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At least 937 records · Page 52Linked to original sources

Mortgaging the future: dumping ethics with nuclear waste.

On August 22, 2005 the U.S. Environmental Protection Agency issued proposed new regulations for radiation releases from the planned permanent U.S. nuclear-waste repository in Yucca Mountain, Nevada. The goal of the new standards is to provide public-health protection for the next million years - even though everyone admits that the radioactive wastes will leak. Regulations now guarantee individual and equal protection against all radiation exposures above the legal limit. Instead E.P.A. recommended different radiation exposure-limits for different time periods. It also recommended using only the arithmetic mean of the dose distribution, to assess regulatory compliance during one time period, but using only the median dose to assess compliance during another period. This piece argues that these two changes - in exposure-limits and in methods of assessing regulatory compliance - have at least four disturbing consequences. The changes would threaten equal protection, ignore the needs of the most vulnerable, allow many fatal exposures, and sanction scientifically flawed dose calculations.

Ethics↗

Integrated Genome Mining and Bioactivity-Guided Isolation of Antimicrobial Peptides from Bacillus amyloliquefaciens BS4.

Bacterial resistance remains a critical global health challenge, driving the continuous search for novel antimicrobial agents. Bacillus amyloliquefaciens is a recognized repository of bioactive metabolites; however, its full biosynthetic potential requires integrated genomic and experimental validation. This study characterized the antimicrobial profile of B. amyloliquefaciens BS4 through a hybrid pipeline. Genome sequencing and de novo assembly revealed a 3.9 Mb chromosome with a G + C content of 46.14%. Functional annotation identified 3,887 coding sequences, including pathways for siderophore biosynthesis and a complete bacilysin biosynthetic cluster. BGC analysis using antiSMASH v7.1.0 and BAGEL4 identified 18 biosynthetic gene clusters, while similarity network analysis via BiG-SCAPE highlighted unique singleton BGCs, indicating untapped biosynthetic diversity. Although in silico screening via Macrel predicted two putative cationic antimicrobial peptides (AMPs), bioactivity-guided purification utilizing sequential RP-HPLC, and de novo sequencing revealed a distinct set of four active peptides. Notably, three of these sequences were identified as fragments derived from the BclA exosporium protein family, highlighting the structural proteome as a non-canonical source of antimicrobials. The purified fractions exhibited activity against M. luteus and E. coli, while displaying no significant hemolytic activity or cytotoxicity, even above the MIC values. Molecular docking further supported the interaction of these candidates with bacterial targets. Overall, this hybrid strategy effectively uncovers the antimicrobial complexity of BS4, revealing 'cryptic' peptide candidates with therapeutic potential.

Bacillus amyloliquefaciens BS4↗

Clinical staging of acute bacterial salpingitis and its therapeutic ramifications.

The use of single-drug therapy results in an overall 13% to 17% failure rate, and even this figure is misleading, because of the high prevalence of patients with uncomplicated disease. In patients with polymicrobial peritonitis, the failure rate varies between 30% and 60%, depending upon whether Neisseria gonorrhoeae can be concomitantly isolated from the cul-de-sac and the criteria used to define therapeutic cure. THe complexity of disease as we now understand it requires a corresponding degree of therapeutic individualization. In the Gainesville staging, acute salpingitis is subdivided into five stages. Stage I is acute endometritis-salpingitis without peritonitis. Stage II is salpingitis with peritonitis. Stage III is acute salpingitis with superimposed tubal occlusion or tuboovarian complex. Stage IV is where a tuboovarian abscess has ruptured. Stage V is a repository category for different etiologic agents which may emulate acute salpingitis, i.e., Mycobacterium tuberculosis. Each stage of disease differs by virtue of its therapeutic goal and the means by which this goal is achieved.

Abscess↗

Dendrite bundles, central programs and the olfactory bulb.

The long secondary dendrites of mitral cells in the olfactory bulb are well developed in the mammalian neonate and show a considerable degree of interweaving and coiling characteristic of dendrite bundles. In a number of other areas throughout the central nervous system, we have made a provisional correlation between the appearance of these bundles and the development of specific items of output performance characteristic of the aras involved. On this basis we have suggested that the dendrite bundles may serve as a repository for the central program shaping the response. This hypothesis is explored further in the case of the olfactory bulb. Mechanisms are suggested whereby rudimentary appetitive programs already encoded along facing dendrite membrane pairs within the specialized intrafascicular milieu, may trigger and control nipple search and suckling in the still blind and only primitively mobile neonate.

Age Factors↗

One vendor's experience: preliminary development of a reminder system based on the Arden Syntax.

This article reviews the efforts of HBO & Company in the production of a first phase clinical alerting system based on the Arden Syntax. The alerting system was integrated with a clinical data repository and clinical workstation to process returning laboratory results. Investigations with expert systems resulted in a C language alerting system. GUI prototyping of an authoring environment led to a Smalltalk language authoring system. Future development is expected to broaden the system scope and address the evolution of the Arden Syntax.

Artificial Intelligence↗

Mid-term report on the Arden Syntax in a clinical event monitor.

In implementing a clinical event monitor (CEM), a decision-support system, we worked with an existing repository of clinical data (Keystone), fed from ancillary systems using HL7. The rules are written in the Arden Syntax, an ASTM standard for expressing medical knowledge as medical logic modules (MLMs). The Arden Syntax leaves unspecified the clinical data model and deductive database access language; we briefly describe our query language and the related medical concepts dictionary (MCD). This paper gives an overview of our implementation of the Arden Syntax, the MCD and the deductive database access language, with reasons for the major design decisions. Overall, less than a quarter of the development effort has gone into the Arden compiler and interpreter; the rest has focused on accessing the data and integrating with other systems. We feel that the Arden Syntax has proved its worth in writing rules; effort should now be focused on medical vocabularies and data models.

Artificial Intelligence↗

Brugia malayi: arachidonic acid uptake into lipid bodies of adult parasites.

Lipid bodies are non-membrane bound intracellular organelles, which have been recognized morphologically in a diversity of mammalian and nonmammalian cells, but are of uncertain function. In mammalian cells, in addition to serving as a storage site of cholesterol and triglyceride, lipid bodies can be a repository of esterified arachidonic acid. Adult worms of the human filarial parasite Brugia malayi have been found to esterify exogenous [3H]arachidonic acid into parasite phospholipids and neutral lipids. Electron microscopic autoradiography demonstrated that [3H]arachidonate was preferentially incorporated into filarial lipid bodies. The dominant incorporation of arachidonate into lipid bodies of a nematode establishes that lipid bodies are a site of arachidonic acid accumulation in nonmammalian, as well as mammalian, cells.

Animals↗

Users conceptual views on medical information databases.

As information databases we consider all the kinds of information repositories that are handled by computer systems. When querying very large information databases, the end-users are often faced with the problem to parse their questions efficiently into the query languages of the computer systems. Conceptual graphs were initially designed for natural language analysis and understanding. Due to their closeness to semantic networks, their expressiveness is powerful enough to be applied to knowledge representation and use by computer systems. This work demonstrates that conceptual graphs are a suitable means to model both the information in patient databases and the queries to these databases, and that operations on graphs can compute the pattern matching process needed to provide the answers. A prototype that exploits this model is presented. Experiments have been made with the material furnished by the Unified Medical Language System project (version 2, 1992) of the National Library of Medicine, USA.

Abstracting and Indexing↗

A clinico-pathological study of a case of kuru.

Kuru was diagnosed in a 42-year-old Melanesian male from the Eastern Highlands Province of Papua New Guinea. The clinical features indicated predominant cerebellar degeneration together with widespread cortical neuronal dysfunction and involvement of the diencephalon, hippocampus and basal ganglia. Dementia was an early and prominent feature. The duration of clinical illness was about 12 months and atypically he spent the last 7 months in hospital allowing continuous assessment. At autopsy, spongiform encephalopathy was demonstrated, and inoculation of brain tissue into 4 squirrel monkeys and 1 capuchin monkey resulted in the development of kuru. This is the longest continuous study of kuru in a hospital setting to be recorded in the adult human subject. The virus isolated from the brain of this patient has been adopted as a standard reference strain of kuru for future use and repository.

Adult↗

Identification and quantification of aberrant crypt foci and microadenomas in the human colon.

The objective of the present study was to determine whether aberrant crypt foci (ACF) similar to those observed in the colons of experimental animals exposed to colon carcinogens could be identified and quantified in the human colon. Twenty-seven colon resections from patients affected by familial adenomatous polyposis (FAP, five cases), colorectal cancer (CRC, 12 cases), and benign diseases of the large bowel (BD, 10 cases) were collected from a pathology repository or immediately after operation. Ten or more 1-cm2 formalin-fixed, methylene-blue--stained samples of colonic mucosa from each colon were scored under light microscopy for ACF. The number of ACF per cm2 and the number of crypts per ACF for each colon were calculated. The average number of ACF per cm2 in the FAP group (20 +/- 19, mean +/- SD) was significantly higher (P less than 0.01) than those of the CRC (0.37 +/- 0.41) and BD (0.18 +/- 0.35) groups. At least one ACF was found in every colon resection from CRC patients and in six out of 10 colon resections from the BD group. The average number of crypts per ACF ranged from five to 35 with absolute values from 1 to over 100. Fifty-five histologic specimens, 43 with ACF of various size and 12 without, were prepared by sectioning the colon parallel to the mucosal surface. There was a close correlation between the number of crypts per ACF in each specimen as scored by methylene-blue and histologic examination. Twenty-six aberrant crypt foci displayed dysplasia as evident by histologic analysis. In these instances we feel the term microadenoma is appropriate and, using this unique approach of examining the human colon, they can be easily identified and quantified. These lesions may well be precursors for adenomatous polyps and colorectal cancer.

Adenoma↗

Ageing and the immune response--a unifying hypothesis?

In this article we review the abnormalities in immune function which have been described in relation to ageing. It is suggested that thymic involution may not be the only underlying cause. Many similar changes can be induced by the endotoxins from the cell walls of Gram-negative bacteria. The colon is a large repository for these organism and bacterial breakdown products are found in portal venous blood. Spillover into the peripheral circulation is prevented by the hepatic Kupffer cells degrading these substances. A waning in Kupffer cell function is well documented in association with ageing and there may be spillover of endotoxins into the peripheral circulation in elderly individuals. It is suggested that such spillover of endotoxins may contribute to some of the immunological changes previously attributed to ageing.

Aging↗

Natural radiation--a perspective to radiological risk factors of nuclear energy production.

Radiation doses from natural radiation and from man-made modifications on natural radiation, and different natural radiological environments in the Nodic countries are summarized and used as a perspective for the radiological consequences of nuclear energy production. The significance of different radiation sources can be judged against the total collective effective dose equivalent from natural radiation in the Nordic countries, 92,000 manSv per year. The collective dose from nuclear energy production during normal operation is estimated to 20 manSv per year and from non-nuclear energy production to 80 manSv per year. The increase in collective dose due to the conservation of heating energy in Nordic dwellings is estimated to 23,000 manSv per year, from 1973 to 1984. An indirect radiological danger index is defined in order to be able to compare the significance of estimated future releases of radionuclides from a final repository of spent nuclear fuel to the consequences of natural radionuclides in different environments. The danger index of natural radiological environments will not be significantly increased by future releases of nuclear fuel radionuclides.

Hot Temperature↗

US-Canada Great Lakes Regional Specimen Bank Feasibility Study.

A study to examine the feasibility of establishing a Regional Specimen Bank in the Great Lakes area of the United States and Canada has recently been initiated by the Michigan Audubon Society. There are several existing formal and informal specimen banking facilities active in the region but their combined adequacy has not been evaluated. This feasibility study will establish the need and use of a regional bank and the institution(s) necessary to satisfy this need will be recommended. The study will address the scope required to meet present and future needs including the types of specimens to be represented in the bank, geographic coverage and protocols for collection, shipping, processing, analysis and storage. A management policy of the bank will be developed encompassing business operation, costs, governing structure and personnel requirements. The legal requirements of the bank will be determined with regards to the acquisition of samples, transport across national boundaries, access to specimens and information, and liability during operation. An effective information dissemination network will be recommended that is compatible with national and international partners, will facilitate technology and information transfer and support the quality and status of the bank. Determination of secure, long-term funding sources will be one of the key elements to ensuring a safe repository. This feasibility study is funded by the Great Lakes Protection Fund.

Animals↗

Germination of seeds from an irradiated forest: implications for waste disposal.

Jack pine (Pinus banksiana Lamb.) retain their seeds from year to year, so that in an irradiated forest, each tree receives a specific dose rate but has seeds that have accumulated a range of total doses. The Field Irradiator-Gamma facility in Pinawa, Manitoba, contains jack pine that have been irradiated longer and at lower dose rates than previously reported. Seed germination and germination rate were examined on seeds irradiated on the parent tree for up to 5 years. Germination rate was most sensitive and showed deleterious effects at 1.1 mGy hr-1. This is not much lower than results reported by others in shorter-term studies. Effects were related to dose rate rather than total dose. Hormesis, indicated by statistically significant increased germination rate, was evident at 0.6 mGy hr-1. To put these results into context, the concentrations of selected radionuclides that, through internal contamination, would deliver 1.1 mGy hr-1 to plants were estimated. For 99Tc and 129I, these concentrations are far above the chemical toxicity thresholds for plants. Clearly, as assessments of waste repositories begin to consider effects on organisms other than humans, such as plants, chemical toxicity will be an important feature.

Dose-Response Relationship, Radiation↗

Chemotherapeutics: a questionable or a promising project.

While repository adjuvants are already established drugs for antigen specific immunomodulation, no unspecific active immunomodulator has successfully passed clinical trials in tumor patients in Western countries yet. As this is in striking contrast to the effects seen with unspecific immunomodulators in experimental immunological and tumor test systems, the value of those screening models to predict clinical success may be asked for. To improve the success rate, it is recommended to test compounds for their immunomodulatory effects as broad as possible in ex vivo and in vivo test systems. Subsequently, the prophylactic as well as therapeutic potency of selected immunomodulating drugs should be evaluated in various models of aptitude, such as chronic infection, autoimmune diseases and chronic inflammatory reactions. Those diseases are at least to a certain extent influenced by the immune system, in contrast to the uncertainty in case of tumor diseases. In a battery of chronic infection models we could find that different chemoimmunotherapeutics with very similar immunopharmacological activity behaved quite different. Most compounds were ineffective, a part enhanced chronic diseases and only in a few cases a therapeutic effect could be shown. On the other hand, effectivity in protection against the pathogenicity of subsequently applied, selected microorganisms does not predict the therapeutic potency for the same pathogen. Altogether the data show that activation of cells of the immune system by an immunostimulating drug does not predict its therapeutic potency. Moreover, activation of immune cells may also impair the immune resistance.

Adjuvants, Immunologic↗

Tabulation and assessment of 113 human surveillance cytogenetic studies conducted between 1965 and 1984.

There is an increasing tendency to monitor human exposure to genotoxic chemicals by the assessment of chromosomal aberrations or sister-chromatid exchanges (SCEs) in peripheral blood lymphocytes. In order to assess the sensitivity of these techniques, and to discern minimal criteria for their conduct, a survey of 113 human lymphocyte cytogenetic surveillance studies conducted between 1965 and 1984 has been undertaken. The present survey indicates the urgent need for standardization of study protocols. It is suggested that a common method of reporting chromosomal aberrations should be adopted, and that this should be based on the system described by Scott et al. It is also suggested that a minimum acceptable size of control and exposed populations should be agreed, and that potentially important factors such as the gender, the period and extent of exposure and individual smoking habits be defined in advance of the commission of future surveillance studies. As general awareness of the possible hazard presented by exposure of man to genotoxic chemicals increases, so appropriate preventative industrial hygiene measures will be instituted. This implies that future human cytogenetic surveillance studies may yield either weakly positive or negative data. This emphasizes the current need for agreement on appropriate study protocols. The formation of a central repository for control databases, and its subsequent updating and use by those involved in human cytogenetic surveillance studies, is recommended. Minimal experimental criteria for the design of future studies are also outlined.

Carcinogens, Environmental↗

Multiplex polymerase chain reaction for human herpesvirus-6, human cytomegalovirus, and human beta-globin DNA.

Human cytomegalovirus and human herpesvirus-6 are closely related viruses which cause similar diseases, have similar cellular repositories of latent infection, and may be detected largely in the same types of clinical specimens. DNA amplification appears likely to play an increasing role in the diagnosis of recent and remote infection with these agents. A sensitive multiplex polymerase chain reaction was therefore developed for the two viruses and for human beta-globin DNA. Optimization of parameters such as the primers, primer concentrations, magnesium concentration, and buffer constituents was crucial in achieving a sensitive assay. Preliminary results indicated that the assay could simultaneously monitor DNA extraction from clinical specimens and allow detection of HCMV or HHV-6 in patients with diseases possibly caused by either pathogen.

Base Sequence↗

Mechanism of endogenous phosphorylation of microtubule proteins during GTP-induced microtubule assembly and implications for stability of the assembled structures.

Cycle-purified microtubule protein from mammalian brain incorporated [32P]Pi upon incubation with [gamma-32P]GTP under the conditions used to promote assembly. This phosphorylation also occurred in the same proteins when phosphorylated with [gamma-32P]ATP and was only slightly stimulated by cAMP. GTP was a much less effective substrate than ATP. The transfer of phosphoryl groups from [gamma-32P]GTP to endogenous proteins followed a linear time-course and was stimulated by low concentrations of ATP and, more efficiently, by ADP. These data are in agreement with the predictions derived from a mechanism of phosphorylation by which [gamma-32P]GTP does not act as a phosphoryl donor for the protein kinase activity but, instead, only as a repository of high group transfer potential phosphoryl groups used to make [gamma-32P]ATP, from contaminating ADP, by means of the nucleoside diphosphate kinase activity. Using 100 mM fluoride, which suppressed protein phosphorylation without inhibiting the nucleoside diphosphate kinase activity, formation of [gamma-32P]ATP was detected. Fluoride was also able to protect microtubules from a slow depolymerization which was found to occur during long-term incubation of microtubules. This indicates that the phosphorylation observed in the presence of GTP is sufficient to destabilize microtubules.

Adenosine Diphosphate↗