bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Depression and Use of Antidepressant Medication at 5-Years Poststroke in the North East Melbourne Stroke Incidence Study
Authors: Paul Seana L. , Dewey Helen M. , Sturm Jonathan W. , Macdonell Richard A.L. , Thrift Amanda G.
Published: September 2006

Background and Purpose—

There are few data on the prevalence or treatment of depression from unselected populations long-term poststroke. We assessed the prevalence of depression and antidepressant use at 5-years poststroke in an unselected stroke population.

Methods—

Five-year survivors from a prospective community-based stroke incidence study were assessed for depression with the Irritability, Depression and Anxiety Scale. Medications indicated primarily for treatment of depression were recorded.

Results—

At 5-years poststroke, 441 (45%) of 978 incident cases were alive (mean age=74±15 years, 49% female). Seventeen percent of those assessed were depressed. Twenty-two percent with depression were taking an antidepressant medication. Of those taking an antidepressant, 72% were not depressed.

Conclusions—

Although nearly one-fifth of survivors were depressed, few were taking antidepressants. Further exploration of this low level of treatment is warranted.
Matrix Metalloproteinase-2 Plays a Critical Role in the Pathogenesis of White Matter Lesions After Chronic Cerebral Hypoperfusion in Rodents
Authors: Nakaji Kayoko , Ihara Masafumi , Takahashi Chiaki , Itohara Shigeyoshi , Noda Makoto , Takahashi Ryosuke , Tomimoto Hidekazu
Published: September 2006

Background and Purpose—

Cerebrovascular white matter (WM) lesions contribute to cognitive impairment and motor dysfunction in the elderly. A disruption of the blood–brain barrier (BBB) is believed to be a critical early event leading to these WM lesions. Previous studies have suggested the involvement of matrix metalloproteinase-2 (MMP-2) in BBB disruptions and the upregulation of MMP-2 after chronic cerebral hypoperfusion in a rat model. In the present study, we asked whether MMP-2 is involved in the BBB disruption and the subsequent WM lesions after chronic cerebral hypoperfusion.

Methods—

We compared the severity of white matter lesions in rats after chronic cerebral hypoperfusion with or without an MMP inhibitor. Then, we also induced the chronic cerebral hypoperfusion in wild-type and MMP-2-null mice.

Results—

In the rats treated with a relatively selective MMP-2 inhibitor, AG3340, the WM lesions after chronic cerebral hypoperfusion were significantly less severe, and the number of activated astroglia and microglia were also significantly lower as compared with the vehicle-treated rats. Gene knockout of MMP-2 also reduced the severity of the WM lesions and the number of activated astroglia and microglia in a mice system. In both rodents, the disruption of BBB function, as assessed by IgM staining and the Evans blue extravasation test, was less severe when MMP-2 activity was attenuated.

Conclusions—

These findings indicate that MMP-2 plays a critical role in the BBB disruption, glial cell activation, and WM lesions after chronic cerebral hypoperfusion and suggest the potential value of MMP-2 inhibitors as a therapeutic tool in cerebrovascular WM lesions.
Off-Pump Surgery Is Associated With Reduced Occurrence of Stroke and Other Morbidity as Compared With Traditional Coronary Artery Bypass Grafting
Authors: Sedrakyan Artyom , Wu Albert W. , Parashar Amish , Bass Eric B. , Treasure Tom
Published: September 2006

Background and Purpose—

There is growing enthusiasm for coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB). Although deleterious effects of CPB are known, it remains to be proven that avoiding CPB will result in reduction in morbidity. We sought to determine whether off-pump surgery is associated with reduced occurrence of adverse outcomes as compared with CABG with CPB.

Methods—

Studies were identified by searching the MEDLINE, EMBASE and the Cochrane Register 1980 to 2006 (February). We also searched the reference lists of randomized clinical trials (RCT) and reviews to look for additional studies. Study selection: RCTs comparing off-pump surgery to CABG with CPB. No restriction applied on the size of the trial or end point reports. Data extraction: 2 reviewers independently searched for studies, read abstracts and abstracted all data. Data synthesis: combined estimates were obtained using fixed or random effect meta-analyses. Relative risks and risk differences were calculated. Heterogeneity was assessed using χ
2
and I
2
values.

Results—

There were 3996 patients enrolled in 41 RCTs (mean age 62, 22% female). No study reported information on race. Off-pump CABG was associated with a 50% reduction in the relative risk of stroke (95% CI, 7% to 73%), 30% reduction in atrial fibrillation (AF; 95% CI, 16% to 43%) and 48% reduction in wound infection (95% CI, 26% to 63%) with no heterogeneity among RCTs. This translated into avoidance of 10 strokes, 80 cases of AF and 40 infections per 1000 CABG. Fewer distal grafts were performed and there was evidence for >10 reinterventions per 1000 with off-pump CABG. Long-term follow-up is not yet reported in the trials.

Conclusions—

Off-pump CABG is associated with reduced risk of stroke, AF and infections as compared with CABG with CPB. Evidence should be generalized taking into account RCT enrollment limitations, drawbacks related to training requirements, propensity to perform fewer grafts and likely reinterventions after off-pump surgery.
Neuroprotection by a Central Nervous System–Type Prostacyclin Receptor Ligand Demonstrated in Monkeys Subjected to Middle Cerebral Artery Occlusion and Reperfusion
Authors: Cui Yilong , Takamatsu Hiroyuki , Kakiuchi Takeharu , Ohba Hiroyuki , Kataoka Yosky , Yokoyama Chihiro , Onoe Hirotaka , Watanabe Yumiko , Hosoya Takamitsu , Suzuki Masaaki , Noyori Ryoji , Tsukada Hideo , Watanabe Yasuyoshi
Published: September 2006

Background and Purpose—

Recently, we found that a novel subtype of prostacyclin (PGI
2
) receptor clearly distinct from the peripheral subtype in terms of ligand specificity is expressed in the central nervous system (CNS). (15R)-16-
m
-tolyl-17,18,19,20-tetranorisocarbacyclin (15R-TIC) was synthesized and demonstrated to be a specific ligand for this CNS-type PGI
2
receptor. Previously, we demonstrated 15R-TIC to be neuroprotective in vivo during transient forebrain ischemia in gerbils and permanent middle cerebral artery occlusion (MCAO) in rats. Furthermore, this compound was shown to exert an anti-apoptotic effect on primary cultured hippocampal neurons, indicating its neuroprotective effect against ischemic insults occurs via direct action on CNS-type PGI
2
receptor.

Methods—

Local cerebral hemodynamics and oxygen metabolism were measured simultaneously by using positron emission tomography with the
15
O steady-state method, before and up to 18 hours after 3-hour transient MCAO reperfusion in cynomolgus monkeys. Methyl ester of 15R-TIC (50 μg/kg, n=4) or its vehicle (10% Intralipos, n=4) was injected intravenously within 5 minutes after onset of MCAO and continuously infused for 5 hours (50 μg/kg per hour).

Results—

Neuropathology showed that 15R-TIC significantly reduced cortical damage after 3-hour MCAO. Positron emission tomography results showed 15R-TIC significantly reduced the volume of “infarct” region of interest and attenuated the decrease in cerebral metabolic rate of oxygen and oxygen extraction fraction, and these protective effects were not attributable to improvement of cerebral circulation.

Conclusions—

These results suggest that 15R-TIC has a potent neuroprotective effect against focal cerebral ischemia in a monkey MCAO via its direct action on CNS-type PGI
2
receptors.
Early Intravenous Infusion of Sodium Nitrite Protects Brain Against In Vivo Ischemia-Reperfusion Injury
Authors: Jung Keun-Hwa , Chu Kon , Ko Song-Yi , Lee Soon-Tae , Sinn Dong-In , Park Dong-Kyu , Kim Jeong-Min , Song Eun-Cheol , Kim Manho , Roh Jae-Kyu
Published: September 2006

Background and Purpose—

The rate of nitric oxide (NO) generation from nitrite is linearly dependent on reductions in oxygen and pH levels. Recently, nitrite-derived NO has been reported to exert a profound protection against liver and heart ischemia-reperfusion injury. In this study, we hypothesized that nitrite would be reduced to NO in the ischemic brain and exert NO-dependent neuroprotective effects.

Methods—

Cerebral ischemia-reperfusion injury was induced by intraluminal thread occlusion of middle cerebral artery in the adult male rats. Solutions of sodium nitrite were infused intravenously at the time of reperfusion. Sodium nitrate and carboxy-PTIO (30 minutes before ischemic surgery), a direct NO scavenger, were infused for comparisons.

Results—

Nitrite reduced infarction volume and enhanced local cerebral blood flow and functional recovery. The effects were observed at concentrations of 48 nmol and 480 nmol, but not at 4800 nmol nitrite and 480 nmol nitrate. The neuroprotective effects of nitrite were inhibited completely by the carboxy-PTIO. The 480 nmol nitrite attenuated dihydroethidium activity, 3-nitrotyrosine formation, and lipid peroxidation in the ischemic brain.

Conclusions—

Nitrite exerted profound neuroprotective effects with antioxidant properties in the ischemic brains. These results suggest that nitrite, as a biological storage reserve of NO, may be a novel therapeutic agent in the setting of acute stroke.
Validity of a Virtual Environment for Stroke Rehabilitation
Authors: Edmans Judi A. , Gladman John R.F. , Cobb Sue , Sunderland Alan , Pridmore Tony , Hilton Dave , Walker Marion F.
Published: September 2006

Background and Purpose—

Virtual environments for use in stroke rehabilitation are in development, but there has been little evaluation of their suitability for this purpose. We evaluated a virtual environment developed for the rehabilitation of the task of making a hot drink.

Methods—

Fifty stroke patients undergoing rehabilitation in a UK hospital stroke unit were involved. The performance of stroke rehabilitation patients when making a hot drink had the neurological impairments associated with performance of this task, and the errors observed were compared for standardized task performance in the real world and in a virtual environment. Neurological impairments were measured using standardized assessments. Errors in task performance were assessed rating video recordings and classified into error types.

Results—

Real-world and virtual environment performance scores were not strongly associated (ρ=0.30;
P
<0.05). Performance scores in both settings were associated with age, Barthel ADL score, Mini Mental State Examination score, and tests of visuospatial function. Real-world performance only was associated with arm function and sequencing ability. Virtual environment performance only was associated with language function and praxis. Participants made different errors during task performance in the real world and in the virtual environment.

Conclusions—

Although this virtual environment was usable by stroke rehabilitation patients, it posed a different rehabilitation challenge from the task it was intended to simulate, and so it might not be as effective as intended as a rehabilitation tool. Other virtual environments for stroke rehabilitation in development require similar evaluation.
An Artist's Journey in Art and Science: From behind the Iron Curtain to Present-Day America
Authors: Epuré Sherban
Published: September 2006

The artist traces his work from its beginnings behind the Iron Curtain in 1967, when cybernetics became the driving force of his creative process, to the present day. Given the scarcity of information and the absence of access to Western experimental work in Romania, this step was the unlikely result of a purely personal train of thought. He went on to lecture and write extensively to promote cybernetics and explain his approach to art, which was highly unconventional in the context of the times. Two directions emerged and remain the focus of his work today: the S-Band, an interactive art machine, and the Meta-Phorm, a behavioral geometry articulated by cybernetic mechanisms.
Communicating Science through the Language of Dance: A Journey of Education and Reflection
Authors: Stolberg Tonie L.
Published: September 2006

Bharatanatyam, the classical dance style of South India, is adept at conveying complex, multilayered narratives. This paper documents and reflects upon the interactions between the author, a scientist and educator, and a professional dance company as they strive to develop and produce a dance-drama about the carbon cycle. The author examines the process by which scientific ideas are shared with the artists and the way a scientific narrative becomes one with an artistic meaning. The paper also examines areas for possible future science-dance collaborations and explores the necessary features for a collaborative science-dance pedagogy.
Musical Agents: Toward Computer-Aided Music Composition Using Autonomous Software Agents
Authors: Dahlstedt Palle , McBurney Peter
Published: September 2006

The authors, a composer and a computer scientist, discuss their collaborative research on the use of multiagent systems and their applicability to music and musical composition. They describe the development of software and techniques for the composition of generative music.
Three-Dimensional Structure and Dynamics of African Easterly Waves. Part II: Dynamical Modes
Authors: Hall Nicholas M. J. , Kiladis George N. , Thorncroft Chris D.
Published: September 2006

A primitive equation model is used to study the linear normal modes of the African easterly jet (AEJ). Reanalysis data from the summertime mean (June–September; JJAS) flow is used to provide zonally uniform and wavy basic states. The structure and growth rates of modes that grow over West Africa on these basic states are analyzed. For zonally uniform basic states, the modes resemble African easterly waves (AEWs) as in many previous studies, but they are quite baroclinic and surface intensified.

For wavy basic states the modes have a longitudinal structure determined by the AEJ. They have a surface-intensified baroclinic structure upstream and a deep barotropic structure downstream, as confirmed by energy conversion diagnostics. These modes look remarkably similar to the composite easterly wave structures found by the authors in a companion paper. The similarity extends to the phase relationship of vertical velocity with streamfunction, which resembles OLR composites, suggesting a dynamical influence on convection.

Without damping, the mode for the wavy basic state has a growth rate of 0.253 day−1. With a reasonable amount of low-level damping this mode is neutralized. It has a period of 5.5 days and a wavelength of about 3500 km. Further results with monthly mean basic states show slight variations, as the wave packet essentially follows displacements of the jet core. Experiments focused on specific active and passive years for easterly waves (1988 and 1990) do not yield significantly different results for the modes. These results, and in particular, the stability of the system, lead to the conclusion that barotropic–baroclinic instability alone cannot explain the initiation and intermittence of AEWs, and a finite-amplitude initial perturbation is required.
Dynamic Adjustment in a Numerically Simulated Mesoscale Convective System: Impact of the Velocity Field
Authors: Nascimento Ernanide Lima , Droegemeier Kelvin K.
Published: September 2006

An identical twin methodology is applied to a three-dimensional cloud model to study the dynamics of adjustment in deep convective storms. The principal goal is to diagnose how mass and velocity fields mutually adjust in order to better understand the relative information content (value) of observations, the physical interdependency among variables, and to help in the design of dynamically consistent analyses to ensure smooth startup of numerical prediction models.

Using a control simulation (“truth” or “nature” run) of an idealized long-lived bow echo convective system, a series of adjustment experiments is created by resetting, in various combinations, the horizontal and vertical velocity components of the control run to their undisturbed base state values during the mature stage of storm system evolution. The integrations then are continued for comparison against the control. This strategy represents a methodology for studying transient response to an impulsive perturbation in a manner conceptually similar to that used in geostrophic and hydrostatic adjustment.

The results indicate that resetting both horizontal velocity components alters the character of the convection and slows considerably the overall storm system evolution. In sharp contrast, when only the vertical velocity component is reset, the model quickly restores both updrafts and downdrafts to nearly their correct (control run) values, producing subsequent storm evolution virtually identical to that of the control run. Other combinations yield results in between these two extremes, with the cross-line velocity component proving to be most important in restoration toward the control run. This behavior is explained by acoustic adjustment of the pressure and velocity fields in direct response to changes in velocity divergence forced by the withdrawal of wind information.
The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration
Authors: Rossi Lara , Manfredini Rossella , Bertolini Francesco , Ferrari Davide , Fogli Miriam , Zini Roberta , Salati Simona , Salvestrini Valentina , Gulinelli Sara , Adinolfi Elena , Ferrari Sergio , Di Virgilio Francesco , Baccarani Michele , Lemoli Roberto M.
Published: September 2006

Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and nonpeptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine triphosphate (ATP) and uridine triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down-regulation by migrating CD34+ cells, and increased cell adhesion to fibronectin. In vivo, preincubation with UTP significantly enhanced the BM homing efficiency of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits (Gαi) may provide a converging signal for CXCR4- and P2Y-activated transduction pathways. In addition, gene expression profiling of UTP- and CXCL12-treated CD34+ cells and in vitro inhibition assays demonstrated that Rho guanosine 5′-triphosphatase (GTPase) Rac2 and downstream effectors Rho GTPase–activated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC migration. Our data suggest that UTP may physiologically modulate the homing of HSCs to the BM, in concert with CXCL12, via the activation of converging signaling pathways between CXCR4 and P2Y receptors, involving Gαi proteins and RhoGTPases.
Promoter SNPs in G1/S checkpoint regulators and their impact on the susceptibility to childhood leukemia
Authors: Healy Jasmine , Bélanger Hélène , Beaulieu Patrick , Larivière Mathieu , Labuda Damian , Sinnett Daniel
Published: September 2006

Mutations leading to the alteration of cell-cycle checkpoint functions are a common feature of most cancers. Because of the highly regulated nature of the cell cycle, it seems likely that variation in gene dosage of key components due to functional regulatory polymorphisms could play an important role in cancer development. Here we provide evidence of the involvement of promoter single-nucleotide polymorphisms (pSNPs) in the cyclin-dependent–kinase inhibitor genes CDKN2A, CDKN2B, CDKN1A, and CDKN1B in the etiology of childhood pre-B acute lymphoblastic leukemia (ALL). A case-control study, conducted in 240 patients with pre-B ALL and 277 healthy controls, combined with a family-based analysis using 135 parental trios, all of French-Canadian origin, were used to evaluate single-site genotypic as well as multilocus haplotypic associations for a total of 10 pSNPs. Using both study designs, we showed evidence of association between variants CDKN2A −222A, CDKN2B −593A, and CDKN1B −1608A, and an increased risk of ALL. These findings suggest that variable expression levels of cell-cycle inhibitor genes CDKN2A, CDKN2B, and CDKN1B due to regulatory polymorphisms could indeed influence the risk of childhood pre-B ALL and contribute to carcinogenesis.
PDGFRα-expressing mesenchyme regulates thymus growth and the availability of intrathymic niches
Authors: Jenkinson William E. , Rossi Simona W. , Parnell Sonia M. , Jenkinson Eric J. , Anderson Graham
Published: September 2006

The thymus provides a specialized site for the production of T cells capable of recognizing foreign antigens in the context of self–major histocompatibility complex (MHC) molecules. During development, the thymus arises from an epithelial rudiment containing bipotent progenitors that differentiate into distinct cortical and medullary epithelial cells to regulate the maturation and selection of self-tolerant CD4+ and CD8+ T cells. In addition to their differentiation, thymic epithelial cells undergo cellular expansion to ensure that sufficient intrathymic cellular niches are available to support the large number of immature thymocytes required to form a self-tolerant T-cell pool. Thus, intrathymic T-cell production is intimately linked to the formation and availability of niches within thymic microenvironments. Here, we show the increase in intrathymic niches caused by the proliferation of the epithelium in the developing thymus is temporally regulated, and correlates with the presence of a population of fetal thymic mesenchyme defined by platelet-derived growth factor receptor α (PDGFRα) expression. Depletion of PDGFRα+ mesenchyme from embryonic thymi prior to their transplantation to ectopic sites results in the formation of functional yet hypoplastic thymic tissue. In summary, we highlight a specialized role for PDGFRα+ fetal mesenchyme in the thymus by determining availability of thymic niches through the regulation of thymic epithelial proliferation.
Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation
Authors: Mullally Ann , Ritz Jerome
Published: September 2006

The last 2 years have seen much excitement in the field of genetics with the identification of a formerly unappreciated level of “structural variation” within the normal human genome. Genetic structural variants include deletions, duplications, and inversions in addition to the recently discovered, copy number variants. Single nucleotide polymorphisms are the most extensively evaluated variant within the genome to date. Combining our knowledge from these studies with our rapidly accumulating understanding of structural variants, it is apparent that the extent of genetic dissimilarity between any 2 individuals is considerable and much greater than that which was previously recognized. Clearly, this more diverse view of the genome has significant implications for allogeneic hematopoietic stem cell transplantation, not least in the generation of transplant antigens but also in terms of individual susceptibility to transplant-related toxicities. With advances in DNA sequencing technology we now have the capacity to perform genome-wide analysis in a high throughput fashion, permitting a detailed genetic analysis of patient and donor prior to transplantation. Understanding the significance of this additional genetic information and applying it in a clinically meaningful way will be one of the challenges faced by transplant clinicians in the future.
Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features
Authors: Falini Brunangelo , Nicoletti Ildo , Martelli Massimo F. , Mecucci Cristina
Published: September 2006

The nucleophosmin (NPM1) gene encodes for a multifunctional nucleocytoplasmic shuttling protein that is localized mainly in the nucleolus. NPM1 mutations occur in 50% to 60% of adult acute myeloid leukemia with normal karyotype (AML-NK) and generate NPM mutants that localize aberrantly in the leukemic-cell cytoplasm, hence the term NPM-cytoplasmic positive (NPMc+ AML). Cytoplasmic NPM accumulation is caused by the concerted action of 2 alterations at mutant C-terminus, that is, changes of tryptophan(s) 288 and 290 (or only 290) and creation of an additional nuclear export signal (NES) motif. NPMc+ AML shows increased frequency in adults and females, wide morphologic spectrum, multilineage involvement, high frequency of FLT3-ITD, CD34 negativity, and a distinct gene-expression profile. Analysis of mutated NPM has important clinical and pathologic applications. Immunohistochemical detection of cytoplasmic NPM predicts NPM1 mutations and helps rationalize cytogenetic/molecular studies in AML. NPM1 mutations in absence of FLT3-ITD identify a prognostically favorable subgroup in the heterogeneous AML-NK category. Due to their frequency and stability, NPM1 mutations may become a new tool for monitoring minimal residual disease in AML-NK. Future studies should focus on clarifying how NPM mutants promote leukemia, integrating NPMc+ AML in the upcoming World Health Organization leukemia classification, and eventually developing specific antileukemic drugs.
The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis
Authors: Dispenzieri Angela , Lacy Martha Q. , Zeldenrust Steven R. , Hayman Suzanne R. , Kumar Shaji K. , Geyer Susan M. , Lust John A. , Allred Jacob B. , Witzig Thomas E. , Rajkumar S. Vincent , Greipp Philip R. , Russell Stephen J. , Kabat Brian , Gertz Morie A.
Published: September 2006

Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, is highly active in patients with multiple myeloma. We studied the toxicity and efficacy of lenalidomide in patients with AL. Patients with symptomatic AL, a measurable plasma cell disorder, and adequate hematologic and renal reserve were eligible. Patients received single-agent lenalidomide. If there was no evidence of progression after 3 months or of hematologic response after 3 cycles, dexamethasone was added. Twenty-three patients were enrolled. Thirteen were previously treated. Organ involvement was cardiac (64%), renal (73%), hepatic (23%), and nerve (14%). Within the first 3 cycles of therapy, 10 patients discontinued treatment: 4 early deaths, 3 adverse events, and 3 other causes. With a median follow-up of 17 months, 10 patients responded to treatment. In these patients, responses included 9 hematologic, 4 renal, 2 cardiac, and 2 hepatic. All but one of the responders had dexamethasone added to their treatment program. The most common grade 3 or 4 adverse events at least possibly attributable to lenalidomide were neutropenia (45%), thrombocytopenia (27%), rash (18%), and fatigue (18%). In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with dexamethasone, which warrants further investigation.
Tropomyosin modulates erythrocyte membrane stability
Authors: An Xiuli , Salomao Marcela , Guo Xinhua , Gratzer Walter , Mohandas Narla
Published: September 2006

The ternary complex of spectrin, actin, and 4.1R (human erythrocyte protein 4.1) defines the nodes of the erythrocyte membrane skeletal network and is inseparable from membrane stability under mechanical stress. These junctions also contain tropomyosin (TM) and the other actin-binding proteins, adducin, protein 4.9, tropomodulin, and a small proportion of capZ, the functions of which are poorly defined. Here, we have examined the consequences of selective elimination of TM from the membrane. We have shown that the mechanical stability of the membranes of resealed ghosts devoid of TM is grossly, but reversibly, impaired. That the decreased membrane stability of TM-depleted membranes is the result of destabilization of the ternary complex of the network junctions is demonstrated by the strongly facilitated entry into the junctions in situ of a β-spectrin peptide, containing the actin- and 4.1R-binding sites, after extraction of the TM. The stabilizing effect of TM is highly specific, in that it is only the endogenous isotype, and not the slightly longer muscle TM that can bind to the depleted membranes and restore their mechanical stability. These findings have enabled us identify a function for TM in elevating the mechanical stability of erythrocyte membranes by stabilizing the spectrin-actin-4.1R junctional complex.
Diffuse panbronchiolitis
Authors: Poletti V. , Casoni G. , Chilosi M. , Zompatori M.
Published: September 2006

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease, well recognised in Japan and principally affecting the respiratory bronchioles, causing a progressive suppurative and severe obstructive respiratory disorder. If left untreated, DPB progresses to bronchiectasis, respiratory failure and death.

It was first described in the early 1960s. Subsequently, in 1969, the disease was named DPB to distinguish it from chronic bronchitis. “Diffuse” refers to the distribution of the lesions throughout both lungs, and “pan-” refers to the involvement of inflammation in all layers of the respiratory bronchioles.

The distinctive imaging and histological features, the coexisting sinusitis, and the isolation ofHaemophilus influenzaeandPseudomonas aeruginosain the sputum enhance disease recognition. Histologically, DPB is characterised by chronic inflammation, localised mainly in the respiratory bronchioles and adjacent centrilobular regions, with characteristic interstitial accumulation of foamy histiocytes, neutrophils and lymphocyte infiltration. Neutrophils and T-lymphocytes, particularly CD8+ cells, together with the cytokines interleukin-8 and macrophage inflammatory protein-1, are believed to play key roles in the development of DPB.

A significant improvement in the prognosis of this potentially fatal disease has been recently reported thanks to the use of long-term therapy with macrolide antibiotics, the effect of which is attributed to an anti-inflammatory and immunoregulatory action.
Eye and neural defects associated with loss of GDF6
Authors: Hanel Meredith L , Hensey Carmel
Published: September 2006

Background

In Xenopus the bone morphogenetic protein growth and differentiation factor 6 (GDF6) is expressed at the edge of the neural plate, and within the anterior neural plate including the eye fields. Here we address the role of GDF6 in neural and eye development by morpholino knockdown experiments.

Results

We show that depletion of GDF6 (BMP13) resulted in a reduction in eye size, loss of laminar structure and a reduction in differentiated neural cell types within the retina. This correlated with a reduction in staining for Smad1/5/8 phosphorylation indicating a decrease in GDF6 signalling through loss of phosphorylation of these intracellular mediators of bone morphogenetic protein (BMP) signalling. In addition, the Pax6 expression domain is reduced in size at early optic vesicle stages. Neural cell adhesion molecule (NCAM) is generally reduced in intensity along the neural tube, while in the retina and brain discreet patches of NCAM expression are also lost. GDF6 knock down resulted in an increase in cell death along the neural tube and within the retina as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.

Conclusion

Our data demonstrate that GDF6 has an important role in neural differentiation in the eye as well as within the central nervous system, and that GDF6 may act in some way to maintain cell survival within the ectoderm, during the normal waves of programmed cell death.
Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach
Authors: Bainbridge Matthew N , Warren René L , Hirst Martin , Romanuik Tammy , Zeng Thomas , Go Anne , Delaney Allen , Griffith Malachi , Hickenbotham Matthew , Magrini Vincent , Mardis Elaine R , Sadar Marianne D , Siddiqui Asim S , Marra Marco A , Jones Steven JM
Published: September 2006

Background

High throughput sequencing-by-synthesis is an emerging technology that allows the rapid production of millions of bases of data. Although the sequence reads are short, they can readily be used for re-sequencing. By re-sequencing the mRNA products of a cell, one may rapidly discover polymorphisms and splice variants particular to that cell.

Results

We present the utility of massively parallel sequencing by synthesis for profiling the transcriptome of a human prostate cancer cell-line, LNCaP, that has been treated with the synthetic androgen, R1881. Through the generation of approximately 20 megabases (MB) of EST data, we detect transcription from over 10,000 gene loci, 25 previously undescribed alternative splicing events involving known exons, and over 1,500 high quality single nucleotide discrepancies with the reference human sequence. Further, we map nearly 10,000 ESTs to positions on the genome where no transcription is currently predicted to occur. We also characterize various obstacles with using sequencing by synthesis for transcriptome analysis and propose solutions to these problems.

Conclusion

The use of high-throughput sequencing-by-synthesis methods for transcript profiling allows the specific and sensitive detection of many of a cell's transcripts, and also allows the discovery of high quality base discrepancies, and alternative splice variants. Thus, this technology may provide an effective means of understanding various disease states, discovering novel targets for disease treatment, and discovery of novel transcripts.
Do functional walk tests reflect cardiorespiratory fitness in sub-acute stroke?
Authors: Tang Ada , Sibley Kathryn M , Bayley Mark T , McIlroy William E , Brooks Dina
Published: September 2006

Background and purpose

The Six-Minute Walk Test (6MWT) has been employed as a measure of functional capacity, but its relationship to cardiorespiratory fitness in stroke is not well established. Gait speed measured over short distances is commonly used as an index of walking competency following stroke. We evaluated the relationship between the 6MWT, aerobic fitness (VO2peak) and walking competency in sub-acute stroke.

Methods

Thirty-six individuals (mean age ± SD, 64.6 ± 14.4 years; time post-stroke 16.2 ± 13.3 days) were evaluated using the 6MWT (distance, speed, heart rate), a maximal exercise test (VO2peak, heart rate, exercise test duration), and walking competency using a five meter walk (speed, symmetry ratio). Correlation analyses were used to examine the relationships between these outcomes.

Results

There was a strong correlation between the 6MWT and five meter walk velocity for preferred (r = 0.79) and fast (r = 0.82) speed (p < 0.001). On average, the 6MWT speed was faster than the preferred gait speed (94.9 cm/s vs. 83.8 cm/s, p = 0.003), but slower than the fast-paced walk (115.1 cm/s, p < 0.001). There was significant though more moderate association between 6MWT distance and VO2peak (r = 0.56, p < 0.001) and exercise test duration (r = 0.60, p < 0.001).

Conclusion

The speed selected during the 6MWT was strongly related to the velocities selected during the five meter walk distance (intermediate to the selected preferred and fast speeds). Although the 6MWT may be challenging to the cardiorespiratory system, it appears to be more strongly influenced by potential limits to walking speed rather than cardiorespiratory capacity. As a result, this test is not, by itself, an adequate measure of aerobic fitness early after stroke.
Postnatally Elevated Levels of Insulin-Like Growth Factor (IGF)-II Fail to Rescue the Dwarfism of IGF-I-Deficient Mice except Kidney Weight
Authors: Moerth Corinna , Schneider Marlon R. , Renner-Mueller Ingrid , Blutke Andreas , Elmlinger Martin W. , Erben Reinhold G. , Camacho-Hübner Cecilia , Hoeflich Andreas , Wolf Eckhard
Published: September 2006

This study tested whether elevated levels of IGF-II in the postnatal period can rescue the dwarfism in IGF-I-deficient mice. Heterozygous Igf1 mutant mice [I+/− IIwt] were crossed with heterozygous Igf1 mutant, phosphoenolpyruvate carboxykinase promoter IGF-II transgenic mice [I+/− IItg], and [I+/+ IIwt], [I+/+ IItg], [I−/− IIwt], and [I−/− IItg] offspring were investigated. IGF-II levels were 11- and 6-fold higher in male and female [I−/− IItg] vs. [I−/− IIwt] animals. Western ligand blot analysis revealed markedly reduced activities of 30- and 32-kDa IGF binding proteins (IGFBPs) (most likely IGFBP-1 and IGFBP-2) and the 39- to 43-kDa IGFBP-3 double band in serum from IGF-I-deficient mice. These binding proteins were partially restored by overexpression of IGF-II. Analysis of weight data from the early postnatal period until d 60 showed that, in the absence of IGF-I, elevated levels of IGF-II have no effect on body weight gain. A detailed analysis of body proportions, bone parameters, and organ weights of 60-d-old mice also failed to show effects of IGF-II with one important exception: in Igf1 mutant and also Igf1 intact male mice, IGF-II overexpression significantly increased absolute (+32.4 and +28.6%; P < 0.01) and relative kidney weights (+29.0 and +22.4%; P < 0.001). These changes in kidney weight were associated with reduced phosphorylation of p38 MAPK. In summary, our genetic model shows that substantial amounts of IGF-II in the circulation do not rescue the postnatal growth deficit of IGF-I-deficient mice but increase absolute and relative kidney weights of normal and IGF-I-deficient male mice, suggesting a gender-specific role of IGF-II for kidney growth.
Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents
Authors: Nogueiras Rubén , Pfluger Paul , Tovar Sulay , Arnold Myrtha , Mitchell Sharon , Morris Amanda , Perez-Tilve Diego , Vázquez Maria J. , Wiedmer Petra , Castañeda Tamara R. , DiMarchi Richard , Tschöp Matthias , Schurmann Annette , Joost Hans-Georg , Williams Lynda M. , Langhans Wolfgang , Diéguez Carlos
Published: September 2006

Ghrelin stimulates food intake and adiposity and thereby increases body weight (BW) in rodents after central as well as peripheral administration. Recently, it was discovered that the gene precursor of ghrelin encoded another secreted and bioactive peptide named obestatin. First reports appeared to demonstrate that this peptide requires an amidation for its biological activity and acts through the orphan receptor, GPR-39. Obestatin was shown to have actions opposite to ghrelin on food intake, BW, and gastric emptying. In the present study, we failed to observe any effect of obestatin on food intake, BW, body composition, energy expenditure, locomotor activity, respiratory quotient, or hypothalamic neuropeptides involved in energy balance regulation. In agreement with the first report, we were unable to find any effect of obestatin on GH secretion in vivo. Moreover, we were unable to find mRNA expression of GPR-39, the putative obestatin receptor, in the hypothalamus of rats. Therefore, the results presented here do not support a role of the obestatin/GPR-39 system in the regulation of energy balance.
Expression, Translation, and Localization of a Novel, Small Growth Hormone Variant
Authors: Baudet M.-L. , Martin B. , Hassanali Z. , Parker E. , Sanders E. J. , Harvey S.
Published: September 2006

A novel transcript of the GH gene has been identified in ocular tissues of chick embryos. It is, however, unknown whether this transcript (small chicken GH, scGH) is translated. This possibility was therefore assessed. The expression of scGH mRNA was confirmed by RT-PCR, using primers that amplified a 426-bp cDNA of its coding sequence. This cDNA was inserted into an expression plasmid to transfect HEK 293 cells, and its translation was shown by specific scGH immunoreactivity in extracts of these cells. This immunoreactivity was directed against the unique N terminus of scGH and was associated with a protein of 16 kDa, comparable with its predicted size. Most of the immunoreactivity detected was, however, associated with a 31-kDa moiety, suggesting scGH is normally dimerized. Neither protein was, however, present in media of the transfected HEK cells, consistent with scGH’s lack of a signal sequence. Similar moieties of 16 and 31 kDa were also found in proteins extracted from ocular tissues (neural retina, pigmented epithelium, lens, cornea, choroid) of embryos, although they were not consistently present in vitreous humor. Specific scGH immunoreactivity was also detected in these tissues by immunocytochemistry but not in axons in the optic fiber layer or the optic nerve head, which were immunoreactive for full-length GH. In summary, we have established that scGH expression and translation occurs in ocular tissues of chick embryos, in which its localization in the neural retina and the optic nerve head is distinct from that of the full-length protein.
TC10α Is Required for Insulin-Stimulated Glucose Uptake in Adipocytes
Authors: Chang Louise , Chiang Shian-Huey , Saltiel Alan R.
Published: September 2006

Previous studies have suggested that activation of the Rho family member GTPase TC10 is necessary but not sufficient for the stimulation of glucose transport by insulin. We show here that endogenous TC10α is rapidly activated in response to insulin in 3T3L1 adipocytes in a phosphatidylinositol 3-kinase-independent manner, whereas platelet-derived growth factor was without effect. Knockdown of TC10α but not TC10β by RNA interference inhibited insulin-stimulated glucose uptake as well as the translocation of the insulin-sensitive glucose transporter GLUT4 from intracellular sites to the plasma membrane. In contrast, loss of TC10α had no effect on the stimulation of Akt by insulin. Additionally, knockdown of TC10α inhibited insulin-stimulated translocation of its effector CIP4. These data indicate that TC10α is specifically required for insulin-stimulated glucose uptake in adipocytes.
Ligand-Selective Interdomain Conformations of Estrogen Receptor-α
Authors: Padron Adrian , Li Li , Kofoed Eric M. , Schaufele Fred
Published: September 2006

Selective estrogen receptor modulators (SERMs) inhibit estrogen activation of the estrogen receptor (ER) in some tissues but activate ER in other tissues. These tissue-selective actions suggest that SERMs may be identified with tissue specificities that would improve the safety of breast cancer and hormone replacement therapies. The identification of an improved SERM would be aided by understanding the effects of each SERM on the structure and interactions of ER. To date, the inability to obtain structures of the full-length ER has limited our structural characterization of SERM action to their antiestrogenic effects on the isolated ER ligand binding domain. We studied the effects of estradiol and the clinically useful SERMs 4-hydroxytamoxifen and fulvestrant on the conformation of the full-length ERα dimer complex by comparing, in living human breast cancer cells, the amounts of energy transfer between fluorophores attached to different domains of ERα. Estradiol, 4-hydroxytamoxifen, and fulvestrant all promoted the rapid formation of ERα dimers with equivalent interaction kinetics. The amino- and carboxyl-terminal ERα domains both contain activation functions differentially affected by these ligands, but the positions of only the carboxyl termini differed upon binding with estradiol, 4-hydroxytamoxifen, or fulvestrant. The association of a specific ERα dimer conformation with the binding of ligands of different clinical effect will assist the identification of a SERM with optimal tissue-selective estrogenic and antiestrogenic activities. These studies also provide a roadmap for dissecting important structural and kinetic details for any protein complex from the quantitative analysis of energy transfer.
In Vivo Transcript Profiling and Phylogenetic Analysis Identifies Suppressor of Cytokine Signaling 2 as a Direct Signal Transducer and Activator of Transcription 5b Target in Liver
Authors: Vidal Oscar M. , Merino Roxana , Rico-Bautista Elizabeth , Fernandez-Perez Leandro , Chia Dennis J. , Woelfle Joachim , Ono Mitsuru , Lenhard Boris , Norstedt Gunnar , Rotwein Peter , Flores-Morales Amilcar
Published: September 2006

The GH-activated signal transducer and activator of transcription 5b (STAT5b) is an essential regulator of somatic growth. The transcriptional response to STAT5b in liver is poorly understood. We have combined microarray-based expression profiling and phylogenetic analysis of gene regulatory regions to study the interplay between STAT5b and GH in the regulation of hepatic gene expression. The acute transcriptional response to GH in vivo after a single pulse of GH was studied in the liver of hypophysectomized rats in the presence of either constitutively active or a dominant-negative STAT5b delivered by adenoviral gene transfer. Genes showing differential expression in these two situations were analyzed for the presence of STAT5b binding sites in promoter and intronic regions that are phylogenetically conserved between rats and humans. Using this approach, we showed that most rapid transcriptional effects of GH in the liver are not results of direct actions of STAT5b. In addition, we identified novel STAT5b cis regulatory elements in genes such as Frizzled-4, epithelial membrane protein-1, and the suppressor of cytokine signaling 2 (SOCS2). Detailed analysis of SOCS2 promoter demonstrated its direct transcriptional regulation by STAT5b upon GH stimulation. A novel response element was identified within the first intron of the human SOCS2 gene composed of an E-box followed by tandem STAT5b binding sites, both of which are required for full GH responsiveness. In summary, we demonstrate the power of combining transcript profiling with phylogenetic sequence analysis to define novel regulatory paradigms.
The deaf :their education‐improvement of conditions‐ responsibilities and participation of the profession
Authors: Wright John Dutton
Published: September 2006

The aim of this department of THE LARYNGOSCOPE will be to bring to the notice of its readers from month to month, facts that may be helpful to physician and patient in dealing with the life‐problems involved In deafness. Suggestions from readers will be gladly received and all questions answered to the best of our ability.
Stammering‐A bibliography of the past decade‐1921 to 1930, inclusive
Authors: Bluemel C. S.
Published: September 2006

This bibliography is supplementary to a similar the year bibliography published in The; Laryngoscope in September, 1921.

Where foreign titles are translated into English, the translations are those given by The Quarterly Cumulative Index Medicus of The American Medical Association.
Fractures of the mandible. An Analysis of 114 Cases with Observations on Treatment.
Authors: Hudson W. R.
Published: September 2006

1. A knowledge of the surgical anatomy of the mandible is necessary in understanding principles of treatment.

2. A precise classification of the injury will aid in electing the treatment of choice.

3. Many methods of treatment have been advocated; however, the majority of patients with fractures of the mandible can be satisfactorily treated utilizing the relatively simple techniques described.

4. An analysis of 114 cases of mandibular fractures treated in an otolaryngology department has been presented. These data have been discussed in regard to the age, sex, etiology, fracture location and treatment method employed.
Removal of glomus jugulare tumor utilizing complete occlusion of the cerebral circulation.
Authors: Michelson Robin P. , Connolly John E.
Published: September 2006

1. The diagnostic features and natural course of glomus jugulare tumors are presented.

2. The difficulties of operative removal are illustrated.

3. The experimental background and clinical application of selective cerebral hypothermia are outlined.

4. A case of recurrent glomus jugulare tumor without neurologic involvement is presented in which excision of the tumor was successfully performed during ten minutes of cerebral vascular occlusion provided by selective brain cooling.