bluuebunny/crossref_metadata_2025 huggingface dataset:
HYPERTENSION 2020: CONFRONTING TOMORROW'S PROBLEM TODAY
Authors: Reid Christopher M , Thrift Amanda G
Published: April 2005

1. In developed countries, the major burden of disease is due to chronic diseases, such as heart disease and stroke. In contrast, the major burden of disease among people in developing countries has been due largely to diseases caused by malnutrition, poor sanitation and infection. In recent years, with increasing economic and demographic development, there has been a shift in developing countries from diseases caused by poverty towards chronic, non‐communicable, lifestyle‐related diseases. The rapid emergence of these chronic diseases has not occurred with a similarly rapid decline in infectious diseases. Therefore, these developing countries are experiencing high rates of both infectious and chronic diseases.

2. The increase in chronic diseases in developing countries has been brought about by the increasing prevalence of risk factors, such as increased alcohol consumption, smoking, obesity, physical inactivity and low fruit and vegetable intake. In parallel with this, there is also increased evidence of high blood pressure and high cholesterol levels.

3. The preventive strategies required to reverse this trend for these emerging diseases include the education of public health professionals, the introduction of surveillance activities to monitor changes in risk factors, the introduction of health promotion, the development of prevention research and improved advocacy for disease prevention programmes. Experience from other countries provides evidence that prevention programmes can work. The global challenge is to ensure that implementation of such programmes in the world's developing nations does not come too late.
MECHANISMS MEDIATING PRESSURE NATRIURESIS: WHAT WE KNOW and WHAT WE NEED TO FIND OUT
Authors: Evans Roger G , Majid Dewan SA , Eppel Gabriela A
Published: April 2005

1. It is well established that pressure natriuresis plays a key role in long‐term blood pressure regulation, but our understanding of the mechanisms underlying this process is incomplete.

2. Pressure natriuresis is chiefly mediated by inhibition of tubular sodium reabsorption, because both total renal blood flow and glomerular filtration rate are efficiently autoregulated. Inhibition of active sodium transport within both the proximal and distal tubules likely makes a contribution. Increased renal interstitial hydrostatic pressure (RIHP) likely inhibits sodium reabsorption by altering passive diffusion through paracellular pathways in ‘leaky’ tubular elements.

3. Nitric oxide and products of cytochrome P450‐dependent arachidonic acid metabolism are key signalling mechanisms in pressure natriuresis, although their precise roles remain to be determined.

4. The key unresolved question is, how is increased renal artery pressure ‘sensed’ by the kidney? One proposal rests on the notion that blood flow in the renal medulla is poorly autoregulated, so that increased renal artery pressure leads to increased renal medullary blood flow (MBF), which, in turn, leads to increased RIHP. An alternative proposal is that the process of autoregulation of renal blood flow leads to increased shear stress in the preglomerular vasculature and, so, release of nitric oxide and perhaps products of cytochrome P450‐dependent arachidonic acid metabolism, which, in turn, drive the cascade of events that inhibit sodium reabsorption.

5. Central to the arguments underlying these opposing hypotheses is the extent to which MBF is autoregulated. This remains highly controversial, largely because of the limitations of presently available methods for measurement of MBF.
PATHOGENESIS OF HYPERTENSION IN RENAL FAILURE: ROLE OF THE SYMPATHETIC NERVOUS SYSTEM and RENAL AFFERENTS
Authors: Phillips Jacqueline K
Published: April 2005

1. The kidney receives a dense innervation of sympathetic and sensory fibres and can be both a target of sympathetic activity and a source of signals that drive sympathetic tone. In the normal state, interactions between the kidney and sympathetic nervous system (SNS) serve to maintain blood pressure and glomerular filtration rate within tightly controlled levels. In renal failure, a defect in renal sodium excretory function leads to an abnormal pressure natriuresis relationship and activation of the renin–angiotensin–aldosterone system, contributing to the development of hypertension and progression of kidney disease.

2. Evidence now strongly indicates a role for the SNS in the pathogenesis of hypertension in renal failure. Hypertension occurs commonly and early in renal disease and is paralleled by increases in SNS activity, as indicated by increased muscle sympathetic nerve activity and circulating catecholamines. This appears to be driven by the diseased kidneys, because nephrectomy or denervation has been shown to correct blood pressure and SNS activity in human and animal studies.

3. Afferent signals from the kidney, detected by chemoreceptors and mechanoreceptors, feed directly into central nuclei of the SNS, including the hypothalamus and circumventricular organs, in addition to the stimulus provided by circulating and brain‐derived angiotensin II. Therefore, the pathogenesis of hypertension in renal failure is complex and arises from the interaction of haemodynamic and neuroendocrine factors.

4. Increased SNS activity has significant implications with regard to increased risk of cardiovascular disease and is an important consideration in the treatment of renal failure.
LONG‐TERM REGULATION OF ARTERIAL BLOOD PRESSURE BY HYPOTHALAMIC NUCLEI: SOME CRITICAL QUESTIONS
Authors: Dampney Ral , Horiuchi J , Killinger S , Sheriff Mj , Tan Psp , McDowall Lm
Published: April 2005

1. The long‐term level of arterial pressure is dependent on the relationship between arterial pressure and the urinary output of salt and water, which, in turn, is affected by a number of factors, including renal sympathetic nerve activity (RSNA). In the present brief review, we consider the mechanisms within the brain that can influence RSNA, focusing particularly on hypothalamic mechanisms.

2. The paraventricular nucleus (PVN) in the hypothalamus has major direct and indirect connections with the sympathetic outflow and there is now considerable evidence that tonic activation of the PVN sympathetic pathway contributes to the sustained increased level of RSNA that occurs in conditions such as heart failure and neurogenic hypertension. The tonic activity of PVN sympathetic neurons, in turn, depends upon the balance of excitatory and inhibitory inputs. A number of neurotransmitters and neuromodulators are involved in these tonic excitatory and inhibitory effects, including glutamate, GABA, angiotensin II and nitric oxide.

3. The dorsomedial hypothalamic nucleus (DMH) also exerts a powerful influence over sympathetic activity, including RSNA, via synapses with sympathetic nuclei in the medulla and, possibly, also other brainstem regions. The DMH sympathetic pathway is an important component of the phasic sympathoexcitatory responses associated with acute stress, but there is no evidence that it is an important component of the central pathways that produce long‐term changes in arterial pressure. Nevertheless, it is possible that repeated episodic activation of this pathway could lead to vascular hypertrophy and, thus, sustained changes in vascular resistance and arterial pressure.

4. Recent studies have reactivated the old debate concerning the possible role of the baroreceptor reflex in the long‐term regulation of sympathetic activity. Therefore, central resetting of the baroreceptor–sympathetic reflex may be an important component of the mechanisms causing sustained changes in RSNA. However, little is known about the cellular mechanisms that could cause such resetting.
NITRIC OXIDE and SYMPATHETIC NERVE ACTIVITY IN THE CONTROL OF BLOOD PRESSURE
Authors: Ramchandra Rohit , Barrett Carolyn J , Malpas Simon C
Published: April 2005

1. Endothelial dysfunction marked by impairment in the release of nitric oxide (NO) is seen very early in the development of hypertension and is considered important in mediating the impaired vascular tone evident in essential hypertensive patients.

2. Recently, a hypothesis has emerged that NO acting as a neurotransmitter in the brain can modulate levels of sympathetic nerve activity and thereby blood pressure. The NO inhibition model of hypertension has been used to explore the possibility that a decrease in levels of NO can cause an increase in levels of sympathetic nerve activity that can mediate the hypertension.

3. In the present review, we examine the literature regarding the role of NO in setting the mean level of sympathetic nerve activity and blood pressure. Although the acute effects of NO inhibition are well understood, the chronic interaction between the sympathetic nervous system and NO has only been investigated using indirect measures of sympathetic nerve activity, such as ganglionic blockade. This has led to inconsistent results regarding the role of NO in modulating sympathetic nerve activity chronically.

4. Some of the conflicting results may be explained by differences in the ‘background’ levels of angiotensin (Ang) II. Evidence suggests that NO may interact with AngII and baroreceptor afferent inputs in the central nervous system to set the mean level of sympathetic nerve activity.

5. We suggest chronic NO inhibition can increase sympathetic nerve activity if baroreceptor input is intact and AngII levels are elevated. Although studies exploring the actions of NO or AngII in isolation are useful for gathering initial information, future studies should focus on their interactions and their role in setting the long‐term levels of sympathetic activity and blood pressure.
ROLE OF THE CENTRAL NUCLEUS OF THE AMYGDALA IN THE CONTROL OF BLOOD PRESSURE: DESCENDING PATHWAYS TO MEDULLARY CARDIOVASCULAR NUCLEI
Authors: Saha S
Published: April 2005

1. One of the key areas that links psychologically induced stress with the blood pressure‐regulatory system is the central nucleus of the amygdala (CeA). This is an integratory forebrain nucleus that receives input from higher centres in the forebrain and has extensive connections with the hypothalamus and the medulla oblongata, areas involved in the regulation of the cardiovascular reflexes.

2. Based on studies using electrical or chemical stimulation or electrolytic lesions of the CeA, it has become clear that the CeA plays an important role in the regulation of blood pressure in response to stressful or fearful stimuli.

3. Two important medullary areas known to receive projections from the CeA are the nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla (RVLM). The NTS is the site of the first synapse for afferent fibres originating from baroreceptors, chemoreceptors and the heart, whereas the RVLM contains neurons that maintain resting blood pressure and sympathetic nerve activity via projections to sympathetic preganglionic neurons in the intermediolateral cell column of the thoracolumbar spinal cord.

4. Electron microscopic studies using combined anterograde tracing and pre‐ and post‐embedding immunogold labelling have shown that the pathways originating from the CeA to the NTS are inhibitory and may use GABA as a neurotransmitter. The results of these studies suggest that blood pressure changes produced by activation of the CeA may be mediated by attenuation of baroreceptor reflexes through a GABAergic mechanism at the level of the NTS.

5. Neuronal tract tracing combined with neurofunctional studies using the Fos protein as a marker of activated neurons indicate that the CeA projects directly to baroreceptive neurons in the NTS and RVLM that are activated by changes in blood pressure.

6. In conclusion, studies that have examined the efferent pathways of the CeA suggest that CeA neurons with projections to medullary baroreceptive neurons may play a vital role in the reflex changes in sympathetic nerve activity that are involved in blood pressure regulation in response to stress or anxiety.
CHRONIC EFFECTS OF ANGIOTENSIN II and AT1 RECEPTOR ANTAGONISTS IN SUBFORNICAL ORGAN‐LESIONED RATS
Authors: Collister John P , Hendel Michael D
Published: April 2005

1. Angiotensin (Ang) II is known to exert some of its effects centrally via circumventricular organs. These unique central nervous system areas lack the normal blood–brain barrier and, therefore, allow peptide hormones access to the brain. Of these, the subfornical organ (SFO) has been shown to be involved in many of the acute dipsogenic and pressor effects of AngII, but much less is known about the role of the SFO in the chronic effects of AngII. We hypothesized that the SFO is a central site involved in the chronic hypotensive effects of endogenous AT1 receptor blockade, as well as the chronic hypertensive effects of exogenously administered AngII.

2. In order to test these hypotheses, SFO‐lesioned (SFOx) or sham Sprague‐Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers for intravenous administration of losartan or AngII and continuous measurement of blood pressure and heart rate. Rats were given 3 days of saline control infusion (7 mL/day of 0.9% NaCl) and were then infused with either losartan (10 mg/kg per day) or AngII (10 ng/kg per min) for 10 days.

3. By day 4 of losartan treatment, arterial pressure had decreased 24 ± 2 and 18 ± 2 mmHg in sham (n = 9) and SFOx (n = 10) rats, respectively. Furthermore, by day 5 of AngII infusion, arterial pressure had increased 12 ± 3 mmHg in sham rats (n = 9), but only by 4 ± 1 mmHg in SFOx rats (n = 9). In each treatment group, these attenuated pressure responses in SFOx rats continued through day 10 of treatment.

4. These results support the hypotheses that the SFO plays a role in both the hypotensive effects of chronic AT1 receptor blockade and the chronic hypertensive phase of exogenously administered AngII.
AUTONOMIC and RESPIRATORY RESPONSES TO MICROINJECTION OF ATP INTO THE INTERMEDIATE OR CAUDAL NUCLEUS TRACTUS SOLITARIUS IN THE WORKING HEART–BRAINSTEM PREPARATION OF THE RAT
Authors: Antunes Vagner R , Braga Valdir A , Machado Benedito H
Published: April 2005

1. Activation of peripheral chemoreceptors with KCN in the working heart–brainstem preparation from young male Wistar rats (70–90 g) increases phrenic (PNA; +105 ± 18%) and thoracic (tSNA; +44 ± 6%) sympathetic nerve activity compared with baseline and reduces heart rate (HR; from 377 ± 27 to 83 ± 6 b.p.m.).

2. Microinjections of increasing doses of ATP (1, 5, 25, 100 and 500 mmol/L;n = 7) into the intermediate nucleus tractus solitarius (NTS) produced a dose‐dependent reduction in PNA (from −6 ± 3 to −82 ± 1%) and in HR (from −12 ± 4 to −179 ± 47 b.p.m.). Microinjections of ATP into the intermediate NTS also produced a reduction in tSNA (from −3 ± 3 to −26 ± 5%), which was not dose dependent.

3. Microinjections of ATP into the caudal NTS (n = 5) produced a dose‐dependent increase in PNA (from 0.2 ± 3 to 115 ± 27%) and minor changes in HR and tSNA, which were not dose dependent.

4. The data show that microinjection of ATP into distinct subregions of the NTS produces different respiratory and autonomic responses and suggest that ATP in the caudal NTS is involved in the respiratory but not in the sympathoexcitatory component of the chemoreflex.
A NEGLECTED ‘ACCESSORY’ VASOMOTOR PATHWAY: IMPLICATIONS FOR BLOOD PRESSURE CONTROL
Authors: McAllen Robin M , Allen Andrew M , Bratton Bradford O
Published: April 2005

1. Distinct from ‘regular’ sympathetic preganglionic neurons, there exists a population of ‘accessory’ preganglionic neurons. The latter are distinguishable by their unmyelinated axons and their different functional properties. They synapse on the same ganglion cells.

2. Ongoing sympathetic activity is driven by ‘regular’ preganglionic neurons.

3. ‘Accessory’ preganglionic neurons drive hexamethonium‐resistant ganglionic transmission: part of this is muscarinic and part not (possibly peptidergic or nitrergic).

4. ‘Accessory’ preganglionic neurons supply cardiovascular (vasomotor, cardiac, adrenal), but apparently not other, sympathetic pathways.

5. ‘Accessory’ preganglionic neurons are activated by arterial chemoreceptors.

6. Brief activation of ‘accessory’ preganglionic neurons potentiates ongoing post‐ganglionic activity for tens of minutes by an action at the ganglion. This is probably by enabling previously subthreshold excitatory post‐synaptic potentials to trigger action potentials.

7. Evidence is presented that microinjections of GABA into the rostral ventrolateral medulla activate the ‘accessory’ pathway while inhibiting the ‘regular’ pathway.

8. A role for this ‘accessory’ pathway in the long‐term control of blood pressure in health and disease is predicted, but still untested.
The empirical and theoretical base of family therapy and multiple family day therapy for adolescent anorexia nervosa
Authors: Eisler Ivan
Published: April 2005

There is growing empirical evidence that family therapy is an effective treatment for anorexia nervosa, particularly in adolescence. This is in spite of the fact that the theoretical model from which most of the empirically based treatments are derived appears flawed. This paper provides a brief overview of the research evidence from treatment studies and studies of family functioning. It suggests that the main limitation of earlier theoretical models is their focus on aetiology rather than on an understanding of how families become organized around a potentially life‐threatening problem. An alternative conceptual model is presented, and its application to family therapy and multiple‐family therapy for adolescent anorexia nervosa is described. The treatment approach focuses on enhancing the families' own adaptive mechanism and mobilizing family strengths.
Scientist‐practitioner family therapists, postmodern medical practitioners and expert parents: second‐order change in the Eating Disorders Program at The Children's Hospital at Westmead
Authors: Rhodes Paul , Madden Sloane
Published: April 2005

The Maudsley model of family‐based treatment for anorexia integrates a variety of schools of family therapy, and has been developed and supported by a number of randomized controlled trials. In this paper we will describe the systemic organizational changes that have occurred as a result of the inclusion of this model in the Eating Disorders Program at The Children's Hospital at Westmead over an eighteen‐month period, including a process of mutual influence between medical practitioners and family therapists. These changes have contributed towards a dramatic improvement in clinical outcomes including a significant drop in readmission rates to hospital.
Mobile Construction Supply Chain Management Using PDA and Bar Codes
Authors: Tserng H. Ping , Dzeng Ren‐Jye , Lin Yu‐Cheng , Lin Sheng‐Tai
Published: April 2005

Abstract:  Construction project control aims to effectively obtain real‐time information and enhance dynamic control by utilizing information sharing and connecting involved participants of the projects to reduce construction conflicts and project delays. However, extending the construction project control system to job sites is not considered efficient because using notebooks in a harsh environment like a construction site is not particularly a conventional practice. Meanwhile, paper‐based documents of the site processes are ineffective and cannot get the quick response from the office and project control center. Integrating promising information technologies such as personal digital assistants (PDA), bar code scanning, and data entry mechanisms, can be extremely useful in improving the effectiveness and convenience of information flow in construction supply chain control systems. Bar code scanning is appropriate for several construction applications, providing cost savings through increased speed and accuracy of data entry. This article demonstrates the effectiveness of a bar‐code‐enabled PDA application, called the mobile construction supply chain management (M‐ConSCM) System, that responds efficiently and enhances the information flow between offices and sites in a construction supply chain environment. The advantage of the M‐ConSCM system lies not only in improving the efficiency of work for on‐site engineers, but also providing the Kanban‐like visual control system for project participants to control the whole project. Moreover, this article presents a generic system architecture and its implementation.
Beyond the Cartoon: George W. Bush and His Biographers
Authors: O-™Connor Brendon
Published: April 2005

Many people seem to see George W. Bush as little more than a caricature. While I acknowledge that Bush-™s electoral success is quite confounding, I argue that a more nuanced and deeper understanding of Bush is required to account for this success and to better comprehend how he makes political decisions. To go beyond the cartoon caricature, I examine the biographies on Bush to explore three key elements of his background and character: Bush-™s relationship with his father; his personal faith; and his development of a Texan persona. Unfortunately this analysis can only be taken so far given that much of the biographical literature is excessively partisan and poorly researched. Thus I conclude by calling for more serious scholarly investigation into Bush-™s personal history and political record.
State of the Art: Addressing the INGO ‘Legitimacy Deficit’
Authors: Collingwood Vivien , Logister Louis
Published: April 2005

While the numbers and competencies of international non-governmental organisations (INGOs) have increased dramatically in the past few decades, questions have been raised about the legitimacy of their new activities. A number of scholars have identified significant tensions between INGOs-™ legitimacy claims and the realities of their working practices. We examine the current state of the debate on INGO legitimacy in two contrasting literatures: normative work on global governance and its implications for the role of INGOs, and policy-oriented work on INGOs-™ legitimacy. The first shows how INGO involvement in global governance opens the door to a range of alternative conceptions of world order, rooted in notions of universal human rights, democracy, and theories of redistributive justice. The latter set of voices is concerned less with locating INGOs-™ roles as agents in global normative structures than with analysing concrete problems arising from increased INGO participation in the development process. Future research might take into account key questions concerning the sources and the scope and nature of INGO legitimacy.
Intra‐Industry Capital Structure Dispersion
Authors: Almazan Andres , Molina Carlos A.
Published: April 2005

Why do firms in some industries exhibit very similar debt ratios, while firms in other industries do not? This paper examines the dispersion in leverage ratios among firms within an industry, and relates this dispersion to industry characteristics. We find that more concentrated industries and industries where the use of leasing is more intense exhibit greater intra‐industry dispersion. We also document greater dispersion in industries where firms use less incentive compensation, sit more insiders in their boards, are older, and have larger capital expenditures in relation to their assets.
Advertising and Coordination in Markets with Consumption Scale Effects
Authors: Clark C. Robert , Horstmann Ignatius J.
Published: April 2005

Many advertised products are established and have little quality variation. For these products advertising signaling explanations are unconvincing. We develop a coordination model of advertising with consumers observing ads probabilistically and never observing advertising levels. Consumers who fail to see an ad for a product believe it will likely have low sales and so be of low value. Firms advertise to avoid these beliefs. The model's predictions on advertising, market share, and profitability are consistent with observed outcomes. The model produces the time series behavior for prices and market share observed in the data and not available from existing coordination models.
National Values and Economic Growth
Authors: Pryor Frederic L.
Published: April 2005

Abstract  Using data on economic values and attitudes for various nations from the World Value Study, I show that the strength of values associated with market success does not appear to have a significant impact on the rate of economic growth in a sample of developing and developed market economies. I also show that such values do not seem related to the economic system and have an ambiguous relation to the overall level of economic development. These negative results suggest that, contrary to common belief, knowledge about such values does not seem very useful in helping us understand economic growth or differences in levels of economic development or economic systems in various countries.
Notional Defined Contribution Accounts
Authors: Williamson John B. , Williams Matthew
Published: April 2005

Abstract  Notional defined contribution (NDC) accounts represent a new model for social security reform that so far has been adopted in seven countries. While NDC schemes remain public, they call for the individual accounts favored by neoliberal policy analysts. NDC schemes would address many of the demographic and fiscal problems threatening pension systems but, depending on the country, could do so in a way that puts low‐paid workers and women at greater risk than do the schemes being replaced. NDC systems are often the result of a compromise between different interest groups, typically between neoliberal economic elites on the right and labor unions or pensioners’ organizations on the left.
The Economics of Anti‐Begging Regulations
Authors: Smith Patricia K.
Published: April 2005

Abstract The Supreme Court has ruled that asking for money is a form of protected speech. However, it has also ruled that restrictions on the time, place, and manner of begging are constitutional. This paper examines 71 U.S. cities to determine what factors influence a city's propensity to enact anti‐begging regulations. The logistic regression results indicate that cities with higher welfare benefits are less likely to regulate begging. Cities with higher crime rates, higher proportions of disabled citizens, and higher proportions of college‐educated citizens, and cities that are more densely populated are more likely to regulate begging.

While historians, ethnographers, and legal scholars have studied issues related to begging, economists generally have not. This paper uses the traditional economic model of rational choice to examine why some U.S. cities regulate begging and others do not.
What If Immigrants Had Not Migrated?
Authors: Lee Seong Woo , Myers Dowell , Ha Seong‐Kyu , Shin Hae Ran
Published: April 2005

Abstract.  Despite strong theoretical arguments and models about international migration, very few empirical studies rigorously test these arguments and models. The purpose of the present study is to analyze determinants and consequences for international migration, focusing particularly on the returns to post‐hoc international migration. The present study compares residential well‐being of Korean international migrants in the United States with that of their hypothetical well‐being if they had not migrated. Our suggested models of the selectivity corrected returns to various characteristics for immigrants and nonimmigrants enable us to estimate the “opportunity well‐being” of individuals and households; that is, the well‐being of immigrants‐had‐they‐stayed and of nonimmigrants‐if‐they‐had‐immigrated. The data for our analyses are drawn from the 1990 Korea Census Data and the Public Use Microdata Samples (PUMS) of the 1990 U.S. Census. In either case of migrants‐had‐they‐stayed or of nonimmigrants‐had‐they‐migrated, international migration to the United States has a significant and positive effect on the probability of homeownership, especially for women. The results show that the predicted probability of homeownership attainment increases as a result of migration by 15 percent to 16 percent for women and by 8 percent for men. The study concludes that migrating to the United States offers better opportunities for homeownership than staying in Korea does, particularly for women.
A Dynamic Approach to Population Change in Central Cities and Their Suburbs, 1980–1990
Authors: Oh Joong‐Hwan
Published: April 2005

Abstract.  With the growing concern over the causal relationship between crime and population change, this study readdresses the importance of economic organization in studying population change in a metropolitan area. This study investigates the dynamic influences of internal and external factors on population change in either central cities or their suburbs. The units of analysis in this study are the 142 U.S. central cities and their suburban rings of Metropolitan Statistical Areas (MSAs) in 1980 and 1990. Two change models (semi‐difference and mixed‐difference models) are used to predict population change. The results demonstrate that population change in one territory of a metropolitan area is affected by crime and employment opportunity in both locations of a metropolitan area.
Mill Versus Liberty
Authors: Waterman A. M. C.
Published: April 2005

Abstract.  Professor Waterman now reviews Linda C. Raeder’s John Stuart Mill and the Religion of Humanity (2002).
Sources and Consequences of Distinctive Familiness: An Introduction
Authors: Chrisman James J. , Chua Jess H. , Steier Lloyd
Published: April 2005

Family firms are unique organizational forms as a result of the interactions between family members, the family, and the business. Distinctive familiness has been used as a notion to encompass these interactions and the consequent systemic synergies that could lead to competitive advantages. This introduction discusses the notion and reviews the papers and commentaries in this special issue within the context of their contributions to our understanding of the possible sources and consequences of distinctive familiness.
Commentary on the Multidimensional Degree of Family Influence Construct and the F–PEC Measurement Instrument
Authors: Cliff Jennifer E. , Jennings P. Devereaux
Published: April 2005

In this commentary, we provide suggestions for further establishing the validity of the multidimensional degree of family influence construct and the reliability of the family influence on power, experience, and culture (F–PEC) measurement instrument. We also delineate a number of creative ways in which future researchers can incorporate this rigorous, relevant, and rich construct into their own research agendas.
Protective effects of etoricoxib, a selective inhibitor of cyclooxygenase‐2, in experimental periodontitis in rats
Authors: Holzhausen Marinella , Spolidorio Denise M. Palomari , Muscará Marcelo Nicolás , Hebling Josimery , Spolidorio Luis Carlos
Published: April 2005

Background:  The purpose of the present study was to evaluate the effect of a potent selective cyclooxygenase‐2 (COX‐2) inhibitor, etoricoxib, on the prevention of alveolar bone loss in experimental periodontitis induced in rats.

Methods:  Ninety Wistar rats were separated into three experimental groups. Cotton ligatures were placed at the gingival margin level of lower right first molars. The rats were randomly assigned to one of the following groups: control received a daily oral dose of 1 ml/kg of saline solution; Eto1 received 6 mg/kg of etoricoxib; Eto2 received 12 mg/kg of etoricoxib. Serum levels of etoricoxib and white blood cells were determined. Standardized digital radiographs were taken after death at 3, 5, 10, 18 and 30 days to measure the amount of bone loss at the mesial root surface of the first molar tooth in each rat.

Results:  One‐way analysis of variance (anova) indicated that groups treated with both doses of etoricoxib had significantly (p < 0.05) less alveolar bone loss when compared to controls. Furthermore, etoricoxib treatment significantly inhibited the leukocytosis observed 3 days after the induction of periodontitis.

Conclusion:  These data provide evidence that systemic therapy with etoricoxib can retard alveolar bone loss in a ligature‐induced periodontitis model in rats.
Marker of cemento‐periodontal ligament junction associated with periodontal regeneration
Authors: Hara Ryohko , Wato Masahiro , Tanaka Akio
Published: April 2005

Objective:  The purpose of this study was to identify factors promoting formation of the cemento‐periodontal ligament junction.

Background:  Regeneration of the cemento‐periodontal ligament junction is an important factor in recovery of the connective tissue attachment to the cementum and it is important to identify all specific substances that promote its formation. To clarify the substances involved in cemento‐periodontal ligament junction formation, we produced a monoclonal antibody (mAb) to human cemento‐periodontal ligament junction (designated as the anti‐TAP mAb) and examined its immunostaining properties and reactive antigen.

Methods:  Hybridomas producing monoclonal antibody against human cemento‐periodontal ligament junction antigens were established by fusing P3U1 mouse myeloma cells with spleen cells from BALB/c mice immunized with homogenized human cemento‐periodontal ligament junction. The mAb, the anti‐TAP mAb for cemento‐periodontal ligament junction, was then isolated. The immunoglobulin class and light chain of the mAb were examined using an isotyping kit. Before immunostaining, antigen determination using an enzymatic method or heating was conducted. Human teeth, hard tissue‐forming lesions, and animal tissues were immunostained by the anti‐TAP mAb.

Results:  The anti‐TAP mAb was positive in human cemento‐periodontal ligament junction and predentin but negative in all other human and animal tissues examined. In the cemento‐osseous lesions, the anti‐TAP mAb was positive in the peripheral area of the cementum and cementum‐like hard tissues and not in the bone and bone‐like tissues. The anti‐TAP mAb showed IgM (kappa) and recognized phosphoprotein.

Conclusion:  The anti‐TAP mAb is potentially useful for developing new agents promoting cementogenesis and periodontal regeneration.
Variance components of gingival thickness
Authors: Müller H. P. , Könönen E.
Published: April 2005

Objectives:  Distinct periodontal phenotypes have been identified by cluster analysis, which is an explorative method with very low external validity. The aim of the present study was to investigate variance components of facial gingival thickness in young adults with mild gingivitis.

Material and methods:  Thirty‐three non‐smoking females, 18–23 years of age, with mild or moderate plaque‐induced gingivitis participated. Gingival thickness was measured at every tooth present by use of ultrasound technology to the next 0.1 mm with a lowest measurement of 0.5 mm. Periodontal probing depth and clinical attachment level were measured with a pressure‐controlled probe. Gingival bleeding index was assessed after probing on a 0–2 scale, where 1 was slight, and 2 was profuse bleeding on probing. The Silness‐Löe plaque index was recorded. Multilevel variance components and random intercept models were built.

Results:  A 2‐level (subject, tooth) variance component model of gingival thickness without any explanatory variable revealed an intercept (mean) of 0.93 ± 0.02 mm. Subject variation of gingival thickness amounted to 4.2% of the total variance. Addition of tooth‐ and subject‐related covariates to the model revealed, after adjusting for tooth type, an association with periodontal probing depth (estimated coefficient 0.067 ± 0.025), and considerable association with average bleeding index (−0.395 ± 0.149) and plaque index (0.125 ± 0.048). Variation at the tooth level was drastically reduced; subject variation amounted to 5.2%.

Conclusion:  Gingival thickness is mainly associated with tooth‐related variables. Bleeding tendency is higher if gingiva is thin. Subject variability related to periodontal phenotype may add to the total variance, however, to a very low extent.
Application of periodontal ligament cell sheet for periodontal regeneration: a pilot study in beagle dogs
Authors: Akizuki Tatsuya , Oda Shigeru , Komaki Motohiro , Tsuchioka Hiroaki , Kawakatsu Noriko , Kikuchi Akihiko , Yamato Masayuki , Okano Teruo , Ishikawa Isao
Published: April 2005

Objective:  The ultimate goal of periodontal treatment is to regenerate the damaged periodontal support. Although periodontal ligament (PDL) cells are essential for periodontal regeneration, few studies have reported the transplantation of periodontal ligament cells to periodontal defects. We developed a new method to apply periodontal ligament cells as a sheet to the defect. The aim of this study was to investigate the periodontal healing after application of the periodontal ligament cell sheet in beagle dogs.

Methods:  Autologous periodontal ligament cells were obtained from extracted premolars of each beagle dog. Periodontal ligament cell sheets were fabricated using a temperature‐responsive cell culture dish. Dehiscence defects were surgically created on the buccal surface of the mesial roots of bilateral mandibular first molars of each dog. In the experimental group (five defects), periodontal ligament cell sheet with reinforced hyaluronic acid carrier was applied to the defect. Only the hyaluronic acid carrier was applied to the contralateral side as a control (five defects). Eight weeks after surgery, the animals were sacrificed and decalcified specimens were prepared. Healing of the periodontal defects was evaluated histologically and histometrically.

Results:  No clinical signs of inflammation or recession of gingiva were observed in both experimental and control groups. In the experimental group, periodontal tissue healing with bone, periodontal ligament and cementum formation was observed in three out of five defects. In the control group, such periodontal tissue formation was not observed except in one defect. Histometric analysis revealed that the formation of new cementum in the experimental group was significantly higher than that in the control group.

Conclusion:  The periodontal ligament cell sheet has a potential to regenerate periodontal tissue and may become a novel regenerative therapy.
Characterization of Actinobacillus actinomycetemcomitans isolated from young Chinese aggressive periodontitis patients
Authors: Leung W. Keung , Ngai Vincent K. S. , Yau Joyce Y. Y. , Cheung Becky P. K. , Tsang Paul W. K. , Corbet Esmonde F.
Published: April 2005

Objective:  This study characterized Actinobacillus actinomycetemcomitans isolates from young Chinese aggressive periodontitis patients.

Methods:  Subgingival plaque samples (two/subject) were collected from diseased subjects < 25 years old (n = 9, mean age 21.1 ± 1.6 years) and age‐matched periodontitis‐free controls (n = 47, mean age 22.0 ± 1.1 years). Selective and anaerobic culture were used. The serotype, leukotoxin gene (ltx) operon promoter and the cytolethal distending toxin (cdt) genes complex of the A. actinomycetemcomitans isolates were investigated. Effects of the isolates on non‐keratinizing periodontal ligament epithelial cells monolayer were studied.

Results:  Diseased subjects had significantly higher full‐mouth bleeding score (p = 0.002) and total viable counts from plaque samples (7.2 × 106 vs. 2.1 × 105 CFU/paperpoint, p < 0.005). A. actinomycetemcomitans was isolated from 67%/56% or 6%/4% of diseased or controls subject/sites, respectively (p < 0.001). The proportion of A. actinomycetemcomitans isolatable from aggressive periodontitis or periodontitis‐free associated subgingival plaque was low (0.7% vs. 0.1%, p < 0.02). The serotype of the isolates was characterized. All isolates possessed 652‐like ltx gene promoter and all but one serotype c isolate from a diseased patient had intact cdtABC genes. That particular strain appeared to confer the least cellular damages on periodontal ligament epithelial monolayer compared to others.

Conclusion:  This preliminary study confirmed the notion of increased prevalence and quantity of A. actinomycetemcomitans associated with aggressive periodontitis in young patients. The overall ltx promoter and cdt characteristics of the A. actinomycetemcomitans isolates, however, were similar among the diseased and control groups. A strain lacking the cdtABC gene appeared to be less damaging to a periodontal ligament epithelial cell model. Further studies therefore are warranted to clarify the pathogenic role and potentials of A. actinomycetemcomitans in aggressive periodontitis.
Identification of small scale biochemical networks based on general type system perturbations
Authors: Schmidt Henning , Cho Kwang‐Hyun , Jacobsen Elling W.
Published: April 2005

New technologies enable acquisition of large data‐sets containing genomic, proteomic and metabolic information that describe the state of a cell. These data‐sets call for systematic methods enabling relevant information about the inner workings of the cell to be extracted. One important issue at hand is the understanding of the functional interactions between genes, proteins and metabolites. We here present a method for identifying the dynamic interactions between biochemical components within the cell, in the vicinity of a steady‐state. Key features of the proposed method are that it can deal with data obtained under perturbations of any system parameter, not only concentrations of specific components, and that the direct effect of the perturbations does not need to be known. This is important as concentration perturbations are often difficult to perform in biochemical systems and the specific effects of general type perturbations are usually highly uncertain, or unknown. The basis of the method is a linear least‐squares estimation, using time‐series measurements of concentrations and expression profiles, in which system states and parameter perturbations are estimated simultaneously. An important side‐effect of also employing estimation of the parameter perturbations is that knowledge of the system's steady‐state concentrations, or activities, is not required and that deviations from steady‐state prior to the perturbation can be dealt with. Time derivatives are computed using a zero‐order hold discretization, shown to yield significant improvements over the widely used Euler approximation. We also show how network interactions with dynamics that are too fast to be captured within the available sampling time can be determined and excluded from the network identification. Known and unknown moiety conservation relationships can be processed in the same manner. The method requires that the number of samples equals at least the number of network components and, hence, is at present restricted to relatively small‐scale networks. We demonstrate herein the performance of the method on two small‐scale in silico genetic networks.
Functional dissection of two Arabidopsis PsbO proteins
Authors: Murakami Reiko , Ifuku Kentaro , Takabayashi Atsushi , Shikanai Toshiharu , Endo Tsuyoshi , Sato Fumihiko
Published: April 2005

PsbO protein is an extrinsic subunit of photosystem II (PSII) and has been proposed to play a central role in stabilization of the catalytic manganese cluster. Arabidopsis thaliana has two psbO genes that express two PsbO proteins; PsbO1 and PsbO2. We reported previously that a mutant plant that lacked PsbO1 (psbo1) showed considerable growth retardation despite the presence of PsbO2 [Murakami, R., Ifuku, K., Takabayashi, A., Shikanai, T., Endo, T., and Sato, F. (2002) FEBS Lett523, 138–142]. In the present study, we characterized the functional differences between PsbO1 and PsbO2. We found that PsbO1 is the major isoform in the wild‐type, and the amount of PsbO2 in psbo1 was significantly less than the total amount of PsbO in the wild‐type. The amount of PsbO as well as the efficiency of PSII in psbo1 increased as the plants grew; howeVER, it neVER reached the total PsbO level observed in the wild‐type, suggesting that the poor activity of PSII in psbo1 was caused by a shortage of PsbO. In addition, an in vitro reconstitution experiment using recombinant PsbOs and urea‐washed PSII particles showed that oxygen evolution was better recoVERed by PsbO1 than by PsbO2. Further analysis using chimeric and mutated PsbOs suggested that the amino acid changes Val186→Ser, Leu246→Ile, and Val204→Ile could explain the functional difference between the two PsbOs. Therefore we concluded that both the lower expression level and the inferior functionality of PsbO2 are responsible for the phenotype observed in psbo1.
Protein dissection enhances the amyloidogenic properties of α‐lactalbumin
Authors: Polverino de Laureto Patrizia , Frare Erica , Battaglia Francesca , Mossuto Maria F. , Uversky Vladimir N. , Fontana Angelo
Published: April 2005

α‐lactalbumin (LA) in its molten globule (MG) state at low pH forms amyloid fibrils. Here, we have studied the aggregation propensities of LA derivatives characterized by a single peptide bond fission (1–40/41–123, named Th1‐LA) or a deletion of a chain segment of 12 amino acid residues located at the level of the β‐subdomain of the native protein (1–40/53–123, named desβ‐LA). We have also compared the early stages of the aggregation process of these LA derivatives with those of intact LA. Th1‐LA and desβ‐LA aggregate at pH 2.0 much faster than the intact protein and form long and well‐ordered fibrils. Furthermore, in contrast to intact LA, the LA derivatives form regular fibrils also at neutral pH, even if at much reduced rate. In acidic solution, Th1‐LA and desβ‐LA adopt a MG state which appears to be similar to that of intact LA, as given by spectroscopic criteria. At neutral pH, both Th1‐LA and desβ‐LA are able to bind the hydrophobic dye 1‐anilinonaphtalene‐8‐sulfonate, thus indicating the presence of exposed hydrophobic patches. It is concluded that nicked Th1‐LA and gapped desβ‐LA are more relaxed and expanded than intact LA and, consequently, that they are more suitable protein species to allow the large conformational transitions required for the polypeptide chain to form the amyloid cross‐β structure. As a matter of fact, the MG of LA attains an even more flexible conformational state during the early phases of the aggregation process at acidic pH, as deduced from the enhancement of its susceptibility to proteolysis by pepsin. Our data indicate that deletion of the β‐subdomain in LA does not alter the ability of the protein to assemble into well‐ordered fibrils, implying that this chain region is not essential for the amyloid formation. It is proposed that a proteolytic hydrolysis of a protein molecule at the cellular level can trigger an easier formation of amyloid precipitates and therefore that limited proteolysis of proteins can be a causative mechanism of protein aggregation and fibrillogenesis. Indeed, a vast majority of protein deposits in amyloid diseases are given by protein fragments derived from larger protein precursors.
The two IQ‐motifs and Ca2+/calmodulin regulate the rat myosin 1d ATPase activity
Authors: Köhler Danny , Struchholz Sandra , Bähler Martin
Published: April 2005

The light chain binding domain of rat myosin 1d consists of two IQ‐motifs, both of which bind the light chain calmodulin (CaM). To analyze the Myo1d ATPase activity as a function of the IQ‐motifs and Ca2+/CaM binding, we expressed and affinity purified the Myo1d constructs Myo1d‐head, Myo1d‐IQ1, Myo1d‐IQ1.2, Myo1d‐IQ2 and Myo1dΔLV‐IQ2. IQ1 exhibited a high affinity for CaM both in the absence and presence of free Ca2+. IQ2 had a lower affinity for CaM in the absence of Ca2+ than in the presence of Ca2+. The actin‐activated ATPase activity of Myo1d was ∼75% inhibited by Ca2+‐binding to CaM. This inhibition was observed irrespective of whether IQ1, IQ2 or both IQ1 and IQ2 were fused to the head. Based on the measured Ca2+‐dependence, we propose that Ca2+‐binding to the C‐terminal pair of high affinity sites in CaM inhibits the Myo1d actin‐activated ATPase activity. This inhibition was due to a conformational change of the C‐terminal lobe of CaM remaining bound to the IQ‐motif(s). Interestingly, a similar but Ca2+‐independent inhibition of Myo1d actin‐activated ATPase activity was observed when IQ2, fused directly to the Myo1d‐head, was rotated through 200° by the deletion of two amino acids in the lever arm α‐helix N‐terminal to the IQ‐motif.