dependent on a Shank-Binding Domain
Authors: Olson Patricia A. , Tkatch Tatiana , Hernandez-Lopez Salvador , Ulrich Sasha , Ilijic Ema , Mugnaini Enrico , Zhang Hua , Bezprozvanny Ilya , Surmeier D. James
Published: February 2005

Voltage-gated L-type Ca2+channels are key determinants of synaptic integration and plasticity, dendritic electrogenesis, and activity-dependent gene expression in neurons. Fulfilling these functions requires appropriate channel gating, perisynaptic targeting, and linkage to intracellular signaling cascades controlled by G-protein-coupled receptors (GPCRs). Surprisingly, little is known about how these requirements are met in neurons. The studies described here shed new light on how this is accomplished. We show that D2dopaminergic and M1muscarinic receptors selectively modulate a biophysically distinctive subtype of L-type Ca2+channels (CaV1.3) in striatal medium spiny neurons. The splice variant of these channels expressed in medium spiny neurons contains cytoplasmic Src homology 3 and PDZ (postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1) domains that bind the synaptic scaffolding protein Shank. Medium spiny neurons coexpressed CaV1.3-interacting Shank isoforms that colocalized with PSD-95 and CaV1.3a channels in puncta resembling spines on which glutamatergic corticostriatal synapses are formed. The modulation of CaV1.3 channels by D2and M1receptors was disrupted by intracellular dialysis of a peptide designed to compete for the CaV1.3 PDZ domain but not with one targeting a related PDZ domain. The modulation also was disrupted by application of peptides targeting the Shank interaction with Homer. Upstate transitions in medium spiny neurons driven by activation of glutamatergic receptors were suppressed by genetic deletion of CaV1.3 channels or by activation of D2dopaminergic receptors. Together, these results suggest that Shank promotes the assembly of a signaling complex at corticostriatal synapses that enables key GPCRs to regulate L-type Ca2+channels and the integration of glutamatergic synaptic events.
Presynaptic D1Dopamine Receptors in Primate Prefrontal Cortex: Target-Specific Expression in the Glutamatergic Synapse
Authors: Paspalas Constantinos D. , Goldman-Rakic Patricia S.
Published: February 2005

Dopaminergic modulation of glutamate neurotransmission in prefrontal cortex (PFC) microcircuits is commonly perceived as a basis for cognitive operations. Yet it appears that although the control of recurrent excitation between deep-layer prefrontal pyramids may involve presynaptic and postsynaptic D1receptor (D1R) mechanisms, pyramid-to-interneuron communication will engage a postsynaptic D1R component. The substrate underlying such target-specific neuromodulatory patterns was investigated in the infragranular PFC with immunoelectron microscopy for D1R and parvalbumin, a marker for fast-spiking interneurons. In addition to their proverbial postsynaptic expression, gold-labeled D1Rs were distinctly distributed on perisynaptic/extrasynaptic membranes and the axoplasm of 13% of excitatory-like, presumably glutamatergic varicosities. Most importantly, presynaptic D1Rs were highly specific with regard to the cellular compartment and neurochemical identity of the postsynaptic neuron, being present in spine-targeting varicosities but distinctly absent from those synapsing with parvalbumin profiles often coexpressing D1Rs. We define therein an axonal D1heteroreceptor component, apparently mediating volume neurotransmission, yet strategically positioned to convey target cell-specific modulation of the glutamatergic drive. We also indicate that presynaptic D1R mechanisms may indeed be associated with recurrent excitation in prefrontal microcircuits, consistent with physiological evidence for a role of these receptors in modulating the persistent activity-profile of neurons essential for working memory.
Interaction with the Unfolded Protein Response Reveals a Role for Stargazin in Biosynthetic AMPA Receptor Transport
Authors: Vandenberghe Wim , Nicoll Roger A. , Bredt David S.
Published: February 2005

The transmembrane protein stargazin enhances levels of functional AMPA receptors at the neuronal plasma membrane and at synapses. To clarify the mechanism for this effect, we studied trafficking of the AMPA receptor subunit glutamate receptor 1 (GluR1) in transfected COS7 cells. GluR1 expressed poorly on the surface of these cells and was primarily retained in the endoplasmic reticulum (ER). Stargazin expression strongly increased the surface fraction of GluR1. This effect was not reduced by a dominant-negative dynamin mutant, suggesting that stargazin does not inhibit AMPA receptor endocytosis. Interestingly, upregulation of ER chaperones as part of the unfolded protein response (UPR) both mimicked and occluded the effect of stargazin, suggesting a role for stargazin in ER processing of AMPA receptors. Consistent with this idea, we detected UPR induction in cerebellar granule cells lacking stargazin. Finally, residual AMPA receptor currents in stargazin-deficient neurons were suppressed by inhibition of the UPR. These findings uncover a role for stargazin in AMPA receptor trafficking through the early compartments of the biosynthetic pathway. Furthermore, they provide evidence for modulation of AMPA receptor trafficking by the UPR.
GABAergic Neurons in the Central Region of the Spinal Cord: A Novel Substrate for Sympathetic Inhibition
Authors: Deuchars Susan A. , Milligan Carol J. , Stornetta Ruth L. , Deuchars Jim
Published: February 2005

Homeostatic maintenance of widespread functions is critically dependent on the activity of the sympathetic nervous system. This activity is generated by the CNS acting on the sole output cells in the spinal cord, sympathetic preganglionic neurons (SPNs). SPNs are subject to control from both supraspinal and spinal inputs that exert effects through activation of direct or indirect pathways. A high proportion of indirect control is attributable to activation of spinal interneurons in a number of locations. However, little is known about the different groups of interneurons with respect to their neurochemistry or function. In this study, we report on a novel group of GABAergic interneurons located in the spinal central autonomic area (CAA) that directly inhibit SPN activity.In situhybridization studies demonstrated a group of neurons that contained mRNA for glutamic acid decarboxylase (GAD)65and GAD67within the CAA. Combiningin situhybridization with trans-synaptic labeling from the adrenal gland using pseudorabies virus identified presympathetic GABAergic neurons in the CAA. Electrical stimulation of the CAA elicited monosynaptic IPSPs in SPNs located laterally in the intermediolateral cell column. IPSPs were GABAergic, because they reversed at the chloride reversal potential and were blocked by bicuculline. Chemical activation of neurons in the CAA hyperpolarized SPNs, an effect that was also bicuculline sensitive. We conclude that the CAA contains GABAergic interneurons that impinge directly onto SPNs to inhibit their activity and suggest that these newly identified interneurons may play an essential role in the regulation of sympathetic activity and thus homeostasis.
Application of Rho Antagonist to Neuronal Cell Bodies Promotes Neurite Growth in Compartmented Cultures and Regeneration of Retinal Ganglion Cell Axons in the Optic Nerve of Adult Rats
Authors: Bertrand Johanne , Winton Matthew J. , Rodriguez-Hernandez Nieves , Campenot Robert B. , McKerracher Lisa
Published: February 2005

Inactivation of Rho promotes neurite growth on inhibitory substrates and axon regenerationin vivo. Here, we compared axon growth when neuronal cell bodies or injured axons were treated with a cell-permeable Rho antagonist (C3-07)in vitroandin vivo. In neurons plated in compartmented cultures, application of C3-07 to either cell bodies or distal axons promoted axonal growth on myelin-associated glycoprotein substrates.In vivo, an injection of C3-07 into the eye promoted regeneration of retinal ganglion cell (RGC) axons in the optic nerve after microcrush lesion. Delayed application of C3-07 promoted RGC growth across the lesion scar. Application of C3-07 completely prevented RGC cell death for 1 week after axotomy. To investigate the mechanism by which Rho inactivation promotes RGC growth, we studied slow axonal transport. Reduction in slow transport of cytoskeletal proteins was observed after axotomy, but inactivation of Rho did not increase slow axonal transport rates. Together, our results indicate that application of a Rho antagonist at the cell body is neuroprotective and overcomes growth inhibition but does not fully prime RGCs for active growth.
Encoding of Palatability and Appetitive Behaviors by Distinct Neuronal Populations in the Nucleus Accumbens
Authors: Taha Sharif A. , Fields Howard L.
Published: February 2005

Obesity is a major public health problem. Palatability (i.e., the reinforcing value of food, derived from orosensory cues) is a significant factor in determining food intake and contributes to increased consumption leading to obesity. The nucleus accumbens is a ventral striatal region that is important for both appetitive and consummatory behaviors and has been implicated in modulating palatability. In this study, we investigated palatability encoding in the firing of nucleus accumbens neurons in rats. Nucleus accumbens neurons with significant changes in firing rate during consummatory behavior displayed one of two principal firing patterns. Firing in one class of nucleus accumbens neurons was correlated with the palatability of sucrose reinforcers; changes in neural activity in this class consisted primarily of excitations. Within this group of neurons, a subset was sensitive to the relative value of sucrose reinforcers, as assessed by a behavioral contrast paradigm. A second and distinct population of nucleus accumbens neurons, with changes in firing that were pre-dominantly inhibitions, was not sensitive to reinforcer palatability; rather, these inhibitions were present even during unreinforced bouts of licking. In addition, the onset of these inhibitions typically occurred before the initiation of the licking behavior itself. We propose that two primary classes of nucleus accumbens neurons contribute to neural processing immediately before and during reinforcer consumption: inhibitions related to initiation and maintenance of consummatory behaviors and excitations that encode reinforcer palatability.
NMDA Receptor Currents Suppress Synapse Formation on Sprouting AxonsIn Vivo
Authors: Colonnese Matthew T. , Zhao Jian-Ping , Constantine-Paton Martha
Published: February 2005

NMDA receptors (NMDARs) play an important role in the structural maintenance and functional strength of synapses. The causal relationship between these anatomical and functional roles is poorly defined. Using quantitative confocal microscopy, synaptic vesicle immunoreactivity, and differential label of retinal projections, we measured axon volume and synapse density along ipsilateral retinal axons (ipsi axons) sprouting into the superficial visual layers of the superior colliculus (sSC) deafferented by a contralateral retinal lesion (a scotoma) 8 d earlier. When retinal lesions were made at postnatal day 6 (P6), glutamatergic synaptic currents on neurons within the scotoma were significantly reduced. Both ipsi axon sprouting and synapse density were increased by chronicd-AP-5 antagonism of NMDARs. Conversely, ipsi axon sprouting and synapse density were reduced by chronic exposure to the agonist, NMDA, known to functionally depress glutamate transmission in this system. After P11 lesions, however, NMDAR blockade had no effect on sprouting or synapse density. Developmental changes in NMDAR current kinetics could not account for this difference in the structural effects of NMDAR function. Also, synaptic current frequencies within the scotoma were not affected after the P11 lesions. The corticocollicular projection matures during the P11 survival interval and, as indicated by previous work, it is a source of competition for synaptic space and probably of maintained activity in the older sSC. Thus, our results suggest that during early development, NMDAR currents predominantly destabilize nascent synapses. As the neuropil matures, however, competition for synaptic space suppresses axon sprouting and synapse formation regardless of NMDAR function.
Activity-Dependent Neuroprotection and cAMP Response Element-Binding Protein (CREB): Kinase Coupling, Stimulus Intensity, and Temporal Regulation of CREB Phosphorylation at Serine 133
Authors: Lee Boyoung , Butcher Greg Q. , Hoyt Kari R. , Impey Soren , Obrietan Karl
Published: February 2005

The dual nature of the NMDA receptor as a mediator of excitotoxic cell death and activity-dependent cell survival likely results from divergent patterns of kinase activation, transcription factor activation, and gene expression. To begin to address this divergence, we examined cellular and molecular signaling events that couple excitotoxic and nontoxic levels of NMDA receptor stimulation to activation of the cAMP response element-binding protein (CREB)/cAMP response element (CRE) pathway in cultured cortical neurons. Pulses (10 min) of NMDA receptor-mediated synaptic activity (nontoxic) triggered sustained (up to 3 h) CREB phosphorylation (pCREB) at serine 133. In contrast, brief stimulation with an excitotoxic concentration of NMDA (50 μm) triggered transient pCREB. The duration of pCREB was dependent on calcineurin activity. Excitotoxic levels of NMDA stimulated calcineurin activity, whereas synaptic activity did not. Calcineurin inhibition reduced NMDA toxicity and converted the transient increase in pCREB into a sustained increase. In accordance with these observations, sustained pCREB (up to 3 h) did not require persistent kinase pathway activity. The sequence of stimulation with excitotoxic levels of NMDA and neuroprotective synaptic activity determined which stimulus exerted control over pCREB duration. Constitutively active and dominant-negative CREB constructs were used to implicate CREB in synaptic activity-dependent neuroprotection against NMDA-induced excitotoxicity. Together these data provide a framework to begin to understand how the neuroprotective and excitotoxic effects of NMDA receptor activity function in an antagonistic manner at the level of the CREB/CRE transcriptional pathway.
A Cytosolic Residue Mediates Mg2+Block and Regulates Inward Current Amplitude of a Transient Receptor Potential Channel
Authors: Obukhov Alexander G. , Nowycky Martha C.
Published: February 2005

Members of the transient receptor potential (TRP) cation channel family control a wide variety of cellular functions by regulating calcium influx. In neurons, TRP channels may also modulate cell excitability. TRPC5 is a neuronal TRP channel that plays a role in controlling neurite extension in the hippocampus. Transiently expressed TRPC5 exhibits a doubly rectifying current-voltage relationship characterized by relatively large inward currents and a unique outwardly rectifying current with a “flat” segment between +10 and +40 mV that may be attributable to Mg2+block. We find that intracellular Mg2+blocks the outward current through TRPC5 with an IC50of 457 μm. The block is mediated by a cytosolic aspartate residue, D633, situated between the termination of the sixth transmembrane domain and the “TRP box.” The substitution of noncharged or positively charged residues for the negatively charged D633 resulted in a channel with markedly reduced inward currents, in addition to decreased Mg2+block. This suggests that electrostatic attraction of cations by D633 may contribute to inward current amplitude in TRPC5. We propose that cytosolic negatively charged residues can modulate the conductivity of TRP cation channels.
Timed and Targeted Differential Regulation of Nitric Oxide Synthase (NOS) and Anti-NOS Genes by Reward Conditioning Leading to Long-Term Memory Formation
Authors: Korneev Sergei A. , Straub Volko , Kemenes Ildikó , Korneeva Elena I. , Ott Swidbert R. , Benjamin Paul R. , O'Shea Michael
Published: February 2005

In a number of neuronal models of learning, signaling by the neurotransmitter nitric oxide (NO), synthesized by the enzyme neuronal NO synthase (nNOS), is essential for the formation of long-term memory (LTM). Using the molluscan model systemLymnaea, we investigate here whether LTM formation is associated with specific changes in the activity of members of the NOS gene family:Lym-nNOS1,Lym-nNOS2, and the antisense RNA-producing pseudogene (anti-NOS). We show that expression of theLym-nNOS1gene is transiently upregulated in cerebral ganglia after conditioning. The activation of the gene is precisely timed and occurs at the end of a critical period during which NO is required for memory consolidation. Moreover, we demonstrate that this induction of theLym-nNOS1gene is targeted to an identified modulatory neuron called the cerebral giant cell (CGC). This neuron gates the conditioned feeding response and is an essential part of the neural network involved in LTM formation. We also show that the expression of theanti-NOSgene, which functions as a negative regulator of nNOS expression, is downregulated in the CGC by training at 4 h after conditioning, during the critical period of NO requirement. This appears to be the first report of the timed and targeted differential regulation of the activity of a group of related genes involved in the production of a neurotransmitter that is necessary for learning, measured in an identified neuron of known function. We also provide the first example of the behavioral regulation of a pseudogene.
Development of a Classification System for Periodontal Diseases and Conditions
Authors: Armitage Gary C.
Published: February 2005

Classification systems are necessary in order to provide a framework in which to scientifically study the etiology, pathogenesis, and treatment of diseases in an orderly fashion. In addition, such systems give clinicians a way to organize the health care needs of their patients. The last time scientists and clinicians in the field of periodontology and related areas agreed upon a classification system for periodontal diseases was in 1989 at the World Workshop in Clinical Periodontics.1 Subsequently, a simpler classification was agreed upon at the 1st European Workshop in Periodontology.2 These classification systems have been widely used by clinicians and research scientists throughout the world. Unfortunately, the 1989 classification had many shortcomings including: 1) considerable overlap in disease categories, 2) absence of a gingival disease component, 3) inappropriate emphasis on age of onset of disease and rates of progression, and 4) inadequate or unclear classification criteria. The 1993 European classification lacked the detail necessary for adequate characterization of the broad spectrum of periodontal diseases encountered in clinical practice. The need for a revised classification system for periodontal diseases was emphasized during the 1996 World Workshop in Periodontics.3 In 1997 the American Academy of Periodontology responded to this need and formed a committee to plan and organize an international workshop to revise the classification system for periodontal diseases. The proceedings in this volume are the result of this reclassification effort. The process involved development by the Organizing Committee of an outline for a new classification and identification of individuals to write state‐of‐the‐science reviews for each of the items on the outline. The reviewers were encouraged to depart from the preliminary outline if there were data to support any modifications. On October 30–November 2, 1999, the International Workshop for a Classification of Periodontal Diseases and Conditions was held and a new classification was agreed upon (Fig. 1). This paper summarizes how the new classification for periodontal diseases and conditions presented in this volume differs from the classification system developed at the 1989 World Workshop in Clinical Periodontics.1 In addition, an analysis of the rationale is provided for each of the modifications and changes. Ann Periodontol 1999;4:1‐6.
Non‐Plaque‐Induced Gingival Lesions
Authors: Holmstrup Palle
Published: February 2005

The origin of gingival inflammation is occasionally different from that of routine plaque‐associated gingivitis, and such non‐plaqueassociated types of gingivitis often present characteristic clinical features. Examples of such forms of gingivitis are specific bacterial, viral, and fungal infections. Specific bacterial infections of gingiva may be due to Neisseria gonorrhea, Treponema pallidum, streptococci, and other organisms. The most important viral infections of gingiva are herpes simplex virus type 1 and 2 and varicella‐zoster virus. Fungal infections may be caused by several fungi, the most important of these being Candida species including C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. guillermondii. Gingival histoplasmosis is a granulomatous disease caused by the fungus Histoplasma capsulatum and, as for the other specific infections of gingiva, a con‐ firmed diagnosis may require histopathologic examination and/or culture. Atypical gingivitis may also occur as gingival manifestations of dermatological diseases, the most relevant of these being lichen planus, pemphigoid, pemphigus vulgaris, erythema multiforme, and lupus erythematosus. Non‐plaque induced gingival inflammation can be caused by allergic reactions to dental restorative materials, toothpastes, mouthwashes, and foods. In addition, gingival inflammation may result from toxic reactions, foreign body reactions, or mechanical and thermal trauma. Ann Periodontol 1999;4:20‐29.
Necrotizing Ulcerative Periodontitis
Authors: Novak M. John
Published: February 2005

In patients with no known systemic disease or immune dysfunction, necrotizing periodontitis (NUP) appears to share many of the clinical and etiologic characteristics of necrotizing ulcerative gingivitis (NUG) except that patients with NUP demonstrate loss of clinical attachment and alveolar bone at affected sites. In these patients, NUP may be a sequela of a single or multiple episodes of NUG or may be the result of the occurrence of necrotizing disease at a previously periodontitis‐affected site. The existence of immune dysfunction may predispose patients to NUG and NUP, especially when associated with an infection of microorganisms frequently associated with periodontal disease such as Treponema and Selenomonas species, Fuscobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis. The role of immune dysfunction is exemplified by the occasionally aggressive nature of necrotic forms of periodontal disease seen in patients with HIV infection or malnutrition, both of which may impact host defenses. Clinical studies of HIV infected patients have shown that patients with NUP are 20.8 times more likely to have CD4+ cell counts below 200 cells/mm3. However, these same studies have demonstrated that most patients with CD4+ cell counts below 200 cells/mm do not have NUP,3 suggesting that other factors, in addition to immunocompromisation, are involved. Further studies are needed to define the complex interactions between the microbial, or viral, etiology of necrotic lesions and the immunocompromised host. It is, therefore, recommended that NUG and NUP be classified together under the grouping of necrotizing periodontal diseases based on their clinical characteristics. Ann Periodontol 1999;4:74‐ 77.
Periodontal Abscess
Authors: Meng Huan Xin
Published: February 2005

This review focuses on the classification of periodontal abscesses, which are localized purulent infections of periodontal tissues, and discusses their etiology and clinical characteristics. Ann Periodontol 1999;4:79‐82.
Survival of Various Implant‐Supported Prosthesis Designs Following 36 Months of Clinical Function
Authors: Rodriguez Arthur M. , Orenstein Ira H. , Morris Harold F. , Ochi Shigeru
Published: February 2005

Background: The use of endosseous dental implants to replace natural teeth lost to trauma, dental caries, or periodontal disease has become a predictable form of prosthetic treatment since gaining popularity in the early 1980s. While numerous clinical studies have focused on the survival of implants, few address the survival of different prosthesis designs.

Methods: Beginning in 1991, 882 prostheses supported by more than 2,900 implants (687 patients) were placed by the Department of Veterans Affairs Dental Implant Clinical Research Group (DICRG). These prostheses were divided into five research strata based on arch location. The recommended design for each stratum was: bar‐supported overdenture (maxillary completely edentulous); screw‐retained hybrid denture (mandibular completely edentulous); screw‐retained fixed partial denture (mandibular and maxillary posterior partially edentulous); and cemented single crown (maxillary anterior single tooth). Alternative overdenture designs were utilized in the edentulous arches when the recommended prosthesis could not be fabricated. Prosthesis success rates for the research strata were calculated for an observation time of up to 36 months following prosthesis placement.

Results: Success rates for the maxillary edentulous stratum ranged from 94.6% for the bar‐retained overdenture supported by five to six fixtures to 81.8% for the cap‐retained overdenture. The mandibular edentulous strata produced success rates of 98.1% for the fixed hybrid prosthesis to 91.7% for the cap‐retained prosthesis. Success rates for maxillary and mandibular posterior fixed partial dentures were 94.3% and 92.6%, respectively, while the maxillary anterior single‐tooth prosthesis yielded a success rate of 98.1% for the 36‐month observation period.

Conclusions: The recommended prosthesis designs investigated in this study proved to be reliable, with encouraging success rates for an observation period of 36 months following placement. Ann Periodontol 2000;5:101‐108.
Long‐Term Assessment (5 to 71 Months) of Endosseous Dental Implants Placed in the Augmented Maxillary Sinus
Authors: Olson John W. , Dent C. Daniel , Morris Harold F. , Ochi Shigeru
Published: February 2005

Background: It is not uncommon for the placement of endosseous dental implants in the maxillary posterior jaw region to be complicated by the pneumatization of the maxillary sinus. When this occurs, the residual bone between the floor of the sinus and the crestal ridge is inadequate for the placement of implants. The sinus lift procedure provides a way to increase the amount of available bone and the placement of longer implants.

Methods: One hundred twenty (120) implants were placed in 45 augmented maxillary sinuses. Patients ranged in age from 34 to 78 years. The implant design included a limited number of non‐hydroxyapatite (HA)‐coated titanium screws, with the majority of the implants being HA‐coated cylinders, grooved cylinders, and screws. The augmentation materials were autogenous bone, allogenic bone (demineralized freeze‐dried bone allograft, DFDBA), alloplastic bone (HA), combination grafts of HA and DFDBA, and combination grafts of autogenous bone and DFDBA. All the cases were successfully restored with implant‐supported, bar‐retained overdentures or fixed partial dentures. The follow‐up began at Stage 2 uncovering and ranged from 5 to 71 months, with a mean of 38.2 and standard deviation of 14.6 months.

Results: Three (2.5%) of the 120 implants failed between the period of implant placement and 36 months. Failures appeared to be associated with a history of smoking. Other complications encountered during the study are presented. Implant survival was higher in those placed in grafted sinuses (97.5%) than in those placed in the posterior maxilla without sinus grafting (90.3%).

Conclusion: These findings support the use of implants placed in augmented sinuses to support dental prostheses. Ann Periodontol 2000;5:152‐156.
A Methodological Study for the Analysis of Apatite‐Coated Dental Implants Retrieved From Humans
Authors: MacDonald D.E. , Betts F. , Doty S.B. , Boskey A.L.
Published: February 2005

The stability of thermally processed hydroxyapatite coatings for oral and orthopedic bioprostheses has been questioned. Information on the chemical changes, which occur with hydroxyapatite biomaterials postimplantation in humans, is lacking. The purpose of this investigation was to begin to examine post‐implantation surface changes of hydroxyapatite‐ coated implants using scanning electron microscopy (SEM), x‐ray microanalysis (EDAX), Fourier transform infrared spectroscopy (FTIR), and x‐ray diffraction (XRD). Three retrieved dental implant specimens from humans following clinical failure due to peri‐implantitis were examined. Unimplanted cylinders served as controls. Clinically, the retrieved specimens were all enveloped by a fibrous tissue capsule with bone present at the apical extent of the implant. SEM analysis showed that the retrieved surfaces were coated with both calcified and proteinaceous deposits. EDAX scans of the retrieved specimens demonstrated evidence of hydroxyapatite coating loss reflected by increasing titanium and aluminum signals. Other foreign ions such as sodium, chloride, sulfur, silica, and magnesium were detected. XRD of the control specimens showed that the samples were predominantly apatite; however, two peaks were detected in the diffraction pattern, which are not characteristic of hydroxyapatite, indicating that small amounts of one or more other crystalline phases were also present. The retrieved specimens showed slightly larger average crystal size relative to the control sample material, and the non‐apatite lines were not present. FTIR evaluation of the retrieved specimens revealed the incorporation of carbonate and organic matrix on or into the hydroxyapatite. Narrowing of and increased detail in the phosphate peaks indicated an increase in average crystal size and/or perfection relative to the controls, as did the XRD results. Based on these results, we conclude that chemical changes may occur within the coating, with the incorporation of carbonate and concomitant reduction in hydroxyapatite coating thickness. Thermodynamic dissolution‐reprecipitation of the coating itself and subsequent surface insult by bacterial and local inflammatory components may be involved with these changes. Ann Periodontol 2000;5:175‐184.
Variables Affecting Survival of Single‐Tooth Hydroxyapatite‐Coated Implants in Anterior Maxillae at 3 Years
Authors: Orenstein Ira H. , Petrazzuolo Vincent , Morris Harold F. , Ochi Shigeru
Published: February 2005

Background: The development and expanded use of endosseous dental implants over the last two decades have been remarkably rapid. It is, therefore, imperative that the dental profession closely monitor the performance of root‐form implants used in a variety of applications. The Dental Implant Clinical Research Group (DICRG) was established in 1990 by the Department of Veterans Affairs as a forum for conducting prospective, multidisciplinary, multicentered studies in the field of implant dentistry. The DICRG comprised 30 VA medical centers and 2 dental schools at the time of this study. This paper reports on the survival of hydroxyapatite (HA)‐coated grooved implants used to replace single missing teeth in anterior maxillae at 3 years post‐implant placement.

Methods: During a 4‐year accrual period, a total of 247 single‐tooth implant restorations were placed in anterior maxillae. This paper focuses on the survival of 222 implants (149 patients) for which 3‐year data were recorded for the period from placement. Survival was examined with respect to patient demographics and health status, implant location, surgical variables, and 2‐week post‐placement use of chlorhexidine digluconate (0.12%) rinses. Implant stability was recorded using a hand‐held probe. Periodontal‐type measures were recorded and evaluated, and all complications related to osseointegration were noted. Failure was defined as removal of the implant for any reason.

Results: Establishment and maintenance of osseointegration at 3 years post‐placement was 97.3%. During this 3‐year period, 6 implants were removed due to either failure to osseointegrate or loss of osseointegration. Implant length correlated positively with 3‐year survival (P = 0.003, exact test). The use of preoperative antibiotics was nearly significant to implant survival (P = 0.051, Pearson chi‐square). Mean stability values (PTVs) increased incrementally from −4.5 at uncovering to +1.1 at 36 months, indicating a decrease in stability of the bone‐implant‐prosthesis complex. The most common complication was related to inadequate available bone to fully house implants.

Conclusions: Three‐year post‐placement survival data suggest that the use of HA‐coated, grooved, endosseous implants to support maxillary anterior single‐tooth replacements is a predictable and reliable procedure that can offer significant benefits. Longer implants demonstrated higher survival than shorter implants. The use of preoperative antibiotics was nearly significant to implant survival, and there was an increase in mean PTVs observed over the duration of the study. Further research is needed to assess stability of the hydroxyapatite‐bone interface over time.Ann Periodontol 2000;5:68‐78.