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PubMedDate not supplied

The remedial year in the general surgery board certification process: how effective is it?

BACKGROUND: The American Board of Surgery (ABS) intends to assure high standards for knowledge and experience in every graduate from an approved general surgery program. They have gone to great lengths to devise an optimal remediation process for every candidate failing to reach these standards. But what is the effectiveness of the remediation process? METHODS: ABS data outlined the history and development of the remediation process up to its current form. A core component of this process is a specifically structured additional year of training at selected institutions. Ten institutions, which were classified as outstanding by the ABS, received a standardized confidential questionnaire to collect data that included the institution's impetus to administer a remedial year (RY), organization of their RY, specific emphasis points, role of advisors, funding, and choice of RY candidates. Each institution was asked to mail a letter to their RY graduates, asking for their participation in a follow-up study aimed at characterizing the failing candidate. RESULTS: ABS data have been available since 1980. Pass rates for the qualifying written examination (QE) improved steadily from about 63% in 1985 to 78% in 2003. Pass rates for the certifying oral examination (CE) have been consistently around 75% since 1985 with improvement to just above 80% within the last 4 years. In 1995, a new ABS policy was announced requiring an additional year of structured training with specific elements. For the QE, the general pool pass rates continued their steady improvement. Although the results for RY candidates did reveal a 20% improved pass rate, they were still 30 percentage points lower when compared with the general pass rates. No improvement was noted in the CE results. In 2003, ABS enacted the latest policy change, which consists of an alternative pathway for QE. The initial experience for 2003 is disappointing. Less than 10 candidates have taken advantage of this alternative, and pass rates have not improved. The policy for CE was changed to allow 5 attempts (up from 3 attempts) in 5 years, and currently it is too early to determine the impact of this change. Nine of 10 institutions agreed to participate in our study. They identified the essential elements of a successful RY. They also emphasized that CE remediation has to go beyond correction of simple knowledge deficits. And they characterized the ideal candidate for remediation. No RY graduates agreed to participate in the planned follow-up study to characterize the failing candidate. CONCLUSION: The RY process seems to have a valid potential if specific conditions are met. We do believe that differentiation is needed between the QE and the CE remedial year programs. Because the CE incorporates rhetorical skills, an emphasis should be placed on public speaking and presentation skills in a remedial year for the CE. We recommend several possible avenues for consideration: identifying the resident at risk and intervening during residency, incorporating the RY process into the ongoing practice routine of the individual candidate, and actively recruiting participation of candidates in a needs assessment study.

Certification↗

PubMedDate not supplied

Anatomy of the human penis: the relationship of the architecture between skeletal and smooth muscles.

To investigate the anatomy of the ischiocavernosus muscle, bulbospongiosus muscle, and tunica albuginea and to determine their relationships to smooth muscle, which is a key element of penile sinusoids, we performed cadaveric dissection and histologic examinations of 35 adult human male cadavers. The tunica of the corpora cavernosa is a bilayered structure that can be divided into an inner circular layer and an outer longitudinal layer. The outer longitudinal layer is an incomplete coat that is absent between the 5-o'clock and 7-o'clock positions where 2 triangular ligamentous structures form. These structures, termed the ventral thickening, are a continuation of the anterior fibers of the left and right bulbospongiosus muscles. On the dorsal aspect, between the 1-o'clock and 11-o'clock positions, is a region called the dorsal thickening, a radiating aspect of the bilateral ischiocavernosus muscles. In the corpora cavernosa, skeletal muscle contains and supports smooth muscle, which is an essential element in the sinusoids. This relationship plays an important part in the blood vessels' ability to supply the blood to meet the requirements for erection, whereas in the corpus spongiosum, skeletal muscle partially entraps the smooth muscle to allow ejaculation when erect. In the glans penis, however, the distal ligament, a continuation of the outer longitudinal layer of the tunica, is arranged centrally and acts as a trunk of the glans penis. Without this strong ligament, the glans would be too weak to bear the buckling pressure generated during coitus. A significant difference exists in the thickness of the dorsal thickening, the ventral thickening, and the distal ligament between the potent and impotent groups (P < or =.01). Together, the anatomic relationships between skeletal muscle and smooth muscle within the human penis explain many physiologic phenomena, such as erection, ejaculation, the intracavernous pressure surge during ejaculation, and the pull-back force against the glans penis during anal constriction. This improvement in the modeling of the anatomic-physiologic relationship between these structures has clinical implications for penile surgeries.

Adult↗

PubMed1992

Molecular determinants of channel function.

The 40 years since the seminal papers of Hodgkin and Huxley appeared have been extraordinarily productive in terms of understanding the molecular basis for electrical activity. The Hodgkin-Huxley proposal that electrical excitability should be understood in terms of voltage-dependent changes in discrete sites has been resoundingly verified. Indeed, the Hodgkin-Huxley framework is remarkable in that its essential elements have remained largely intact as molecular understanding has advanced. This robustness is, at least in part, a result of the fact that Hodgkin and Huxley developed a mathematical model, based on simple physical arguments, that was sufficiently comprehensive to describe the kinetics of the voltage-clamped currents and yet simple enough to be predictive. The predictive features were demonstrated early by the reconstruction of both space-clamped and propagated action potentials on a desk-top calculator (293) and, later, when the sites of Hodgkin and Huxley developed into being well-characterized molecular structures. Voltage- and ligand-dependent ion-selective channels are now the established framework within which cellular electrophysiology is being pursued. Moreover, electrophysiological measurements of membrane and single-channel currents have become essential tools to examine molecular questions pertaining to channel structure and activity. The last 10 years have witnessed spectacular activity, which has resulted from two developments, the giga-seal patch clamp (249) and the elucidation of primary sequences of a number of channel-forming proteins (494), along with the first outlines of their low-resolution three-dimensional structures (651). The stage is now set for 1) applying a variety of convergent techniques to decipher molecular structural details at high resolution, and 2) seeking to understand the complex dynamic functions, gating, and ion selectivity at the molecular level. The early successes are likely to be in understanding the molecular determinants of ion conductance and selectivity, initially in terms of quantitative descriptions of how a sequence modification can alter a channel's permeability characteristics. Channel gating is a far more elusive target because it involves molecular rearrangements, which are poorly understood at any level of description and which may be modified by the channel's environment. The general mechanisms of ion permeation and gating will differ among different classes of ion channels, but a molecular understanding of either phenomenon must eventually be based on an understanding of intermolecular forces, which are invariant among all channel types.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1999

Cobalt.

Cobalt is a relatively rare magnetic element with properties similar to iron and nickel. The two valance states are cobaltous (II) and cobaltic (III) and the former is the most common valance used in the chemical industry. Cobalt occurs in nature primarily as arsenides, oxides, and sulfides. Most of the production of cobalt involves the metallic form used in the formation of cobalt superalloys. The term "hard metal" refers to compounds containing tungsten carbide (80-95%) combined with matrices formed from cobalt (5-20%) and nickel (0-5%). For the general population, the diet is the main source of exposure to cobalt. In the occupational setting, exposure to cobalt alone occurs primarily during the production of cobalt powders. In other industrial exposures (e.g., hard metal, diamond polishing), additional agents (tungsten) modulate the toxicity of cobalt. Cobalt is an essential element necessary for the formation of vitamin B12 (hydroxocobalamin); however, excessive administration of this trace element produces goiter and reduced thyroid activity. In 1966, the syndrome "beer drinker's cardiomyopathy" appeared in Quebec City, Canada, and was characterized by pericardial effusion, elevated hemoglobin concentrations, and congestive heart failure. An interstitial pulmonary fibrosis has been associated with industrial exposure to hard metal dust (tungsten and cobalt), but not to cobalt alone. Exposure to cobalt alone produces an allergic contact dermatitis and occupational asthma. Treatment of cobalt toxicity is primarily supportive.

Animals↗

PubMedDate not supplied

The influence of curcumin and manganese complex of curcumin on cadmium-induced oxidative damage and trace elements status in tissues of mice.

Curcumin (diferuoyl methane) from turmeric is a well-known biologically active compound. It has been shown to ameliorate oxidative stress and it is considered to be a potent cancer chemopreventive agent. In our previous study the antioxidative effects of curcumin in cadmium exposed animals were demonstrated. Also manganese exerts protective effects in experimental cadmium intoxication. The present study examined the ability of the manganese complex of curcumin (Mn-curcumin) and curcumin to protect against oxidative damage and changes in trace element status in cadmium-intoxicated male mice. Curcumin or Mn-curcumin were administered at equimolar doses (0.14 mmol/kg b.w.) for 3 days, by gastric gavages, dispersed in methylcellulose. One hour after the last dose of antioxidants, cadmium chloride (33 micromol/kg) was administered subcutaneously. Both curcumin and Mn-curcumin prevented the increase of hepatic lipid peroxidation -- expressed as MDA level, induced by cadmium intoxication and attenuated the Cd-induced decrease of hepatic GSH level. No change in hepatic glutathione peroxidase or catalase activities was found in Cd-exposed mice. A decreased GSH-Px activity was measured in curcumin and Mn-curcumin alone treated mice. Neither curcumin nor Mn-curcumin treatment influenced cadmium distribution in the tissues and did not correct the changes in the balance of essential elements caused by Cd-treatment. The treatment with Mn-curcumin increased the Fe and Mn content in the kidneys of both control and Cd-treated mice and Fe and Cu content in the brain of control mice. In conclusion, regarding the antioxidative action, introducing manganese into the curcumin molecule does not potentiate the studied effects of curcumin.

Animals↗

PubMed2005

The Manganese Health Research Program (MHRP): status report and future research needs and directions.

The manganese (Mn) research health program (MHRP) symposium was a full day session at the 22nd International Neurotoxicology Conference. Mn is a critical metal in many defense and defense-related private sector applications including steel making and fabrication, improved fuel efficiency, and welding, and a vital and large component in portable power sources (batteries). At the current time, there is much debate concerning the potential adverse health effects of the use of manganese in these and other applications. Due to the significant use of manganese by the Department of Defense, its contractors and its suppliers, the Manganese Health Research Program (MHRP) seeks to use the resources of the federal government, in tandem with manganese researchers, as well as those industries that are involved with manganese, to determine the exact health effects of manganese, as well as to devise proper safeguard measures for both public and private sector workers. Humans require manganese as an essential element; however, exposure to high levels of this metal is sometimes associated with adverse health effects, most notably within the central nervous system. Exposure scenarios vary extensively in relation to geographical location, urban versus rural environment, lifestyles, diet, and occupational setting. Furthermore, exposure may be brief or chronic, it may be to different types of manganese compounds (aerosols or salts of manganese with different physical and/or chemical properties), and it may occur at different life-stages (e.g., in utero, neonatal life, puberty, adult life, or senescence). These factors along with diverse genetic composition that imposes both a background and disease occurrence likely reflect on differential sensitivity of individuals to manganese exposure. Unraveling these complexities requires a multi-pronged research approach to address multiple questions about the role of manganese as an essential metal as well as its modulation of disease processes and dysfunction. A symposium on the Health Effects of Manganese (Mn) was held on Wednesday, September 14, 1005, to discuss advances in the understanding on role of Mn both in health and disease. The symposium was sponsored by the Manganese Health Research Program (MHRP). This summary provides background on the MHRP, identifies the speakers and topics discussed at the symposium, and identifies research needs and anticipated progress in understanding Mn health- and disease-related issues.

Biomedical Research↗

PubMedDate not supplied

An assessment of boric acid and borax using the IEHR Evaluative Process for Assessing Human Developmental and Reproductive Toxicity of Agents. Expert Scientific Committee.

BACKGROUND: Boron is a ubiquitous element widely distributed in nature in the form of borates at low concentrations in soils and rocks. Boron is released from these minerals by the natural weathering processes in the form of boric acid, which is water soluble and biologically available. High levels of boric acid are naturally found in sea water. Boric acid and borax are used in the greatest quantities and represent the major boron chemical exposures to humans and the environment. The principal use of boric acid and borax is in the manufacture of various types of glass products that do not result in exposure to the consumer. Boric acid and borax are also found in an array of consumer goods including fireproofing for fabrics and wood, insecticides, and in many cosmetics and personal care products as well. Boron may be an essential element for higher animals including humans. HUMAN EXPOSURE: Boric acid and borax are considered to be completely absorbed by the oral route of exposure. Absorption through intact skin is considered negligible, although absorption can occur through denuded or irritated skin. Boron levels in the body do not persist upon cessation of exposure. People may be exposed to boron through three primary sources: 1) consumption of private, municipal, or commercial (bottled) sources of drinking water; 2) dietary consumption of crops and other foodstuffs (including dietary supplements for body building); and 3) inhalation of boron compounds during their mining, manufacturing, and other industrial processing. While boron has been detected in 81.8% of the municipal water systems, it is a minor source of boron in most parts of the U.S. The mean boron concentration is reported as 0.2 mg B/L. However, residents of California and other western states with boron-rich geologic deposits may be regularly exposed to higher levels in drinking water. Individuals who drink bottled mineral water may also increase their exposure to boron. An EPA health advisory, recommends boron concentrations in drinking water not exceed 0.6 mg B/L [0.06 mM B] over a lifetime of exposure. Dietary exposure to boron for an adult typically ranges from ranges from 0.25 to 3.1 mg B/d with an average of 1.5 mg B/d. The high end of the exposure range, 3.1 mg B/d, was selected by the Expert Committee as best estimate of exposure. It should be noted that a diet high in fruits, vegetables, grains, legumes, and other food stuffs with high boron contents may lead to daily exposures as high as 10 mg B/d from diet alone. Some body building supplements contain boron at levels ranging from 1.5 to 10 mg B, with a median of 4 mg B. Use of the supplements containing the median concentration of boron could equal the daily intake an individual receives from diet and drinking water combined. Adults in the U.S. at the high end of the food exposure range may typically ingest up to 3.5 mg B/d, or a daily dose of 0.005 mmol B/kg b.wt., through exposure from diet (3.1 mg B/d) and drinking water (0.4 mg B/d). Individuals who also use body-building supplements may have a total daily boron intake of 7.5 mg B resulting in a daily dose of 0.01 mmol B/kg b.wt./d. Occupational exposure to boron is mainly through inhalation of borate containing dust during mining and manufacturing processes. Current occupational exposures to boron are reported to result in a daily dose of < 0.0001 to 0.2 mmol B/kg b.wt./d. Current U.S. OSHA permissible exposure limit (PEL) for sodium tetraborates is 10 mg/m3, and the California Occupational Safety and Health Administration PEL is 5 mg/m3. An exposure of 5 mg B/m3 translates to approximately 0.01 mmol B/kg b.wt./d that, coincidentally, is the same as exposure levels associated with combined municipal drinking water, diet, and body building supplement consumption. Infants may receive exposures to boric acid when it is used as a household insecticide for cockroach control. Exposure from boric acid-containing cosmetic and personal care products applie

Animals↗

PubMed2005

The pathogenesis and significance of the urinary alcohol cycle in rats fed ethanol intragastrically.

The blood alcohol level cycle (BALC) of the intragastric tube feeding model first described by Tsukamoto et al., has three separate essential mechanistic components. The first is the requirement for an intact functioning thyroid. The evidence for this is that propylthiouracil or severance of the pituitary stalk completely prevents the cycle. What happens instead of the cycle is that the blood alcohol level rises to a lethal level when ethanol is given continuously at a dose of 11 g/kg/day by stomach tube. When excess thyroid hormone is given orally it markedly attenuates the cycle because it interferes with the changes in the level of thyroid hormone during the cycle. The second component is norepinephrine. Catecholamines are markedly elevated at the peaks of the cycle. Both propranolol and phenoxybenzamine, which are beta- and alpha-blockers, prevent the cycle. Also, when catecholamines are fed in excess in the form of ephedrine, the cycle is eliminated. The third element essential to the cycle is the generation of NAD to support the oxidation of alcohol by alcohol dehydrogenase. When complex I (NADH dehydrogenase) of the mitochondrial electron transport chain is inhibited by feeding rotenone, the cycle is totally eliminated and blood alcohol levels remain constant at 200 mg/%. Thus NADH increases and NAD decreases at the peak of the cycle. Without the fluxuation of NAD, ADH activity cannot fluctuate during the cycle and the cycle is prevented. The significance of the BALC in the understanding of alcohol liver disease pathogenesis is that there's a marked difference in the gene expression and liver toxicity when the peaks and troughs of the cycle are compared. The expression of 1000+ genes is either two-fold up or down regulated as determined by microarray analysis. At the peaks there is increased liver pathology, especially inflammatory changes in the liver associated with an increase of iNOS expression. The genes responsive to hypoxia inducible factor 1alpha (HIF1alpha) regulation are increased including the expression of erythropoietin, adrenomedullin and adrenergic receptor alpha 1a and d. The expression of prolyl hydroxylase, which destabilizes HIF1alpha, increases when the BAL drops to low levels during the cycle. The level of oxygen, as measured on the surface of the liver, is decreased at the peaks, compared to control livers. The NADH/NAD ratio is markedly increased and ATP levels are markedly decreased at the BAL peaks. Also, endotoxin in the blood is very high at the peaks and very low at the troughs. When the blood alcohol levels fall during the cycle, there is an increase in ALT, suggesting that reoxygenation from the hypoxic state at the peaks causes an ischemic reperfusion injury-like lesion in the liver. At this time there is also an increase in expression of many important enzymes such as manganese SOD. Genes such as c-fos and CTGF are increased in expression. These contrasting findings at the peaks and troughs indicate that the blood alcohol levels, which fluctuate up and down, change the gene expression and the pathology of the liver.

Animals↗

PubMed2001

CD13/APN is activated by angiogenic signals and is essential for capillary tube formation.

In the hematopoietic compartment, the CD13/APN metalloprotease is one of the earliest markers of cells committed to the myeloid lineage where it is expressed exclusively on the surface of myeloid progenitors and their differentiated progeny. CD13/APN is also found in nonhematopoietic tissues, and its novel expression on the endothelial cells of angiogenic, but not normal, vasculature was recently described. Treatment of animals with CD13/APN inhibitors significantly impaired retinal neovascularization, chorioallantoic membrane angiogenesis, and xenograft tumor growth, indicating that CD13/APN plays an important functional role in vasculogenesis and identifying it as a critical regulator of angiogenesis. To investigate the mechanisms of CD13/APN induction in tumor vasculature, the regulation of CD13/APN by factors contributing to angiogenic progression was studied. In this report, it is shown that endogenous CD13/APN levels in primary cells and cell lines are up-regulated in response to hypoxia, angiogenic growth factors, and signals regulating capillary tube formation during angiogenesis. Transcription of reporter plasmids containing CD13/APN proximal promoter sequences is significantly increased in response to the same angiogenic signals that regulate the expression of the endogenous gene and in human tumor xenografts, indicating that this fragment contains elements essential for the angiogenic induction of CD13/APN expression. Finally, functional antagonists of CD13/APN interfere with tube formation but not proliferation of primary vascular endothelial cells, suggesting that CD13/APN functions in the control of endothelial cell morphogenesis. These studies clearly establish the CD13/APN metalloprotease as an important regulator of endothelial morphogenesis during angiogenesis.

Angiogenesis Inducing Agents↗

PubMed2006

Characterization of the promoter for the alpha3 integrin gene in various tumor cell lines: roles of the Ets- and Sp-family of transcription factors.

The alpha3beta1 integrin is an adhesion receptor for extracellular matrix proteins, including laminin isoforms, and plays crucial roles in the organization of epithelial and endothelial tissues. The aberrant expression of this adhesion molecule on tumor cells is associated with their invasive and metastatic potentials. In the present study, we analyzed the elements essential for alpha3 integrin gene expression in various tumor cell lines with different tissue origins by luciferase assay. An approximately 0.3 kb fragment of the 5'-flanking region of the mouse alpha3 integrin gene (-260/+84, relative to the major transcription start site) showed strong promoter activity in all six examined tumor cell lines. However, we found that these cell lines could be divided into two groups according to the level of dependency on the putative Ets-transcription factor binding motif located at -133. This motif was previously shown to be crucial for alpha3 integrin expression in MKN1 gastric carcinoma cells. The gene expression in one group of cell lines was upregulated mainly by the Ets motif, whereas that in the other group was less dependent on the Ets motif. We then postulated that additional regulatory elements were responsible for the expression of alpha3 integrin, and found that a GC-rich motif at -69 was another important element. An electrophoretic mobility shift assay using specific antibodies and a Western blot analysis of nuclear proteins revealed that the Sp3-transcription factor bound to this GC-rich motif. These results suggest that the Sp3 and Ets transcription factors cooperatively regulate alpha3 integrin gene expression and that the contribution of each element depends on the type of tumor cells.

Animals↗

PubMed2004

Diabetes is a community issue: the critical elements of a successful outreach and education model on the U.S.-Mexico border.

BACKGROUND: Diabetes is reaching epidemic proportions on the U.S.-Mexico Border, and culturally competent diabetes education is not available in many communities. CONTEXT: People with diabetes often do not have access to regular medical care, cannot afford medication, and lack the community infrastructure that supports self-management practices. Self-management education and support have great potential to impact diabetes control in this environment. METHODS: To address this need, partners of the Border Health Strategic Initiative (Border Health iSI!) collaboratively developed a culturally relevant diabetes outreach and education program. The model included a five-week series of free diabetes education classes that assisted participants in gaining the knowledge and skills necessary to be physically active, control diet, monitor blood sugar, take medications, and be aware of complications. Central to the model was the use of community health workers - or promotores de salud - to conduct outreach, participate in patient education, and provide individual support. CONSEQUENCES: Program participants achieved significant improvements in self-management behaviors and HbA1c, random blood glucose, and blood pressure levels. INTERPRETATION: Quantitative and qualitative evaluation helped to identify the essential elements of a successful program, including partnership of providers, community diabetes classes, promotores outreach and support, linkage between diabetes education and clinical care, and program evaluation.

Community Health Services↗

PubMed2003

Reverse genetic system for the analysis of parvovirus telomeres reveals interactions between transcription factor binding sites in the hairpin stem.

The left-hand or 3'-terminal hairpin of minute virus of mice (MVM) contains sequence elements essential for both viral DNA replication at the left-hand origin (oriL) and for the modulation of the P4 promoter, from which the viral nonstructural gene cassette is transcribed. This hairpin sequence has proven difficult to manipulate in the context of the viral genome. Here we describe a system for generating mutant viruses using synthetic hairpin oligonucleotides and a truncated form of the infectious clone. This allows manipulation of the sequence of the left-hand hairpin and examination of the effects in the context of the viral life cycle. We have confirmed the requirement for a functional parvovirus initiation factor (PIF) binding site and determined that an optimized PIF binding site, with 6 bases between the half-sites, was actually detrimental to viral growth. The distal PIF half-site overlaps a cyclic AMP-responsive element (CRE), which was shown to play an important role in initiating infection, particularly in 324K simian virus 40-transformed human fibroblasts. Interestingly, reducing the spacing of the PIF half-sites, and thus the affinity of the binding site for PIF, increased viral fitness relative to wild type in 324K cells, but not in murine A9 cells. These results indicate that the relative importance of factor binding to the CRE and PIF sites during the establishment of an infection differs markedly between these two host cells and suggest that the suboptimal spacing of PIF half-sites found in wild-type virus represents a necessary reduction in the affinity of the PIF interaction in favor of CRE function.

Animals↗

PubMed2001

Dietary intakes of selected elements from longitudinal 6-day duplicate diets for pregnant and nonpregnant subjects and elemental concentrations of breast milk and infant formula.

As part of a longitudinal investigation into mobilization of lead from the maternal skeleton during pregnancy and lactation, we have determined the daily intake of selected elements (hereafter called micronutrients) for various subjects and compared these intakes with recommended and/or published intakes, especially those of the United States, through the U.S. National Health and Nutrition Examination Survey (NHANES). We also sought to ascertain whether there was any seasonal effect in the diets. Six-day duplicate diets were collected from 15 pregnant and 16 nonpregnant migrants to Australia, 6 pregnant Australian control subjects, and 8 children of nonpregnant migrants (6 to 11 years). Samples of breast milk and infant formula were also analyzed. Blended samples were analyzed by inductively coupled plasma mass spectrometry for the elements Ca, Cu, Fe, Mg, P, K, Na, Zn, Ba, Sr, and Pb. Daily intakes of micronutrients were only about half of the daily intake estimated for non-Hispanic white females and infants in the U.S. NHANES III. Estimates of daily intakes from breast milk were also considerably lower for the migrant and Australian infants compared with the values extracted from tables of food composition and dietary recall for non-Hispanic white infants in the U.S. NHANES III. For example, Ca was a factor of approximately 3 times lower, Fe approximately 50, and Zn approximately 4. We consider our estimates a reliable indication of the daily intakes for several reasons, including the collection of up to nine quarterly collections of 6-day duplicate diets and retention of subjects in a longitudinal prospective study. The low intakes of the essential elements such as Ca, Fe, and Zn in all these population groups are of potential concern from a public health viewpoint.

Adult↗

PubMed2001

Quantitative analysis of the elemental composition and the mass of bacterial polyphosphate bodies using STEM EDX.

The quantitative analysis of laboratory grown organisms (Plectonema boryanum and Staphylococcus aureus) revealed that a typical in vivo polyphosphate body (PPB) contains O (4.3 x 10(-8) microg), C (1.2 x 10(-8) microg), P (6.7 x 10(-9) microg), Mg (1.3 x 10(-9) microg), Ca (6.7 x 10(-10) microg), K (6.7 x 10(-10) microg), Fe (6.0 x 10(-10) microg), S (5.4 x 10(-10) microg) and Al (5.9 x 10(-10) microg). Quantitative X-ray analysis of samples from nature showed PPB contain O (1.63 x 10(-8) microg), C (4.75 x 10(-9) microg), P (2.50 x 10(-9) microg), Mg (5.0 x 10(-10) microg), Ca (2.50 x 10(-10) microg), K (2.50 x 10(-10) microg), Fe (2.25 x 10(-10) microg) and S (2.0 x 10(-10) microg). The mass of an average polyphosphate body was 6.7 x 10(-8) microg for P. boryanum, 2.5 x 10(-8) microg for S. aureus and for microbes from the natural environment 6.3 x 10(-8) microg. The results indicate that the PPB may have other unknown functions in addition to essential element storage, acting as a detoxification method by sequestering heavy metals and providing a homeostasis system in the cell.

Bacteria↗

PubMed1995

Assessment of toxic metal exposure following the Camelford water pollution incident: evidence of acute mobilization of lead into drinking water.

Following the incident of acidic pollution of water by aluminium sulfate centred around Camelford in July 1988, we have carried out a retrospective analysis of the mobilization of toxic metals to residents of the area. An advanced nuclear technique was used to measure trace levels of elements within hair, thus, avoiding surface contamination. In contrast to controls, lead, but no other toxic metals, was consistently found within sections of hair that dated to mid-1988 from four residents; they must, therefore, have consumed this metal around the time of the incident. The source of this lead was probably local water pipe residue, and this was found on analysis to have a matrix specific to such soft-water areas that, prior to the incident, had slowly accumulated certain toxic metals such as cadmium and uranium and particularly lead. Lead is mobilized from such residues by acidic water and could, therefore, have heavily contaminated mains water after the incident. However, analyses of residents' plasma and whole blood, and of urine following a lead-chelation test, showed no evidence of either long-term increased body burdens of toxic metals or depletion of essential elements. In addition, we found no evidence of continued poor water quality in the area. In conclusion, during a short period following the pollution, some residents who consumed mains water would have been acutely exposed to lead and other toxic metals. Prediction of the scale of metal exposure to individuals was not possible owing to heterogeneity of the water distribution network, but long-term effects to residents from lead are not anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1995

Domains required for CENP-C assembly at the kinetochore.

Chromosomes segregate at mitosis along microtubules attached to the kinetochore, an organelle that assembles at the centromere. Despite major advances in defining molecular components of the yeast segregation apparatus, including discrete centromere sequences and proteins of the kinetochore, relatively little is known of corresponding elements in more complex eukaryotes. We show here that human CENP-C, a human autoantigen previously localized to the kinetochore, assembles at centromeres of divergent species, and that the specificity of this targeting is maintained by an inherent destruction mechanism that prevents the accumulation of CENP-C and toxicity of mistargeted CENP-C. The N-terminus of CENP-C is not only required for CENP-C destruction but renders unstable proteins that otherwise possess long half-lives. The conserved targeting of CENP-C is underscored by the discovery of significant homology between regions of CENP-C and Mif2, a protein of Saccharomyces cerevisiae required for the correct segregation of chromosomes. Mutations in the Mif2 homology domain of CENP-C impair the ability of CENP-C to assemble at the kinetochore. Together, these data indicate that essential elements of the chromosome segregation apparatus are conserved in eukaryotes.

Amino Acid Sequence↗

PubMed1994

[Radiological exploration of the thorax. Strategy and indications].

The widespread use of computed tomography and the advent of magnetic resonance imagery have considerably modified the methods and strategies of thoracic exploration over the last 10 years. Standard radiography remains the first-line examination for all thoracic diseases, and often is the only imagery required; further explorations are indicated on the basis of the information seen on standard films. Computed tomography has become an essential element in the work-up of all diseases involving a tumoural process in the lung. It is also indicated in bronchiestasis and for the exploration of chronic lung diseases. Further information may be obtained with magnetic resonance imagery. Although this method cannot be used to explore the pulmonary parenchyma, it is particularly adapted in cases involving the pleura, mediastinum (tumours and vessels) and the thoracic wall. Scintigraphy is mainly used to detect pulmonary migrations and to investigate lung function before thoracic surgery. Pulmonary angiography remains the reference imagery for the diagnosis of pulmonary embolism but has lost its other indications. Tomobronchography is exceptionally required. Current strategy in infectious diseases is to always begin with standard radiography, then to complete the work-up with further examinations only when necessary. Correct evaluation of tumoural processes relies heavily on tomography even for very small masses since it provides essential information on localization and extension. Management of primary bronchogenic cancers also requires repeated tomographic studies. Magnetic resonance images are indicated on the basis of the tomography results and are particularly useful in tumours of the apex and extension to the spinal column or mediastinum. For chronic bronchopathy, pulmonary scintigraphy is performed after standard films in the preoperative work-up then is sometimes completed with other techniques. In cases of suspected pulmonary emboli, a normal scintigraphy can eliminate the diagnosis. Inversely, certain teams propose coupling perfusion scintigraphy with ventilation scintigraphy to detect mismatches, particularly distinctive signs of pulmonary emboli. When the diagnosis remains uncertain, pulmonary angiography is the reference imagery technique.

Angiography↗

PubMed1985

Dietary factors in essential hypertension.

Dietary alteration or intervention is an ideal method of preventing or treating hypertension. Medication may be eliminated or reduced in many cases. Correction of obesity and alcohol abuse are confirmed methods of treating hypertension. Reduction of sodium intake is effective in that portion of the population which is salt-sensitive. Probably, the ratio of sodium to potassium is of importance and increasing potassium intake while reducing sodium intake is effective in many situations. Evidence is being reported which indicates that adequate intake of calcium, and perhaps magnesium, is effective in preventing hypertension. Limited information indicates that a sufficiency of dietary essential fatty acids and fibre are effective in hypertension prevention. The role of dietary protein, carbohydrates, fat, cholesterol, vitamins, and essential elements (other than those mentioned above) in the pathogenesis has not been fully elucidated at this time, but there are indications that adequate intakes are beneficial in hypertension. Water hardness may have some effect in reducing hypertension incidence, and any effectiveness would probably result from calcium and magnesium in the drinking water. Animal studies and limited human studies indicate some detrimental effects of heavy metals, such as lead and cadmium, upon the pathogenesis of hypertension. Information regarding caffeine intake is inconclusive.

Alcoholism↗