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Effect of iron availability on expression of the Bradyrhizobium japonicum hemA gene.

Bradyrhizobium japonicum produces delta-aminolevulinic acid, the universal precursor of tetrapyrroles, in a reaction catalyzed by the product of the hemA gene. Expression of the B. japonicum hemA gene is affected by iron availability. Activity of a hemA-lacZ fusion is increased approximately threefold by iron, and RNA analysis indicates that iron regulation is at the level of mRNA accumulation. To our knowledge, this is the first example of an iron-regulated heme biosynthetic gene in prokaryotes.

Aldehyde Oxidoreductases↗

Representation and simulation of biochemical processes using the pi-calculus process algebra.

Despite the rapidly accumulating body of knowledge about protein networks, there is currently no convenient way of sharing and manipulation of such information. We suggest that a formal computer language for describing the biomolecular processes underlying protein networks is essential for rapid advancement in this field. We propose to model biomolecular processes by using the pi-Calculus, a process algebra, originally developed for describing computer processes. Our model for biochemical processes is mathematically well-defined, while remaining biologically faithful and transparent. It is amenable to computer simulation, analysis and formal verification. We have developed a computer simulation system, the PiFCP, for execution and analysis of pi-calculus programs. The system allows us to trace, debug and monitor the behavior of biochemical networks under various manipulations. We present a pi-calculus model for the RTK-MAPK signal transduction pathway, formally represent detailed molecular and biochemical information, and study it by various PiFCP simulations.

Biochemistry↗

Yttrium-90 microsphere therapy for hepatic malignancy: devices, indications, technical considerations, and potential complications.

Management of hepatic malignancies is a ubiquitous medical problem. Surgical resection of primary or metastatic liver cancer, with or without adjuvant chemotherapy, is the most effective method for enhancing survival; however, hepatic malignancies in the vast majority of patients are unresectable both at initial manifestation and at recurrence. In these patients, palliative cytoreductive therapies may help to retard tumor progression and therefore favorably alter the course of the disease. Since hepatic neoplasms are principally supplied by the hepatic artery, various arterially delivered cytotoxic agents have been developed to achieve these objectives. Recently, the Food and Drug Administration approved the transarterial administration of yttrium-90 microspheres for liver-directed therapy. Effective use of these devices requires knowledge of the accumulated clinical experience and a dedicated multidisciplinary effort to ensure optimal outcomes and avoid therapy-specific life-threatening complications.

Adult↗

Neurophysiology of perceptual and motor aspects of interception.

The interception of moving targets is a complex activity that involves a dynamic interplay of several perceptual and motor processes and therefore involves a rich interaction among several brain areas. Although the behavioral aspects of interception have been studied for the past three decades, it is only during the past decade that neural studies have been focused on this problem. In addition to the interception itself, several neural studies have explored, within that context, the underlying mechanisms concerning perceptual aspects of moving stimuli, such as optic flow and apparent motion. In this review, we discuss the wealth of knowledge that has accumulated on this topic with an emphasis on the results of neural studies in behaving monkeys.

Animals↗

Ionic mechanism of electroresponsiveness in cerebellar granule cells implicates the action of a persistent sodium current.

Although substantial knowledge has been accumulated on cerebellar granule cell voltage-dependent currents, their role in regulating electroresponsiveness has remained speculative. In this paper, we have used patch-clamp recording techniques in acute slice preparations to investigate the ionic basis of electroresponsiveness of rat cerebellar granule cells at a mature developmental stage. The granule cell generated a Na+-dependent spike discharge resistant to voltage and time inactivation, showing a linear frequency increase with injected currents. Action potentials arose when subthreshold depolarizing potentials, which were driven by a persistent Na+ current, reached a critical threshold. The stability and linearity of the repetitive discharge was based on a complex mechanism involving a N-type Ca2+ current blocked by omega-CTx GVIA, and a Ca2+-dependent K+ current blocked by charibdotoxin and low tetraethylammonium (TEA; <1 mM); a voltage-dependent Ca2+-independent K+ current blocked by high TEA (>1 mM); and an A current blocked by 2 mM 4-aminopyridine. Weakening TEA-sensitive K+ currents switched the granule cell into a bursting mode sustained by the persistent Na+ current. A dynamic model is proposed in which the Na+ current-dependent action potential causes secondary Ca2+ current activation and feedback voltage- and Ca2+-dependent afterhyperpolarization. The afterhyperpolarization reprimes the channels inactivated in the spike, preventing adaptation and bursting and controlling the duration of the interspike interval and firing frequency. This result reveals complex dynamics behind repetitive spike discharge and suggests that a persistent Na+ current plays an important role in action potential initiation and in the regulation of mossy fiber-granule cells transmission.

2-Amino-5-phosphonovalerate↗

Factors of the hemostatic system in diabetic patients. A survey of controlled studies.

Diabetes mellitus is associated with a variety of vascular complications like diabetic retinopathy, myocardial infarction, stroke and peripheral vessel disease. These complications are of utmost importance because they lead to disability and premature death of the patients. The pathogenesis of these lesions has been thought to depend at least partly on defects in the hemostatic system. Many alterations of the coagulation and the fibrinolytic system as well as of the reaction of platelets have been found in diabetics. In general these tend to suggest a state of slightly activated coagulation, of increased platelet reactivity and of decreased fibrinolysis. However, no conclusive picture of the role of hemostasis in the development of vascular lesions in diabetics has emerged yet, as contradictive results have been found by many investigators. The aim of this review article is to sum up the knowledge that has accumulated in the last years in controlled clinical trials concerning the state of the diabetic hemostatic system.

Blood Coagulation Factors↗

Establishing diagnosis of pulmonary malignant lymphoma by gene rearrangement analysis of lymphocytes in bronchoalveolar lavage fluid.

We report the successful application of gene rearrangement analysis to the lymphocytes obtained by bronchoalveolar lavage (BAL) for the diagnosis of pulmonary malignant lymphoma. A 45-yr-old female patient who had been suffering from back pain was shown to have macroglobulinemia and pulmonary infiltrative shadow by chest radiography. Transbronchial lung biopsy revealed a small B-cell infiltrate with monotypic immunoglobulin expression (IgM/kappa light chain), and malignant lymphoma was highly suspected. BAL was performed to evaluate the cell profiles. The phenotyping of lavaged lymphocytes by flow cytometry revealed that the major component of the lymphocytes was CD3-positive T cells, and that CD21-positive B cells accounted for only 10% of all lymphocytes. This result was contradictory to the immunohistochemical population of lymphocytes in biopsied specimens. However, gene analysis of lavaged lymphocytes revealed positive immunoglobulin heavy chain rearrangement and negative immunoglobulin light chain and T-cell receptor rearrangement, suggesting that B cells making up a minor population of lavaged lymphocytes were proliferating monoclonally. Thus, in this case, gene analysis was an effective procedure for detecting the origin of tumor cells and distinguishing monoclonality from reactive accumulations. To our knowledge, this case represents the first reported application of gene rearrangement analysis to cells obtained by BAL. The sensitivity and usefulness of this analysis for the accurate evaluation of pulmonary lymphoproliferative lesions, when applied to BAL cells, should be emphasized.

Bronchoalveolar Lavage Fluid↗

Diabetes patient education research: an integrative literature review.

PURPOSE: The purpose of this study is to summarize the accumulated state of knowledge in the area of diabetes patient education research and highlight important issues that research has left unanswered. METHODS: An integrative literature review was conducted on the topic of diabetes patient education between the years 1985 and 1998. Keywords used in the computerized search were diabetes mellitus, patient education, health education, research, and behavior change. The databases searched were MEDLINE, CINAHL, HealthSTAR, EMBASE, and CHID-HE. A total of 78 papers were reviewed. RESULTS: Most studies lacked a theoretical framework and the majority of studies were conducted in an outpatient setting. HbA1c was the most frequently employed outcome measure, with little, if any, description of the interventions. CONCLUSIONS: Much has been learned in terms of the effectiveness of diabetes education on improving knowledge. However, other topic areas and outcomes need further exploration.

Diabetes Mellitus↗

Sickness absence: a review of performed studies with focused on levels of exposures and theories utilized.

BACKGROUND: Despite the major impact sickness absence has on society, companies and individuals, surprisingly little scientific knowledge has been accumulated, and the studies that have been performed vary greatly. AIM AND METHOD: Examination of about 320 studies of sickness absence regarding structural levels of exposures studied and theories utilized. RESULTS: Theories concerning sickness absence were found to vary greatly. Along with exposures and factors explaining sickness absence these theories were categorized with respect to different structural levels, i.e. they were deemed national, occupational, or individual. A classification of different types of absences is presented. CONCLUSION: Although most of the reviewed studies were performed within the realm of medicine, only a few of the investigators used medical explanatory models or even considered the health status of individuals. Moreover, it is known that factors at "higher" structural levels have a substantial effect on sickness absence, but these were seldom taken into account, or even mentioned, in the reports scrutinized.

Absenteeism↗

Assessing the impact of humanitarian assistance in the health sector.

There have been significant improvements in the design and management of humanitarian aid responses in the last decade. In particular, a significant body of knowledge has been accumulated about public health interventions in emergencies, following calls for developing the evidence base of humanitarian health interventions. Several factors have prompted this, such as the increased volume of humanitarian assistance with subsequent higher levels of scrutiny on aid spending, and greater pressure for improving humanitarian aid quality and performance. However, documentation of the ability of humanitarian interventions to alleviate suffering and curb mortality remains limited. This paper argues that epidemiological studies can potentially be a useful tool for measuring the impact of health interventions in humanitarian crises. Survey methods or surveillance systems are mainly used for early warning or needs assessment and their potential for assessing the impact of aid programmes is underutilised.

Journal Article↗

"There's no place like home" a pilot study of perspectives of international health and social care professionals working in the UK.

BACKGROUND: Many countries are reporting health workforce shortages across a range of professions at a time of relatively high workforce mobility. Utilising the global market to supply shortage health skills is now a common recruitment strategy in many developed countries. At the same time a number of countries report a 'brain drain' resulting from professional people leaving home to work overseas. Many health and social care professionals make their way to the UK from other countries. This pilot study utilises a novel 'e-survey' approach to explore the motives, experiences and perspectives of non-UK health and social care professionals who were working or had worked in the UK. The study aims to understand the contributions of international health and social care workers to the UK and their 'home' countries. The purpose of the pilot study is also in part to test the appropriateness of this methodology for undertaking a wider study. RESULTS: A 24-item questionnaire with open-ended and multiple choice questions was circulated via email to 10 contacts who were from a country outside the UK, had trained outside the UK and had email access. These contacts were requested to forward the email to other contacts who met these criteria (and so on). The email was circulated over a one month pilot period to 34 contacts. Responses were from physiotherapists (n = 11), speech therapists (n = 4), social workers (n = 10), an occupational therapist (n = 1), podiatrists (n = 5), and others (n = 3). Participants were from Australia (n = 20), South Africa (n = 10), New Zealand (n = 3) and the Republic of Ireland (n = 1). Motives for relocating to the UK included travel, money and career opportunities. Participants identified a number of advantages and disadvantages of working in the UK compared to working in their home country health system. Respondents generally reported that by working in the UK, they had accumulated skills and knowledge that would allow them to contribute more to their profession and health system on their return home. CONCLUSION: This pilot study highlights a range of issues and future research questions for international learning and comparison for the health and social care professions as a result of international workforce mobility. The study also highlights the usefulness of an e-survey technique for capturing information from a geographically diverse and mobile group of professionals.

Journal Article↗

Coagulation abnormalities in critically ill patients.

Many critically ill patients develop hemostatic abnormalities, ranging from isolated thrombocytopenia or prolonged global clotting tests to complex defects, such as disseminated intravascular coagulation. There are many causes for a deranged coagulation in critically ill patients and each of these underlying disorders may require specific therapeutic or supportive management. In recent years, new insights into the pathogenesis and clinical management of many coagulation defects in critically ill patients have been accumulated and this knowledge is helpful in determining the optimal diagnostic and therapeutic strategy.

Blood Coagulation↗

Conceptual complexity and construct validity.

Despite a century of methodological and conceptual advances in the technology of psychosocial measurement, poor correspondence between indicators and the constructs they are intended to represent remains a limiting factor to the accumulation of scientific knowledge. Longstanding conventions in measurement may contribute to the failure to develop optimal criteria. These conventions include the focus on complex over simple constructs and the use of multi-item measures of disparate content to represent those constructs. Several arguments suggest that such a measurement model compromises the potential for developing measures that accurately reflect psychosocial phenomena. The article concludes with some preliminary suggestions concerning an alternative model that may address this construct validity problem more effectively.

Humans↗

Roles for the kallikrein-kinin system in inflammatory exudation and pain: lessons from studies on kininogen-deficient rats.

Roles for the kallikrein-kinin system in inflammation have been investigated extensively, and many reviews on this topic have been published during the 50 years since the discovery of bradykinin in 1949. Recent progress in the field has been remarkable with the help of experiments using gene-targetted transgenic or knockout mice, which have added further valuable information in addition to previous results obtained from pharmacological and biochemical studies using purified and isolated components of the system. Furthermore, much knowledge has been accumulated as a result of the development of various bradykinin agonists and antagonists. In this review, we focused on the data obtained from the kininogen-deficient rat, which is a natural mutant, and discuss the results in comparison with those from bradykinin receptor knockout mice. These data have clarified that endogenous bradykinin exerts a most important role in inflammatory exudation along with prostanoids, preferentially to histamine, serotonin, or neuropeptides. In inflammatory pain perception also, bradykinin produced in the local perivascular spaces stimulates polymodal pain receptors in conjunction with co-helpers such as prostanoids, vanilloids, and neuropeptides. These important roles are concluded based on consistent results obtained from experiments using several antagonists of bradykinin, kininogen-deficient rats, and bradykinin receptor knockout mice.

Animals↗

IL-6: from laboratory to bedside.

In the late 1960s, the essential role of T-cells in antibody production was reported. This suggested to us that certain molecules should be released from T-cells for the stimulation of B-cells. We discovered activities in the culture supernatant of T-cells that induced proliferation and differentiation of B-cells. The factor that induced B-cells to produce immunoglobulins was named B-cell stimulatory factor (BSF)-2. The complementary DNA that encoded human BSF- 2 was cloned in 1986. Simultaneously, interferon-beta2 and 26-kDa protein in the fibroblasts were independently cloned by different groups and were found to be identical to BSF-2. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte-stimulating factor also were proven to be the same molecule as BSF-2. Various names were used for this molecule because of its multiple biological activities, and thereafter, these names were unified as interleukin (IL)-6. Since the discovery of IL-6, rapid progress has been made in understanding its actions, the IL-6 receptor system, and the IL-6 signal transduction mechanism. More importantly, it was involved in numerous diseases, such as rheumatoid arthritis and Castleman's disease. By accumulating the basic knowledge, a new therapeutic approach by blocking IL-6 actions appeared to be feasible for chronic inflammatory diseases.

Animals↗

Consuming research, producing policy?

The authors' 1990 article "Producing Health, Consuming Health Care" presented a conceptual framework for synthesizing a rapidly growing body of findings on the nonmedical determinants of health. The article received a very positive response, and here the authors reflect on what lessons might be learned from that response about the style or content of effective interdisciplinary communication. Much substantive knowledge has been accumulated since 1990, and a number of different frameworks have been developed before and since. The authors situate theirs within this literature and consider how they might have modified it if they "knew then what they know now." They ask what impact this article, and the much broader stream of research on the determinants of health, has had on public policy?

Canada↗

Clinical pharmacokinetics of phenylbutazone.

More than 25 years after phenylbutazone was introduced as a non-steroidal anti-inflammatory agent, basic knowledge is still accumulating on its pharmacokinetics in man. Phenylbutazone is almost completely absorbed after oral administration. A large fraction of the drug in plasma is bound to proteins, and the drug has a small volume of distribution. Phenylbutazone is eliminated by metabolism, only 1% being excreted unchanged in the urine. Approximately 10% of a single dose of phenylbutazone is excreted in bile as metabolites. About 60% of the urinary metabolites have been identified. A novel type of drug metabolite in man, the C-glucuronide, is formed by direct coupling of the pyrazolidine ring of phenylbutazone to glucuronic acid via a C-C bond. Phenylbutazone is oxidised in a phenyl ring or in the side chain to hydroxylated metabolites, which may undergo subsequent O-glucuronidation. After a single dose, C-glucuronidation seems to be the dominant reaction, while oxidation becomes increasingly important after repeated administration. Due to different pharmacokinetic properties of the metabolites, the C-glucuronides are detected in highest concentrations in the urine, while the pharmacologically active compounds oxyphenbutazone and gamma-hydroxyphenbutazone predominate in plasma. The biological (elimination) half-life of phenylbutazone in man is long, with a mean of about 70 hours, and exhibits large interindividual and intraindividual variation. The interindividual variation is largely due to genetic factors. The intraindividual variation is dose and time dependent. In an individual there may be several critical dose levels where a change in the elimination kinetics takes place. Since there is no correlation between the plasma level and the clinical or toxic effects of phenylbutazone, there is at present no need for routine monitoring of plasma concentrations of the drug.

Age Factors↗

Evaluation of occupational environment in two textile plants in Northern India with specific reference to noise.

Occupational Noise exposure has been linked with a range of negative health effects by various researchers. The resulting injury of occupational hearing loss is also a well recognized and global problem. To protect workers from hearing damage due to noise exposure and other related health effects, a vast store of knowledge has been accumulated till date about its nature, etiology and time course. There is still ignorance, amongst majority of people working in industries in developing and third world countries including India about ill effects of exposure to high values of noise. The study being reported here has been carried out in two textile plants located in Northern Indian state of Punjab. Equivalent sound pressure level L(eq) has been measured in various sections of these plants with the help of a Class-I type digital sound level meter. The noise spectrum has been evaluated with the help of 1/3 octave filter set. A cross sectional study involving 112 workers exposed to different levels of occupational noise has been conducted. The results of the study establish the fact that noise level in certain sections of the plants i.e Loom Shed, Spinning, Ring Frame, TFO Area is more than the acceptable limit of 90 dBA for 8 h exposure stipulated by OSHA. The noise level in other sections like carding, blow room, combing etc., although is less than 90 dB(A), but is quite higher than limits used for assessment of noise for community response. Octave band analysis of the noise shows the presence of high sound level in 4,000 Hz frequency range, which can be a major reason for causing occupational hearing loss. The results of the interview questionnaire which included a number of parameters reveal the following; (i) only 29% workers are aware about the effects of noise on health (ii) 28% workers are using ear protectors (iii) the satisfaction with the working environment is related to noise level, as workers exposed to comparatively less noise level report better satisfaction (iv) 70% of the workers reported that high noise level causes speech interference (v) 42% workers report the noise to be annoying. The study thus demonstrates the presence of gross occupational noise exposure in both the plants and the author believes that occupational noise exposure and the related effects in India is a widespread problem.

Humans↗