bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant Human Erythropoietin for the Treatment of Anaemia in Patients with Chronic Idiopathic Myelofibrosis
Authors: Tsiara S.N. , Chaidos A. , Bourantas L.K. , Kapsali H.D. , Bourantas K.L.
Published: December 2006

Background: Patients with chronic idiopathic myelofibrosis (CIMF) usually present with anaemia. Treatment is often palliative and the majority of patients receive regular red blood cell (RBC) transfusions. Although recombinant human erythropoietin (rhu-EPO) has been proved effective for the treatment of anaemia in several chronic diseases, including haematological malignancies, its role in the treatment of the anaemia in CIMF is not well established. We report the beneficial effect of rhu-EPO administration in 20 patients with CIMF and discuss the parameters predicting favourable response. Patients: Twenty patients with CIMF (9 women and 11 men) regularly treated with supportive RBC transfusions were included in the study. The median age was 70 years (range 45–81 years). Rhu-EPO, 10,000 U, was given subcutaneously 3 times a week. The median duration of therapy was 83 months, ranging from 13 to 87 months. Results: Treatment was considered effective if haemoglobin levels increased over 2 g/dl within 12 weeks after enrolment or the RBC transfusion requirements were reduced by 50% within the same interval. Twelve patients (60%) responded to therapy. Responders were mainly female, had smaller spleen size (p = 0.024), low RBC transfusion requirements (≤1–2 units per month), and significantly lower endogenous serum erythropoietin (EPO) and β2-microglobulin (β2-M) levels when compared with non-responders (p < 0.0001 and 0.00001, respectively). Treatment was well tolerated and none of the patients was withdrawn from the treatment protocol because of side effects. Conclusions: Rhu-EPO administration is an effective, safe and well-tolerated treatment for patients with CIMF and anaemia leading to a significant reduction in RBC transfusion requirements. Factors predicting favourable response are low endogenous EPO and β2-M serum levels and slight to moderate splenomegaly.
Von Willebrand Factor Short Sequence Repeat Locus 2 (Intron 40) Consists of Three Polymorphic Subloci
Authors: Othman Maha , Elbatarny Hisham S. , Byrne Christopher D. , O’Shaughnessy Denise Frances
Published: December 2006

Currently, identification of alleles within the short sequence repeat locus (SSR locus) of intron 40 of the von Willebrand factor gene ( previously known as VNTR II) is based on the size of PCR products that only predicts a certain number of repeats. Through cloning and sequencing, we demonstrated the complexity of nucleotide sequence structure of this region by describing three polymorphic tetranucleotide repeat subloci SSR ‘a’, SSR ‘b’ and SSR ‘c’ within the same originally described locus: the original TCTA (9–14 repeats), a small TCTA repeat locus (2 or 3 repeats) located at the 5′ end and 30 nucleotides upstream from the original locus and a TGTA repeat locus (5 or 6 repeats), adjacent to the 2/3 repeat locus. Sequencing of 54 VWF alleles has revealed 14 different sequence combinations in this region while the size variability in the region only amounts to a 7-allele system. While the determination of VNTR alleles by PCR remains a practical methodology in linkage analysis, this may not be applicable in forensic medicine since not all alleles of identical length based on PCR are the same. Our study reveals the important implication of the identification of SSR 2 subloci and concludes that at least in some situations, there may be a necessity to take into consideration these polymorphic subloci.
Auditory Sensory Memory and Working Memory Processes in Children with Normal Hearing and Cochlear Implants
Authors: Watson D.R. , Titterington J. , Henry A. , Toner J.G.
Published: December 2006

There can be wide variation in the level of oral/aural language ability that prelingually hearing-impaired children develop after cochlear implantation. Automatic perceptual processing mechanisms have come under increasing scrutiny in attempts to explain this variation. Using mismatch negativity methods, this study explored associations between auditory sensory memory mechanisms and verbal working memory function in children with cochlear implants and a group of hearing controls of similar age. Whilst clear relationships were observed in the hearing children between mismatch activation and working memory measures, this association appeared to be disrupted in the implant children. These findings would fit with the proposal that early auditory deprivation and a degraded auditory signal can cause changes in the processes underpinning the development of oral/aural language skills in prelingually hearing-impaired children with cochlear implants and thus alter their developmental trajectory.
Multifrequency Immittancemetry in Experimentally Induced Stapes, Round Window and Cochlear Lesions
Authors: Darrouzet Vincent , Dulon Didier , Franco-Vidal Valérie
Published: December 2006

Objectives: To establish that admittance (Y) and susceptance (B) conductance (G) tympanograms at 2 kHz can reflect the status of the annular ligament and the cochlear pressure. Methods: Seven experiments were set up in 22 guinea pigs: ventilation of the bulla, blockage of the stapes and round window membrane (RWM), fistula, fluid removal from the cochlea, injection of saline in the scala tympani and acoustic trauma. Resonance frequency, Y, B and G at 2 kHz and curve shapes were analyzed before and after lesions. Results: A supplementary peak was observed in Y/G tympanograms in all RWM fistulas and in some cases of acoustic trauma; injection of saline into the scala tympani induced constant, immediate and reproducible changes; RWM and stapes blockages induced foreseeable peaking at 2 kHz; fluid removal from the cochlea induced multiple peak curves. Conclusion: Experimentally induced modifications at the AL result in noticeable, constant and reproducible changes in tympanogram curves at 2 kHz and seem to reflect inner ear pressure.
Electrically Evoked Auditory Steady-State Responses in Guinea Pigs
Authors: Jeng Fuh-Cherng , Abbas Paul J. , Brown Carolyn J. , Miller Charles A. , Nourski Kirill V. , Robinson Barbara K.
Published: December 2006

Most cochlear implant systems available today provide the user with information about the envelope of the speech signal. The goal of this study was to explore the feasibility of recording electrically evoked auditory steady-state response (ESSR) and in particular to evaluate the degree to which the response recorded using electrical stimulation could be separated from stimulus artifact. Sinusoidally amplitude-modulated electrical stimuli with alternating polarities were used to elicit the response in adult guinea pigs. Separation of the stimulus artifact from evoked neural responses was achieved by summing alternating polarity responses or by using spectral analysis techniques. The recorded response exhibited physiological response properties including a pattern of nonlinear growth and their abolishment following euthanasia or administration of tetrodotoxin. These findings demonstrate that the ESSR is a response generated by the auditory system and can be separated from electrical stimulus artifact. As it is evoked by a stimulus that shares important features of cochlear implant stimulation, this evoked potential may be useful in either clinical or basic research efforts.
Relationship between Intraoperative eCAP Thresholds and Postoperative Psychoacoustic Levels as a Prognostic Tool in Evaluating the Rehabilitation of Cochlear Implantees
Authors: Basta Dietmar , Dahme Andreas , Todt Ingo , Ernst Arne
Published: December 2006

A sufficient correlation between objective (e.g. eCAP of the auditory nerve) and psychoacoustic data has not yet been possible due to high interindividual variability in cochlear implantees. Therefore, the application of objective data in the evaluation of speech rehabilitation after cochlear implantation was investigated. eCaps of all electrodes were measured intraoperatively. The ‘threshold’ and ‘comfort’ levels, speech recognition and pure tone thresholds were determined at follow-up. The correlation coefficient was calculated between eCap thresholds and psychoacoustic levels. This correlation coefficient was ranked with other individual items in relation to their influence on the development of speech recognition. Only the duration of preimplant deafness, the pure tone hearing threshold and the correlation between eCAP and psychoacoustic levels have a significant influence on the rehabilitation within this selection of variables. Based on these results, an individualized mathematical modeling approach was introduced to predict the development of postoperative speech recognition by incorporating objective data.
Sendai Virus Vector-Mediated Transgene Expression in the Cochlea in vivo
Authors: Kanzaki Sho , Shiotani Akihiro , Inoue Makoto , Hasegawa Mamoru , Ogawa Kaoru
Published: December 2006

We injected a recombinant Sendai virus (SeV) vector into the guinea pig cochlea using two different approaches – the scala media and scala tympani – and investigated which cell types took up the vector. The hearing threshold shift and distribution of transfected cells in animals using the scala media approach were different compared to those using the scala tympani approach. SeV can transfect very different types of cells, including stria vascularis, spiral ganglion neurons, and sensory epithelia of the organ of Corti, and fibrocytes of the scala tympani. Because SeV vectors can potentially deliver stimuli to the cochlea to induce hair cell regeneration, it may be a powerful tool for repairing the organ of Corti.
Middle Ear Admittance and Hearing Abnormalities in Individuals with Osteoarthritis
Authors: Rawool Vishakha W. , Harrington Brian T.
Published: December 2006

In osteoarthritis, the joint cartilage breaks down. Cartilage exists within the incudomalleolar and incudostapedial joints. In addition, the cartilage-covered base of the stapes footplate is bound to the cartilage-covered rim of the oval window by the annular ligament. Thus, higher prevalence of middle ear abnormalities and hearing loss can be expected in osteoarthritis due to degeneration of the cartilage and the subsequent abnormal repair response. In this study, tympanometric and audiometric data were obtained from 15 individuals diagnosed with osteoarthritis and 15 gender- and age-matched individuals without the diagnosis of arthritis. Results showed a significantly higher prevalence of middle ear abnormalities and hearing loss in ears with arthritis when compared to the control group. Interestingly, osteoarthritis and hearing loss are considered among the top chronic health concerns in older individuals although the connection between these two conditions has not been previously reported.
The Emerging Role of Vascular Smooth Muscle Cell Apoptosis in Atherosclerosis and Plaque Stability
Authors: Clarke Murray , Bennett Martin
Published: December 2006

Accelerated atherosclerosis is both a cause and a consequence of chronic renal failure. Vascular smooth muscle cells (VSMCs) are an important component of atherosclerotic plaques, responsible for promoting plaque stability in advanced lesions. In contrast, VSMC apoptosis has been implicated in a number of deleterious consequences of atherosclerosis, including plaque rupture, vessel remodelling, co- agulation, inflammation and calcification. Although VSMC apoptosis occurs in association with these processes, its precise contribution to these diseases is unknown, given that apoptosis frequently accompanies vessel injury or alterations to flow. Using transgenic mice with selective induction of VSMC apoptosis, a recent study has precisely determined the direct consequences of VSMC apoptosis in both normal vessels and atherosclerotic plaques. Surprisingly, normal arteries can withstand huge cell losses with little change in active or passive properties. Normal vessels demonstrate highly efficient clearance of apoptotic bodies, even in the absence of professional phagocytes. In contrast, VSMC apoptosis alone is sufficient to induce multiple features of vulnerability to rupture in plaques. This study identifies VSMC apoptosis as a critical process determining plaque stability and thus the most important consequence of atherosclerosis, plaque rupture.
Androgen Deficiency and Endothelial Dysfunction in Men with End-Stage Kidney Disease Receiving Maintenance Hemodialysis
Authors: Karakitsos Dimitrios , Patrianakos Alexandros P. , De Groot Eric , Boletis John , Karabinis Andreas , Kyriazis John , Samonis George , Parthenakis Frangiskos I. , Vardas Panos E. , Daphnis Eugene
Published: December 2006

Objectives and Methods: Two thirds of men with end-stage kidney disease (ESKD) have serum testosterone levels in the hypogonadal range. We examined if low serum testoster- one levels were correlated with measures of endothelial dysfunction in ESKD. Bilateral common carotid artery (CCA) intima-media thickness (IMT) and atherosclerotic plaque occurrence, left ventricular mass index, flow- (FMD) and nitrate-mediated vasodilatation (NMD) of the brachial artery were determined by ultrasound imaging in 100 nondiabetic men with ESKD (50 men exhibited androgen deficiency; serum testosterone concentrations <300 ng/dl). Results: Left-ventricular mass index, CCA diameter, CCA-IMT and atherosclerotic plaque occurrence were all significantly increased in ESKD patients with androgen deficiency compared with patients without androgen deficiency (p < 0.05). Also, FMD and NMD measurements were significantly reduced in the former compared with the latter (p < 0.05). Testosterone levels were inversely correlated with age and duration of hemodialysis therapy (r = –0.44 and r = –0.55; p < 0.001). Testosterone levels were negatively correlated to CCA-IMT and atherosclerotic plaque occurrence in patients with androgen deficiency (r = –0.32, p < 0.003, and r = –0.23, p < 0.04, respectively). FMD and NMD measurements were positively correlated to total (r = 0.65 and r = 0.61; both p < 0.0001) and free (r = 0.52 and r = 0.48; both p < 0.001) testosterone levels in patients with low androgenicity. Conclusion: The present results indicated that ESKD patients with androgen deficiency had increased CCA-IMT, atherosclerotic plaque occurrence and reduced FMD and NMD compared with patients without androgen deficiency. Testosterone serum levels were negatively correlated to CCA-IMT and positively correlated to endothelium-dependent vasodilatation in ESKD patients with androgen deficiency.
In vitro Effect of Carvedilol on Professional Phagocytes
Authors: Pečivová Jana , Mačičková Tatiana , Lojek Antonín , Gallova Lucia , Číž Milan , Nosál’ Rado , Holomáňová Dagmar
Published: December 2006

Aim: Superfluous reactive nitrogen and oxygen species generation is implicated in the damage of tissues at sites of inflammation where activated neutrophils and macrophages are involved. This study was conducted to investigate whether the beneficial effects of carvedilol involve modulation of respiratory burst, degranulation-myeloperoxidase release and inducible nitric oxide synthase (iNOS) expression. Methods: Spectrophotometry and chemiluminescence were used to evaluate the effect of carvedilol on opsonized zymosan (0.5 mg/ml)- or N-formyl-methionyl-leucyl-phenyl-alanine (fMLP, 0.1 µmol/l)-stimulated superoxide generation and myeloperoxidase release in human neutrophils. Western blot analysis was used for iNOS expression and Griess reagent for nitric oxide production in RAW 264.7 macrophages (lipopolysaccharide (0.1 µg/ml) stimulated). Results: Carvedilol (10 and 100 µmol/l) significantly decreased opsonized zymosan- and fMPL-stimulated superoxide generation and myeloperoxidase release. Carvedilol (100 µmol/l) enhanced the effect of wortmannin (50 nmol/l), a specific inhibitor of 1-phosphatidylinositol 3-kinase and decreased iNOS expression and nitric oxide production. Conclusion: Carvedilol appears to have a non-specific effect on membranes and to interfere with the phospholipase D signaling pathway, with subsequent inhibition of reactive oxygen species generation and myeloperoxidase release, without affecting iNOS expression.
Prenatal Diagnosis of Jarcho-Levin Syndrome in the First Trimester
Authors: Dane Cem , Yayla Murat , Dane Banu
Published: December 2006

Introduction: Jarcho-Levin syndrome is a congenital segmental costo-vertebral deformation with multiple vertebral and numerical or structural rib abnormalities resulting in the ‘crab-like’ aspect of the chest. We desribe an ultrasound antenatal diagnosis of the Jarcho-Levin syndrome with spina bifida during the first trimester of pregnancy. Case Report: Prenatal ultrasonography showed shortened spine with marked kyphoscoliosis and spina bifida. Conclusion: If a prenatal diagnosis of Jarcho-Levin syndrome is made before viability, the choice of pregnancy termination should be offered to the parents.
Posterior Intravaginal Slingplasty with Preservation of the Uterus: A Modified Surgical Technique in a Young Myelomeningocele Patient
Authors: Verguts Jasper , Roovers Jan-Paul , De Ridder Dirk , Coremans Georges , Deprest Jan
Published: December 2006

We report a case of uterine prolapse in a young woman, treated by posterior intravaginal slingplasty with preservation of the uterus as a feasible and safe surgical procedure. Posterior intravaginal slingplasty is commonly used to correct vaginal vault prolapse, but may be a valuable alternative to correct uterine prolapse. We compare this technique to other techniques to correct uterine prolapse.
Prevalence and Clinical Features of Epilepsy in Argentina
Authors: Melcon Mario O. , Kochen Silvia , Vergara Rodolfo H.
Published: December 2006

Objective: To ascertain the prevalence of epilepsy in Junín, a town of 70,000–80,000 inhabitants from the Province of Buenos Aires, Argentina. Background: Some South American communities have reported extremely high prevalences of epilepsy. We investigated whether Junín would also have a high prevalence.Design/Methods: Systematic sampling was used to select 5,839 households (sampling fraction = 25%). Participating households amounted to 5,648 (97%), with 17,049 persons. A two-phase case-finding strategy was used. Phase 1 was the screening of the 17,049 persons, which was performed by trained but medically unsophisticated interviewers. Phase 2 was the neurological evaluation of the 250 persons who were screened positive for epilepsy. Diagnoses were based on defined diagnostic criteria. Results: As of January 1, 1991 (prevalence day), 106 persons had epilepsy, including 64 (60%) with active epilepsy. Among these, 9 (14%) were epilepsy cases newly diagnosed by survey neurologists, and 50 (78%) were on antiepileptic treatment at the time of the survey. Regarding the same 64 persons, seizures were generalized in 37 (58%) and partial in 24 (38%). Lifetime prevalence of epilepsy was 6.2/1,000 (6.3/1,000, age adjusted to the world standard population). Total point prevalence for active epilepsy was 3.8/1,000 (4.0 for females and 3.5 for males). In addition, prevalence peaked at the ages of 40–59 for females and 0–4 for males. Conclusions: This is one of the first community-based studies of epilepsy in Argentina, and the prevalence results provide new epidemiological data contributing to our understanding of the different prevalence rates found in Latin America.
Mortality due to Amyotrophic Lateral Sclerosis and Parkinson’s Disease among Melanoma Patients
Authors: Baade P.D. , Fritschi L. , Freedman D.M.
Published: December 2006

Recent studies in the USA and elsewhere have identified a possible association between Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and melanoma. However, empirical evidence is very limited. We conducted a study of all people diagnosed as having melanoma in Australia since 1982 (n = 127,037). The subjects, excluding those who had died within 12 months of diagnosis, were followed until 31 December 2001. We then compared their mortality risk of ALS and PD to that of the general population. There were a total of 53 ALS deaths and 129 deaths due to PD. Although the absolute risk is small, the melanoma cohort had a risk of death due to ALS 70% higher (standardised mortality ratio = 169.4, 95% CI = 127–221) than the general population, and nearly a 3-fold increased risk of dying from PD (standardised mortality ratio = 266.3, 95% CI = 222–317). These increased risks continued for long-term survivors, arguing against a surveillance effect (particularly for ALS). The consistency of these results in 2 separate populations (Australia and USA) strengthens the evidence for an association between melanoma and each of the 2 neurodegenerative diseases.
High Prevalence and Fast Rising Incidence of Multiple Sclerosis in Caltanissetta, Sicily, Southern Italy
Authors: Grimaldi Luigi M.E. , Palmeri Barbara , Salemi Giuseppe , Giglia Giuseppe , D’Amelio Marco , Grimaldi Roberto , Vitello Gaetano , Ragonese Paolo , Savettieri Giovanni
Published: December 2006

Background: Epidemiological studies conducted in Sicily and Sardinia, the two major Mediterranean islands, showed elevated incidence and prevalence of multiple sclerosis (MS)and a recent increase in disease frequency. Objective: To confirm the central highlands of Sicily as areas of increasing MS prevalence and elevated incidence, we performed a follow-up study based on the town of Caltanissetta (Sicily), southern Italy. Methods: We made a formal diagnostic reappraisal of all living patients found in the previous study performed in 1981. All possible information sources were used to search for patients affected by MS diagnosed according to the Poser criteria. We calculated prevalence ratios, for patients affected by MS who were living and resident in the study area on December 31, 2002. Crude and age- and sex-specific incidence ratios were computed for the period from January 1, 1993, to December 31, 2002. Results: The prevalence of definite MS rose in 20 years from 69.2 (retrospective prevalence rate) to 165.8/100,000 population. We calculated the incidence of definite MS for the period 1970–2000. These rates calculated for 5-year periods increased from 2.3 to 9.2/100,000/year. Conclusion: This survey shows the highest prevalence and incidence figures of MS in the Mediterranean area and confirms central Sicily as a very-high-risk area for MS.
Trends in Hospitalization Rate, Hospital Case Fatality, and Mortality Rate of Stroke by Subtype in Minneapolis-St. Paul, 1980–2002
Authors: Sturgeon Jared D. , Folsom Aaron R.
Published: December 2006

Background: The stroke mortality rates have been declining in the USA for decades. Less is known about trends in stroke incidence rates, but some studies indicate they have declined. The stroke case fatality has also been declining. Little information exists on trends in stroke subtypes. We examined trends in mortality, hospitalization rate, and hospital case fatality of stroke by subtype in the Minneapolis-St. Paul area from 1980 to 2002. Methods: We estimated hospitalization rates and case fatality for ≧30-year-olds with data from the Minnesota Hospital Association. We estimated mortality rates with counts from the Minnesota Department of Health. Rates were age adjusted to the US 2000 standard by the direct method using census estimates. We tested for significant trends using linear regression. Results: Total stroke mortality and hospital case fatality both declined by almost 50% over the study period, while the rate of stroke hospitalization was relatively stable. Ischemic stroke hospitalization rates increased, while hospital case fatality and mortality rates decreased. Subarachnoid hemorrhage in-hospital case fatality and mortality rates declined, while the hospitalization rate was stable. Intracerebral hemorrhage hospitalization rates increased minimally, hospital case fatality declined, and the mortality rate was stable. Conclusion: These data suggest that declines in total stroke case fatality are contributing most to declining mortality rates in the presence of stable total stroke attack rates.
Management of Steroid-Resistant Focal Segmental Glomerulosclerosis in Children Using Tacrolimus
Authors: Bhimma Rajendra , Adhikari Miriam , Asharam Kareshma , Connolly Catherine
Published: December 2006

Background: The use of tacrolimus in steroid-resistant (SR) focal segmental glomerulosclerosis (FSGS) has been reported in single and small series case reports. Aim: To determine the efficacy of tacrolimus in the management of SR FSGS in children. Study Design: This was a prospective study of 20 children with SR FSGS treated with tacrolimus (0.2–0.4 mg/kg/day in two divided doses over 12 h adjusted to a trough level between 7 and 15 ng/ml) for 12 months in combination with low-dose steroids. Other therapies included angiotensin-converting enzyme inhibitors, folic acid, multivitamins and lipid-lowering agents. Results: The mean age at study entry was 11.1 years (range 5.6–16.8). The mean duration of nephrotic syndrome before initiation of tacrolimus therapy was 4.7 years (range 2.1–7.6). At the end of the treatment period, 8 (40%) children were in complete remission, 9 (45%) were in partial remission, and 3 (15%) failed to respond. The average follow-up period following cessation of tacrolimus treatment was 27.5 months (range 13.7–43.7). At last hospital follow-up, 5 (25%) children were in complete remission, 10 (50%) in partial remission, and 2 (10%) in relapse. Three children died from dialysis-related complications following cessation of tacrolimus treatment. Adverse events included sepsis (2), nausea (2), diarrhea (2), anemia (4) and worsening of hypertension (4). Conclusion: Tacrolimus is a safe and effective treatment for SR FSGS. However, like cyclosporine, some children tend to relapse following cessation of treatment.
Cholesterol Enrichment of Human Monocyte/Macrophages Induces Surface Exposure of Phosphatidylserine and the Release of Biologically-Active Tissue Factor–Positive Microvesicles
Authors: Liu Ming-Lin , Reilly Michael P. , Casasanto Peter , McKenzie Steven E. , Williams Kevin Jon
Published: December 2006

Objective—Biologically significant amounts of two procoagulant molecules, phosphatidylserine (PS) and tissue factor (TF), are transported by monocyte/macrophage-derived microvesicles (MVs). Because cellular cholesterol accumulation is an important feature of atherosclerotic vascular disease, we now examined effects of cholesterol enrichment on MV release from human monocytes and macrophages.

Methods and Results—Cholesterol enrichment of human THP-1 monocytes, alone or in combination with lipopolysaccharide (LPS), tripled their total MV generation, as quantified by flow cytometry based on particle size and PS exposure. The subset of these MVs that were also TF-positive was likewise increased by cellular cholesterol enrichment, and these TF-positive MVs exhibited a striking 10-fold increase in procoagulant activity. Moreover, cholesterol enrichment of primary human monocyte-derived macrophages also increased their total as well as TF-positive MV release, and these TF-positive MVs exhibited a similar 10-fold increase in procoagulant activity. To explore the mechanisms of enhanced MV release, we found that cholesterol enrichment of monocytes caused PS exposure on the cell surface by as early as 2 hours and genomic DNA fragmentation in a minority of cells by 20 hours. Addition of a caspase inhibitor at the beginning of these incubations blunted both cholesterol-induced apoptosis and MV release.

Conclusions—Cholesterol enrichment of human monocyte/macrophages induces the generation of highly biologically active, PS-positive MVs, at least in part through induction of apoptosis. Cholesterol-induced monocyte/macrophage MVs, both TF-positive and TF-negative, may be novel contributors to atherothrombosis.
Antiproliferative Agents Alter Vascular Plasminogen Activator Inhibitor-1 Expression
Authors: Muldowney James A.S. , Stringham John R. , Levy Shawn E. , Gleaves Linda A. , Eren Mesut , Piana Robert N. , Vaughan Douglas E.
Published: December 2006

Objectives—

Drug eluting stents (DES) reduce the incidence of restenosis after coronary angioplasty. Enthusiasm has been tempered by a possible increased risk of in-stent thrombosis. We examined the effects of paclitaxel and rapamycin on the endothelial transcriptome to identify alterations in gene expression associated with thrombosis.

Methods and Results—

Gene expression profiling was performed on human coronary artery endothelial cells treated with rapamycin or paclitaxel. Plasminogen activator inhibitor-1 (PAI-1) was the most consistently induced transcript in rapamycin-treated human coronary artery endothelial cells. RT-PCR and ELISA were performed to confirm positive findings. Transgenic mice engineered to express enhanced green fluorescent protein under control of the human PAI-1 promoter were also treated. Rapamycin and paclitaxel treated endothelial cells produced dose-dependent increases in PAI-1. There was a variable effect on endothelial tissue-type plasminogen activator (t-PA) expression. Enhanced expression of PAI-1 and enhanced green fluorescent protein were detected in coronary arteries, the aorta, and kidney of the mice.

Conclusion—

Antiproliferative agents stimulate the expression of prothrombotic genes. PAI-1 expression may also play a role in the prevention of restenosis through an antimigratory mechanism. The effects of antiproliferatives on vascular gene expression deserve further scrutiny in view of the increasing utilization of drug-eluting stents.
The Sphingosine-1-Phosphate Analogue FTY720 Reduces Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Keul Petra , Tölle Markus , Lucke Susann , von Wnuck Lipinski Karin , Heusch Gerd , Schuchardt Mirjam , van der Giet Markus , Levkau Bodo
Published: December 2006

Objective—The sphingosine-1-phosphate (S1P) analogue FTY720 is a potent immunosuppressive agent currently in Phase III clinical trials for kidney transplantation. FTY720 traps lymphocytes in secondary lymphoid organs thereby preventing their migration to inflammatory sites. Previously, we have identified FTY720 as a potent activator of eNOS. As both inhibition of immune responses and stimulation of eNOS may attenuate atherosclerosis, we administered FTY720 to apolipoprotein E−/−mice fed a high-cholesterol diet.

Methods and Results—FTY720 dramatically reduced atherosclerotic lesion volume (62.5%), macrophage (41.8%), and collagen content (63.5%) after 20 weeks of high-cholesterol diet. In isolated aortic segments and cultured vascular smooth muscle cell, FTY720 potently inhibited thrombin-induced release of monocyte chemoattractant protein-1. This effect was mediated by the S1P3sphingolipid receptor as FTY720 had no effect on thrombin-induced monocyte chemoattractant protein-1 release in S1P3−/−mice. In contrast to S1P receptors on lymphocytes, FTY720 did not desensitize vascular S1P receptors as arteries from FTY720-treated mice retained their vasodilator response to FTY720-phosphate.

Conclusions—We suggest that FTY720 inhibits atherosclerosis by suppressing the machinery involved in monocyte/macrophage emigration to atherosclerotic lesions. As vascular S1P receptors remained functional under FTY720 treatment, S1P agonists that selectively target the vasculature and not the immune system may be promising new drugs against atherosclerosis.
Bone Marrow Transplantation Reveals That Recipient AT1a Receptors Are Required to Initiate Angiotensin II–Induced Atherosclerosis and Aneurysms
Authors: Cassis Lisa A. , Rateri Debra L. , Lu Hong , Daugherty Alan
Published: December 2006

Objective—

Angiotensin II (AngII) infusion into hypercholesterolemic mice accelerates atherosclerosis and promotes formation of abdominal aortic aneurysms (AAAs). The purpose of this study was to define whether AngII interacts with receptors on infiltrating versus resident cells in promoting vascular pathologies.

Methods and Results—

Male LDL receptor−/− mice, that were either AT1a receptor +/+ or −/−, were fed a fat enriched diet and infused with either saline or AngII. AngII-induced augmentation of atherosclerosis and formation of AAAs was ablated in AT1a receptor−/− mice. Bone marrow transplantation studies were performed to determine the role of AT1a receptors expressed on infiltrating cells. AT1a receptor +/+ and −/− mice were irradiated and repopulated with bone marrow–derived stem cells of either genotype. These 4 groups of chimeric mice were infused with either saline or AngII. Repopulation of irradiated AT1a receptor +/+ mice with −/− bone marrow–derived cells resulted in modest reductions in AngII-induced atherosclerosis. Unexpectedly, AT1a receptor–deficient recipient mice were dramatically protected from AngII-induced vascular pathologies, irrespective of donor genotype.

Conclusion—

AngII promotes vascular pathology via AT1a receptors. AT1a receptors expressed on infiltrating cells exert modest regulation of AngII-induced atherosclerosis. However, the presence of this receptor in resident tissue is required for the initiation of AngII-induced atherosclerosis and AAAs.
Critical Role of Endothelial Notch1 Signaling in Postnatal Angiogenesis
Authors: Takeshita Kyosuke , Satoh Minoru , Ii Masaaki , Silver Marcy , Limbourg Florian P. , Mukai Yasushi , Rikitake Yoshiyuki , Radtke Freddy , Gridley Thomas , Losordo Douglas W. , Liao James K.
Published: December 2006

Notch receptors are important mediators of cell fate during embryogenesis, but their role in adult physiology, particularly in postnatal angiogenesis, remains unknown. Of the Notch receptors, only Notch1 and Notch4 are expressed in vascular endothelial cells. Here we show that blood flow recovery and postnatal neovascularization in response to hindlimb ischemia in haploinsufficient global or endothelial-specific Notch1
+/−
mice, but not Notch4
−/−
mice, were impaired compared with wild-type mice. The expression of vascular endothelial growth factor (VEGF) in response to ischemia was comparable between wild-type and Notch mutant mice, suggesting that Notch1 is downstream of VEGF signaling. Treatment of endothelial cells with VEGF increases presenilin proteolytic processing, γ-secretase activity, Notch1 cleavage, and Hes-1 (hairy enhancer of split homolog-1) expression, all of which were blocked by treating endothelial cells with inhibitors of phosphatidylinositol 3-kinase/protein kinase Akt or infecting endothelial cells with a dominant-negative Akt mutant. Indeed, inhibition of γ-secretase activity leads to decreased angiogenesis and inhibits VEGF-induced endothelial cell proliferation, migration, and survival. Overexpression of the active Notch1 intercellular domain rescued the inhibitory effects of γ-secretase inhibitors on VEGF-induced angiogenesis. These findings indicate that the phosphatidylinositol 3-kinase/Akt pathway mediates γ-secretase and Notch1 activation by VEGF and that Notch1 is critical for VEGF-induced postnatal angiogenesis. These results suggest that Notch1 may be a novel therapeutic target for improving angiogenic response and blood flow recovery in ischemic limbs.
Frequency of Cognitive Impairment Without Dementia in Patients With Stroke
Authors: Serrano Soledad , Domingo Julio , Rodríguez-Garcia Elena , Castro Maria-Dolores , del Ser Teodoro
Published: December 2006

Background and Purpose—

Studies on cognitive impairment without dementia (CIND) after stroke are scarce and there are no widely accepted diagnostic criteria for this condition. The purpose of this study was to determine the frequency of CIND in a hospital cohort before and after stroke during a 2-year follow up according to two alternative operational criteria.

Methods—

Three hundred twenty-seven consecutive stroke inpatients were prospectively evaluated with an extensive neuropsychological battery and the Informant Questionnaire of Cognitive Decline in the Elderly (IQCODE) on admission and then at 3, 12, and 24 months after discharge. CIND was established according to two alternative operational criteria: proxy information (a cutoff score of 3.35 in the IQCODE: IQ-c) or to neuropsychologic examination (a score below the sixth percentile in ≥50% of the tests exploring one cognitive domain: NPE-c).

Results—

A total of 12.6% patients had CIND (IQ-c) before stroke. After 3 months, the CIND frequency was 26.9% (IQ-c) or 19.6% (NPE-c); after 12 months, 39.5% or 26.8%; and after 24 months, 36.6% or 21%. The risk for developing delayed dementia was significantly higher for poststroke patients with CIND diagnosed by IQ-c (OR 8.8), NPE-c (OR 10.3), or both criteria (OR 20.8).

Conclusions—

Patients with CIND are frequent before and after stroke and prone to delayed dementia. Both criteria are valid for identifying CIND cases and predicting long-term conversion to dementia, but NPE-c may be more adequate for the long-term follow up and IQ-c for detecting changes from prestroke status.
An Analytical Hydrological Model for the Study of Scaling Issues in Land Surface Modeling
Authors: Ren Diandong , Henderson-Sellers Ann
Published: December 2006

Besides the atmospheric forcing such as solar radiation input and precipitation, the heterogeneity of the surface cover also plays an important role, especially in the distribution characteristics of the latent heat flux (LE). In this study, scaling issues are discussed based on an analytical hydrological model that describes the transpiration and diffusion processes of soil water.

The solution of this analytical model is composed of a transient part that depends primarily on initial conditions and a steady part that depends on the boundary conditions. To know how sensitive the different averaging approaches are to the initial conditions, three initial profiles are chosen that cover the prevailing soil moisture regimes. After analyzing its solution, the study shows that 1) upon reaching the steady state, directly taking an average of soil properties will cause systematic overestimation in the calculation of area-averaged LE. For an initially very dry condition, averaging of a sandy soil and a clay soil can cause a percentage error as large as 40%. 2) For vegetation growing on sandy soils, a direct averaging of the transpiration rate results in persistent overestimation of LE. For vegetation growing on clay soil, however, even after reaching the steady state, averaging of two water extraction weights can be either an overestimation or an underestimation, depending on which two vegetation types are involved. 3) During the interim stage of drying down, averaging of the soil/vegetation properties can lead to either an overestimation or an underestimation, depending on the evolving stage of the soil moisture profile. 4) The initial soil moisture condition matters during the transient stage of drying down. Different initial soil moisture conditions yield different scenarios of underestimation and overestimation patterns and a differing severity of errors.

The simplicity of the analytical model and the heuristic initial soil profiles make the generalization easier than using sophisticated numerical models and make the causality mechanism clearer for physical interpretations.
Inequality and Sociology
Authors: Kenworthy Lane
Published: December 2006

Sociologists have contributed relatively little to our understanding of rising inequality of earnings and income in the United States. The author considers both why that has been the case and the degree to which it matters. Suggestions are offered about how a comparative perspective can help to shed some light on developments in the United States.
Social Class and Earnings Inequality
Authors: Weeden Kim A. , Kim Young-Mi , Di Carlo Matthew , Grusky David B.
Published: December 2006

The authors examine whether growth in earnings inequality has played out in ways that are class strengthening or class weakening. Using the Current Population Survey, they show that the absolute amount of inequality is increasing (a) between big classes, (b) between the occupations constituting big classes, and (c) within occupations. In relative terms, the share of total inequality occurring within occupations has declined, whereas the share of total inequality occurring between classes and between the occupations constituting big classes has tended to increase, most clearly for men. Although the majority of earnings inequality is still generated within occupations, especially rapid growth of the between-class and between-occupation components implies that the well-known takeoff in inequality has generated a “lumpier” earnings distribution with relatively stronger class and occupational distinctions.
Economic Inequality, Pareto, and Sociology
Authors: Nielsen François
Published: December 2006

Economist and sociologist Vilfredo Pareto (1848-1923) developed a general theory of social inequality inspired by his discovery of similarities in the shape of the income distribution across societies. Pareto’s approach is characterized by (a) a focus on individual, continuous income variation rather than discrete classes; (b) attention paid to the entire socioeconomic distribution rather than summary statistics; (c) an emphasis on social heterogeneity (labor supply) rather than a view of social structure as a collection of empty places (labor demand); and (d) a conception of the inequality structure—and movements of individuals within it—as resulting from the distribution of human abilities interacting with a structure of opportunities (i.e., a structure of social selection). Pareto’s vision—part of the common patrimony of economics and sociology—foreshadows emergent approaches to socioeconomic inequality.
Value Priorities of Japanese and American Service Academy Students
Authors: Malone Eloise Forgette , Paik Chie Matsuzawa
Published: December 2006

The exceptional demands placed upon military organizations throughout the world today render comparative analysis of military culture and values important, particularly as defense policies become increasingly integrative and cooperative to combat global terrorism. Using an instrument designed to prioritize value orientations, this study examines value priorities of prospective officers at Japanese and American military academies. Findings suggest that Japanese students are more individualistic and self-directed and American students more benevolent and traditional than popular conceptions suggest. The study discusses the findings within the social and cultural contexts of the service academies and societies at large. The article also discusses the implications for military relations with their civil society and with each other.
Attitudes toward Expanding Roles for Navy Women at Sea
Authors: Iskra Darlene M.
Published: December 2006

This article explores the discourse and gendered constructions that surrounded the debates on expanding seagoing roles for women in the U.S. Navy between 1978 and 2000. By comparing arguments against the expansion of women's seagoing roles across multiple years, it is possible to assess whether the arguments about women's exclusion have essentially changed. The arguments against expanding women's roles were framed in the context of diminishing military effectiveness based on stereotypical notions of women's capabilities. The arguments in favor of expanding women's roles were also framed within the construct of military effectiveness, with an emphasis on equal citizenship responsibility and democratic values. These results show a consistency of discourse throughout the periods studied.
ROTC and the Catholic Campus
Authors: Thomas Ward
Published: December 2006

Among the more perennially contentious issues on the campuses of many Catholic colleges and universities is the presence of the Reserve Officers'Training Corps, or ROTC. While opposition to ROTC has been by no means limited to Catholic schools, the centrality of moral and religious principles to the mission of these institutions has provided purchase for many of the arguments of ROTC critics. This article examines the major arguments put forth in support of the claim that ROTC is fundamentally inconsistent with Catholic Church teaching and, therefore, at odds with the mission of Catholic colleges and universities. The article concludes that each rests on interpretations of Catholic moral thought and teaching that are not only incomplete but also incorrect and that claims of a basic contradiction between the religious identity of Catholic institutions of higher learning and ROTC programs do not stand up well to scrutiny.
The Essence of Military Group Cohesion
Authors: Siebold Guy L.
Published: December 2006

In July 2006, Armed Forces & Society published an article by Anthony King, “The Word of Command: Communication and Cohesion in the Military.” This commentary takes exception to certain statements and conclusions in King's article, and in the process, sketches a standard model of military group cohesion. This model is based on social integration in the military and is composed of both primary group cohesion (peer and leader bonding) and secondary group cohesion (organizational and institutional bonding). The essence of peer bonding is given as social relationships based on trust and teamwork. The standard model is presented as a tool to sensitize ethnographers about what to look for when observing military interactions and to help them interpret what they see.
Making Claims about Standardization and Orthopraxy in Late Imperial China
Authors: Szonyi Michael
Published: December 2006

This article presents research on popular cults and ancestral sacrifice from the Fuzhou region in order to reflect on James Watson’s theories of ortho-praxy and standardization. It argues that substantive standardization and adherence to orthopraxy should be distinguished analytically from claims to standardization and adherence to orthopraxy, that the historical sources sometimes indicate the latter rather than the former, and that the distinction between the two limits the theories’ capacity to fully account for social and cultural integration in late imperial China.
Orthopraxy, Orthodoxy, and the Goddess(es) of Taishan
Authors: Pomeranz Kenneth
Published: December 2006

This article examines James Watson’s influential work on orthopraxy and cultural unification in late imperial China through a study of the cult of the goddess of Taishan. In this case the state (a crucial promoter of standardization for Watson) was internally divided, local elites took a hard line against popular practices, and ritual became increasingly disunified across classes, regions, and genders. Eventually, popular lore about the goddess changed to reflect an awareness of elite rejection and to celebrate the goddess’s ability to pursue her own goals despite often hostile male authorities. What “cultural unity” one can find here is paradoxical and based not on rituals but beliefs: a shared sense that Taishan was sacred territory worth contesting, popular awareness that elites did not welcome their claims on it, and other signs that groups marked their disagreements with each other, rather than either ignoring differences of ideas or disguising them behind shared ritual.
Death Rites and Chinese Culture
Authors: Sutton Donald S.
Published: December 2006

This essay argues for a modification of James L. Watson’s influential ideas on official cultural standardization via ritual in late imperial China. Focusing on Watson’s introduction to Death Ritual in Late Imperial and Modern China, co-edited with Evelyn Rawski (1988), it refutes Watson’s hypothesis that officials deliberately confined themselves to effective reform of death rituals in the period before the corpse’s expulsion from the community: gazetteers show that officials tried—and failed—to modify numerous practices, both before and after expulsion. The essay proposes that some reported orthoprax standardization was illusory, resulting from defensive, subversive, or self-deceiving writings of local elites, and it also recognizes forms of unofficial standardization that did not follow Zhu Xi’s Family Rituals. In explaining resistance to official standardization, it emphasizes local agency: as key sites of culturally appropriate emotional expression and as important vehicles for upholding and redrawing local status, funerals tended to develop distinct regional patterns and ramifying variation within them.