bluuebunny/crossref_metadata_2025 huggingface dataset:
Helicobacter pyloriInduces Apoptosis of Macrophages in Association with Alterations in the Mitochondrial Pathway
Authors: Menaker Rena J. , Ceponis Peter J. M. , Jones Nicola L.
Published: April 2004

Helicobacter pyloriis a gastric bacterial pathogen that evades host immune responses in vivo and is associated with the development of gastritis, peptic ulcer disease, and gastric cancers. Induction of macrophage apoptosis is a method employed by multiple pathogens to escape host immune responses. Therefore, we hypothesized thatH. pyloriinduces apoptosis of infected macrophages. RAW 264.7 cells were infected withH. pyloristrain 60190, and apoptosis was assessed. Transmission electron microscopy and fluorescence microscopy showed that infected macrophages displayed morphological features characteristic of apoptosis. Quantification by acridine orange-ethidium bromide fluorescent-dye staining showed that apoptosis was dose and time dependent, and apoptosis was further confirmed by increased binding of annexin V-fluorescein isothiocyanate (FITC) to externalized phosphatidylserine of infected but not of control macrophages. Macrophages infected with isogenic mutants ofH. pyloristrain 60190 deficient in eithercagAorvacAinduced significantly less apoptosis than the parental strain, as assessed by increased binding of annexin V-FITC. Western blot analysis of whole-cell protein lysates revealed that infection with strain 60190 induced a time-dependent increase in cleavage of procaspase 8 and disappearance of full-length Bid compared with uninfected cells. Furthermore, pharmacological inhibition of caspase 8 caused a decrease in levels of apoptosis. Finally, infection caused a time-dependent increase in mitochondrial-membrane permeability and release of cytochromecinto the cytosol. These results suggest thatH. pyloriinduces apoptosis of macrophages in association with alterations in the mitochondrial pathway. Elimination of this key immunomodulatory cell may represent a mechanism employed by the bacterium to evade host immune responses.
LuxS Is Required for Persistent Pneumococcal Carriage and Expression of Virulence and Biosynthesis Genes
Authors: Joyce Elizabeth A. , Kawale Amita , Censini Stefano , Kim Charles C. , Covacci Antonello , Falkow Stanley
Published: April 2004

Streptococcus pneumoniaecauses several diseases, including otitis media, pneumonia, and meningitis. Although little is known about the regulation of or how individual pneumococcal factors contribute to these disease states, there is evidence suggesting that some factors are regulated by a cell-density-dependent mechanism (quorum sensing). Quorum sensing allows bacteria to couple transcription with changes in cell density; bacteria achieve this by sensing and responding to small diffusible signaling molecules. We investigated how the LuxS signaling system impacts the biology ofS. pneumoniae. An analysis of the transcriptional profiles of a serotype 2 strain and an isogenicluxSdeletion strain utilizing anS. pneumoniae-specific microarray indicated that LuxS regulates gene expression involved in discrete cellular processes, including pneumolysin expression. Contrary to the paradigm for quorum sensing, we observed pronounced effects on transcription in early log phase, where gene expression was repressed in the mutant. Assessing the mutant for its ability to infect and cause disease in animals revealed a profound defect in ability to persist in the nasopharyngeal tissues. Our analysis of anS. pneumoniaetranscriptome revealed a function for LuxS in gene regulation that is not dependent upon high cell density and is likely involved in the maintenance of pneumococcal load in susceptible hosts.
Protection Elicited by a Double Leucine and Pantothenate Auxotroph of
Mycobacterium tuberculosis
in Guinea Pigs
Authors: Sampson Samantha L. , Dascher Christopher C. , Sambandamurthy Vasan K. , Russell Robert G. , Jacobs William R. , Bloom Barry R. , Hondalus Mary K.
Published: April 2004

We developed a live, fully attenuated
Mycobacterium tuberculosis
vaccine candidate strain with two independent attenuating auxotrophic mutations in leucine and pantothenate biosynthesis. The Δ
leuD
Δ
panCD
double auxotroph is fully attenuated in the SCID mouse model and highly immunogenic and protective in the extremely sensitive guinea pig tuberculosis model, reducing both bacterial burden and disease pathology.
TwoSalmonellaOmpC Kb-Restricted Epitopes for CD8+-T-Cell Recognition
Authors: Diaz-Quiñonez Alberto , Martin-Orozco Natalia , Isibasi Armando , Ortiz-Navarrete Vianney
Published: April 2004

We report the identification of two peptides fromSalmonellaOmpC porin that can bind to major histocompatibility complex class I Kbmolecules and are targets of cytotoxic T lymphocytes fromSalmonella-infected mice. These peptides are conserved in gram-negative bacterial porins and are the firstSalmonellaporin-specific epitopes described for possible CD8+-T-cell elimination of infected cells.
Upregulation of angiotensin II type 2 receptor expression in estrogen-induced pituitary hyperplasia
Authors: Suarez Cecilia , Díaz-Torga Graciela , González-Iglesias Arturo , Cristina Carolina , Becu-Villalobos Damasia
Published: April 2004

Recent evidence shows that reexpression and upregulation of angiotensin II (ANG II) type 2 (AT2) receptor in adult tissues occur during pathological conditions such as tissue hyperplasia, inflammation, and remodeling. In particular, expression of functional AT2 receptors in the pituitary and their physiological significance and regulation have not been described. In this study, we demonstrate that chronic in vivo estrogen treatment, which induces pituitary hyperplasia, enhances local AT2 expression (measured by Western blot and RT-PCR) concomitantly with downregulation of ANG II type 1 (AT1) receptors. In vivo progesterone treatment of estrogen-induced pituitary hyperplasia did not modify either the ANG II receptor subtype expression pattern or octapeptide-induced and AT1-mediated calcium signaling. Nevertheless, an unexpected potentiation of the ANG II prolactin-releasing effect was observed in this group, and this response was sensitive to both AT1 and AT2 receptor antagonists. These data are the first to document that ANG II can act at the pituitary level through the AT2 receptor subtype and that estrogens display a differential regulation of AT1 and AT2 receptors at this level.
Extra-adipocyte leptin release in human obesity and its relation to sympathoadrenal function
Authors: Eikelis Nina , Lambert Gavin , Wiesner Glen , Kaye David , Schlaich Markus , Morris Margaret , Hastings Jacqueline , Socratous Florentia , Esler Murray
Published: April 2004

The link between the human sympathoadrenalmedullary system and the adipocyte hormone leptin is controversial. We measured total and regional norepinephrine spillover, epinephrine secretion rate, and extra-adipocyte leptin release in 22 lean [body mass index (BMI) <26] and 20 obese (BMI >28) normotensive men who underwent arterial and central venous catheterization. Because plasma clearance of leptin is primarily by renal removal, for men at steady state we could estimate whole body leptin release to plasma from renal plasma leptin extraction. Whole body leptin release was 1,950 ± 643 (means ± SE) ng/min in obese men and 382 ± 124 ng/min in lean men ( P < 0.05). Total and renal norepinephrine spillover rates correlated directly with whole body leptin secretion rate. Leptin is released from multiple nonadipocyte sites, which we tested by use of simultaneous arteriovenous blood sampling. We found a surprisingly large contribution of brain leptin release to the plasma leptin pool, 529 ± 175 ng/min (>40% whole body leptin release), with greater leptin release in obese than in lean men, 935 ± 321 vs. 160 ± 59 ng/min ( P = 0.045). In parallel with leptin measurements, we also quantified brain serotonin turnover and jugular overflow of neuropeptide Y (NPY). Brain serotonin turnover was higher in obese than in lean men, 227 ± 112 vs. 21 ± 14 ng/min ( P = 0.019), as was overflow of NPY from the brain, 12.9 ± 1.4 vs. 5.3 ± 2.2 ng/min ( P = 0.042). These results suggest that leptin is released within the brain and at an increased rate in obese humans, in whom activation of brain serotonergic and NPY mechanisms also exists.
Transplacental delivery of retinoid: the role of retinol-binding protein and lipoprotein retinyl ester
Authors: Quadro Loredana , Hamberger Leora , Gottesman Max E. , Colantuoni Vittorio , Ramakrishnan Rajasekhar , Blaner William S.
Published: April 2004

Retinoids are required for normal embryonic development. Both embryonic retinoid deficiency and excess result in congenital malformations. There is little understanding of the physiology underlying retinoid transfer from the maternal circulation to the embryo. We now report studies that explore this process using retinol-binding protein-deficient (RBP−/−) mice and mice that express human RBP on the RBP−/−background. Our studies establish that dietary retinoid, bound to lipoproteins, can serve as an important source for meeting tissue retinoid requirements during embryogenesis. Indeed, retinyl ester concentrations in the circulations of pregnant RBP−/−mice are significantly elevated over those observed in wild-type mice, suggesting that lipoprotein retinyl esters may compensate for the absence of retinol-RBP during pregnancy. We also demonstrate, contrary to earlier proposals, that maternal RBP does not cross the placenta and cannot enter the fetal circulation. Overall, our data indicate that both retinol-RBP and retinyl esters bound to lipoproteins are able to provide sufficient retinoid to the embryo to allow for normal embryonic development.
Random sums of random vectors and multitype families ofproductive individuals
Authors: Rahimov I. , Muttlak H.
Published: April 2004

We prove limit theorems for a family of random vectors whose
coordinates are a special form of random sums of
Bernoulli random variables. Applying these limit theorems, we
study the number of productive individuals in n‐type
indecomposable critical branching stochastic processes with types
of individuals T1, …, Tn.
Sobolev space estimates for solutions of the equation∂¯u=f on polycylinders
Authors: Darko Patrick W. , Lutterodt Clement H.
Published: April 2004

In trying to improve Weinstock′s results on approximation
by holomorphic functions on certain product domains, we
are led to estimates in Sobolev spaces for the ‐operator on polycylinders for (γ, q)‐forms.
This generalizes our results for the same operator on
polycylinders previously obtained, and can be applied to a number
of other problems such as the Corona problem.
Atherosclerosis in the Apolipoprotein E–Deficient Mouse
Authors: Meir Karen S. , Leitersdorf Eran
Published: April 2004

Arguably the most critical advancement in the elucidation of factors affecting atherogenesis has been the development of mouse models of atherosclerosis. Among available models, the apolipoprotein E–deficient (apoE−/−) mouse is particularly popular because of its propensity to spontaneously develop atherosclerotic lesions on a standard chow diet. A Medline search reveals over 645 articles dedicated to studies using this reliable and convenient “super” animal model since its inception (Piedrahita JA et al,
Proc Natl Acad Sci U S A
1992;89:4471–4475; Plump AS et al,
Cell
1992;71:343–353) with a more or less steady increase from year to year. This review will examine our present understanding of the pathology and progression of plaques in this animal and highlight some of the nutritional, pharmacological, and genetic studies that have enhanced this understanding.
Parecoxib Sodium, an Injectable COX‐2‐Specific Inhibitor, Does Not Affect Unfractionated Heparin‐Regulated Blood Coagulation Parameters
Authors: Noveck Robert J. , Hubbard Richard C.
Published: April 2004

The objective of this study was to evaluate the potential for hemostatic interaction between a full analgesic dose of parecoxib sodium (parecoxib), a prodrug of the COX‐2 specific inhibitor valdecoxib, and unfractionated heparin (UFH) in healthy male subjects. This open‐label, single‐center study comprised two treatment periods. In treatment period I, fasted, eligible subjects (n = 18) received a UFH bolus (4000 U) followed by a 36‐hour UFH infusion (start dose 10–14 U/ kg). Activated partial thromboplastin time (aPTT), prothrombin time (PT), and platelet counts were measured at regular intervals up to 24 hours after the end of the UFH infusion. After a 2‐day washout, patients randomized to treatment period II received a full analgesic dosage of parecoxib 40 mg bid intravenously (IV) for 6 days (n = 18), with concomitant UFH (same regimen as treatment period I) on day 5 (n = 18). APTT, PT, and platelet counts were evaluated at regular intervals up to 24 hours after UFH infusion. Coadministration of parecoxib 40 mg bid IV with UFH (treatment period II) had no significant effect on aPTT, PT, or platelet counts, which were similar to those of participants receiving UFH alone (treatment period I) at all time points. These results show that a full analgesic dose of parecoxib, a COX‐2‐specific inhibitor available for parenteral administration, can be coadministered with UFH without affecting blood coagulation parameters. Therefore, parecoxib may be administered to patients who are receiving UFH for thromboprophylaxis.
History and Memory: Construction, Deconstruction and Reconstruction
Authors: Aymard Maurice
Published: April 2004

For once our societies are in agreement with the social and human sciences, that is, the sciences that have made these societies their subject of study and claim to provide them with a knowledge of themselves that the societies treat with a distant respect without being very sure they really need it: for our societies, as well as for the social and human sciences, memory is on the agenda, it has become a compulsory reference point. Our societies even agree to hear about a ‘duty to remember’ resembling an ethical and political requirement they could not evade. The preservation and promotion of every trace of the past has become one of the most general and least discussed aspects of every cultural policy. The term ‘heritage’ has entered the official language and is combined with a large number of adjectives: artistic, ethnological, archaeological, ecological, animal and plant. It is as if, in order to find an excuse and make people forget, societies, which on one hand are clearly ambitious for strong economic growth, progress and adaptation to new technologies, had on the other to compensate by making frequent reference to a past they do not wish to lose, destroy or consign to oblivion, even though they continually turn their back on it.
Migrant Memories and Temporality
Authors: Neves Luiz Felipe Baêta
Published: April 2004

Social memory does not exist only as a collection of remembrances that a group recognizes as theirs. Much more than simple forms of expression of memory, the more or less ritualized situations it is involved in serve to express its continuity. Rituals are an attempt to preserve the cultural identity of a people, or a section of a people. It is clear that the social imaginary more often than not tends to give them a very big part to play. And so rituals appear to be an expression of memory that should be represented, or presented again, as synonymous with history. This imaginary sets up memory as something absolute: it must know everything. Symbolically confused with history, memory may even, in this imaginary, make it possible for people to find their place in the world. Memory and history may then be the elements making up reason. In losing their memory - or their history - they would lose the ability to distinguish and discern.
Afro-Brazilian Identity and Memory
Authors: Prandi Reginaldo
Published: April 2004

The problem of the construction of memory that faces the Afro-Brazilian population presents itself as more than a simple need for an identity connected to an original past, but in addition as essential, because for historical reasons their social reality has not yet reached the end of its struggle.
Memory and Distance: Learning from a Gilded Silver Vase (Antwerp, c. 1530)
Authors: Ginzburg Carlo
Published: April 2004

1. In 1929, a few months before his death, Aby Warburg wrote an introduction to his last intellectual project: the ‘Picture Atlas’ (Bilderatlas) which he dedicated to Mnemosyne, the Greek goddess of memory, whose name was inscribed on the front door of the Kulturwissenschaftliche Bibliothek he had founded. The opening sentences of Warburg's introduction, first published 70 years after his death in Italian translation, read: ‘The conscious creation of distance between the self and the external world may be called the fundamental act of civilization. Where this gap conditions artistic creativity, this awareness of distance can achieve a lasting social function.’
The Evolution of Research in Family and Consumer Sciences: Food, Nutrition, and Health
Authors: Schlenker Eleanor D.
Published: April 2004

Changing perspectives in food, nutrition, and health are bringing new research opportunities. Knowledge that nutrients and other food substances prevent chronic disease expanded the study of dietary requirements beyond merely obviating deficiency. Government policy makers mandate food guidance programs to enable consumers to choose foods that are culturally appropriate yet support health. Intervention strategies leading to suitable food behavior are needed to address the rising health costs associated with aging and chronic diseases. Functional foods carrying added health benefits have gripped the attention of food producers and consumers, yet much is to be learned regarding long term effects. FCS professionals are uniquely qualified to study not only the theoretical bases of these issues but also their impact on the physical and psychosocial well‐being of families. Research methods and applications must be incorporated at all academic levels to prepare FCS professionals to meet the research opportunities and challenges ahead.
The Evolution of Research in Consumer Science: A 200‐Year Perspective
Authors: Abdel‐Ghany Mohamed
Published: April 2004

This article traces the evolution of research in consumer science and highlights historical, social, institutional, and economic events that shaped the field. It gives an overview of research conducted from the late 1790s to the 1990s in the areas of family economics, consumer economics, consumption economics, and home management and chronicles legislative and administrative developments that affected consumer science research. Research topics, the use of theory or lack thereof, and typical statistical techniques are summarized at the end of each historic period.
Housing, Equipment, and Design Research and Scholarship: A Family and Consumer Sciences Perspective
Authors: Beamish Julia O. , Ahn Mira , Seiling Sharon
Published: April 2004

Periodic reviews of research in the housing, equipment, and design specializations within family and consumer science have occurred in the past, documenting the status of research topics, methods, and theory. This article addresses research and scholarship in the housing, equipment, and design disciplines over the past 16 years by analyzing relevant publications with a family and consumer science perspective. Articles from three journals were analyzed to determine the number, university affiliation, topic, purpose, type, data collection, data analysis, and use of theory. Results indicate a decline in the total number of articles in these journals related to housing, equipment, and design. About one third of the articles utilized theory, and these articles used three theories frequently. Scholars in housing, equipment, and design should continue to publish in family and consumer science‐related journals to continue the expansion and further the depth of these disciplines within the broader field.
Saturday Morning Children's Television Advertising: A Longitudinal Content Analysis
Authors: Byrd‐Bredbenner Carol
Published: April 2004

The content of advertisements broadcast in 1993 and 1999 during top‐ranked Saturday morning children's network television programs was analyzed and compared with dietary recommendations and advertising guidelines. Study data were compared to earlier work to create a longitudinal perspective. One fourth to one sixth of broadcast time was devoted to commercials. Over the past three decades, food was the largest advertisement category. Produce, protein‐rich foods, and dairy products were rarely advertised. Advertisements for breakfast cereals and foods high in sugar or fat predominated. Food advertisements over the past 30 years are not reflective of dietary recommendations. However, most adhered to advertising guidelines.
Acceptability of Fudge Prepared Using Tofu as a Fat‐Ingredient Substitute
Authors: Keller Jay R. , Rankin Linda L. , Harris Karla D.
Published: April 2004

The palatability and overall acceptability of fudge prepared using pureed tofu as a replacement for 50%, 75%, and 100% of the fat ingredient were determined by a sensory panel. Eighty‐three percent to 89% of the sensory panelists gave the 50% tofu substitution an acceptable score (< 5) for all the parameters (appearance, texture, flavor, and overall acceptability), 85% to 91% of the panelists gave the 75% tofu substitution an acceptable score for all parameters, and 73% to 89% of the panelists gave the 100% tofu substitution an acceptable score. This study showed that using pureed tofu as a partial fat replacement resulted in acceptable fudge, even when tofu was substituted for the entire fat ingredient.
A mouse model for visualization and conditional mutations in the erythroid lineage
Authors: Heinrich Achim C. , Pelanda Roberta , Klingmüller Ursula
Published: April 2004

Hematologic disorders can be caused by sporadic or inherited mutations. However, the molecular mechanisms that lead to pathogenicity are only partially understood. An accurate method to generate mouse models is conditional gene manipulation facilitated by the Cre-loxP recombination system. To enable identification and genomic manipulation of erythroid progenitor cells, we established a knock-in mouse model (ErGFPcre) that expresses an improved GFPcre fusion protein controlled by the endogenous erythropoietin receptor (EpoR) promoter. We show that ErGFPcre mice enable the identification of GFP-positive erythroid progenitor cells and the highly specific genomic manipulation of the erythroid lineage. Analysis of GFP-positive erythroid progenitor cells suggests a developmental switch in lineage progression from the hematopoietic stem cell compartment to early erythroid progenitor cells that are stem cell antigen-1–negative (Sca-1–) and c-kithigh. Within the hematopoietic system, Cre-mediated recombination is limited to erythroid progenitor cells and occurs in the adult bone marrow at a frequency of up to 80% and in the fetal liver with an efficiency close to 100%. Differential transcriptional activity of the wild-type and the knock-in locus was observed in nonhematopoietic tissues. Thus, our ErGFPcre mouse model could promote the identification of regulatory elements controlling nonhematopoietic EpoR expression and facilitates the characterization and genomic manipulation of erythroid progenitor cells.
Asthma severity and medical resource utilisation
Authors: Antonicelli L. , Bucca C. , Neri M. , De Benedetto F. , Sabbatani P. , Bonifazi F. , Eichler H‐G. , Zhang Q. , Yin D.D.
Published: April 2004

Asthma represents a growing public health problem and the cost of asthma has been rising in many countries. The aim of this study was to estimate the direct and indirect cost of asthma among adult patients in Italy, and to assess the relationship between healthcare resource use and asthma severity according to the Global Initiative for Asthma (GINA) classification system.

A multicentre cross-sectional study was conducted in 16 Italian hospital-based specialised asthma clinics. Data collection was based on self-administered questionnaires and took place during the period May 1–November 30, 1999, and 500 consecutive patients with asthma, aged 18–55 yrs, were enrolled during regularly scheduled visits. Direct costs (drugs, physician visits, emergency service use and hospitalisation), indirect costs (loss of paid workdays) and total costs were determined in euros () for 1999.

Patients with more severe disease, as classified by the GINA guideline, exhibited more night-time and daytime symptoms and were more limited in performing normal daily activities. The mean total cost of asthma per patient per year was estimated to be 1,260; drug costs accounted for 16%, physician costs 12%, emergency service and hospitalisation costs 20% and indirect costs 52% of the mean cost. Stratified by severity, the total annual cost per patient amounted to 720, 1,046, 1,535 and 3,328 for patients with intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively.

Asthma severity, as determined by the Global Initiative for Asthma classification, is significantly associated with symptoms, limitations in normal daily activities, asthma-related medical resource utilisation and both direct and indirect costs. Asthma control is not only a clinical but also an economic imperative.
Report of a workshop: quantitative computed tomography scanning in longitudinal studies of emphysema
Authors: Newell J.D. , Hogg J.C. , Snider G.L.
Published: April 2004

It has been reported that quantitative computed tomography (CT) scanning of the lungs showed decreased progression of emphysema in a randomised clinical trial in patients with severe α1‐antitrypsin (α1‐AT) deficiency receiving monthly intravenous augmentation therapy with human α1‐AT. Comparable results were not obtained using rate of decline of forced expiratory volume in one second.

Accordingly, the Alpha‐1 Foundation convened a workshop to explore the feasibility of using quantitative CT data as a primary outcome variable in trials of drugs for treating α1‐AT deficiency.

This report reviews the following: the principles for the use of modern CT scanners for quantifying emphysema; the methods and data on validation by comparison with measurements of severity of emphysema in inflation-fixed specimens of lungs; and the possibility of decreasing radiation dosage from CT to make it safe and ethically possible to use CT in longitudinal studies.

The workshop concluded that it is feasible, safe and ethically possible to use computed tomography in longitudinal studies of emphysema. It recommended that the primary end-point should be a significant shift in the 15th percentile of lung density.
Inhaled corticosteroids and the risk of a first exacerbation in COPD patients
Authors: de Melo M.N. , Ernst P. , Suissa S.
Published: April 2004

The role of inhaled corticosteroids (ICS) in asthma is well established, but their benefit in the management of chronic obstructive pulmonary disease (COPD) is still controversial. The current study assessed whether ICS are effective in preventing a first exacerbation of COPD.

A cohort of newly treated COPD patients was formed from the Administrative Databases of Saskatchewan Health. The outcome was the occurrence of a first moderate or severe exacerbation from 1990–1999. Moderate exacerbations involved prescriptions for an antibiotic and an oral corticosteroid on the same day. Severe exacerbations were hospitalisations with a primary discharge diagnosis of COPD. A nested case-control design was used and matched on year of birth and cohort entry. Rate ratios (RR) were further adjusted for use of other medication and other confounders.

There were 995 exacerbations among 4,455 subjects. The rate of a first exacerbation was increased with any use of ICS in the year prior to the index date (RR: 1.27; 95% CI: 1.08–1.48) and with current use (RR: 1.51; 95% CI: 1.22–1.87), and it increased with increasing daily doses of ICS.

Inhaled corticosteroids do not seem to be beneficial in reducing the risk of a first exacerbation of chronic obstructive pulmonary disease.
Suppression of matrix metalloproteinase production from nasal fibroblasts by macrolide antibioticsin vitro
Authors: Kanai K. , Asano K. , Hisamitsu T. , Suzaki H.
Published: April 2004

It is well known that low-dose and long-term administration of macrolide antibiotics favourably modify the clinical status of chronic airway inflammatory diseases. However, the therapeutic mode of action of macrolide antibiotics is not well understood. The present study aimed to examine the influence of macrolide antibiotics, roxithromycin (RXM) and josamycin (JM) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts (NPF)in vitro.

NPF, at a concentration of 2.5×105cells·mL−1, were stimulated with tumour necrosis factor (TNF)-α in the presence of various concentrations of RXM or JM for 24 h. MMP‐2 and ‐9 levels in culture supernatants were analysed by ELISA, and MMP mRNA expression was examined by RT-PCR. The influence of RXM on nuclear factor (NF)-κB and activator protein (AP)‐1 activation was also examined.

Addition of RXM (but not JM) at 5.0 and 7.5 µg·mL−1significantly suppressed the production of MMP‐2 and ‐9 from NPF induced by TNF-α stimulation. RXM also suppressed MMP mRNA expression through the inhibition of NF-κB and AP-1 activation.

The present results suggest that the suppressive activity of roxithromycin on MMP‐2 and ‐9 production is, in part, responsible for the therapeutic action of macrolides on chronic airway inflammatory diseases.
Increased long-term mortality in heart failure due to sleep apnoea is not yet proven
Authors: Roebuck T. , Solin P. , Kaye D.M. , Bergin P. , Bailey M. , Naughton M.T.
Published: April 2004

Previous small-scale studies of the effect of sleep-disordered breathing (SDB) on prognosis in congestive heart failure (CHF) are either lacking or conflicting.

The aim of this study was to assess the impact of the presence and type of SDB on mortality in a patient group with severe CHF referred to a specialised heart failure centre.

Out of 78 patients ((mean±sd) 53±9 yrs, left ventricular ejection fraction 19.9±7.2% and pulmonary capillary wedge pressure 16.5±8.3 mmHg) followed-up over a median period of 52 months, 29% had no apnoea (CHF‐N), 28% had obstructive sleep apnoea (CHF‐OSA) and 42% had central sleep apnoea (CHF‐CSA). At 52 months, their overall mortality was 40%, and combined mortality and transplantation was 72%. Mortality rates were similar between the three apnoea groups. Survivors had a similar prevalence of SDB (71%) as the nonsurvivors (70%). Although a significant increase in mortality was evident at 500 days in those patients with either CHF‐SDB or CHF‐CSA as compared with CHF‐N, this was not significant at final follow-up (52 months) using Kaplan Meier analysis. Multivariate analysis identified transplantation but not SDB type or severity as a significant predictor of survival.

In conclusion, sleep-disordered breathing impacts upon early (500 day), but not long-term (52 month), mortality in a specialised heart failure centre.
Masquerade syndrome: sebaceous carcinoma presenting as an unknown primary with pagetoid spread to the nasal cavity
Authors: Shet Tanuja , Kelkar Gauri , Juvekar Shashi , Mistry Rajesh , Borges Anita
Published: April 2004

Sebaceous carcinoma of the eyelid is an uncommon tumour with unusual modes of presentation. It can remain occult at the primary site, without producing any mass, masquerading as chronic blepharoconjunctivitis, while setting up metastases in the regional lymph nodesespecially in the pre-auricular group.

We report here a case that not only masqueraded as chronic blepharoconjunctivitis with nodal metastases from an ’unknown primary’ in the neck, but whose tumour spread in a pagetoid manner along the nasolacrimal duct producing a nasal tumour that was believed to be the ’unknown primary’.

This case emphasizes the need for ophthalmologists, ENT surgeons and pathologists to keep sebaceous carcinoma in mind while evaluating patients with chronic blepharoconjunctivitis and cervical node metastases from ’unknown primary’. Histological clues for picking up a sebaceous carcinoma at a metastatic site include a tumour with comedo or ductal growth pattern and intracytoplasmic lipid.
50th Anniversary Article: The Marketing Department in Management Science: Its History, Contributions, and the Future
Authors: Morrison Donald G. , Raju Jagmohan S.
Published: April 2004

This year marks the 50th anniversary of Management Science. We take this opportunity to trace the history of the Marketing Department in Management Science, outline the role that the Marketing Department has played in supporting management science research in Marketing, its impact on the field, and its plans for the future.
Optokinetic Deficits in Albino Ferrets (Mustela putorius furo): A Behavioral and Electrophysiological Study
Authors: Hoffmann Klaus-Peter , Garipis Nicolaos , Distler Claudia
Published: April 2004

We compared the horizontal optokinetic reaction (OKR) and response properties of retinal slip neurons in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) of albino and wild-type ferrets (Mustela putorius furo). In contrast to pigmented ferrets, we were unable to observe OKR in albino ferrets during binocular and monocular viewing using random dot full field stimulation and electro-oculography (EOG). Observations during early postnatal life indicate that regular OKR is present in pigmented pups 3 d after eye opening but is absent at any stage during development in albino ferrets. Unilateral muscimol injections to inactivate all neurons in the NOT-DTN containing GABAAand GABACreceptors caused spontaneous horizontal nystagmus with slow phases away from the injected hemisphere in albino as well as in pigmented animals. Retinal slip neurons in the NOT-DTN of albino ferrets identified by antidromic activation from the inferior olive and orthodromic activation from the optic chiasm were well responding to intermittent bright light stimuli, but many showed a profound reduction of responsiveness to moving stimuli. The movement-sensitive neurons exhibited no clear direction selectivity for ipsiversive stimulus movement, a characteristic property of these neurons in pigmented ferrets and other mammals. Thus, the defect rendering albino ferrets optokinetically nonresponsive is located in the visual pathway subserving the OKR, namely in or before the NOT-DTN, and not in oculomotor centers.
Transient Blockade of the CD11d/CD18 Integrin Reduces Secondary Damage after Spinal Cord Injury, Improving Sensory, Autonomic, and Motor Function
Authors: Gris Denis , Marsh Daniel R. , Oatway Mark A. , Chen Yuhua , Hamilton Eilis F. , Dekaban Gregory A. , Weaver Lynne C.
Published: April 2004

The early inflammatory response to spinal cord injury (SCI) causes significant secondary damage. Strategies that nonselectively suppress inflammation have not improved outcomes after SCI, perhaps because inflammation has both adverse and beneficial effects after SCI. We have shown that the selective, time-limited action of a monoclonal antibody (mAb) to the CD11d subunit of the CD11d/CD18 integrin, delivered intravenously during the first 48 hr after SCI in rats, markedly decreases the infiltration of neutrophils and delays the entry of hematogenous monocyte-macrophages into the injured cord. We hypothesized that this targeted strategy would lead to neuroprotection and improved neurological outcomes. In this study the development of chronic pain was detected in rats by assessing mechanical allodynia on the trunk and hindpaws 2 weeks to 3 months after a clinically relevant clip-compression SCI at the twelfth thoracic segment. The anti-CD11d mAb treatment reduced this pain by half. Motor performance also improved as rats were able to plantar-place their hindpaws and use them for weight support instead of sweeping movements only. Improved cardiovascular outcome was shown after SCI at the fourth thoracic segment by significant decreases in autonomic dysreflexia. Locomotor performance was also improved. These functional changes correlated with significantly greater amounts and increased organization of myelin and neurofilament near the lesion. The improved neurological recovery after the specific reduction of early inflammation after SCI demonstrates that this selective strategy increases tissue at the injury site and improves its functional capacity. This early neuroprotective treatment would be an ideal foundation for building later cell-based therapies.
Bildfolgenauswertung zur Inspektion geschliffener Oberflächen (Analysis of Image Sequences for the Inspection of Grinded Surfaces)
Authors: Xin Binjian , Heizmann Michael , Kammel Sören , Stiller Christoph
Published: April 2004

Thema des Beitrags ist die automatische visuelle Inspektion geschliffener Oberflächen. Dazu werden neuartige Strategien auf der Grundlage von Bildfolgen mit variiertem Azimut einer gerichteten Beleuchtung vorgestellt, die sich zur Detektion von Fehlstellen in Schleiftexturen mit mehreren Riefenscharen eignen. Im Parameterraum der Beleuchtung werden geeignete Merkmale definiert, um Defektstellen in der Schleiftextur sicher zu klassifizieren. Gegenüber Standardverfahren, die eine Texturanalyse durch Auswertung lokaler Nachbarschaftsbeziehungen vornehmen, benötigen die hier gezeigten Strategien eine bedeutend geringere Bildauflösung und erweisen sich auch bei den i. Allg. schwierig zu beleuchtenden Schleiftexturen als zuverlässig und robust.
Electrospray‐Assisted Fabrication of Uniform Photonic Balls
Authors: Moon J. H. , Yi G.‐R. , Yang S.‐M. , Pine D. J. , Park S. B.
Published: April 2004

Photonic balls have been fabricated (see Figure) by field‐enhanced electrospray of an aqueous colloidal suspension. The polystyrene (PS) beads inside the suspension droplets self‐organize into opaline balls while the solvent evaporates. The opaline balls are used as templates for inverse opaline photonic balls, and both types exhibit varying reflection colors depending on the diameter of the beads and the reflective index contrast.
Soft Lithographic Patterning of Hyaluronic Acid on Hydrophilic Substrates Using Molding and Printing
Authors: Suh K. Y. , Khademhosseini A. , Yang J. M. , Eng G. , Langer R.
Published: April 2004

Hyaluronic acid (HA) was patterned using two soft lithographic methods on various substrates including glass, silicon dioxides, poly(hydroxyethyl methacrylate) [poly(HEMA)], polystyrene cell culture dishes, and biodegradable polylactic glycolic acid (PLGA), with no or minor chemical modification. Results indicate that HA could be used as a general platform on hydrophilic substrates for cell and protein patterning (see Figure).
All‐Organic Permanent Memory Transistor Using an Amorphous, Spin‐Cast Ferroelectric‐like Gate Insulator
Authors: Schroeder R. , Majewski L. A. , Grell M.
Published: April 2004

An all‐organic memory transistor (“FerrOFET”) with a solution‐ deposited ferroelectric‐like nylon gate insulator is demonstrated. Cheaper and easier to build than inorganic ferroelectric transistors, yet with comparable performance and compatible with flexible substrates, this device is suitable for most information storage organic electronics applications. The Figure shows the memory function of the FerrOFET as hysteresis in the transfer characteristics.
Second Phase Effects on the Conductivity of Non‐Aqueous Salt Solutions: “Soggy Sand Electrolytes”
Authors: Bhattacharyya A. J. , Maier J.
Published: April 2004

Introducing insulating phases into non‐aqueous salt solution leads to remarkable conductivity enhancements, an effect ascribed to breaking up of ion pairs. This new class of electrolytes combines the high ionic conductivities of liquids and beneficial mechanical properties of soft matter (“soggy sand”; see Figure).
Induction of premature chromatid separation (PCS) in individuals with PCS trait and in normal controls
Authors: Ikeuchi Tatsuro , Yang Zeng‐Quan , Wakamatsu Kyoko , Kajii Tadashi
Published: April 2004

Cultured peripheral blood lymphocytes from ten normal individuals, treated with 0.075 M KCl at 37°C for 20 min, showed 0–2% cells in premature chromatid separation (PCS), a configuration with split centromeres and chromatids of most or all chromosomes. When treated for 30 min, they increased to 19% in the average, and at 45 min to 63%. Similar and significant effects of temperature and duration of hypotonic treatment on the frequencies of PCSs were found also in mitotic lymphocytes from patients with homozygous PCS trait, a cancer‐prone disorder with >50% lymphocytes in PCS, mosaic variegated aneuploidy, and a variety of clinical manifestations; and from their heterozygous carrier parents. B lymphoblastoid cells from two infants with the homozygous PCS trait did not show PCSs when processed without hypotonic treatment. The frequencies of their PCSs increased with increasing temperature and duration of hypotonic treatment, attaining more than 65% after 20 min treatment and 90% after 45 min at 37°C. PCS is thus likely to be induced largely by hypotonic treatment. Treatment at 37°C for 20 min was found to be most suitable for the count of PCSs, in which the frequency of PCSs becomes almost zero in cells from normal individuals, and the difference in frequency of PCSs was most remarkable between the patients and heterozygous carriers, and between the heterozygous carriers and normal individuals. Chromosomes from the patients with the homozygous PCS trait tended to be long, and their PCSs tended to have a large number of widely separated sister chromatids. Chromosomes from normal individuals tended to be short, and the sister chromatids in their PCSs were set close to each other. © 2004 Wiley‐Liss, Inc.
Hermansky–Pudlak syndrome type 4 in a patient from Sri Lanka with pulmonary fibrosis
Authors: Bachli Esther B. , Brack Thomas , Eppler Elisabeth , Stallmach Thomas , Trüeb Ralph M. , Huizing Marjan , Gahl William A.
Published: April 2004

Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a platelet storage pool deficiency. Some patients also develop fatal pulmonary fibrosis and some have granulomatous colitis. Six human genes HPS1, ADB3A, HPS3, HPS4, HPS5, and HPS6 have been identified as cause of the six known subtypes of HPS. While there exist nearly 500 Puerto Rican and non‐Puerto Rican HPS‐1 patients, very few HPS‐4 patients have been reported, and most of these have not been described in detail. We now delineate the clinical characteristics of an HPS‐4 patient homozygous for a novel HPS‐4 mutation, P685delC. The patient, the first individual with HPS reported from Sri Lanka, had severe pulmonary fibrosis, typical of HPS‐1 disease, without granulomatous colitis. We conclude that pulmonary fibrosis occurs as part of HPS‐4 and that HPS should be considered in all ethnic groups. © 2004 Wiley‐Liss, Inc.
Confirmation of a dyslexia susceptibility locus on chromosome 1p34‐p36 in a set of 100 Canadian families
Authors: Tzenova Jordana , Kaplan Bonnie J. , Petryshen Tracey L. , Field L. Leigh
Published: April 2004

Dyslexia is a common and genetically complex trait that manifests primarily as a reading disability independent of general intelligence and educational opportunity. Strong evidence for a dyslexia susceptibility locus on chromosome 1p34‐p36 (near marker D1S199) was recently reported, and an earlier study found suggestive evidence for linkage to the same region. We tested for the presence of a dyslexia gene in this region in a sample of 100 Canadian families using both qualitative and quantitative definitions of the phenotype. Using a qualitative definition of dyslexia (affected, unaffected, or uncertain), the largest multipoint Genehunter Maximum LOD‐Score (MLS) in 100 core nuclear families was 3.65 at D1S507, distal to D1S199. Quantitative trait locus (QTL) linkage analysis was performed for four measures of dyslexia (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) employing the variance components approach implemented in Genehunter. Using a model with QTL additive and dominance variance and polygenic additive variance, the multipoint LOD scores maximized proximal to D1S199 (between D1S552 and D1S1622), with peaks of 4.01 for spelling and 1.65 for phonological coding (corresponding LOD scores under 1 degree of freedom were 3.30 and 1.13, respectively). In conclusion, our study confirms and strengthens recent findings of a dyslexia susceptibility gene on chromosome 1p34‐p36 (now designated DYX8). © 2003 Wiley‐Liss, Inc.
COMT158 polymorphism and hostility
Authors: Volavka Jan , Kennedy James L. , Ni Xingqun , Czobor Pal , Nolan Karen , Sheitman Brian , Lindenmayer Jean‐Pierre , Citrome Leslie , McEvoy Joseph , Lieberman Jeffrey A.
Published: April 2004

The main study was designed primarily to compare the clinical effects of four antipsychotics in 157 patients with schizophrenia or schizoaffective disorder. The secondary genetic study, reported here, is based on a subset of 60 patients who consented to genotyping assays. Based on previous work with the catechol‐O‐methyltransferase (COMT) 158 polymorphism, we hypothesized that the Met–Met homozygotes would be more hostile than the heterozygotes and the Val–Val homozygotes. Hostility ratings at baseline were used to test this hypothesis. The Met–Met homozygotes (N = 7) were found to have significantly higher levels of hostility than the other patients (N = 53). The hypothesis was thus supported. The finding should be replicated in a larger sample. © 2003 Wiley‐Liss, Inc.
Tourette syndrome is not caused by mutations in the central cannabinoid receptor (CNR1) gene
Authors: Gadzicki Dorothea , Müller‐Vahl Kirsten R. , Heller Daniela , Ossege Sebastian , Nöthen Markus M. , Hebebrand Johannes , Stuhrmann Manfred
Published: April 2004

Tourette syndrome (TS) is a complex inherited disorder of unknown aetiology, characterized by multiple motor and vocal tics. Involvement of the central cannabinoid (CB1) system is suggested because of therapeutic effects of marijuana (Cannabis sativa L.) consumption and Δ9‐tetrahydrocannabinol (‐THC) treatment in TS patients. The central cannabinoid receptor (CNR1) gene encoding the CNR1 was considered as a candidate gene for TS and systematically screened by single‐strand conformation polymorphism (SSCP) analysis and sequencing. Compared with the published CNR1 sequence, three single base substitutions were identified: 1326T → A, 1359G → A, 1419 + 1G → C. The change at position 1359 is a common polymorphism (1359 G/A) without allelic association with TS. 1326T → A was present in only one TS patient and is a silent mutation which does not change codon 442 (valine). 1419 + 1G → C affects the first nucleotide immediately following the coding sequence. It was first detected in three of 40 TS patients and none of 81 healthy controls. This statistically significant association with TS (P = 0.034) could not be confirmed in two subsequent cohorts of 56 TS patients (one heterozygous for 1419 + 1G → C) and 55 controls and 64 patients and 66 controls (one heterozygous for 1419 + 1G → C), respectively. Transcript analysis of lymphocyte RNA from 5 1419 + 1G → C carriers revealed no systematic influence on the expression level of the mutated allele. In addition, segregation analysis of 1419 + 1G → C in affected families gave evidence that 1419 + 1G → C does not play a causal role in the aetiology of TS. We conclude that genetic variations of the CNR1 gene are not a plausible explanation for the clinically observed relation between the cannabinoid system and TS. © 2004 Wiley‐Liss, Inc.