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PubMed2004

Internal metal sequestration and its ecotoxicological relevance: a review.

Organisms are able to control metal concentrations in certain tissues of their body to minimize damage of reactive forms of essential and nonessential metals and to control selective utilization of essential metals. These physiological aspects of organisms are not accounted for when assessing the risk of metals in the environment. The Critical Body Residue (CBR) approach relates toxicity to bioaccumulation and biomagnification and might at first sight provide a more accurate estimation of effects than the external concentration. When expressing CBRs on total internal concentrations, the capacity of organisms to sequester metals in forms that are not biologically reactive is neglected. The predictability of toxic effects will increase when knowledge on metal compartmentalization within the organisms' body is taken into account. Insight in metal compartmentalization sheds light on the different accumulation strategies organisms can follow upon metal exposure. Using a fractionation procedure to isolate metal-rich granules and tissue fragments from intracellular and cytosolic fractions, the internal compartmentalization of metals can be approximated. In this paper, current knowledge regarding metal compartmentalization in organisms is summarized, and metal fractions are identified that are indicators of toxicity. Guidance is provided on future improvement of models, such as the Biotic Ligand Model (BLM), for risk assessment of metal stress to biota.

Animals↗
PubMed1993

Prevention of hypertension.

This review summarizes papers and reports published during the past year that contribute important knowledge or perspectives about prevention of elevated arterial blood pressure. Emphasis is on controlled intervention trials, particularly the large, multicenter Trials of Hypertension Prevention-Phase I, but all relevant randomized trials known to the author are included. Observational epidemiologic studies that are cross-sectional, eg, the INTERSALT study and the US Pitt County Study, or longitudinal, eg, the large Health Professionals Followup Study and the National Health and Nutrition Examination Survey (I) Epidemiologic Followup Study, are also discussed. The recent evidence, when viewed in the context of the previously accumulated literature, supports the recommendations of two recent expert reports to the effect that 1) much knowledge is available to help avoid the rise of blood pressure with age that is the hallmark of the epidemic of hypertension in industrialized societies, and 2) efforts should be particularly directed toward control of obesity, increased physical activity, reduced salt intake, and moderation of alcohol use.

Diet↗
PubMed1986

Abdominal patterns of indium-111 labeled leukocyte imaging.

In-111 oxine WBC abdominal scanning is now a widely accepted technique for the detection of abdominal infectious processes. High sensitivity and specificity are achieved. In-111 labeled leukocyte accumulation, however, does not always suggest the diagnosis of abscess. Higher specificity could be obtained by the knowledge of the In-111 leukocyte distribution pattern in the abdomen in other pathologic states like inflammation of abdominal wounds, stoma; surgical complication without abscess formation; inflammatory or ischemic bowel disease; or swallowing leukocytes which subsequently are visualized in the intestinal lumen. One hundred fifty-two consecutive WBC scans performed over 18 months were reviewed and classified according to their pattern of uptake: 96 cases showed no abdominal uptake, and 56 had accumulation of leukocytes in the abdomen. Twenty-eight of these patients had proven abdominal abscess, and the remaining 26 were positive due to other causes. This report briefly discusses the distribution pattern of In-111 labeled leukocytes in the latter patients and compares the results obtained using different diagnostic criteria.

Abdomen↗
PubMed1996

Staurosporine and herbimycin A augment agonist-induced elevation of cAMP in Jurkat T-lymphoblasts.

Cross-talk between signalling pathways appears to play an important role in T-lymphocyte activation. In the present work, we have studied the effects of different inhibitors of protein tyrosine kinases or protein serine/ threonine kinases on the agonist-induced cAMP accumulation in the human T-lymphoblast cell line Jurkat. Staurosporine, a potent but nonspecific inhibitor of protein kinases, produced a ten-fold enhancement of the response to PGE2. No significant effect was obtained with two specific protein kinase C inhibitors (GF 109203X and H7), whereas herbimycin A, a specific protein tyrosine kinase inhibitor, markedly enhanced the PGE2-induced cAMP accumulation: its effect was approximately 60% that of staurosporine. It was confirmed that both staurosporine and herbimycin A inhibited by more than 90% the release of IP3 induced by ligation of the T-cell receptor, a known protein tyrosine kinase-dependent mechanism. To our knowledge, this study provides the first indication of a protein tyrosine kinase-mediated inhibition of agonist-induced cAMP accumulation. The possible targets of this inhibition are discussed.

Adenosine Monophosphate↗
PubMed1983

Regulation and compartmentalization of androgens in rat prostate and muscle.

Male rats were castrated and treated with various doses of testosterone (T) or 5 alpha-dihydrotestosterone (DHT) by implantation of steroid releasing polydimethylsiloxane depots. After 14 days, the animals were killed and the concentration of T, DHT and 5 alpha-androstane-3 alpha,17 beta-diol (Diol) was measured by radioimmunoassay in plasma, in the homogenates of the prostate (PR), the bulbocavernosus/levator ani muscle (BCLA), skeletal muscle (SM) and heart muscle (HM), as well as in the cytosol and the nuclear fraction of these tissues. Additionally, the weight and DNA content of PR and the levator ani muscle were measured. The main results were: After T or DHT administration the main androgens in plasma were T or Diol, respectively, the concentration of each being linearly dependent from the administered steroid dose (T after T-: r = 0.97, P less than 0.001. Diol after DHT administration: r = 0.97, P less than 0.001). T in a dose of 60 micrograms/24 h maintained the concentrations of T, DHT and Diol in plasma in the range of untreated controls. Irrespective of the T doses administered, its concentration in PR tissue was comparatively low. T administration resulted in a significant accumulation of DHT in PR, when compared to plasma T. The steepest increase of DHT in PR was found with low doses of T administered (0.6-12 micrograms/24 h). At higher doses (12-600 micrograms/24 h) the further increase in the tissue was rather parallel to that of plasma T. A comparable picture was found for the DHT concentration in cytosol and in nuclei. The Diol concentration in the cytosol was linearly related to the administered T dose (r = 0.80, P less than 0.001). This steroid could not be detected in nuclei (less than 0.5 pmol/mg DNA). Administration of DHT in principle mimicked the DHT data observed after T treatment. In muscle homogenates no accumulation of neither T, DHT nor Diol was observed. In the nuclear fractions only after the highest doses of T measurable amounts of T and DHT were found. Whereas a positive correlation between DHT values in nuclei and weight increases in prostate was present, no such parallelism could be demonstrated in muscular tissue. The data are discussed with respect to the present knowledge of androgen binding and metabolism in different organs and to a possible specific role of nuclear DHT accumulation in mediating androgen dependent processes.

Androgens↗
PubMed1995

Vocal load as measured by the voice accumulator.

Voice disorders related to occupation and work environment are often observed in ENT consultations. Advising these patients requires not only the investigation of their vocal capacities but also knowledge about their vocal load. The patient will name extreme demands as the reason for vocal problems whereas the employer will want to know if the patient is capable of doing the work required of him. For an objective measurement of vocal load, a voice accumulator has been developed. This portable instrument records total speaking time and sound level over a period of several hours. The data can be transferred to a personal computer which analyses voiced time (s) between 60 and 112 dB(A)s. Thus, more precise and objective documentation of vocal demands in some professions can finally be obtained. With these results, it is possible to monitor vocal ability or disability during vocal rehabilitation.

Equipment Design↗
PubMed1997

[Medical practice-supporting system in pulmonary function testing].

A pulmonary function testing system which automates measurement, storage and reporting as much possible has been functioning in Mitsui Memorial Hospital since 1992. Data obtained from four measurement apparatus are transferred to the central microcomputer by a local area network (LAN). To facilitate automatic interpretation, we developed a knowledge-based system using 87 production rules called 'PADRES', because the knowledge-based system had the following advantages over other systems; (1) The expression of knowledge is understandable and new pieces of knowledge can be easily added, (2) the process of reasoning can be clearly shown, and (3) the accumulation of many instances of data is not required. Using 'PADRES', it takes 2.6 seconds to interpret one set of data on average. Our system performs about 5,000 routine pulmonary function tests per year without faults. Because the program for interpretation is a separate module written in C language, it is readily portable to other operating systems (OS), although its original target was OS-9, a multitask operating system for microcomputers. In conclusion, the application of a knowledge-based system for microcomputers in the pulmonary function test laboratory was considered successful.

Electronic Data Processing↗
PubMed1993

Cytokines and growth factors in the regulation of bone remodeling.

Osteoporosis and periodontal disease both represent examples of abnormal bone remodeling. As knowledge of the cellular and molecular events in the normal bone remodeling process has accumulated in the last decade, better understanding of the pathophysiology of bone loss associated with periodontal disease and with aging has occurred. This short review does not attempt to include all aspects of this topic but covers specific areas in which there have been recent advances. (1) Observations made in the last few years have indicated that a hierarchy of both receptor and nonreceptor tyrosine kinases may be involved in normal osteoclastic bone resorption and that certain members of these tyrosine kinase families may mediate cytokine effects. Studies in the op/op variant of murine osteopetrosis have shown that normal production of monocyte-macrophage colony-stimulating factor 1 (M-CSF, also called CSF-1) and activation of its receptor (the receptor tyrosine kinase c-fms) are required for normal osteoclast formation. (2) Studies in mice made deficient in nonreceptor tyrosine kinase by gene knockout have shown that expression of this nonreceptor tyrosine kinase is required for normal osteoclast action and ruffled border formation, although not for osteoclast formation. (3) Recent studies have shown that in addition to prostaglandins of the E series, other arachidonic acid metabolites may be involved in normal and abnormal osteoclastic bone resorption. 5-Lipoxygenase metabolites, the leukotrienes, stimulate isolated osteoclasts to form resorption pits as well as cause osteoclastic bone resorption in organ cultures of neonatal mouse calvariae. These compounds, which are unstable in tissue culture media, are readily inhibitable by agents that inhibit 5-lipoxygenase enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1998

A transcriptional Map of the FMF region.

Familial Mediterranean fever (FMF) is a recessively inherited disorder characterized by attacks of fever and serositis, which affects primarily non-Ashkenazi Jews, Armenians, Turks, and Arabs. We present here a transcriptional map covering the FMF locus that we constructed in the course of the positional cloning of the gene responsible for this disease. This map was established from a contig constructed with YAC, BAC, and cosmid clones and covers about 500 kb of 16p13.3. It contains nine transcriptional units corresponding to known genes or to genes belonging to known gene families, 23 gene fragments characterized by partial sequences, and an endogenous retrovirus sequence. It thus considerably increases the number of genes in this interval and improves our knowledge concerning some of the genes or gene families present in this region. Data accumulated in this region were also used in a comparative study of different methods of exon detection.

Base Sequence↗
PubMed1996

The zebrafish brain: a neuroanatomical comparison with the goldfish.

The zebrafish Danio rerio is an important model system for genetic and developmental studies of the vertebrate central nervous system. Considerable knowledge concerning the embryonic development of the central nervous system of the zebrafish has accumulated in recent years. However, there is an apparent lack of information on the organization of the adult zebrafish brain. We have therefore recently studied in detail the neuroanatomy of the adult zebrafish. Here we compare the brains of the zebrafish and of the closely related and neurobiologically well-investigated goldfish, Carassius auratus. Two sensory systems, the visual and the gustatory systems, were identified as differing on the gross morphological and histological levels in the two species. The goldfish shows the simple (evolutionarily reduced) pattern of pretectal organization, and its gustatory system is massively enlarged. The pretectum of the zebrafish conforms to this simplified visual pretectal pattern, although the retention of some ancestral pretectal characters indicates a lesser degree of reduction of the visual system compared to the goldfish. The gustatory system shows many similarities with the evolutionarily derived and functionally specialized gustatory system of the goldfish. However, some peripheral and central gustatory characters are missing in the zebrafish, indicating a less specialized gustatory system.

Animals↗
PubMed2002

The subventricular zone: new molecular and cellular developments.

The subventricular zone (SVZ), which lines the lateral walls of the lateral ventricle, persists as a neurogenic zone into adulthood and functions as the largest site of neurogenesis in the adult brain. In recent years, with the acceptance of the concept of postembryonic mammalian neurogenesis, neurogenesis in the adult SVZ has been an area of active research. With the rapid accumulation of new information on the SVZ, some of which is contradictory, summarizing existing knowledge on the SVZ and outlining future research directions in this area become important. In this review, we will cover recent molecular and cellular investigations that characterize the SVZ niche, SVZ neurogenesis, and SVZ cell migration within the adult brain.

Animals↗
PubMed2006

Sideline management of asthma.

The timely, efficient, and effective sideline management of asthma must be grounded on an understanding of the disease processes, awareness of evidence-based therapeutic intervention, and thorough knowledge of the individual athlete's medical history and current physical condition. There is accumulating evidence that exercise-induced airway narrowing, if unrecognized or inadequately treated, can progress to a severe life-threatening status and should always be viewed as a potential medical emergency. A widening range of therapeutic measures is currently available to prevent and to treat exercise asthma, and treatment must be tailored to the individual circumstances to optimize response.

Journal Article↗
PubMed1995

Methylmalonic aciduria in pregnancy: a case report.

Methylmalonic aciduria is a rare metabolic disorder of amino acid metabolism that is characterized by accumulation of large amounts of methylmalonic acid in the blood and urine. To our knowledge this is the first case report of a patient with methylmalonic aciduria who carried a pregnancy to term; the outcome was favorable despite high levels of methylmalonic acid in the serum and urine.

Adult↗
PubMedDate not supplied

Semiconduction of proteins as an attribute of the living state: the ideas of Albert Szent-Györgyi revisited in light of the recent knowledge regarding oxygen free radicals.

Oxyradicals have been considered as harmful byproducts causing molecular damage during aging. However, evidence is accumulating to show that the actual situation is more complex: the living state implicitly involves the production of oxyradicals. (1) Blast type cells produce much less oxyradicals than the differentiated ones, and an increased production of OH radicals induce differentiation of various lines of leukemia cells; meanwhile, their superoxide dismutase expression increases to a very high extent. (2) The supramolecular organization of the cells is developed by means of "useful" crosslinking effects OH radicals. (3) Repiratory inhibition of oxyradical production (KCN-intoxication, suffocation, etc.) would kill living organisms prior to the exhaustion of energy reserves. It is assumed that the continuous flux of OH radicals is a prerequisite for a electron delocalization on the proteins, which is a semiconduction of p-type, proposes already in 1941 by Albert Szent-Györgyi, and refuted on a "theoretical" basis. It has become clear by now that the carbon-based semiconduction is possible because diamond transistors are known to exist. The recently developed atomic force microscopy offers some real possibilities for experimental testing of this assumption. This concept may lead us to new horizons in interpretation of living functions, such as the basic memory mechanisms in brain cells and their impairment during aging.

Aging↗
PubMed1998

A criterion-referenced measure of latex allergy knowledge.

The exponential use of latex products has increased patients' and health care workers' sensitization to natural rubber latex. The purpose of this research study was to develop and test a set of items designed to measure professional nurses' knowledge about natural rubber latex reactions and interventions appropriate for latex precautions. The items were developed from research reports in the literature and changed to reflect the suggestions offered by experienced perioperative nurses (pilot = 8) and three nationally known experts in latex allergy responses. The revised form was mailed to the home or distributed at the workplace of perioperative nurses (n = 158). Criteria for item retention were < .90 difficulty index and clinical relevance. Certified nurses (i.e., CNORs) scored significantly higher than other nurses who took the test at the same time (t-test = 2.00, P = .05). A pretest and posttest evaluation of the revised 20 items was conducted before and after a latex allergy continuing education program during the spring of 1998. The current knowledge test (i.e., version 1.1) has reliability (alpha = .80); content validity (CVI = .92); and accumulated evidence of construct validity (preinstruction mean = 14.16, postinstruction mean = 17.15, t-paired = 10.54, df = 70, P = < .001). An empirically developed professional nurse latex allergy competency test suitable for clinical use was the outcome of this research study.

Clinical Competence↗
PubMed2001

Identification of nuclei associated proteins by 2D-gel electrophoresis and mass spectrometry.

In clinical neuroscience as well as in many other clinical disciplines, the completion of the human genome project offers a new possibility to identify and localize the products of the genes, the proteins. Nuclear proteins are synthesized in the cytoplasm and imported into the nucleus by multiple pathways. The mechanisms by which nuclear accumulation of different molecular species occur are unclear but it is apparent that changes in the cellular and molecular events associated with the accumulation of nuclear proteins sometimes precedes transformation of cells into diseased states. The significance of the accumulation and the operation of nuclear proteins remain to be elucidated in detail. Such knowledge will play a key role in the understanding of the regulation of transcription and its disturbances in several of our most devastating diseases. In this paper we present a strategy to identify nuclear associated proteins in small samples by using two-dimensional electrophoresis and mass spectrometry. We have used human blood lymphocytes as a model, but the method should be rather general for any kind of tissue. Twenty two proteins were randomly chosen, and of these 18 proteins were identified by database searching of mass spectrometric data, obtained from in-gel tryptic digests of the spots. Thirteen proteins recently described with nuclear localization and function were identified, and five proteins; calgranulin B, glyceraldehyde-3-phosphate dehydrogenase (G3P2), a TATA-binding protein (ATBP), tubulin beta chain and moesin were also identified as being nuclear associated. The presented data clearly shows of the great role of two-dimensional gel electrophoresis and modern mass spectrometry in the excavation of the protein patterns on the subcellular level, and the ability to use small samples well suited for clinical screening.

Central Nervous System Diseases↗
PubMed2000

Regulation of adenylyl cyclase in the central nervous system.

Adenylyl cyclases (ACs) are a family of enzymes that synthesize one of the major second messengers, cAMP, upon stimulation. Since the report of the first adenylyl cyclase (AC) gene in 1989, tremendous efforts have been devoted to identifying and characterizing more AC isozymes. In the past decade, significant knowledge regarding the basic structure, tissue distribution, and regulation of AC isozymes has been accumulated. Because members of the AC superfamily are tightly controlled by various signals, one of the most important impacts of these AC isozymes is their contribution to the complexity and fine-tuning of cellular signalling, especially in the central nervous system (CNS) where multiple signals constantly occur. This review focuses on recent progress toward understanding the physiological roles of ACs in the CNS.

Adenylyl Cyclases↗
PubMed1999

The WD repeat: a common architecture for diverse functions.

Our knowledge of the large family of proteins that contain the WD repeat continues to accumulate. The WD-repeat proteins are found in all eukaryotes and are implicated in a wide variety of crucial functions. The solution of the three-dimensional structure of one WD-repeat protein and the assumption that the structure will be common to all members of this family has allowed subfamilies of WD-repeat proteins to be defined on the basis of probable surface similarity. Proteins that have very similar surfaces are likely to have common binding partners and similar functions.

Animals↗