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At least 19 recordsLinked to original sources
PubMed2002

Unconventional biological threats and the molecular biological response to biological threats.

This article concludes this symposium on potential agents of warfare and terrorism with discussion of 3 topics. First, influenza A virus is discussed as a potential biological weapon. Although it does not receive much attention in this role, the potential for mass casualties and public panic certainly exist if an epidemic of a virulent influenza A virus were initiated. Second, agroterrorism, terrorism directed at livestock or poultry or crops, is briefly discussed. Finally, the potential role of techniques of modern molecular biology to create new agents for bioterrorism or enhance the terrorist potential of available agents, and the known roles of these techniques in defense against biological warfare or terrorism are discussed.

Agriculture↗
PubMed2026

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans↗
PubMed2000

Linking the fields--the interplay of organic synthesis, biophysical chemistry, and cell biology in the chemical biology of protein lipidation.

Research in the biological sciences has undergone a fundamental and dramatic change during the last decades. Whereas biology was more phenomenologically oriented for a long time, today many biological processes are investigated and understood in molecular detail. It has become evident that all biological phenomena have a chemical basis: Biology is based on chemical principles. In the past, this insight had led to the development of biochemistry, molecular biology, and modern pharmacology. Today it increasingly determines the manner in which various biological phenomena are studied. The tools provided by classical biological techniques often are not sufficient to address the prevailing issues in precise molecular detail. Instead, the strengths of both chemical and biological methodology have to be used. Several recent research projects have proven that combining the power of organic synthesis with cell biology may open up entirely new and alternative opportunities for the study of biological problems. In this review we summarize the successful interplay between three disciplines-organic synthesis, biophysics, and cell biology-in the study of protein lipidation and its relevance to targeting of proteins to the plasma membrane of cells in precise molecular detail. This interplay is highlighted by using the Ras protein as a representative example. The development of methods for the synthesis of Ras-derived peptides and fully functional Ras proteins, the determination of their biophysical properties, in particular the ability to bind to model membranes, and finally the use of synthetic Ras peptides and Ras proteins in cell biological experiments are addressed. The successful combination of these three disciplines has led to a better understanding of the factors governing the selective targeting of Ras and related lipid-modified proteins to the plasma membrane.

Biophysical Phenomena↗
PubMed1993

Evaluation of a rapid readout biological indicator for flash sterilization with three biological indicators and three chemical indicators.

OBJECTIVE: Flash sterilization is most commonly used for emergency sterilization of unwrapped items in a gravity displacement sterilizer for three minutes. Sterilization quality assurance is monitored by biological indicators that require a 24-hour incubation prior to reading. In this study, we compared a new biological indicator that provides results within 60 minutes with three conventional, 24-hour biological indicators for monitoring flash sterilization and three chemical indicators. DESIGN: Conventional biological indicators tested included the conventional Attest 1261, Proof Flash and Assert, while the rapid readout indicator tested was Attest 1291. Attest Rapid Readout detects the presence of a Bacillus stearothermophilus enzyme by reading a fluorescent product that is produced by the enzymatic break-down of a nonfluorescent substrate. Chemical indicators tested included Comply, Incheque, and Thermalog S. Survival at 132 degrees C in a gravity displacement sterilizer was measured by media color change after incubation for 24 hours at 56 degrees C for the three conventional biological indicators, fluorescence at 60 minutes for the Attest Rapid Readout biological indicator, and color change for the chemical indicators. Each exposure time was replicated four times with 10 of each biological and chemical indicator per run. RESULTS: The conventional biological indicators (Attest, Proof Flash, and Assert) had 90%, 48%, and 40% spore survival at two minutes exposure; 23%, 3%, and 0% at three minutes exposure; and 3%, 0%, and 0% at four minutes exposure respectively. The Attest Rapid Readout biological indicator had 88%, 33%, and 0% enzyme activity detectable at 2, 3, and 4 minutes exposure. The chemical indicators Comply, Incheque, and Thermalog S revealed sterilization failure rates of 100%, 100%, and 100% at 0 minutes exposure; 100%, 100%, and 45% at one minute; 0%, 0%, and 28% at two minutes exposure; 0%, 0%, and 18% at three minutes exposure; and 0%, 0%, and 0% at four minutes exposure, respectively. CONCLUSION: The sensitivity of the Attest Rapid Readout parallels the conventional biological indicators. These data suggest that a 60-minute rapid readout biological indicator is equivalent to the 24-hour biological indicators. If further studies demonstrate that a four-minute flash sterilization cycle provides a needed safety margin to ensure sterilization, then consideration should be given to requiring a four-minute flash sterilization cycle. Chemical indicators were too sensitive to the processing conditions (eg, steam) and are inadequate to ensure adequate sterilization.

Evaluation Studies as Topic↗
PubMed1996

Comparison of a rapid readout biological indicator for steam sterilization with four conventional biological indicators and five chemical indicators.

OBJECTIVE: In this study, we compare a new biological indicator that provides results within 3 hours with four conventional, 48-hour biological indicators and five chemical indicators. DESIGN: Biological indicators tested included the conventional Attest 1262, Proof Plus, Assert, and Biosign, and the new Attest 1292 Rapid Readout biological indicator. Chemical indicators tested included Comply, Propper, Chemdi, Sterigage, and Thermalog S. Spore survival following 121 degrees C in a gravity displacement sterilizer was measured by media color change after incubation for 24 and 48 hours at 56 degrees C for the conventional biological indicators, fluorescence at 3 hours for the Attest 1292 Rapid Readout biological indicator, and color change for the chemical indicators. Each exposure time was replicated 12 times with 5 samples of each indicator per run (ie, 60 replicates per indicator). RESULTS: At 48 hours, the conventional biological indicators Attest 1262, Proof Plus, Assert, and Biosign showed 100%, 95%, 88%, and 93% spore survival at 5 minutes' exposure 0%, 0%, 0% and 8% at 10 minutes; and all showed 0% survival at 15 minutes' exposure. Following a 3-hour incubation, the Attest 1292 Rapid Readout biological indicator showed fluorescence at 100%, 72%, and 0% at 5, 10, and 15 minutes, respectively. The chemical indicators Comply, Propper, Chemdi, Sterigage, and Thermalog S revealed sterilization failure rates of 100%, 100%, 100%, 100%, and 100% at 5 minutes' exposure; 0%, 0%, 0%, 92%, and 100% at 10 minutes; and 0%, 0%, 0%, 3%, and 27% at 15 minutes' exposure, respectively. CONCLUSIONS: The sensitivity of the Attest 1292 Rapid Readout biological indicator parallels that of conventional biological indicators. These data suggest that a 3-hour rapid readout biological indicator is equivalent to a standard 48-hour biological indicator. Some chemical indicators (eg, Thermalog S) failed to indicate adequate sterilization at 15 minutes' exposure. These chemical indicators have the potential of causing unnecessary recall of adequately sterilized items.

Equipment Contamination↗
PubMed1986

[Inhalational exposure to rapidly eliminated substances: possibility and strategies for biological monitoring. A proposal for the use of biological limits equivalent to environmental limits].

Some advantages of biological compared with environmental monitoring and some preparatory steps and difficulties to be overcome during the planning of a biological monitoring program are firstly discussed. Then the biological compartments, their peculiarities and their use in the field of biological monitoring are described. The problem concerning the biological thresholds of the reference normal values and the biological limits corresponding to environmental limits (biological equivalent limits, BEL) is the next topic, followed by the description of the methods for measuring the BELs (in case of linear regression between biological and environmental values) and of the methods for the upper and lower confidence limits (UCL, LCL) of a biological value. They are to be used for a decision of compliance or noncompliance biological exposure. Finally some ways of using biological UCL-LCL and variation coefficients during cross-sectional and longitudinal studies (biological monitoring strategies) are shown.

Air Pollutants, Occupational↗
PubMed2002

Bridging the gap between cell biology and organic chemistry: chemical synthesis and biological application of lipidated peptides and proteins.

We have developed a basic concept for studying cell biological phenomena using an interdisciplinary approach starting from organic chemistry. Based on structural information available for a given biological phenomenon, unsolved chemical problems are identified. For their solution, new synthetic pathways and methods are developed, which reflect the state of the art in synthesising lipidated peptide conjugates. These compounds are used as molecular probes for the investigation of biological phenomena that involve both the determination of biophysical properties and cell biological studies. The interplay between organic synthesis, biophysics and cell biology in the study of protein lipidation may open up new and alternative opportunities to gain knowledge about the biological phenomenon that could not be obtained by employing biological techniques alone. This fruitful combination is highlighted using the Ras protein as an outstanding example. Included herein is: the development of methods for the synthesis of Ras-derived peptides and fully functional Ras proteins, the determination of the biophysical properties, in particular the ability to bind to model membranes, and finally the use of synthetic Ras peptides and proteins in cell biological experiments.

Amino Acid Sequence↗
PubMed2000

Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality.

PURPOSE: The goals of this study were to survey and summarize the advances in imaging that have potential applications in radiation oncology, and to explore the concept of integrating physical and biological conformality in multidimensional conformal radiotherapy (MD-CRT). METHODS AND MATERIALS: The advances in three-dimensional conformal radiotherapy (3D-CRT) have greatly improved the physical conformality of treatment planning and delivery. The development of intensity-modulated radiotherapy (IMRT) has provided the "dose painting" or "dose sculpting" ability to further customize the delivered dose distribution. The improved capabilities of nuclear magnetic resonance imaging and spectroscopy, and of positron emission tomography, are beginning to provide physiological and functional information about the tumor and its surroundings. In addition, molecular imaging promises to reveal tumor biology at the genotype and phenotype level. These developments converge to provide significant opportunities for enhancing the success of radiotherapy. RESULTS: The ability of IMRT to deliver nonuniform dose patterns by design brings to fore the question of how to "dose paint" and "dose sculpt", leading to the suggestion that "biological" images may be of assistance. In contrast to the conventional radiological images that primarily provide anatomical information, biological images reveal metabolic, functional, physiological, genotypic, and phenotypic data. Important for radiotherapy, the new and noninvasive imaging methods may yield three-dimensional radiobiological information. Studies are urgently needed to identify genotypes and phenotypes that affect radiosensitivity, and to devise methods to image them noninvasively. Incremental to the concept of gross, clinical, and planning target volumes (GTV, CTV, and PTV), we propose the concept of "biological target volume" (BTV) and hypothesize that BTV can be derived from biological images and that their use may incrementally improve target delineation and dose delivery. We emphasize, however, that much basic research and clinical studies are needed before this potential can be realized. CONCLUSIONS: Whereas IMRT may have initiated the beginning of the end relative to physical conformality in radiotherapy, biological imaging may launch the beginning of a new era of biological conformality. In combination, these approaches constitute MD-CRT that may further improve the efficacy of cancer radiotherapy in the new millennium.

Fluorodeoxyglucose F18↗
PubMedDate not supplied

Biological UV dosimeters in the assessment of the biological hazard from environmental radiation.

To determine the impact of environmental UV radiation, biological dosimeters that weight directly the incident UV components of sunlight have been developed, improved and evaluated in the frame of the BIODOS project. Four DNA-based biological dosimeters ((i) phage T7, (ii) uracil thin layer, (iii) spore dosimeter and (iv) DLR-biofilm) have been assessed from the viewpoint of their biological relevance, spectral response and quantification of their biological effectiveness. The biological dosimeters have been validated by comparing their readings with weighted spectroradiometer data, by comparison with other biological doses, as well as with the determined amounts of DNA UV photoproducts. The data presented here demonstrate that the biological dosimeters are potentially reliable field dosimeters for measuring the integrated biologically effective irradiance for DNA damage.

Bacillus subtilis↗
PubMed1977

Biological and immunological characterization of human luteinizing hormone: II. A comparison of the immunological and biological activities of pituitary extracts after electrofocusing using different standard preparations.

The profile of immunologically active human luteinizing hormone (hLH) was determined in aqueous pituitary extracts after electrofocusing using two radioimmunoassay systems and the estimates for each fraction were compared to those obtained by an in vitro bioassay method. Similar biological and immunological profiles were obtained in the pH 7.0-9.0 region, where most of the biological activity was present. Biological to immunological (B/I) ratios ranging from 0.6 to 1.7 (mean ratio 1.01; n = 21) were found in the major biologically active fractions of this pH region when a highly purified human pituitary LH preparation (68/40) was used as standard in both types of assays. The close proximity of these ratios to unity indicates a similar composition of biological and immunological activities in all these fractions in relation to that of the highly purified standard. However, marked discrepancies were observed in the pH region 3.0-7.0 where the B/I ratios ranged from 0.1 to 0.9, indicating the presence of immunological activity associated with relatively little biological activity. When impure human LH preparations of pituitary (69/104) and urinary (hMG 2nd IRP) origin were used as standards for the bioassay and radioimmunoassay of the hLH present in the major fractions of the pH region 7.0-9.0, significantly higher B/I ratios were obtained than with the use of the highly purified standard (68/40). These elevated B/I ratios are attributed to the presence in the impure standard preparations of immunological activity, which is associated with little or no biological activity. These observations may provide an explanation for the differences in B/I ratios which were reported for hLH in plasma, using different standard preparations.

Biological Assay↗
PubMed1978

Biological and immunological characterization of human luteinizing hormone: IV. Biological and immunological profile of two international reference preparations after electrofocusing.

The first IRP of Human Pituitary Gonadotrophins (FSH/LH) for bioassay (69/104) and the 1st IRP of Human Pituitary Luteinizing Hormone (LH) for immunoassay (68/40) were fractionated by an electrofocusing technique in a sucrose density gradient and the profile of biological and immunological activities was determined. The partially purified LH preparation (69/104) gave a broad pattern of biolgical and immunological activities which extended from pH 4 to 10. The biological : immunological (B/I) ratio of the various fractions (using the 68/40 preparation as standard) ranged from 0.04 to 1.05. The low B/I ratios indicate the presence of high levels of immunologically active, biologically inactive material in this preparation. In contrast to the behaviour of the 69/104 preparation, the major proportion (88%) of the biological activity recovered after electrofocusing of the highly purified LH preparation (68/40) was found within the pH range 7--9, with B/I ratios (again using as standard the 68/40 preparation) ranging from 0.4 to 1.5. Multiple dose parallel line design radioimmunoassays revealed a lack of parallelism between the 69/104 and 68/40 International Reference Preparations. This was attributed to the presence of acidic material in the former preparation, which is practically absent from the latter. The biological LH profiles of both the 69/104 and 68/40 preparations differed from those previously reported for aqueous extracts of pituitaries. It is concluded that the dissimilarity in the electrofocusing profiles of the biological and immunological activities of the 69/104 preparation renders this preparation unsuitable as a reference preparation for the quantitation of biologically active LH by radioimmunoassay methods. Using the same criteria, the 68/40 preparation would appear to be a more suitable standard.

Animals↗
PubMed1979

Biologically active luteinizing hormone (LH) in plasma. V. A re-analysis of the differences in the ratio of biological to immunological LH activities during the menstrual cycle.

The relationship between the biological and immunological activities of human luteinizing hormone (hLH) in plasma collected from female subjects was examined. The biological activity was measured by an in vitro bioassay and the immunological activity by an hLH radioimmunoassay (RIA), using improved reagents, such as the 1st IRP for human pituitary LH for immunoassay (code No. 68/40) as standard, a subunit-free biologically active iodinated hLH preparation as tracer and an anti-hLH serum of relatively high specificity. Similar profiles of biological (B) and immunological (I) activity were obtained in the plasma samples collected daily throughout 40 menstrual cycles (5 cycles from each of 8 subjects). However, the B/I ratios were significantly lower during the period of LH surge (P less than 0.001) than throughout the remainder of the cycle. The within- and between-assay variation in B/I ratios was investigated by the simultaneous assay of biological and immunological activities in plasma pools obtained by combining equal aliquots of plasma from each daily sample of the menstrual cycle from each of 5 cycles of each of 4 subjects. The analysis of these 20 pools revealed highly significant individual differences in B/I ratios, ranging from 0.81 to 1.33. The coefficient of variation was 20% between-subjects and 5% within-subjects. There was no seasonal variation in B/I ratios. That the individual differences in plasma B/I ratios were not attributable to the procedure of pooling was ascertained by the simultaneous assay of both activities in parellel in daily plasma samples and in the pools formed from these samples from three complete cycles. Thus the analysis of the differences in B/I ratios obtained throughout the menstrua- cycle revealed three major sources of variation. The first occurs in the form of generally elevated (higher than unity) B/I ratios, the second consists of a significant drop in B/I ratios during the midcycle LH surge, and the third source is represented by the significant between-subject differences. It is concluded that the first source is attributable to the relatively higher levels of "impurity" (i.e. biologically inactive, immunologically active material) in the standard preparation compared to those present in plasma of biologically inactive, immunologically active material of unknown composition and origin. If so, the latter source limits the quantitative significance of the RIA procedures employed. It is suggested that these three sources of variation account for most of the differences in B/I ratios for plasma lLH reported in the literature.

Adult↗
PubMed1999

Reference values and human biological monitoring values for environmental toxins. Report on the work and recommendations of the Commission on Human Biological Monitoring of the German Federal Environmental Agency.

This article describes the working principles and working procedures of the Commission on Human Biological Monitoring, which was established in 1993 as a joint commission of the Federal Health Office (Bundesgesundheitsamt) and the Federal Environmental Agency (Umweltbundesamt) in Germany. One of the main tasks of the commission is to develop scientifically based criteria for the application of human biological monitoring and for the evaluation of human monitoring data in environmental medicine. In principle, two different kinds of criteria are recommended: (a) reference values and (b) human biological monitoring values (HBM values). Reference values are intended to indicate the upper margin of the current background exposure of the general population to a given environmental toxin at a given time. Reference values can be used to identify subjects with an increased level of exposure (in relation to background exposure) to a given environmental toxin. However, reference values do not represent health-related criteria for the evaluation of human biological monitoring data. HBM values are derived from human toxicology and epidemiology studies and are intended to be used as a basis for a health-related evaluation of human biological monitoring data. Usually the commission recommends two different HBM values: HBM I, the concentration of an environmental toxin in a human biological material (usually blood, serum, plasma, or urine) below which there is--according to the knowledge and judgement of the commission--no risk for adverse health effects in individuals of the general population: and HBM II, the concentration of an environmental toxin in a human biological material (usually blood, serum, plasma, or urine) above which there is--according to the knowledge and judgement of the commission and with regard to the environmental toxin under consideration--an increased risk for adverse health effects in susceptible individuals of the general population. The HBM I value can be considered a kind of alert value (from the toxicological point of view), whereas the HBM II value represents a kind of action level, at which attempts should be undertaken to reduce the level of exposure immediately and to carry out further medical examinations. Values between HBM I and HBM II should be considered a warning signal of the need to control the analytical measurement and to reduce the level of exposure of the concerned individual as reasonably as is achievable. At present, reference and HBM values are available for lead in blood, for cadmium and mercury in blood and urine, and for pentachlorophenol in plasma/serum and urine. Reference values have been established for some polychlorinated biphenyls in blood and plasma as well as for hexachlorocyclohexane and hexacholorobenzene in blood as well as for some organochlorine in human milk.

Adolescent↗