A single sub-kilometre Kuiper belt object from a stellar occultation in archival data.

The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects. Small, sub-kilometre-sized, Kuiper belt objects elude direct detection, but the signature of their occultations of background stars should be detectable. Observations at both optical and X-ray wavelengths claim to have detected such occultations, but their implied abundances are inconsistent with each other and far exceed theoretical expectations. Here we report an analysis of archival data that reveals an occultation by a body with an approximately 500-metre radius at a distance of 45 astronomical units. The probability of this event arising from random statistical fluctuations within our data set is about two per cent. Our survey yields a surface density of Kuiper belt objects with radii exceeding 250 metres of 2.1(-1.7)(+4.8) x 10(7) deg(-2), ruling out inferred surface densities from previous claimed detections by more than 5sigma. The detection of only one event reveals a deficit of sub-kilometre-sized Kuiper belt objects compared to a population extrapolated from objects with radii exceeding 50 kilometres. This implies that sub-kilometre-sized objects are undergoing collisional erosion, just like debris disks observed around other stars.

Occurrence of perfluoroalkyl sulfonates and carboxylates in German drinking water sources compared to other countries.

Different homologues of C4 to C8 perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFASs) were detected in German surface waters, bank filtrates, artificially recharged groundwaters, and drinking waters. If no point sources are located nearby, the typically measured levels are in the low ng/L range. In the presence of point sources, such as a fluorochemical production site, a leaching agricultural fertilizer contaminated with PFCAs and PFASs, or drained PFC containing fire-fighting foams, much higher concentrations in the microg/L range occur. This situation is similar in Germany and other countries.

[Concept and effectiveness of a treatment program for patients with dementia and their relatives. Results from the Bad Aibling Alzheimer Disease Therapy Center]. / Konzept und Wirksamkeit eines Behandlungsprogrammes für Demenzkranke und deren Angehörige. Ergebnisse aus dem Alzheimer Therapiezentrum Bad Aibling.

A short-term residential treatment programme designed to prepare patients with dementia and caregivers for life with a progressive disease was evaluated in a pre-treatment post-treatment design. The multicomponent programme included: 1) intensive rehabilitation for patients, based on the concept of Self-Maintenance Therapy, and 2) an intervention programme for caregivers. Based on the concept of Self-Maintenance Therapy, it was hypothesised that experiences which are in accordance with patients' self-system would support patients' well-being, reduce psychopathological symptoms and facilitate social participation. In this study treatment effects in FTLD are analysed and compared with treatment effects in AD. The results for both groups show a consistent improvement in patients' depression and in other psychopathological symptoms, which can be seen as directly beneficial for patients. Following treatment, caregivers also felt less depressed, less mentally fatigued and restless, and more relaxed. It was predicted that FTLD patients challenge caregivers in a different way compared to patients with AD due to the particular profile of cognitive and psychiatric problems but there are no significant differences between groups. Further controlled follow-up studies are needed to evaluate the effects of the intervention as dementia progresses and to address hypotheses about factors responsible for benefits as well as for treatment resistance.

[Weil's syndrome with bone marrow involvement after collecting walnuts]. / Morbus Weil mit Knochenmarkbefall nach Walnusssammeln.

HISTORY AND CLINICAL FINDINGS: A 65 year-old man was transferred to our department from a neighbouring hospital with anuria and epistaxis. A few days prior to hospitalization, he had experienced severe muscular and joint pain accompanied by chills. A careful history revealed that, in recent weeks, the patient had frequently collected wild walnuts growing, for the most part, on the banks of a small stream, known to have an infestation of rats. The physical examination revealed pronounced jaundice of the skin and sclerae, and petechia on the lower legs. INVESTIGATIONS: Laboratory results showed marked thrombocytopenia, hyperbilirubinaemia, appreciably elevated urine retention parameters and increased C-reactive protein. During the subsequent course of his illness, serum leptospiral antibody titres were elevated, indicating an acute leptospiral infection manifesting as Weil's syndrome. Silver staining (>>Warthin-Starry<<) revealed rod-shaped bacteria, presumably representing leptospires, in some bone marrow macrophages. TREATMENT AND COURSE: Treatment with i. v. penicillin was immediately initiated, and urine output established by intravenous fluid resuscitation in the intensive care unit, so that haemodialysis was not necessary. The platelet count returned to normal and bilirubin began to decrease again. The patient was discharged home after 2 weeks in the hospital. CONCLUSION: When a patient presents with the triad of renal failure, jaundice and thrombocytpenia in the setting of a possible infection, then the severe form of leptospirosis known as Weil inverted question marks syndrome must be considered, and antibiotic treatment initiated without delay. Of importance for the definitive diagnosis is the repeated determination of the titres of antibodies to leptospires in the serum and urine, which usually become positive only in the second week of the illness. In our case, we detected bacteria directly in some bone marrow macrophages as well.

Detection of sodium chloride in cured salmon roe by SW-NIR spectroscopy.

Salt and moisture content of cured salmon roe (ikura) was determined using short-wavelength-near-infrared (SW-NIR) reflectance spectroscopy (600-1100 nm). SW-NIR can be used to measure chloride species. Calibrations for salt in bulk samples of high-quality roe (R(2) = 0.904, SEP = 0.421%, RPD = 3.21) and average-quality roe (R(2) = 0.711, SEP = 1.13%, RPD = 1.81), crushed eggs (R(2) = 0.857, SEP = 0.509%, RPD = 2.62), and individual eggs (R(2) = 0.731, SEP = 0.698%, RPD = 1.98) were developed using partial least squares (PLS) regression models. The heterogeneous distribution of lipid and moisture in the individual eggs limit the sensitivity of this method; however, this method provides a rapid nondestructive method for high-value food products where destructive testing is expensive or impractical and for process control applications.

Angiotensin II formation and endothelin clearance in ARDS patients in supine and prone positions.

OBJECTIVE: In patients with acute respiratory distress syndrome (ARDS), the prone position may enhance oxygenation by changing ventilation/perfusion ratio. In this study, we investigated whether the prone position affects the net balance between pulmonary endothelin (ET-1) and angiotensin II (Ang II) production and clearance, two metabolic functions of lung endothelial cells. SETTING: Anaesthesiological intensive care unit of a university hospital. PATIENTS: Ten ARDS patients (Murray score > 2.5) were studied in both the supine position (SP) and the prone position (PP). MEASUREMENTS AND DESIGN: Blood samples were taken simultaneously from the patient in SP for assessment of mixed venous and arterial ET-1 and Ang II concentrations, and plasma renin concentration (PRC). This was repeated after 60 min in SP, immediately after turning the patient into PP, and 60 min thereafter. Net arterial/mixed venous ET-1 clearances and net Ang II formations were calculated. RESULTS: arterial oxygen tension increased from SP to PP by an average of 60 mmHg, about 20%. Arterial ET-1 concentrations of ARDS patients were 1.57 +/- 1.1 pg/ml (mean +/- SD) and within the range of healthy persons. Net ET-1 clearances were negative in SP, indicating pulmonary release of ET-1, and did not change in PP. Arterial Ang II concentrations (73 +/- 56 pg/ml) as well as PRC (126 +/- 85 pg/ml) were markedly elevated. Net transpulmonary Ang II formation did not change. CONCLUSION: Acute changes of oxygenation in ARDS patients by positioning do not induce any short-term effects on pulmonary ET-1 net clearance or Ang II net formation.

Acute hypoxic pulmonary vasoconstriction in conscious dogs decreases renin and is unaffected by losartan.

Acute hypoxic pulmonary vasoconstriction (HPV) may be mediated by vasoactive peptides. We studied eight conscious, chronically tracheostomized dogs kept on a standardized dietary sodium intake. Normoxia (40 min) was followed by hypoxia (40 min, breathing 10% oxygen, arterial oxygen pressures 36 +/- 1 Torr) during both control (Con) and losartan experiments (Los; iv infusion of 100 microg. min-1. kg-1 losartan). During hypoxia, minute ventilation (by 0.9 l/min in Con, by 1.3 l/min in Los), cardiac output (by 0.36 l/min in Con, by 0.30 l/min in Los), heart rate (by 11 beats/min in Con, by 30 beats/min in Los), pulmonary artery pressure (by 9 mmHg in both protocols), and pulmonary vascular resistance (by 280 and 254 dyn. s. cm-5 in Con and Los, respectively) increased. Mean arterial pressure and systemic vascular resistance did not change. In Con, PRA decreased from 4.2 +/- 0.7 to 2.5 +/- 0.5 ng ANG I. ml-1. h-1, and plasma ANG II decreased from 11.9 +/- 3.0 to 8.2 +/- 2.1 pg/ml. The renin-angiotensin system is inhibited during acute hypoxia despite sympathetic activation. Under these conditions, ANG II AT1-receptor antagonism does not attenuate HPV.

Tetrahymena pyriformis in the ciliate mobility test. Validation and description of a testing procedure for the registration of harmful substances in the air as well as the effects of cigarette smoke on the human respiratory ciliated epithelium.

The damage of the human respiratory ciliated epithelium or its ciliar activity caused by mixtures of harmful substances in the air and cigarette smoke is a considerable parameter for the judgment of acute harmful influences on the human respiratory tract. As an immediate measuring or a quantitative statement about the influence on cilia in vivo at human beings is extremely difficult and problematic, a convenient model experimental system in form of the so called ciliate mobility test (CMT) has been used. In this connection the influence on cilia of the protozan single-celled organism Tetrahymena pyriformis, regarding its average speed of locomotion has been taken as standard. The proof, that the cilia are identical in morphological and functional respect at the human ciliated epithelium and at T. pyriformis has been reached by electron optical comparative representation and bibliographical known substances, influencing cilia (theophylline, bromhexine, ambroxol, terpin hydrate, mercaptoethanesulfonat-sodium, amrinon, salbutamol, tetracosactid-hexaacetate, histamine, and phenol). With regard to the comparability and applicability to the human respiratory ciliated epithelium we have been able to gain statements by means of the CMT. By constructing a special reaction vessel the influence of harmful gases at a thin layer of ciliate culture suspension (1 cm) for a standardised exposure time (1 hour) has been made possible and with that a model for the comparability with the conditions of the human respiratory ciliated epithelium has been created. A number of harmful gases, that are relevant in the air hygiene (CO, CO2, N2, N2O, NO2, O3, SO2) as well as cigarette smoke at active smokers (primary stream smoke) and the inhalation of the smoke of other people's cigarettes has been tested. It turned out, that especially NO2 (nitric oxide) shows a high ciliar toxicity, while the controversially discussed ozone (O3) has not resulted in detraction of cilia. CO, N2O and SO2 have been--to a great extent--harmless on cilia in the concentration range relevant in the air hygiene. Remarkable are the results, that cigarette smoke shows clear toxic effects on cilia both at active smoking, as well as the inhalation of the smoke of other people's cigarettes. With that another contribution to the discussion about the harmfulness of active smoking and the inhalation of the smoke of other people's cigarettes is made.

Inhaled nitric oxide does not change transpulmonary angiotensin II formation in patients with acute respiratory distress syndrome.

STUDY OBJECTIVE: To investigate the effect of short-term inhalation of nitric oxide (NO) on transpulmonary angiotensin II formation in patients with severe ARDS. DESIGN: Prospective, clinical study. SETTING: Anesthesiology ICU of a university hospital. PATIENTS: Ten ARDS patients who responded to inhalation of 100 ppm NO by decreasing their pulmonary vascular resistance (PVR) by at least 20 dyne x s x cm(-5) were included in the study. INTERVENTIONS AND MEASUREMENTS: In addition to standard treatment, the patients inhaled 0, 1, and 100 ppm NO in 20-min intervals. Fraction of inspired oxygen was 1.0. Hemodynamics were measured and recorded online. Mixed venous (pulmonary arterial catheter) and arterial (arterial catheter) blood samples were taken simultaneously for hormonal analyses at the end of each inhalation period. RESULTS: Pulmonary arterial pressure decreased from 33+/-2 mm Hg (0 ppm NO, mean+/-SEM) to 29+/-2 mm Hg (1 ppm NO, p<0.05), and to 27+/-2 mm Hg (100 ppm NO, p<0.05, vs 0 ppm). PVR decreased from 298+/-56 (0 ppm NO) to 243+/-45 dyne x s x cm(-5) (1 ppm NO, not significant [NS]), and to 197+/-34 dyne x s x cm(-5) (100 ppm NO, p<0.05, vs 0 ppm). Arterial oxygen pressure increased from 174+/-23 mm Hg (0 ppm NO) to 205+/-26 mm Hg (1 ppm NO, NS), and to 245+/-25 mm Hg (100 ppm NO, p <0.05, vs 0 ppm). Mean plasma angiotensin II concentrations were 85+/-20 (arterial) and 57+/-13 pg/mL (mixed venous) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary plasma angiotensin II concentration gradient (=difference between arterial and mixed venous blood values) was 28+/-8 pg/mL (range, 0 to 69) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary angiotensin II formation (transpulmonary angiotensin II gradient multiplied with the cardiac index) was 117+/-39 ng/min/m2 (range, 0 to 414) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean arterial plasma cyclic guanosine monophosphate concentration was 11+/-2 pmol/mL (0 ppm NO), did not change during 1 ppm NO, and increased to 58+/-8 pmol/mL (100 ppm NO, p<0.05). Arterial plasma concentrations of aldosterone (142+/-47 pg/mL), atrial natriuretic peptide (114+/-34 pg/mL), angiotensin-converting enzyme (30+/-5 U/L), and plasma renin activity (94+/-26 ng/mL/h of angiotensin I) did not change. CONCLUSION: The decrease of PVR by short-term NO inhalation in ARDS patients was not accompanied by changes in transpulmonary angiotensin II formation. Our results do not support any relationship between transpulmonary angiotensin II formation and the decrease in PVR induced by inhaled NO.

Substrate oxidation at rest and during exercise: effects of menstrual cycle phase and diet composition.

The estrogen hormones have been shown to be highly glycogenic as well as lipolytic in nature. It is unknown whether the metabolic actions of estrogens impact upon energy metabolism during exercise. The composition of prior diet, however, does affect exercise energy metabolism. This study examined the influence of menstrual cycle phase (mid-follicular [FP; low estrogen] vs. mid-luteal [LP; high estrogen]) and diet composition on the rate of substrate oxidation for carbohydrate (CHO) and lipid at rest and during various intensities of physical exercise. Nine subjects completed an experimental session under four different menstrual cycle-diet conditions: 1) FP following a 3-day high CHO diet [75% total caloric intake], 2) FP following a 3-day low CHO diet [35% total caloric intake], 3) LP following a 3-day high CHO diet, and 4) LP following a 3-day low CHO diet. In each of the experimental sessions substrate oxidation was determined at rest and during cycle ergometer exercise at intensities of 30, 50, and 70% VO2max, respectively. Statistically significant (p < 0.05) interaction effects on substrate oxidation due to the menstrual cycle phase and diet conditions were found at rest and during 30%-50% exercise. In general, CHO oxidation was lowest and lipid oxidation highest in the LP under a low CHO diet condition.

Short-term ACE inhibition has no effect on sodium and water excretion during PEEP ventilation.

The short-term effect of intravenous (i.v.) angiotensin converting enzyme (ACE) inhibitor enalaprilat in 10 critically ill patients, being ventilated with positive end-expiratory pressure (PEEP), on sodium and water excretion was investigated. Mean arterial pressure (MAP) decreased. Heart rate and central venous pressure (CVP) did not change. Glomerular filtration rate (GFR), urine volume (V) and sodium excretion (UNaV) decreased in two patients with reduced MAP. GFR, V and UNaV increased in two patients with decreased MAP. No relation between changes in MAP and excretion was observed in six patients. ACE decreased in all patients. Plasma renin activity increased, aldosterone decreased, while atrial natriuretic peptide as well as antidiuretic hormone did not change. Enalaprilat did not facilitate sodium and water excretion during ventilation with PEEP. Decreased MAP indicates that the investigated patients were very dependent on their renin-angiotensin system to maintain systemic perfusion pressure. Base-line MAP and CVP values were no predictors of haemodynamic and excretory changes following acute ACE inhibition.

Rapid and efficient oligonucleotide synthesis with low reagent consumption via a new synthesis column design: preparation of fluorescent dye labelled primers for application in PCR.

A low dead-volume, 40 nmole scale column was designed for automated, solid-support oligonucleotide synthesis. The LV40 columns are filled with 1000A, high-cross link polystyrene beads at the 40 nmole scale. Reducing the unoccupied volume and optimizing the column dimensions allows efficient and fast synthesis on existing commercial synthesizers with low reagent consumption. Three spectrally distinct fluorescent dyes were applied as phosphoramidites in the synthesis of PCR primers. Fluorescent labelled PCR products of the Mfd11 microsatellite locus were analyzed.

Protein-DNA interactions at steroid hormone regulated genes.

This work summarizes binding data that were obtained with partially purified glucocorticoid and progesterone receptors, as well as with a crude nuclear protein extract, to DNA sequences in and around hormonally regulated genes. The sequence recognition by the glucocorticoid receptor at the different defined glucocorticoid regulatory elements (GRE) is discussed and a consensus sequence formulated. A three dimensional representation gives an impression of the mode of interaction between the protein and the double helix of DNA. In the promoters of mouse mammary tomour virus (MTV) and chicken lysozyme overlapping binding sites for both, glucocorticoid and progestine-receptors are found that are responsible for the hormonal inducibility of the genes. In crude extract from rat liver nuclei, a nonhistone protein is found that specifically binds to sequences on the MTV-LTR region overlapping the GRE. The possible implication of this protein in hormonal regulation of transcription is discussed.

Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.

A DNA-transfection protocol has been developed that makes use of a synthetic cationic lipid, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA). Small unilamellar liposomes containing DOTMA interact spontaneously with DNA to form lipid-DNA complexes with 100% entrapment of the DNA, DOTMA facilitates fusion of the complex with the plasma membrane of tissue culture cells, resulting in both uptake and expression of the DNA. The technique is simple, highly reproducible, and effective for both transient and stable expression of transfected DNA. Depending upon the cell line, lipofection is from 5- to greater than 100-fold more effective than either the calcium phosphate or the DEAE-dextran transfection technique.

The nucleotide sequences recognized by the glucocorticoid receptor in the rabbit uteroglobin gene region are located far upstream from the initiation of transcription.

Although the expression of the uteroglobin gene in the lung is regulated by glucocorticoids, no binding sites for the glucocorticoid receptor are found in the promoter region nor can they be observed in the coding sequences. Instead a fragment situated 2.6 kb upstream from the start of transcription of the uteroglobin gene shows a high affinity for the receptor. Deoxyribonuclease I and methylation protection studies show three contiguous binding sites located within this fragment. All three sites show homology to the glucocorticoid receptor binding sites described for other genes. Two of them encompass the hexanucleotide 5'-TGTTCT-3', and the other binding site contains the homologue hexanucleotide, 5'-AGTCCT-3', but the contacts between the receptor and the hexanucleotides are equivalent to those found in other functional regulatory elements for glucocorticoids. These elements may therefore be responsible for the glucocorticoid regulation of uteroglobin gene expression by acting over a relatively long stretch of nucleotide sequences.

The uteroglobin gene region: hormonal regulation, repetitive elements and complete nucleotide sequence of the gene.

Differential uteroglobin induction represents an appropriate model for the molecular analysis of the mechanism by which steroid hormones control gene expression in mammals. We have analyzed the structure and hormonal regulation of a 35 Kb region of genomic DNA in which the uteroglobin gene is located. The complete sequence of 3,700 nucleotides including the uteroglobin gene and its flanking regions has been determined, and the limits of the gene established by S1 nuclease mapping. Several regions containing repeated sequences were mapped by blot hybridization, one of which is located within the large intron in the uteroglobin gene. Analysis of the RNAs extracted from endometrium, lung and liver, after treatment with estrogen and/or progesterone shows that within the 35 Kb region, the uteroglobin gene is the only DNA segment whose transcription into stable RNA is induced by progesterone.

Isolation and structure of the gene for the progesterone-inducible protein uteroglobin.

Uteroglobin is a small steroid-binding protein that is differentially regulated by steroid hormones in several tissues of the rabbit. In endometrium, the levels of uteroglobin mRNA increase after progesterone administration due to an enhanced rate of transcription of the uteroglobin gene. As a prerequisite for understanding the molecular mechanisms that modulate uteroglobin gene expression, we have isolated and characterized the uteroglobin gene. We first synthesized, cloned, and sequenced a uteroglobin cDNA that was used to screen a rabbit gene library and to show that the uteroglobin gene is not reiterated in the rabbit genome. We obtained three recombinant phages containing uteroglobin gene sequences and covering 35 kilobases of the rabbit genome. The uteroglobin gene is 3 kilobases long and is composed of three short exons separated by a long and a short intron. The complete coding sequence, the short intron, part of the large intron, and the flanking sequences have been subjected to sequence analysis. The salient features of the nucleotide sequence, including the absence of a canonical "T-A-T-A box," are discussed. A possible relationship is considered between the exon-intron structure of the gene and the known structure and function of uteroglobin.