bluuebunny/crossref_metadata_2025 huggingface dataset:
AUTOMATING SOFTWARE EVOLUTION
Authors: LIU ZHENG-YANG
Published: November 2004

This paper presents a pragmatic knowledge-based approach to evolving and reengineering legacy business software systems. We describe a CASE tool for assisting legacy system evolution by automating the tedious and knowledge-intensive conversion process and show how we developed and maintained the tool and how it is used with payoff. This work demonstrates that timely technology upgrades of legacy systems are only possible with carefully engineered knowledge-based tools. Viewing software as an artifact with structure, behavior, and function, we can represent most program conversion knowledge explicitly for function-preserving transformation in an automated conversion system. The payoff for using the knowledge-based approach to software evolution is not only in terms of valuable resources saved, but also in terms of improved quality of the upgraded software systems.
ADVANCES IN NETWORK INFORMATION DISCOVERY AND RETRIEVAL
Authors: EICHMANN DAVID
Published: November 2004

Access to information using the Internet has undergone dramatic change and expansion recently. The unrivaled success of the World Wide Web has altered the Internet from something approachable only by the initiated to something of a media craze — the information superhighway made manifest in the personal "home page". This paper surveys the beginnings of network information discovery and retrieval, how the Web has created a surprising level of integration of these systems, and where the current state of the art lies in creating globally accessible information spaces and supporting access to those information spaces.
FORMAL TRANSFORMATIONAL PROGRAM DEVELOPMENTS DIRECTED BY OPERATIONAL PROPERTIES EVALUATIONS
Authors: AIT-AMEUR YAMINE
Published: November 2004

Transformation systems allow us to support developments leading from an initial specification to a final program in a totally formal way. Transformations use valid properties of input objects to produce new equivalent ones. Most transformations use functional properties to increase the efficiency of programs. In doing so, they affect nonfunctional properties, which are usually not formally expressed. The problem we address is to recognize situations in which transformations can be achieved on the basis of the evaluation of a defined, nonfunctional property, and the aim of the present paper is to relate program transformations to nonfunctional properties evaluations. Indeed, a particular transformation tactic can be applied when a given property does not hold. The DEVA language has been used as a support of our experiments in the development of programs.
SOFTWARE PROCESS REPRESENTATION TO SUPPORT MULTIPLE VIEWS
Authors: JACOBS DAVID , MARLIN CHRIS
Published: November 2004

Current interest in improving the effectiveness and predictability of software development has led to a recent focus on software process modeling and improvement. Process-centered software development environments (PCSDEs), have been examined as a useful adjunct to software process modeling. A number of PCSDEs have been designed and built; an examination of the range of potential users of such environments reveals a wide range of needs with respect to information about an enacted software process and how this information is presented. This paper describes one aspect of a PCSDE supporting multiple simultaneous views: the design of a representation of enacted software processes which is suitable for the generation of multiple simultaneous views.
A HYBRID KNOWLEDGE-BASED AND EVOLUTIONARY PROCESS MODEL OF AIRPORT GATE SCHEDULING
Authors: DE SILVA GARZA ANDRÉS GÓMEZ , LICASTRO ANA PATRICIA TORRES CAMPOS , JUSTO ROSA MARÍA OGANDO
Published: November 2004

The problem of assigning gates to aircraft that are due to arrive at an airport is one that involves a dynamic task environment. Airport gates can only be assigned if they are currently available, but deciding which gate to assign to which flight also involves satisfying multiple additional constraints. Once a solution has been found, new incoming flights will have approached the airspace of the airport in question, and these will require arrival gates to be assigned to them, so the entire process must be repeated. We have come up with a combined knowledge-based and evolutionary approach for performing the airport gate scheduling task. In this paper we present our model from a theoretical point of view, and then discuss a particular implementation of it for the scheduling of arrival gates in a specific airport and show some experimental results.
SMALL BUSINESS TRAINING PROGRAMS IN VICTORIA: A SURVEY OF COURSE CONTENT AND EFFECTIVENESS
Authors: BARNES LISA , JONES STEWART
Published: November 2004

Australian research efforts have established some strong relationships between small business training and education and improved managerial skill. Ultimately, this impacts on increased survival rates of small firms (Williams, 1990). While the literature suggests that management training programs are generally inadequate in Australia, there is comparatively little empirical research that has concentrated on the effectiveness of these programs in terms of course content and delivery. By surveying course providers and participants, this study seeks to determine the strengths and limitations in the current provision of such services and to identify policy avenues for the future development of more effective training programs. In contrast to previous research, the results of this paper indicate that the general effectiveness of training programs has noticeably improved since the 1980s. However, while providers have become more aware of the training needs of small businesses, and the means by which course effectiveness can be improved, providers need to make more concerted efforts to incorporate this knowledge into the development and delivery of specific training programs.
MARKETING PRACTICES AMONG SMALL NEW ZEALAND ORGANIZATIONS
Authors: TAYLOR DAVID B. , BROOKSBANK ROGER
Published: November 2004

The ongoing deregulation of the New Zealand economy since 1984 has resulted in more importance than ever being attached to marketing. Small firms play an important role in the economy and the recent improvement in the country's economic position has been attributed in no small part to the success of small firms in the export sector. This paper reports the results of an investigation into the marketing practices of small firms, an area in New Zealand about which relatively little is known. The research is part of a larger exercise, the international marketing effectiveness project [I.M.E.P.]
MARKETING IN CHINESE SMALL BUSINESS: TENTATIVE THEORY
Authors: SIU WAI-SUM , KIRBY DAVID A.
Published: November 2004

Much of the literature on small firm marketing has adopted the Western marketing paradigm. Though researchers such as Kindle (1982) and Waldie (1980) have pointed to the importance of using traditional cultural values in understanding Chinese marketing decisions, there is no major study of Chinese small firm marketing which adopts this approach. Siu and Kirby (1995) suggest an integrative approach — blending the process model and the contingency approach in building and advancing small firm marketing theory. Hence the marketing process model proposed by Brooksbank (1990) is adopted as the research framework for understanding the marketing activities of small firms in Hong Kong. Six broad areas relating to business philosophy, strategic analysis, marketing objectives, marketing strategy, marketing organization and marketing control are identified. The contingency model used by Brooksbank, Kirby and Wright (1992) is adopted to identify different types of performing companies. In addition, Yau's (1994) Chinese cultural value orientations are adopted to explain the likely Chinese cultural influences. Five types of value orientation are used as to provide the analytical framework, namely Man-to-nature Orientation, Man-to-himself Orientation, Relational Orientation, Time Orientation, and Personal-activity Orientation. The research results reveal that Chinese small firms in Hong Kong exhibit different marketing behaviour from their western counterparts, when compared with UK findings for example. Higher performing Chinese small firms place marketing as the leading or joint leading role in their corporate planning processes and also adopt a longer-term strategic planning approach. They also use more aggressive marketing strategies and put more emphasis on product performance and credit support. However, explicit marketing control devices appear not to be used. The influence of Chinese cultural values on the marketing activities of Chinese small firms in Hong Kong is found to be significant.
A PROJECTION OF DISTRIBUTION SYSTEM DEVELOPMENT TREND IN CHINA
Authors: LEE DON Y
Published: November 2004

This article reviews the distribution systems in the People's Republic of China in a systematic way and corrects some misconceptions about the ownership of enterprises. The study proposes a framework for explaining and analyzing distribution systems, both of the central government and the manufacturers, based on transaction cost analysis. The article also offers a projection of the distribution system development trend, based on the proposed framework.
PLANNING, ENTERPRISE PERFORMANCE AND OWNER/MANAGER PERSONAL VALUES
Authors: KOTEY BERNICE
Published: November 2004

The research demonstrates that owner/managers who undertake planning are distinguishable from those who do not plan in terms of personal values and performance levels. Data was obtained from a mail survey of small business furniture manufacturers in New South Wales, Australia. The analysis was based on 224 responses, a response rate of 34%.

A typology of owner/managers was constructed, based on personal value factors, using cluster analysis. Differences among personal value types with respect to planning and enterprise performance were examined by multivariate analyses of variance using deviation contrasts.

The results suggest that, in general, owner/managers place little emphasis on planning. However, some owner/managers undertake more planning than others. Owner/managers who placed greater emphasis on planning were identified with entrepreneurial personal values and with higher performance levels than those with lesser emphasis on planning.
VALUE-ADDED APPROACH TO CORPORATE MANAGEMENT: QUALITY MANAGEMENT PRACTICES IN THE AUSTRALIAN BUSINESS SERVICE INDUSTRY
Authors: SIMON ALAN
Published: November 2004

A survey was conducted in 1993 on the Chief Executive Officers of large Australian companies such as finance companies, advertising agencies and suppliers of software that provide a service to businesses.

The aim of the study was to survey the nature and extent of quality management practices with special reference to inhouse care in these organisations. Questionnaires were sent to 428 companies and 219 (51 per cent) responded.

CEOs considered an ability to bring out the best in, motivate and communicate with internal customers (the staff) to be important principles of good management.

More than two thirds of the responding companies had quality management practices, usually Total Quality Management, in place. However, only 54% had a mechanism in their companies for formally recording complaints made by external customers. Despite the fact that nearly all the CEOs agreed that they should be concerned with providing a good service to external and internal customers, only about half said they conduct formal customer and/or staff satisfaction surveys.

Most important, a statistically significant relationship was found between profitability and the conducting of external customer satisfaction surveys. There was also a relationship between profitability and whether or not firms formally registered customers' complaints.
ARMING ASIAN INTELLECTUALS INTERNATIONAL CONSULTANCY
Authors: CHANG CHIU-CHENG , CHEN GERALDINE
Published: November 2004

The ability to change is vital for corporate survival and growth and knowledge is the engine of change. While consultancy is generally associated with the West, we believe that the Asian heritage, particularly the Confucian reverence for knowledge and teachers, make Asian intellectuals best suited for performing the consultancy role effectively. But what exactly is the role of consultancy? What are the objectives and functions? And in what areas will Asian consultants stand out? Prospective Asian consultants must be able to marry Western and Eastern business cultures and practices. The critical factors for success as Asian international consultants will be examined.
COMPARISON OF FAILURE INTENSITIES FROM TWO POISSON PROCESSES
Authors: YANG HANN-PYI JAMES , SHIUE WEI-KEI
Published: November 2004

Statistical inferences for ratio and difference of intensities from two Poisson processes are reviewed. Both fixed time periods case and fixed number of failures case are considered. Exact results whenever available are described with emphasis on hypothesis testing procedures and confidence intervals construction. Some approximate confidence intervals are studied and simulation results indicate that these intervals are adequate even with small sample size.
DESIGN OF A MULTI-LEVEL FAULT-TOLERANT MESH (MFTM) FOR HIGH RELIABILITY APPLICATIONS
Authors: UPADHYAYA SHAMBHU J. , HWANG I-SHYAN
Published: November 2004

This paper presents a novel technique for the enhancement of operational reliability of processor arrays by a multi-level fault-tolerant design approach. The key idea of the design is based on the well known hierarchical design paradigm. The proposed fault-tolerant architecture uses a flexible reconfiguration of redundant nodes, thereby offering a better spare utilization than existing two-level redundancy schemes. A variable number of spares is provided at each level of redundancy which enables a flexible reconfiguration as well as area efficient layouts and better spare utilization. The spare nodes at each level can replace any of the failed primary nodes, not only at the same level but also those at the lower levels. The architecture can be adopted to increase the system reliability in Multi Chip Modules (MCMs). The main contributions of our work are the higher degree of fault tolerance, higher overall reliability, flexibility, and a better spare utilization.
GROWTH AND CHARACTERIZATION OF SILICON CARBIDE NANOWIRES
Authors: PARK BYOUNGTAE , RYU YONGHWAN , YONG KIJUNG
Published: November 2004

A simple, direct synthesis method was used to grow the core-shell SiC - SiOx nanowires by heating the NiO catalyzed silicon substrate. The carbothermal reduction of WO3 by C provided a reductive environment to synthesize the crystalline SiC nanowires covered with the SiO x sheath in the growth temperature of 1000–1100°C. After hydrofluoric acid (HF) etching, the cubic β- SiC nanowires were extracted from the core-shell nanowires in large quantities. A solid-liquid-solid (SLS) mechanism was proposed for the growth of the core-shell SiC - SiO x nanowires.
Novel and quantitative DNA dot-blotting method for assessment of in vivo proliferation
Authors: Ueda Junji , Saito Hiroshi , Watanabe Hiroaki , Evers B. Mark
Published: November 2004

Immunohistochemical assessment of 5-bromo-2-deoxyuridine (BrdU) in tissue sections is a widely used method to evaluate cell proliferation in vivo. However, this method requires time-consuming preparation of paraffin sections and laborious counting of BrdU-labeled nuclei on multiple sections. Here, we report the development of a rapid and reliable method to quantitate BrdU incorporation in intestinal and liver tissues using a dot-blot method. In vivo models of colon or liver proliferation were used to analyze the usefulness and reliability of this new method. Mice were killed after BrdU injection, and genomic DNA was isolated from the tissues, denatured, and dot-blotted onto a nitrocellulose membrane. The incorporated BrdU was detected with a BrdU monoclonal antibody, and the signal intensity was densitometrically quantified. Results were compared with BrdU index determined by conventional immunohistochemistry on the same tissue samples. The patterns of colonic BrdU incorporation during fasting and refeeding, measured by the dot-blotting method and the immunohistochemical method, were similar. The BrdU incorporation in the regenerating liver after partial hepatectomy, evaluated by these two different methods, showed a strong correlation ( R2= 0.91, P < 0.01). In addition, the inhibition of colon proliferation by the phosphoinositol 3-kinase inhibitor wortmannin was demonstrated by this dot-blotting method. In conclusion, the dot-blotting technique described in this report provides an accurate, more efficient, and possibly more reliable method for the assessment of in vivo proliferation compared with conventional immunohistochemical determination of BrdU-labeling index.
Redox regulation of Ito remodeling in diabetic rat heart
Authors: Li Xun , Xu Zhi , Li Shumin , Rozanski George J.
Published: November 2004

Oxidative stress and the resulting change in cell redox state are proposed to contribute to pathogenic alterations in ion channels that underlie electrical remodeling of the diseased heart. The present study examined whether K+ channel remodeling is controlled by endogenous oxidoreductase systems that regulate redox-sensitive cell functions. Diabetes was induced in rats by streptozotocin, and experiments were conducted after 3–5 wk of hyperglycemia. Spectrophotometric assays of ventricular tissue extracts from diabetic rat hearts revealed divergent changes in two major oxidoreductase systems. The thioredoxin (TRX) system in diabetic rat heart was characterized by a 52% decrease in TRX reductase (TRXR) activity from control heart ( P < 0.05), whereas TRX activity was 1.7-fold greater than control heart ( P < 0.05). Diabetes elicited similar changes in the glutaredoxin (GRX) system: glutathione reductase was decreased 35% from control level ( P < 0.05), and GRX activity was 2.5-fold greater than in control heart ( P < 0.05). The basal activity of glucose-6-phosphate dehydrogenase, which generates NADPH required by the TRX and GRX systems, was not altered by diabetes. Voltage-clamp studies showed that the characteristically decreased density of the transient outward K+ current ( Ito) in isolated diabetic rat myocytes was normalized by in vitro treatment with insulin (0.1 μM) or the metabolic activator dichloroacetate (1.5 mM). The effect of these agonists on Ito was blocked by inhibitors of glucose-6-phosphate dehydrogenase. Moreover, inhibitors of TRXR, which controls the reducing activity of TRX, also blocked upregulation of Ito by insulin and dichloroacetate. These data suggest that K+ channels underlying Ito are regulated in a redox-sensitive manner by the TRX system and the remodeling of Ito that occurs in diabetes may be due to decreased TRXR activity. We propose that oxidoreductase systems are an important repair mechanism that protects ion channels and associated regulatory proteins from irreversible oxidative damage.
Contribution of KATP+ channels to coronary vasomotor tone regulation is enhanced in exercising swine with a recent myocardial infarction
Authors: Merkus Daphne , Houweling Birgit , van Vliet Marion , Duncker Dirk J.
Published: November 2004

Previous studies demonstrated a decreased flow reserve in the hypertrophied myocardium early after myocardial infarction (MI). Previously, we reported that exacerbation of hemodynamic abnormalities and neurohumoral activation during exercise caused slight impairment of myocardial O2 supply in swine with a recent MI. We hypothesized that increased metabolic coronary vasodilation [via ATP-sensitive K+ (KATP+) channels and adenosine] may have partially compensated for the increased extravascular compressive forces and increased vasoconstrictor neurohormones, thereby preventing a more severe impairment of myocardial O2 balance. Chronically instrumented swine were exercised on a treadmill up to 85% of maximum heart rate. Under resting conditions, adenosine receptor blockade [8-phenyltheophylline (8-PT), 5 mg/kg iv] and KATP+ channel blockade (glibenclamide, 3 mg/kg iv) produced similar decreases in myocardial O2 supply in normal and MI swine. However, while glibenclamide's effect waned in normal swine during exercise ( P < 0.05), it was maintained in MI swine. 8-PT's effect was maintained during exercise and was not different between normal and MI swine. Finally, in normal swine combined treatment with 8-PT and glibenclamide produced a vasoconstrictor response that equaled the sum of the responses to blockade of the individual pathways. In contrast, in MI swine the vasoconstrictor response to 8-PT and glibenclamide was similar to that produced by glibenclamide alone. In conclusion, despite significant hemodynamic abnormalities in swine with a recent MI, myocardial O2 supply and O2 consumption in remodeled myocardium are still closely matched during exercise. This close matching is supported by increased KATP+ channel-mediated coronary vasodilation. Although the net vasodilator influence of adenosine was unchanged in remodeled myocardium, it became exclusively dependent on KATP+ channel opening.
Urinary trypsin inhibitor reduces LPS-induced hypotension by suppressing tumor necrosis factor-α production through inhibition of Egr-1 expression
Authors: Molor-Erdene Perenlei , Okajima Kenji , Isobe Hirotaka , Uchiba Mitsuhiro , Harada Naoaki , Okabe Hiroaki
Published: November 2004

Although urinary trypsin inhibitor (UTI) has been shown to inhibit tumor necrosis factor (TNF)-α- production, the detailed mechanism(s) remains unclear. This study was undertaken to elucidate the molecular mechanism(s) underlying this inhibitory effect in monocytes in vitro and in rats given lipopolysaccharide (LPS). TNF-α production by monocytes stimulated with LPS (100 ng/ml) was inhibited by UTI at concentrations higher than 100 U/ml. Expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated protein kinases 1/2 in monocytes stimulated with LPS were inhibited by UTI. UTI (50,000 U/kg iv) inhibited LPS (5 mg/kg iv)-induced increases in lung tissue levels of Egr-1, TNF-α mRNA, and TNF-α in rats. UTI inhibited LPS-induced hypotension by inhibiting pulmonary induction of inducible nitric oxide synthase (iNOS). We previously demonstrated that anti-TNF-α antibody and aminoguanidine, a selective inhibitor of iNOS, reduced LPS-induced hypotension in this animal model. Furthermore, we also reported that reduction of LPS-induced coagulation abnormalities in rats did not affect inflammatory responses and hypotension in this animal model. Taken together, these observations strongly suggested that UTI inhibited LPS-induced production of TNF-α by inhibiting activation of the extracellular signal-regulated protein kinases 1/2-Egr-1 pathway in monocytes, which might at least partly contribute to reduction of hypotension through inhibition of iNOS induction in rats given LPS.
Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle
Authors: Anderson Marianne S. , Thamotharan M. , Kao Doris , Devaskar Sherin U. , Qiao Liping , Friedman Jacob E. , Hay William W.
Published: November 2004

To test the effects of acute fetal hyperinsulinemia on the pattern and time course of insulin signaling in ovine fetal skeletal muscle, we measured selected signal transduction proteins in the mitogenic, protein synthetic, and metabolic pathways in the skeletal muscle of normally growing fetal sheep in utero. In experiment 1, 4-h hyperinsulinemic-euglycemic clamps were conducted in anesthetized twin fetuses to produce selective fetal hyperinsulinemia-euglycemia in one twin and euinsulinemia-euglycemia in the other. Serial skeletal muscle biopsies were taken from each fetus during the clamp and assayed by Western blot for selected insulin signal transduction proteins. Tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and the p85 subunit of phosphatidylinositol 3-kinase doubled at 30 min and gradually returned to control values by 240 min. Phosphorylation of extracellular signal-regulated kinase 1,2 was increased fivefold through 120 min of insulin infusion and decreased to control concentration by 240 min. Protein kinase B phosphorylation doubled at 30 min and remained elevated throughout the study. Phosphorylation of p70 S6K increased fourfold at 30, 60, and 120 min. In the second experiment, a separate group of nonanesthetized singleton fetuses was clamped to intermediate and high hyperinsulinemic-euglycemic conditions for 1 h. GLUT4 increased fourfold in the plasma membrane at 1 h, and hindlimb glucose uptake increased significantly at the higher insulin concentration. These data demonstrate that an acute increase in fetal plasma insulin concentration stimulates a unique pattern of insulin signal transduction proteins in intact skeletal muscle, thereby increasing pathways for mRNA translation, glucose transport, and cell growth.
Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. V. Role of purinergic receptors
Authors: Xu Jiang , Kussmaul William , Kurnik Peter B. , Al-Ahdav Mohamad , Pelleg Amir
Published: November 2004

The mechanism of extracellular ATP-triggered vagal depressor reflex was further studied in a closed-chest canine model. Adenosine and ATP were administered individually in equimolar doses (0.01–1.0 μmol/kg) into the right coronary artery (RCA) and left circumflex coronary artery (LCA). When administered into the RCA, adenosine and ATP exerted an identical and relatively small negative chronotropic effect on sinus node automaticity; the time to peak negative chronotropic effect was ≥7 s. When administered into the LCA, adenosine had no effect on sinus node automaticity, whereas ATP markedly suppressed sinus node automaticity. This effect of ATP 1) reached its peak in <2 s after its administration, 2) was short lasting, and 3) was completely abolished by either intravenous administration of the muscarinic cholinergic blocker atropine (0.2 mg/kg) or intra-LCA administration of 2′,3′- O-(2,4,6 -trinitrophenyl)-ATP (TNP-ATP), a potent P2X2/3 purinergic receptor (P2X2/3R) antagonist, but not by diinosine pentaphosphate (Ip5I), a potent inhibitor of P2X1R and P2X3R. Repetitive administrations of ATP were not associated with reduced effects, indicative of receptor desensitization, thereby excluding the involvement of the rapidly desensitized P2X1R in the action of ATP. It was concluded that ATP triggers a cardio-cardiac vagal depressor reflex by activating P2X2/3R located on vagal sensory nerve terminals localized in the left ventricle. Because these terminals mediate vasovagal syncope, these data could suggest a mechanistic role of extracellular ATP in this syndrome and, in addition, give further support to the hypothesis that endogenous ATP released from ischemic myocytes is a mediator of atropine-sensitive bradyarrhythmias associated with left ventricular myocardial infarction.
Novel Insights into the Aetiology and Pathogenesis of Hypopituitarism
Authors: Dattani Mehul T.
Published: November 2004

Recent advances in our knowledge of pituitary development, acquired mainly from animal models, have enhanced our understanding of the aetiology of isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD), as well as several syndromic forms of growth hormone deficiency (GHD). A number of developmental genes known to be important for organ commitment and cell differentiation and proliferation (HESX1, LHX3, LHX4, PROP1 and PIT1) have been implicated in CPHD with or without other syndromic features. Phenotypes associated with these genetic mutations and their inheritance may be highly variable. Functional analyses of these mutations reveal valuable insights into the function of the proteins and hence into the effect of these mutations on phenotype. Novel insights have been gained into the mechanisms whereby these genes are associated with particular phenotypes as a result of murine transgenesis, e.g. type II autosomal dominant GHD. Mutations within known genes account for a small proportion of cases of IGHD and CPHD, suggesting the role of other as yet unidentified genetic and environmental factors. Hence, genetic testing will in the future have a greater role to play in understanding the mechanisms leading to particular hypopituitary phenotypes and also in predicting the evolution of these disorders. There is, however, no substitute for careful delineation of the phenotype prior to undertaking genetic studies.
The Adrenal
Authors: Lin Lin , Achermann John C.
Published: November 2004

During the past 15 years, considerable progress has been made in our understanding of the genetic basis of adrenal development and function. More than 30 single gene disorders have now been identified that can affect the hypothalamic-pituitary-adrenal axis in humans (fig. 1, 2; table 1). This review highlights recent advances in the molecular pathology of: (1) adrenal hypoplasia, (2) adrenal destruction, (3) disorders of adrenal steroidogenesis, (4) adrenal steroid resistance and (5) activation of the adrenal axis/tumorigenesis. Characterizing the molecular basis and natural history of these conditions is providing fascinating insight into adrenal development and function and can help to focus treatment and counselling of patients appropriately. However, ongoing translation of research findings into clinical practice is needed if patient care is to be influenced significantly.
Growth Hormone and Glucose Homeostasis
Authors: Jørgensen Jens O.L. , Krag Morten , Jessen Niels , Nørrelund Helene , Vestergaard Esben T. , Møller Niels , Christiansen Jens S.
Published: November 2004

Patients with active acromegaly are insulin-resistant and glucose-intolerant, whereas children with growth hormone (GH) deficiency (GHD) are insulin-sensitive and may develop fasting hypoglycaemia. Surprisingly, however, hypopituitary adults with unsubstituted GHD tend to be insulin-resistant, which may worsen during GH substitution. During fasting, which may be considered the natural domain for the metabolic effects of GH, the induction of insulin resistance by GH is associated with enhanced lipid oxidation and protein conservation. In this particular context, insulin resistance appears to constitute a favourable metabolic adaptation. The problem is that GH substitution results in elevated circadian GH levels in non-fasting patients. The best way to address this challenge is to employ evening administration of GH and to tailor the dose. Insulin therapy may cause hypoglycaemia and GH substitution may cause hyperglycaemia. Such untoward effects should be minimized by carefully monitoring the individual patient.
Molecular Basis of Sotos Syndrome
Authors: Niikawa Norio
Published: November 2004

This paper describes the isolation of a novel human gene, NSD1, from the 5q35 breakpoint of t(5;8)(q35; q24.1) in a patient with Sotos syndrome, and NSD1 mutation analysis. Of 112 (95 Japanese and 17 non-Japanese) patients analyzed, 16 (14%) had a heterozygous NSD1 point mutation (10 protein truncation types and six missense types) and 50 (45%) a ∼0.7-Mb microdeletion involving NSD1. The results indicated that haploinsufficiency of NSD1 is the major cause of Sotos syndrome, and NSD1 plays a role in growth and brain development in humans. Detailed clinical examinations provided a genotype-phenotype correlation in Sotos syndrome, i.e. in patients with deletions, overgrowth is less obvious and mental retardation is more severe than in those with point mutations, and major anomalies were exclusively seen in the former. The results also indicated that Sotos syndrome due to a deletion falls into a contiguous gene syndrome, while Sotos syndrome due to an NSD1 point mutation is a single gene defect, occasionally with an autosomal dominant mode of inheritance. The genomic structure around the deleted and flanking regions revealed the presence of two sets of low copy repeats through which the microdeletion in Sotos syndrome is mediated.
Clinical Genetics in Developing Countries: The Case of Brazil
Authors: Marques-de-Faria Antonia Paula , Ferraz Victor E. Faria , Acosta Angelina Xavier , Brunoni Décio
Published: November 2004

There are many impediments to the progress of clinical and medical genetics in developing countries. Higher priorities concerning basic health care usually take precedence over genetic diseases and birth defects among medical professionals and public health officials. This is so in spite of the fact that the global prevalence of these conditions seems higher than in the developed world and that limited resources enhance the burden on individuals, families and populations. Furthermore, as a consequence of recent advances in medical genetics, demand for genetic services has increased, reinforcing the need for programs for the management and prevention of genetic diseases and birth defects, especially at primary health care level. An overview of these issues in Brazil is presented here, with information on the health system, the evolution of medical and clinical genetics in the country, and the situation of medical and clinical genetic services. We discuss proposals for implementing appropriate, ethically acceptable and equitable clinical genetic services for the Brazilian population.
MDMA (3,4-Methylenedioxymethamphetamine) or Ecstasy: The Neuropsychobiological Implications of Taking It at Dances and Raves
Authors: Parrott A.C.
Published: November 2004

MDMA (3,4-methylenedioxymethamphetamine) or ‘ecstasy’ is a ring-substituted amphetamine derivative, which is widely used as a recreational drug, most particularly at dances and raves. Around 80–95% of dancers/ravers report using ecstasy/MDMA, compared to 5–15% of young people in general. This paper will consider the possible contribution of stimulatory environmental conditions to the neuropsychobiological effects of MDMA. Animal research shows that heat and crowding potentiate the acute effects of MDMA. Social interaction and intravenous drug self-administration in laboratory rats are significantly enhanced when MDMA is given under hot ambient temperatures. Loud noise and physical activity can also contribute to the general overarousal. Furthermore, MDMA impairs homeostatic thermal control in rats, leading them to overheat in hot environments. The human implications of these findings are that the hot, noisy and overcrowded conditions at raves may be providing the ideal environment to heighten the acute drug response. In recreational users, the acute medical dangers of MDMA comprise a constellation of hyperthermia-related abreactions, which generally only occur when it has been taken in hot and crowded environments. MDMA is well established as a serotonergic neurotoxin in laboratory animals, but heat and overcrowding increase the degree of distal axon terminal loss. If this also occurs in humans, then the stimulatory environments of clubs and raves may heighten the likelihood of adverse neuropsychological sequelae in recreational ecstasy users. Consistent with this prediction, the extent of self-reported dancing/exercise when on MDMA has recently been shown to be associated with significantly more psychobiological problems afterwards.
Characterization of Breast Milk Received by Infants with Gross Blood in Stools
Authors: Laitinen Kirsi , Arvola Taina , Moilanen Eeva , Lampi Anna-Maija , Ruuska Tarja , Isolauri Erika
Published: November 2004

Objective: The aim of this study was to ascertain factors that might be protective of the appearance of gross blood in the stools of breast-fed infants. Methods: Logistic regression models were formed to search for variables possibly explaining the condition. In addition to the analyzed breast milk factors, mother’s allergic disease was introduced into the models to control for its possible confounding effect. The breast milk samples, collected from mothers of infants with gross blood in stools (n = 23) and from mothers of healthy age-matched infants (n = 71), were analyzed for concentrations of transforming growth factor-β2, tumor necrosis factor-α, interleukin (IL)-4, IL-10, prostaglandin (PG)E2, cysteinyl leukotrienes (Cys-LTs) and fatty acid composition. Results and Conclusions: Increase in the concentrations of PGE2 and Cys-LTs in the breast milk together with mother’s allergic disease reduced the likelihood of gross blood in stools in the breast-fed infant. The results suggest that no single factor, but a combination of immunomodulatory factors may protect the child from gross blood in the stools of breast-fed infants. Allergic disease was not a risk factor as mother’s allergic disease appeared to counterbalance the gross blood in stools. Due to the preliminary nature of the study, the results need to be verified in a larger setting. The challenge for the future lies in identifying of such active compounds for dietary modification to enforce particularly the properties of the breast milk which are immunoprotective for the infant and to reduce the likelihood of intestinal disorders in at risk infants.
Fish Protein Stimulated the Fibrinolysis in Rats
Authors: Murata Masakazu , Sano Yoko , Bannai Seiko , Ishihara Kenji , Matsushima Ryoji , Uchida Motoharu
Published: November 2004

Objective: We hypothesized that fish protein affects blood coagulation and/or fibrinolysis, and compared the activity and amounts of factors involved in blood coagulation and fibrinolysis in rats fed the fish protein, which was treated to remove water-soluble and ethanol-soluble elements, from sardine (sardine protein). Methods: In the first experiment, rats were fed for 21 days an AIN-93G-based control diet, and diets in which the casein of the control diet was exchanged for sardine protein at 5, 10 and 20% levels. In the second experiment, rats were fed an AIN-93G control diet and diets containing 5% fish oil, 10% sardine protein or both (5% fish oil + 10% sardine protein) for 21 days. At the end of the experiments, blood coagulation time, hemostatic parameters and fibrinolysis parameters were measured. Results: The activated partial thromboplastin time (APTT), which is an assay for blood coagulation time in the intrinsic blood coagulation pathway, of rats fed the 20% sardine protein diet was significantly prolonged compared to that of rats fed the control diet. The prolonged APTT by dietary sardine protein was due to a significant decrease of the activities of plasma blood coagulation factors VIII, IX, XI and XII. On the other hand, dietary sardine protein significantly increased the activity of tissue-type plasminogen activator, and the amount of plasma plasmin–α2-plasmin inhibitor complex, which are markers of activated plasmin. Moreover, we observed that the 20% sardine protein diet increased the amount of plasma D-dimer, which is a degraded product of the fibrin polymer by plasmin. In the second experiment, the APTT and PT of rats fed the F diet were prolonged compared to those of rats fed the control diet, however the concentration and amount of fibrinolytic parameters in the plasma were almost the same as those of rats fed the control diet. In contrast, the F+S diet not only prolonged APTT and PT, but also increased the concentration and amount of fibrinolytic parameters in plasma. Conclusions: We consider that the beneficial effects to health and amelioration of cardiovascular and cerebrovascular diseases by fish consumption are caused by a combination of the suppressing effect on blood coagulation of n–3 polyunsaturated fatty acids and the promoting effect on fibrinolysis of fish protein.
Does Dissociation Offer a Useful Explanation for Psychopathology?
Authors: Jureidini Jon
Published: November 2004

Background: Dissociation is often conceptualised as an altered state of consciousness, a trance-like state in which normal barriers between conscious and unconscious memories, desires and beliefs break down and other amnestic barriers emerge. This review explores whether it is likely that there is a neurophysiology of pathological dissociative processes that will elucidate management. Method: A critical reading of current research, sourced through Medline and Psychinfo searches from 1990 to 2002, using subject headings: dissociative disorders, hypnosis and stress disorder (post-traumatic), as well as keywords: dissociation, hypnosis and trance. Results: Current knowledge does not support the notion of dissociation as a discrete brain state or process. Conclusions: Psychiatric and neurophysiological research and theory development are better directed towards individual components that contribute to dissociative experience.
Distribution of Symptoms of Conduct Disorder and Antisocial Personality Disorder in Turkey
Authors: Doğan Orhan , Önder Zuhal , Doğan Selma , Akyüz Gamze
Published: November 2004

Background: A variety of conduct disorder (CD) symptoms are seen together as a symptom cluster. Among CD symptoms there are serious and stubborn antisocial behaviors: lying, swindling, running away from home/school, destructiveness, arson, kidnapping women, sexual abuse, and armed robbery. The objective of this study was to discover the relationship between CD and antisocial personality disorder (APD) and the distribution of the symptoms of these disorders. Sampling and Methods: The research sample consisted of 994 individuals between the ages of 18 and 65 years in Sivas province. Subjects were given the Diagnostic Interview Schedule-III-R (DIS-III-R) APD subscale. Results: The lifetime prevalence for CD and APD was found to be 21.03 and 3.02%, respectively. In both disorders the percentage of men was higher than for women. The comorbidity of both disorders was found to be 14.35%. The most frequently seen CD symptom in normal society is ‘lying’, but in those with CD ‘initiates a fight several times’ is the most frequently seen symptom. In those with APD the most frequently seen symptom is ‘truant from school several times’. Conclusions: Identifying risk factors in children could be an important step in preventing the progression of CD and APD.
Richard Morton: Origins of Anorexia nervosa
Authors: Pearce J.M.S.
Published: November 2004

Sir William Gull coined the name ‘anorexia nervosa’. Examples of self-starvation appeared in the Hellenistic era. Holy anorexics abused their bodies, rejected marriage and sought religious asylum where many perished and became saints. The condition then paled into obscurity until the 19th century. Louis-Victor Marce (1828–1864) described such a patient in 1859, but Richard Morton is generally credited with the first medical description of anorexia nervosa in 1689. Two neurologists in 1873 separately described anorexia nervosa. Ernest Charles Lasègue, a student friend of Claude Bernard, and a favourite pupil of Trousseau wrote of a refusal of food that may be indefinitely prolonged. Historical precedence is explored and citations included.
Mechanism of Disorientation in Alzheimer’s Disease
Authors: Joray Sabine , Herrmann François , Mulligan Reinhild , Schnider Armin
Published: November 2004

In nondemented amnesics, disorientation mostly reflects a failure to select memories that pertain to ongoing reality (increased temporal context confusion; TCC), a failure strongly associated with orbitofrontal damage. In the present study, we used the same paradigm – 2 runs of a continuous recognition task – in 23 patients with mild to moderate Alzheimer’s disease (AD) (Clinical Dementia Rating Scale score of 1–2). We found that disorientation was frequent in this sample (52%). However, although it correlated moderately well with general measures of dementia severity, verbal episodic memory and executive functioning, there was no significant correlation with TCC. Thus, disorientation in AD appears to reflect general cognitive decline rather than a specific cognitive failure such as increased TCC. This finding is compatible with the different distribution of degeneration in AD and the orbitofrontal damage typically present in severely disoriented amnesics.
Interferon Beta-1a and Intravenous Immunoglobulin Treatment for Multiple Sclerosis in Iran
Authors: Kalanie Hossein , Gharagozli Kurosh , Hemmatie Abolfazl , Ghorbanie Mehdie , Kalanie Amir Reza
Published: November 2004

The aim of the study was to evaluate the efficacy and safety of interferon beta-1a (Avonex) and intravenous immunoglobulin (IVIG) in clinical practice for the treatment of relapsing-remitting multiple sclerosis. Avonex is the most common disease-modifying therapy used in Iran due to its ease of administration. IVIG is also frequently used due to its alleged effectiveness and fewer side effects. Eighty patients were selected and prospectively monitored according to a predefined protocol. They were then randomized to receive either weekly intramuscular injections of Avonex or 0.4 g/kg monthly IVIG in a single blind fashion and following an attack of exacerbation which was treated with steroids. Basal relapse rate and Expanded Disability Status Scale (EDSS) were similar in both groups of patients (p > 0.4). Seventy-two patients remained in the study. The annual relapse rate consistently decreased from 0.95 ± 0.41 to 0.60 ± 0.67 (∼32%, p < 0.001) for 34 patients treated with Avonex and from 1.05 ± 0.34 to 0.55 ± 0.46 for 38 patients in the IVIG group (∼47%, p < 0.001). EDSS decreased by 0.4 units in IVIG-treated patients (p < 0.001) and remained stable (0.2 < p < 0.3) in the Avonex arm. This study confirms the relative efficacy of both treatments with better safety profile for IVIG in the studied Iranian population. However, the results are very preliminary ones, due to limited numbers of patients and only 12 months of treatment.
Left Ventricular Hypertrabeculation/Noncompaction and Stroke or Embolism
Authors: Stöllberger Claudia , Finsterer Josef
Published: November 2004

Left ventricular hypertrabeculation/noncompaction (LVHT) is reported to be associated with embolism. This retrospective study assessed the number of strokes/embolisms in 62 patients with LVHT and in 62 control patients matched with regard to age, sex and left ventricular systolic function. The incidence of strokes or embolism was 10% in patients with LVHT and 15% in controls. LVHT by itself does not seem to be a risk factor for stroke or embolism and thus is not an indication for oral anticoagulation. However, if LVHT is associated with systolic dysfunction, oral anticoagulation should be considered.
Polymorphisms of the Interleukin-1β Gene Affect the Risk of Myocardial Infarction and Ischemic Stroke at Young Age and the Response of Mononuclear Cells to Stimulation In Vitro
Authors: Iacoviello L. , Di Castelnuovo A. , Gattone M. , Pezzini A. , Assanelli D. , Lorenzet R. , Del Zotto E. , Colombo M. , Napoleone E. , Amore C. , D’Orazio A. , Padovani A. , de Gaetano G. , Giannuzzi P. , Donati M.B.
Published: November 2004

Objectives—

To investigate the role of interleukin-1β (IL-1β) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age.

Methods and Results—

A total of 406 patients with myocardial infarction (MI) at young age, frequency-matched for age, sex, and recruitment center, with 419 healthy population-based controls and 134 patients with ischemic stroke at young age, matched by age and sex, with 134 healthy population-based controls, were studied. Subjects carrying the TT genotype of the −511C/T IL-1β polymorphism showed a decreased risk of MI (odds ratio [OR], 0.36; 95% CI, 0.20 to 0.64) and stroke (OR, 0.32; 95% CI, 0.13 to 0.81) after adjustment for conventional risk factors. In both studies, the T allele showed a codominant effect (
P
=0.0020 in MI;
P
=0.021 in stroke). Mononuclear cells from volunteers carrying the T allele showed a decreased release of IL-1β and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1β during cell stimulation resulted in a marked reduction of tissue factor activity expression.

Conclusions—

-511C/T IL-1β gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.