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Two decades of measuring GnRH secretion.

It is almost 20 years since it was first demonstrated that serial hypophysial portal blood samples could be obtained from conscious sheep and, subsequently, from cattle, goats and pigs. Accumulated data have defined the patterns of secretion of GnRH in the normal physiological state and the effects of gonadal steroids have also been largely defined. In particular, changes across the oestrous cycle of females have been studied in detail. These data show that there is an increase in the frequency of pulsatile discharges of GnRH in the transition from the luteal to the follicular phase of the oestrous cycle, with an inverse change in the amplitude of GnRH pulses; such changes are reflected in the patterns of LH secretion from the pituitary gland. A surge in GnRH secretion is observed in a number of species, and is the primary stimulus for the preovulatory LH surge. Patterns of GnRH secretion and regulation by gonadal steroids have also been described in males. With respect to FSH, secretion per se is not dependent on pulsatile GnRH input to the pituitary gland and regulation of secretion is dependent on other factors, such as inhibin. With the bank of knowledge that has now accumulated on the secretion of GnRH in sheep under normal conditions and with respect to steroidal feedback regulation, we are now in a commanding position to define and decipher the neural systems that are involved in the regulation of its secretion.

Animals↗

Gene structure prediction using an orthologous gene of known exon-intron structure.

Given the availability of complete genome sequences from related organisms, sequence conservation can provide important clues for predicting gene structure. In particular, one should be able to leverage information about known genes in one species to help determine the structures of related genes in another. Such an approach is appealing in that high-quality gene prediction can be achieved for newly sequenced species, such as mouse and puffer fish, using the extensive knowledge that has been accumulated about human genes. This article reports a novel approach to predicting the exon-intron structures of mouse genes by incorporating constraints from orthologous human genes using techniques that have previously been exploited in speech and natural language processing applications. The approach uses a context-free grammar to parse a training corpus of annotated human genes. A statistical training procedure produces a weighted recursive transition network (RTN) intended to capture the general features of a mammalian gene. This RTN is expanded into a finite state transducer (FST) and composed with an FST capturing the specific features of the human orthologue. This model includes a trigram language model on the amino acid sequence as well as exon length constraints. A final stage uses the free software package ClustalW to align the top n candidates in the search space. For a set of 98 orthologous human-mouse pairs, we achieved 96% sensitivity and 97% specificity at the exon level on the mouse genes, given only knowledge gleaned from the annotated human genome.

Algorithms↗

Gene therapy for platelet disorders: studies with Glanzmann's thrombasthenia.

Current research aimed at correcting platelet defects are designed to further our knowledge in the use of hematopoietic stem cells for gene therapies of hemorrhagic disorders. Information gained from these studies may be directly applicable to treatment of disorders affecting platelets (e.g. Glanzmann's thrombasthenia, Bernard Soulier syndrome, gray platelet syndrome, and von Willebrand disease) as well as other disorders affecting distinct hematopoietic cell lineages. This work specifically addresses three questions: (i) can bone marrow stem cells be given sufficient genetic information to induce abnormal megakaryocytes to synthesize transgene products that help newly formed platelets to participate in normal hemostasis? (ii) can the newly synthesized receptor be maintained as a platelet-specific protein at therapeutic levels for a reasonable period of time? and (iii) will newly expressed proteins be tolerated by the immune system or become a target for B- and T-cell mediated immunity resulting in the premature destruction and clearing of the genetically altered megakaryocytes and platelets? Answers to these questions should indicate the feasibility of targeting platelets with genetic therapies that will in turn enable better management of patients with inherited bleeding disorders. The long-range benefit of this research will be an improved understanding of the regulation of protein expression during normal megakaryocytopoiesis, and the accumulation of additional scientific knowledge about normal platelet function and the way in which platelets and other cells recognize and interact with each other.

Animals↗

Lymphoedema care of breast cancer patients in a breast care clinic: a survey of knowledge and health practice.

Lymphoedema, an accumulation of protein-rich fluid in interstitial tissue, is a well-recognised life-altering result of breast cancer treatment. With the goal of studying the prevalence and management of lymphoedema after breast cancer therapy, 171 patients were invited to complete a self-administered questionnaire following completion of treatment for breast cancer. The survey revealed that 82.5% of patients knew they were at-risk of developing lymphoedema. However, the level of knowledge about preventive care in lymphoedema was inadequate, with a mean score of 4.07 out of a full mark of 10 (SD=2.35, mode=2). A substantial proportion (45.6%; n=78) of respondents reported that they had experienced lymphoedema and subsequently developed multiple sites of lymphoedema, but only 34.7% (n=26) had been referred for physiotherapy. The study also revealed that patients who had received the combined regimen of mastectomy, lymph node dissection, radiotherapy and chemotherapy were at a higher risk of developing lymphoedema (chi2=6.305, P=0.043). Interestingly, it was found that nurses were the most frequently cited resource for information, but the least consulted professionals for discussion on treatment. It is apparent from our patient survey that there is a lack of knowledge on lymphoedema care amongst breast cancer patients. In order to improve patients' level of knowledge and their awareness of lymphoedema care, the provision for systematic and comprehensive patient education, including management protocols for lymphoedema, needs to be addressed. Education and training, will be essential components of efforts to ensure appropriate care for lymphoedema patients.

Adult↗

The construction of web database server-client system for functional food factors.

In food, other than known nutrients, such as lipid, carbohydrate, protein, vitamins, and minerals, many substances with physiological function and medicinal action exist, and it is contributing to healthy improvement and/or prevention of illness. Although carotenoid, flavonoid and polyphenol, terpenoid, volatile substance and sulfur compounds, peptide, etc. have the function of illness prevention, and research of those non-nutrient functional food factors (FFF) became globally active, the research of this field is not yet done systematically. We evaluate function of FFF and reappraise known knowledge, and this knowledge is standardized and accumulated, aimed at building a web database server-client system which is easy to use for the people and nutritional research. We also collected related data such as chemical characters of FFF from literatures and other source, and formatted them into the database. We constructed the web database server-client system with MySQL database server and Apache web server based on Linux, and used Tomcat JSP engine for data connecting since they were reliable in stability and speed. We are opening the database at http://www.life-science.jp/FFF for test now.

Database Management Systems↗

Pediatric liver tumors and hepatic ontogenesis: common and distinctive pathways.

Several types of pediatric liver tumors exhibit structural features apparently reflecting processes which normally occur during hepatic ontogenesis: some hepatoblastomas mimic distinct phases of hepatogenesis, including the formation of mesenchymal structures closely associated with immature epithelia, and there are tumors almost exclusively consisting of complex mesenchymal patterns. Current classifications of hepatoblastomas refer to the identification of more or less mature (differentiated) single or mixed components seen in histologic preparations. These do not, however, attempt to integrate ontogenic pathways, in contrast for example, to nephroblastoma and associated lesions, where such a view has proved to be highly fruitful. Based on the fact that an enormous amount of knowledge has recently been accumulated regarding hepatic ontogenesis, time may have come to look at these tumors with a new eye. In what follows, we aim at trying to analyze distinct features of pediatric hepatic tumors (except vascular tumors) within the background of ontogenesis. Some key steps of hepatogenesis and the regulatory factors involved may, in the future, deliver an armamentarium to search for novel molecular mechanisms involved in tumorigenic pathways.

Bile Duct Neoplasms↗

Forces exerted by locomoting cells.

The movement of cells along substrata is a complex phenomenon involving cell extension and retraction, and cell-substratum adhesion. Knowledge is beginning to accumulate about the forces required for cell protrusion and retraction. Both of these processes also require traction to be exerted on the substratum, and new assays for these forces are under development. This review briefly discusses the forces that locomotory cells exert, in terms of both recent force measurements and possible mechanisms for their generation.

Actins↗

Model-based inference of gene expression dynamics from sequence information.

A dynamic model of prokaryotic gene expression is developed that makes considerable use of gene sequence information. The main contribution arises from the fact that the combined gene expression model allows us to access the impact of altering a nucleotide sequence on the dynamics of gene expression rates mechanistically. The high level of detail of the mathematical model is considered as an important step towards bringing together the tremendous amount of biological in-depth knowledge that has been accumulated at the molecular level, using a systems level analysis (in the sense of a bottom-up, inductive approach). This enables to the model to provide highly detailed insights into the various steps of the protein expression process and it allows us to access possible targets for model-based design. Taken as a whole, the mathematical gene expression model presented in this study provides a comprehensive framework for a thorough analysis of sequence-related effects on the stages of mRNA synthesis, mRNA degradation and ribosomal translation, as well as their nonlinear interconnectedness. Therefore, it may be useful in the rational design of recombinant bacterial protein synthesis systems, the modulation of enzyme activities in pathway design, in vitro protein biosynthesis, and RNA-based vaccination.

Base Sequence↗

[Sub-specialization within the field of radiology].

Medical knowledge and skills are accumulating at an ever increasing speed. Therefore, it becomes more and more difficult for a single one to have a complete overview of a whole discipline. This general observation also applies for radiology. Radiology has to cooperate with almost all medical disciplines and has to provide competent experts. It is therefore mandatory to support differentiation within the field of radiology and at the same time to save coherence and future developments.

Germany↗

Determining time of death using blow fly eggs in the early postmortem interval.

A forensic entomology case is presented which is interesting for two reasons; firstly, it uses egg development, but secondly, it involves a case which is over 20 years old, and was recently re-opened. The only entomological evidence was in the form of photographs. Usually, it is not possible to make any determinations from photographs alone, as species and age cannot be determined. However, this case was particularly unusual, as close up photographs taken by police at the crime scene showed the first egg eclosion. Weather records, developmental data and degree day accumulations, together with a knowledge of local species and their habitats, allowed determination of the time since death. Time of death was affirmed when the defendant was convicted of first degree murder more than 20 years after the killing.

Adult↗

Approaches towards understanding methionine biosynthesis in higher plants.

Plants are able to synthesise all amino acids essential for human and animal nutrition. Because the concentrations of some of these dietary constituents, especially methionine, lysine, and threonine, are often low in edible plant sources, research is being performed to understand the physiological, biochemical, and molecular mechanisms that contribute to their transport, synthesis and accumulation in plants. This knowledge can be used to develop strategies allowing a manipulation of crop plants, eventually improving their nutritional quality. This article is intended to serve two purposes. The first is to provide a brief review on the physiology of methionine synthesis in higher plants. The second is to highlight some recent findings linked to the metabolism of methionine in plants due to its regulatory influence on the aspartate pathway and its implication in plant growth. This information can be used to develop strategies to improve methionine content of plants and to provide crops with a higher nutritional value.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Can pregnancy be a placebo effect?: Terminology, designs, and conclusions in the study of psychosocial and pharmacological treatments of behavior disorders.

This paper discusses several salient issues in the clinical research enterprise which were stimulated by chapters on research methods and placebo phenomena in White, Tursky and Schwartz (1985), Placebo: Theory, Research, and Mechanisms. These issues include the commonalities of questions, domains and classes of variables, and research strategies needed for the discovery, accumulation and application of knowledge regarding effective clinical treatments. Problems of unwarranted uniformity assumptions and absolute design requirements as well as the failure to attend to the conceptual relevance, strength and integrity of procedures are noted with examples from the systematic desensitization literature. Meta-analyses and indexes of effect size are also examined with examples demonstrating the need for especially cautious interpretation of these procedures. A re-emphasis of the construct validity approach with better designed and executed individual studies is endorsed as the best means to improve progress.

Adaptation, Psychological↗

Collagen engineering for biomaterial use.

Collagen is a typical biological macromolecule having been utilized for a long period of time as a material like cellulose. However, its application is becoming comprehensive, ranging from classical applications such as the leather, gelatine and food industries to the current one, namely, biomaterial and biotechnological uses. The diversification of collagen applications was enhanced by two factors, the accumulation of the scientific knowledge that permitted proper engineering of collagen for a biomaterial use, and the demand for new biomaterials with characteristic biological properties including interaction with cells. The collagen engineering described in this paper is designed for biomaterial use, based on the fundamental chemical and biological properties of collagen; however, it would be useful also for other applications apart from biomaterials.

Biocompatible Materials↗

Prevention of mental disorder among Hmong refugees in the U.S.: lessons from the period 1976-1986.

Scientifically valid, well controlled studies on the prevention of mental disorders are sparse. Nonetheless, much quasi-experimental and descriptive work does exist. Published findings permit an evaluation of the mental health effects of policies, procedures and programs designed for refugees. The federal government assigns legal status to refugees and is paramount in matters of refugee relocation and readjustment within its borders. In matters of social adjustment and prevention of mental disorder, agents of the federal government must consider the accumulation and distribution of knowledge, skill and expertise on refugee social and mental health issues; policies and procedures for relocation; premigration education, training, assessment, and orientation; postmigration support and acculturation; and the development of treatment resources to meet the mental health needs. Once refugees arrive in the United States of America, much of the actual implementation of policy and procedures has been left to state governments. At this level there have been neither the resources nor the expertise to develop programs for the mental health of refugees. Limited resources have been wasted and the mental health of refugees has been neglected or made worse by some state initiated programs.

Adolescent↗

HFSA 2006 Comprehensive Heart Failure Practice Guideline.

Heart failure (HF) is a syndrome characterized by high mortality, frequent hospitalization, reduced quality of life, and a complex therapeutic regimen. Knowledge about HF is accumulating so rapidly that individual clinicians may be unable to readily and adequately synthesize new information into effective strategies of care for patients with this syndrome. Trial data, though valuable, often do not give direction for individual patient management. These characteristics make HF an ideal candidate for practice guidelines. The 2006 Heart Failure Society of America comprehensive practice guideline addresses the full range of evaluation, care, and management of patients with HF.

Cardiac Output, Low↗

Executive summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline.

Heart failure (HF) is a syndrome characterized by high mortality, frequent hospitalization, reduced quality of life, and a complex therapeutic regimen. Knowledge about HF is accumulating so rapidly that individual clinicians may be unable to readily and adequately synthesize new information into effective strategies of care for patients with this syndrome. Trial data, though valuable, often do not give direction for individual patient management. These characteristics make HF an ideal candidate for practice guidelines. The 2006 Heart Failure Society of America comprehensive practice guideline addresses the full range of evaluation, care, and management of patients with HF.

Cardiac Output, Low↗

From concepts to clinical reality: an essay on the benchmarking of biomedical terminologies.

It is only by fixing on agreed meanings of terms in biomedical terminologies that we will be in a position to achieve that accumulation and integration of knowledge that is indispensable to progress at the frontiers of biomedicine. Standardly, the goal of fixing meanings is seen as being realized through the alignment of terms on what are called 'concepts.' Part I addresses three versions of the concept-based approach--by Cimino, by Wüster, and by Campbell and associates--and surveys some of the problems to which they give rise, all of which have to do with a failure to anchor the terms in terminologies to corresponding referents in reality. Part II outlines a new, realist solution to this anchorage problem, which sees terminology construction as being motivated by the goal of alignment not on concepts but on the universals (kinds, types) in reality and thereby also on the corresponding instances (individuals, tokens). We outline the realist approach and show how on its basis we can provide a benchmark of correctness for terminologies which will at the same time allow a new type of integration of terminologies and electronic health records. We conclude by outlining ways in which the framework thus defined might be exploited for purposes of diagnostic decision-support.

Animals↗

A simple model for early morphogenesis.

Despite the large amount of knowledge which continues to accumulate about early developmental events, very little is known about the processes which control them. Part of the problem may lie in that workers applying different approaches and techniques have different points of view and appear to be reluctant to read each others' literature. My aim in this paper is not to give a generative, formal model for early development, but rather to suggest several connecting strands between the physiological, biochemical, cell biological and experimental embryological approaches which may stimulate new research in fields between those already exploited.

Amphibians↗