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Organic dust toxic syndrome: an acute febrile reaction to organic dust exposure distinct from hypersensitivity pneumonitis.

Organic dust toxic syndrome is a term recently coined to describe a noninfectious, febrile illness associated with chills, malaise, myalgia, a dry cough, dyspnea, headache and nausea which occurs after heavy organic dust exposure. Organic dust toxic syndrome shares many clinical features with acute farmer's lung and other forms of hypersensitivity pneumonitis, including the presence of increased numbers of neutrophils in bronchoalveolar lavage. However, organic dust toxic syndrome differs from acute hypersensitivity pneumonitis in several respects: the chest X-ray does not show infiltrates, severe hypoxemia does not occur, prior sensitization to antigens in the organic dust is not required and there are no known sequelae of physiological significance, such as the recurrent attacks and the pulmonary fibrosis which may be seen with chronic hypersensitivity pneumonitis. Organic dust toxic syndrome is thought to be much more common than farmer's lung. It is important for clinical and investigational purposes that organic dust toxic syndrome be distinguished from acute farmer's lung.

Acute Disease↗

Transforming your manufacturing organization into a learning organization.

Many experts believe the only sustainable advantage an organization will have in the future is its ability to learn faster than its competitors. This competitive advantage can be achieved by transforming the organization into a learning organization. This article describes the basic elements of a learning organization and how to transform an organization to focus on learning. The article also describes methods for evaluating the training and learning that occurs within the organization to ensure that training dollars are wisely spent. Finally, the article describes what individuals can do to focus on their own learning and personal development within an organization.

Economic Competition↗

Vascular nitric oxide-generating activities for organic nitrites and organic nitrates are distinct.

Like organic nitrates, the organic nitrites are assumed to undergo vascular metabolic activation to nitric oxide (NO) to produce vasodilating activity, but this assumption has never been examined. In this study, isobutyl nitrite and amyl nitrite were incubated with subcellular fractions of bovine coronary arterial smooth muscle at 37 degrees C, and NO generation was assessed by redox chemiluminescence assay of headspace NO. Bovine vascular subfractions exhibited substantial and significant catalytic activity for NO generation towards both organic nitrite substrates, and NO-generating activity could be inhibited by heating and irradiation. These observations suggest that organic nitrites are converted enzymatically to NO in vascular smooth muscle. Analysis of marker enzyme activities suggested that the primary NO-generating activity was associated with the cytosol, whereas a distinct, but relatively minor NO-generating activity was also identified in the microsomal fraction. The cytosolic and microsomal NO-generating activities exhibited different temperature dependencies for heat-induced inhibition of activity. The molecular weights of the NO-generating enzymes, determined by radiation inactivation target-size analysis, were 263 kDa (95% confidence interval: 236-298 kDa) for the cytosolic enzyme and 79 kDa (95% confidence interval: 54-148 kDa) for the microsomal enzyme. Previous studies in this laboratory have shown that the representative organic nitrate, nitroglycerin (NTG), is metabolized to NO by an enzyme associated with the plasma membrane of bovine vascular smooth muscle cells. Thus, the enzymes responsible for vascular bioconversion of organic nitrates and organic nitrites to NO are apparently different.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyl Nitrite↗

Organization of nucleoskeleton and its relation to DNA topological organization.

The organization of nucleoskeleton fibers and its relation to DNA organization in the interphase micronucleus of a ciliate (Stylonychia mytilus Muller) were investigated mainly by the macromolecular spreading procedure combined with electron microscopy. It was shown that the nucleoskeleton fibers are organized as a regular organization termed the nucleoskeleton subunit which is composed of a structural center and a number of branch-like fibers extending radiately from the center. The whole micronuclear skeletal network is composed of a number of the essential subunits which are connected with each other. The micronuclear DNA is closely associated with the nucleoskeleton subunit and constructed as highly ordered DNA loops which appear in some different forms of topological organization. After the DNA-rich nucleoskeleton is digested with proteinase K, the nucleoskeleton subunit disappears, while the DNA loses its regular organization and becomes very random and loose, which suggests that the nucleoskeleton subunit plays very important roles in maintaining the topological organization of the interphase DNA. The nucleoskeleton subunit may be the essential organizational and functional unit of the interphase nucleoskeleton.

Animals↗

[Therapeutic principle of organ replacement--artificial organs].

The natural or artificial replacement of organs provides the aimed influence on terminal phases of organ diseases. The hitherto obtained solutions for the replacement in diseases of kidneys, the heart, the lungs, the pancreas and the liver are developed in a different way. For the natural replacement of organs ameliorations in the fields of recipient conditioning, immunotherapy, prophylaxis against infections in operative and technical prerequisites given are subject of further efforts. The complex of problems artificial replacement of organs in the sense of the influence on global and partial organ dysfunctions organ-related reveals different consideration and development. The most advanced perfectioning is existing for the artificial kidney. The elementary and relatively high need of replacement of organs is another challenge to medical and technological sciences.

Humans↗

[Studies on DNA content of tissues and organs. 1st communication: changes in cell content of some mesenchymal and parenchymatous rat organs during development, maturation, and in part aging (determinations of DNA) (author's transl)].

In this study the cell content was analyzed by means of the DNA content of certain mesenchymal and parenchymal organs of the rat. The main aspects were the postnatal stages of development and maturation. Their correlation to aging was examined only on examples, so was their correlation to the prenatal development (on 2 examples: liver and skin). One important result of this research is that a gradual reduction in the exponential growth takes place with increasing maturation and development. The "growth by production" prevails over the "growth by division" (of cells). This is the explanation for the "relative" (= apparent) decrease in the cell content of the tissues and organs analyzed during the decisive postnatal development and maturation phases. In this period the complete differentiation of the cytoplasmic structures and of the differentiation products of the tissues and organs here analyzed occurs. This leads to a shift in their relative amounts to the disadvantage of the cell nuclei, which prevailed in the total weight of tissues and organs during the early phases of development. This concerns determinations of the DNA content related to wet weight even more than such of the DNA content related to dry weight. As already shown clearly, the different tissues and organs of the mammalian organism (here on the example of the rat) grow, mature and age differently. During growth different phases can be distinguished, too, by analysis of the DNA content which partly correlate with phases of growth which were differentiated morphologically. Determinations of DNA contents are necessary as parameters for determinations of the production metabolism (e.g. activities of enzymes, products of formation and differentiation) of the different tissues and organs during their development, maturation and aging.

Aging↗

Should people who commit themselves to organ donation be granted preferred status to receive organ transplants?

Granting preferred status for transplantation to people who commit themselves to posthumous organ donation is an intriguing proposal designed to increase the pool of cadaveric organ donors. Under one version of this plan, all competent adults who had previously consented to having their organs removed and transplanted upon their deaths would be given priority to receive organs, should they ever need them, over potential recipients of equal need who had not agreed to donate. To see if this plan would be acceptable to the public, I contracted Harris Interactive to conduct a national telephone survey about this issue. One thousand fourteen adults living in the United States were queried. Fifty-three percent of the respondents thought that people who agree to donate their organs after death should be granted priority to receive cadaveric organ transplants over those who do not agree to donate. Only 30% of the respondents would definitely oppose this plan. These data suggest that a pilot study of preferred status should be considered.

Adult↗

Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors.

The organic anion transport system is involved in the tubular excretion and reabsorption of various drugs and substances. The purpose of this study was to characterize the effects of various organic anion transport inhibitors on renal organic anion transport using proximal tubule cells stably expressing human organic anion transporter 2 (hOAT2) and hOAT4. Immunohistochemical analysis revealed that hOAT2 is localized to the basolateral side of the proximal tubule in the kidney. hOAT2 mediated a time- and concentration-dependent increase in prostaglandin F(2alpha) (PGF(2alpha)) uptake. The organic anion transport inhibitors used for this study were probenecid, 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), betamipron, and cilastatin. Probenecid, but not KW-3902, betamipron, and cilastatin, significantly inhibited hOAT2-mediated PGF(2alpha) uptake. In contrast, probenecid, KW-3902, and betamipron, but not cilastatin, inhibited hOAT4-mediated estrone sulfate (ES) uptake. Kinetic analyses revealed that these inhibitions were competitive. The K(i) value of probenecid for hOAT2 was 766 microM, whereas those of probenecid, KW-3902, and betamipron for hOAT4 were 54.9, 20.7, and 502 microM, respectively. These results suggest that probenecid, KW-3902, and betamipron could inhibit hOAT4-mediated ES uptake in vitro, whereas probenecid alone could inhibit the hOAT2-mediated PGF(2alpha) uptake. Comparing the K(i) values with the therapeutically relevant concentrations of unbound inhibitors in the plasma, probenecid alone was predicted to inhibit hOAT4-mediated organic anion transport in vivo.

Amino Acid Sequence↗

Organ and tissue procurement system: a novel intervention to increase organ donation rates in Venezuela.

The limited number of organs and tissues available for transplantation in Venezuela and the need to improve outcomes for patients with life-threatening end-stage organ failure or inadequate quality of life resulted in the development and implementation of an organ and tissue procurement system by the Venezuelan National Transplant Organization. This procurement system, a 24-hour, nationwide, free phone service for detection of potential organ donors, connects callers with transplant coordinators. The on-call coordinator supervises family approach as well as maintenance, transport, and allocation of the organs and tissues. During a period of 21 months, the phone service received 1191 calls (713 requesting information to become a voluntary donor, 207 requesting information about donation and transplantation, and 271 reporting potential donors). Of the potential donors, 74% were men and 67% were aged between 11 and 40 years, and most came from hospital intensive care units, emergency departments, and trauma shock units. The main causes of death were trauma and stroke. Reasons why donation was not accomplished included early cardiorespiratory arrest and denied consent. In conclusion, establishing the procurement system resulted in an increase in the detection, referral, and maintenance of potential donors; doubling of the number of donors per million population; and an increase in the number of cadaveric transplants.

Adolescent↗

Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.

We have demonstrated in the present study that novel organic cation transporter (OCTN) 2 is a transporter for organic cations as well as carnitine. OCTN2 transports organic cations without involving Na(+), but it transports carnitine only in the presence of Na(+). The ability to transport organic cations and carnitine is demonstrable with human, rat, and mouse OCTN2s. Na(+) does not influence the affinity of OCTN2 for organic cations, but it increases the affinity severalfold for carnitine. The short-chain acyl esters of carnitine are also transported by OCTN2. Two mutations, M352R and P478L, in human OCTN2 are associated with loss of transport function, but the protein expression of these mutants is comparable to that of the wild-type human OCTN2. In situ hybridization in the rat shows that OCTN2 is expressed in the proximal and distal tubules and in the glomeruli in the kidney, in the myocardium, valves, and arterioles in the heart, in the labyrinthine layer of the placenta, and in the cortex, hippocampus, and cerebellum in the brain. This is the first report that OCTN2 is a Na(+)-independent organic cation transporter as well as a Na(+)-dependent carnitine transporter and that OCTN2 is expressed not only in the heart, kidney, and placenta but also in the brain.

Acetylcarnitine↗

Benchmarking organ procurement organizations: a national study.

OBJECTIVE: An exploratory examination of the technical efficiency of organ procurement organizations (OPOs) relative to optimal patterns of production in the population of OPOs in the United States. DATA SOURCES: A composite data set with the OPO as the unit of analysis, constructed from a 1995 national survey of OPOs (n = 64), plus secondary data from the Association of Organ Procurement Organizations and the United Network for Organ Sharing. STUDY DESIGN: The study uses data envelopment analysis (DEA) to evaluate the technical efficiency of all OPOs. PRINCIPAL FINDINGS: Overall, six of the 22 larger OPOs (27 percent) are classified as inefficient, while 23 of the 42 smaller OPOs (55 percent) are classified as inefficient. Efficient OPOs recover significantly more kidneys and extrarenal organs; have higher operating expenses; and have more referrals, donors, extrarenal transplants, and kidney transplants. The quantities of hospital development personnel and other personnel, and formalization of hospital development activities in both small and large OPOs, do not significantly differ. CONCLUSIONS: Indications that larger OPOs are able to operate more efficiently relative to their peers suggest that smaller OPOs are more likely to benefit from technical assistance. More detailed information on the activities of OPO staff would help pinpoint activities that can increase OPO efficiency and referrals, and potentially improve outcomes for large numbers of patients awaiting transplants.

Benchmarking↗

Organization of tracheal epithelium in the cartilaginous portion of adult rabbit and its persistence in organ culture.

BACKGROUND: The rabbit trachea provides a model system to test the physiological responses of the airways to various agents. Since three-dimensional organization may affect responses of an organ, an organ culture model was established in serum free medium. METHODS: Tracheas were fixed in situ, at steps in the preparation of organ cultures, and after one day to three weeks in organ culture. Samples were examined by light microscopy and scanning and transmission electron microscopy for surface morphology, distribution of cell types, and characteristics of the epithelial cell layer. RESULTS: The normal tracheal mucosa was discovered to consist of extensive circumferential folds in the cartilaginous portion, which were enhanced upon isolation of the trachea from the animal. The folds consisted principally of differences in epithelial cell height rather than folding of the lamina propria. Enhancement of folding upon removal of the trachea coincided with increased secretion by Clara and possibly mucous cells. In organ culture, epithelial cell height initially increased, producing tall folds and cell types were retained in normal proportions. After prolonged culture, cilia were lost but glandular secretion continued. CONCLUSIONS: Changes in the arrangement of basal cells and secretory activity in isolated trachea and in culture may give insight into the functional significance of the epithelial folds.

Animals↗

From embryo to adult: anatomy and development of a leg sensory organ in Phormia regina Meigen (Insecta: Diptera). I. Anatomy and physiology of a larval "leg" sensory organ.

Neurons within the precursor of the adult leg, the imaginal disc, innervate a larval sense organ, Keilin's organ. Electron microscopical investigations of first instar larvae show that five dendrites end at the organ: three insert at the bases of the three hairs of the organ and two end against the cuticle, without any apparent cuticular specialization. In third instar larvae, the imaginal leg discs invaginate into the body cavity, and only four of the dendrites (the outer segments of which become greatly elongated) remain in contact with Keilin's organ. The axons of the neurons that supply Keilin's organ project into a ventral neuropile region of the central nervous system, with a pattern that resembles the projections of other larval sensilla. Electrical activity can be recorded from neurons of the imaginal disc in response to mechanical stimulation.

Afferent Pathways↗

The mammalian iris-ciliary complex affects organization and synthesis of cytoskeletal proteins of organ and tissue cultured lens epithelial cells.

A water soluble growth inhibitor was isolated from the mammalian ocular iris-ciliary complex. The molecular weight of this protein is 10 kD or lower as determined by ultrafiltration fractionation. The iris-ciliary (IC) complex water soluble protein(s) significantly inhibits synthesis of lower molecular weight proteins of the epithelial cells of the organ cultured mammalian ocular lens. It was also found that this inhibitory effect of IC is mediated via the structural organization of the lens. Monolayer cultures of the lens epithelial cells exposed to IC did not manifest any inhibition of their protein synthesis. Moreover, these tissue cultured lens epithelial (TCLE) cells showed a significant increase in their protein synthetic activities in response to the presence of IC factors in the culture medium. It is postulated that the IC activity is modulated via either the lens capsule, an extracellular matrix, or due to the specific organization of the intact lens. The specific effects of IC on the cytoskeletal organization and synthesis in the organ cultured lens epithelial (OCLE) and TCLE cells were also examined. Both groups, treated with IC factors, manifested significant alterations in their protein synthetic activities and cytoskeletal architecture. The 3H-leucine incorporation experiments showed that alpha-actin and alpha-tubulin synthesis is partially inhibited by IC factors in OCLE cells but vimentin synthesis is not, whereas in TCLE cells all of them showed increased synthesis in response to IC factors. Turnover rates of these proteins in both OCLE and TCLE cells were also computed. The immunofluorescence and microscopic evaluation of OCLE and TCLE cells exposed to IC factors illustrated significant alteration in the cytoarchitecture of the filaments. We demonstrate that an inhibitor(s) molecule of 10 kD or lower size isolated from IC inhibited protein synthesis of OCLE cells and stimulated protein synthesis in TCLE cells. The IC factor also affects the synthesis and organization of cytoskeletal filaments of both the OCLE and TCLE cells.

Actins↗

Cytopathic effects of the pathogenic Neisseria. Studies using human fallopian tube organ cultures and human nasopharyngeal organ cultures.

Infection of mucosal surfaces by N. gonorrhoeae and N. meningitidis may result in inflammation indicating potential injury to host cells. We used human fallopian tube organ cultures (FTOC) and human nasopharyngeal organ cultures (NPOC) to study the mechanisms by which gonococci and meningococci damage human mucosal surfaces. Early in the course of FTOC infected with gonococci and NPOC infected with meningococci, damage was most apparent to ciliary activity. Loss of ciliary activity was accompanied by sloughing of ciliated cells. The damage to ciliated cells was not associated with attachment of gonococci or meningococci to these cells or the presence of organisms within ciliated cells. Infection with the commensal N. subflava did not result in significant damage to human FTOC or NPOC ciliary activity. LPS appears to be a major toxin of gonococci for human FTOC ciliated cells. Gonococcal peptidoglycan fragments also damage FTOC ciliary activity. Both piliated (P+) and nonpiliated (P-) gonococci and meningococci damage FTOC and NPOC ciliary activity, but P+ organisms damage ciliary activity more rapidly than P- organisms. Damage to FTOC ciliated cells was produced by less than 10 micrograms/ml of purified gonococcal and meningococcal LPS. By 1-2h after exposure to LPS, vesicles containing LPS were distributed throughout the cytoplasm of ciliated cells. Polymyxin B neutralized LPS-induced damage, suggesting that the lipid A portion of LPS was the toxic moiety. In contrast, purified gonococcal and meningococcal LPS at 100 micrograms/ml did not damage human NPOC or FTOC from rabbits, pigs and cows. These studies indicate that N. gonorrhoeae and possibly N. meningitidis damage ciliated epithelial cells indirectly by release of toxins from the organisms. The differences in susceptibility of FTOC and NPOC to LPS may suggest changes in density of receptors for LPS and may help explain variation in severity of gonococcal and meningococcal interactions at different human mucosal surfaces.

Cilia↗

Evaluation of the logistic organ dysfunction system for the assessment of organ dysfunction and mortality in critically ill patients.

OBJECTIVES: To evaluate the performance of the logistic organ dysfunction (LOD) system for the assessment of morbidity and mortality in multiple organ dysfunction/failure (MOD/F) in an independent database and to evaluate the use of sequential LOD measurements for the prediction of outcome. DESIGN AND SETTING: Prospective, multicentric cohort study in 13 adult medical, surgical, and mixed intensive care units (ICUs) in Austria. PATIENTS: A total of 2,893 consecutive admissions to the ICUs. MEASUREMENTS AND MAIN RESULTS: Patient vital status at ICU and hospital discharge was recorded. Univariate analysis showed that the LOD was able to distinguish between survivors and nonsurvivors (2 vs. 6 median score). Within organ systems, higher levels of the severity of organ dysfunction were consistently associated with higher mortality. For the prediction of hospital mortality, the original prognostic LOD model did not perform well in our patients, as indicated by the goodness-of-fit C statistic. Using multiple logistic regression we developed a prognostic model with a satisfactory fit in our patients. The integration of further measurements during the ICU stay increased discrimination but not calibration. CONCLUSIONS: The LOD system is well correlated well with the numbers and levels of organ dysfunctions and discriminates well between survivors and nonsurvivors. It can thus be used to quantify the baseline severity of organ dysfunction. Moreover, after customization of the predictive equation the LOD predicted hospital mortality in our patients with high precision. It thus provides a combined measure of morbidity and mortality for critically ill patients with MOD/F.

Aged↗

Ontogeny of the electric organ discharge and the electric organ in the weakly electric pulse fish Brachyhypopomus pinnicaudatus (Hypopomidae, Gymnotiformes).

I recorded the electric organ discharges (EODs) of 331 immature Brachyhypopomus pinnicaudatus 6-88 mm long. Larvae produced head-positive pulses 1.3 ms long at 7 mm (6 days) and added a second, small head-negative phase at 12 mm. Both phases shortened duration and increased amplitude during growth. Relative to the whole EOD, the negative phase increased duration until 22 mm and amplitude until 37 mm. Fish above 37 mm produced a "symmetric" EOD like that of adult females. I stained cleared fish with Sudan black, or fluorescently labeled serial sections with anti-desmin (electric organ) or anti-myosin (muscle). From day 6 onward, a single electric organ was found at the ventral margin of the hypaxial muscle. Electrocytes were initially cylindrical, overlapping, and stalk-less, but later shortened along the rostrocaudal axis, separated into rows, and formed caudal stalks. This differentiation started in the posterior electric organ in 12-mm fish and was complete in the anterior region of fish with "symmetric" EODs. The lack of a distinct "larval" electric organ in this pulse-type species weakens the hypothesis that all gymnotiforms develop both a temporary (larval) and a permanent (adult) electric organ.

Animals↗

Changes in the chemical composition of water-extractable organic matter during composting: distribution between stable and labile organic matter pools.

Aerobic decomposition and stabilization of organic matter during the composting of waste materials is primarily due to the biochemical transformation of water-soluble compounds in the liquid phase by the microbial biomass. For this reason water-soluble organic matter represents the most active fraction of compost, both biologically and chemically, and thus should directly reflect the biochemical alteration of organic matter. This work aims to elucidate the microbial-mediated processes responsible for the distribution of soluble organic matter between stable and labile pools with composting time. Accordingly, chemical analysis as well as UV absorption, and 1H and 13C-NMR spectroscopy of samples collected during the industrial composting of urban waste revealed microbial induced transformation of water-extractable organic matter over time. The chemical composition changed from labile, hydrophilic, plant-derived organic compounds in the beginning to predominately stable, hydrophobic moieties comprising lignin-derived phenols and microbially-derived carbohydrates at later stages of composting.

Carbon Isotopes↗