Femtosecond laser ablation inductively coupled plasma mass spectrometry: achievements and remaining problems.
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Journal Article↗
Biomedical subjects
D Günther
Publications and source records attributed to D Günther.
Element partitioning: the role of melt structure and composition.
We segregated coexisting gabbroic and granitic melts by centrifuging them at high pressures and temperatures and measured the trace element compositions of the melts by laser ablation inductively coupled plasma mass spectrometry. Our results demonstrate that the effect of melt structure contributes about one order of magnitude to crystal/melt partition coefficients. Partitioning of alkali and alkaline earth elements strongly depends on field strength: Amphoteric and lone pair electron elements partition into the polymerized granitic melt; and rare earth, transition, and high field strength elements coordinated by nonbridging oxygens partition remarkably similar into the gabbroic melt. A regular solution model predicts these effects.
Journal Article↗
Intrapleural topical application of cisplatin with the surgical carrier Vivostat increases the local drug concentration in an immune-competent rat model with malignant pleuromesothelioma.
OBJECTIVE: We sought to investigate whether intrapleural topical application of cisplatin with a surgical carrier has a prolonged local tissue level in comparison with cisplatin solution while reducing systemic toxicity. METHODS: Forty immune-competent Fischer rats were inoculated with 10(6) mesothelioma cells. Ten days later, left pneumonectomy with tumor debulking was performed. Twenty animals underwent local application of cisplatin solution (100 mg/m2), whereas the same quantity of cisplatin was topically applied as a gel with the Vivostat (Vivolution) system in 20 other animals. In each group 5 subgroups of 4 animals were defined according to the harvesting time of blood and tissue samples (2, 4, 24, and 72 hours and 1 week) after local therapy. Platinum concentrations in serum and tissue and systemic toxicity were analyzed. RESULTS: Platinum concentrations in tissue were significantly higher in the gel group (group 1) than in the solution group (group 2) at 1, 3, and 7 days after therapy (1510, 1224, and 1069 pg/mg for group 1 vs 598, 382, and 287 pg/mg for group 2; P = .007, P = .005, and P = .0002, respectively). Laboratory findings showed renal insufficiency in the animals of the solution group at 1 week, with values of 98 mmol/L versus 7.7 mmol/L for urea and 410 mumol/L versus 43 mumol/L for creatinine (P = .02 and P = .01, respectively), which was confirmed by means of pathologic analysis. CONCLUSIONS: Intrapleural administration of cisplatin with the carrier Vivostat significantly provides sustained higher platinum concentrations up to 1 week in tissue in comparison with application of cisplatin solution without conferring systemic toxicity in this model.
Administration, Topical↗
Lethal child neglect.
The jurisdiction of the Hannover Institute of Legal Medicine recently experienced an unusually high incidence of lethal child neglect, with three cases in a 5-month period in 1999. Case 1: A girl received an inappropriate and inadequate diet of tea and oatmeal. The child was never breastfed, nor did it ever receive any other formula. The parents report the infant to have been healthy until she suddenly began projectile vomiting at the age of 13 weeks. For the next 3 days the infant was not able to maintain an adequate intake. The mother reports finding the child dead in its bed on the morning of the fourth day. Attempts by medical personnel to revive the child were unsuccessful. Case 2: A mother began spoon-feeding the infant puree on the fourth day of life, which according to the manufacturer's specifications is suitable for children between 4 and 8 months of age. At the age of 5 weeks, the infant was reported to have vomited half the just previously ingested meal, after which she took a nap. Some time later the parents observed the infant to be quite pale, however, assumed this was a result of sleep. When the mother finally did pick her up, the child was lifeless, and the parents brought her to the hospital. Medical personnel could however, only declare the infant dead, documenting a rectal temperature of 30 degrees C. Case 3: A 3.5-year-old girl died after her mother left the locked apartment and did not return for several weeks. The body of the child was found lying dressed on the floor in a state of advanced decay and mummification. Common findings in all three cases include lack of prenatal care, home birth without the help of a midwife, low socioeconomic status or maternal alcohol abuse, body weights below the 3rd percentile, extreme dehydration, fatty hepatic degeneration, thymic atrophy and signs of aspiration.
Alcoholism↗
Simultaneous ultratrace determination of Zr and Nb in chromium matrixes with ICP-dynamic reaction cell MS.
A dynamic reaction cell (DRC) has been used to minimize the formation of metal-argide ions in inductively coupled plasma mass spectrometry and applied to the determination of Zr and Nb in Cr-rich samples. The formation of ArCr+ species from the plasma gas and the sample matrix was reduced by ion molecule reactions inside a DRC of the ICPMS used. Hydrogen was used as reaction gas, and the efficiency in the reduction of ArCr+ was similar to that of other plasma-based polyatomic ions as reported in an earlier study. The formation of CrOx+ ions is enhanced when the DRC is operated in pressurized mode. Adjustment of the transmission properties of the band-pass quadrupole to reject precursor ions can be achieved without dramatic decrease of sensitivity but with a significant improvement in the signal/background ratio. Measurements in solutions containing concentrations of up to 2 g/L Cr showed that the determination of Nb and Zr is possible in the nanogram per liter range in such a matrix. The limits of detection for Nb and Zr in pure Cr metal have been estimated at 2 ng/g for Nb and 5 ng/g for Zr. Analysis of basaltic reference samples resulted in very good agreement with previously published data.
Journal Article↗
Human cathepsin W, a cysteine protease predominantly expressed in NK cells, is mainly localized in the endoplasmic reticulum.
Human cathepsin W (also called lymphopain) is a recently described papain-like cysteine protease of unknown function whose gene expression was found to be restricted to cytotoxic cells. Here we demonstrate that cathepsin W is expressed predominantly in NK cells and, to a lesser extent, in CTLs. Quantitative RT-PCR revealed that NK cells contained approximately 21 times more cathepsin W transcript than CTLs. The predominant expression of cathepsin W in NK cells was further confirmed by Western blot analysis and immunohistochemistry. IL-2-mediated stimulation of NK cells and CTLs revealed a stronger up-regulation of the cathepsin W gene and protein expression in NK cells (7-fold) than in CTLs (2-fold). Transfection experiments of HeLa cells and biochemical analyses revealed that cathepsin W is exclusively "high mannose-type" glycosylated and is mainly targeted to the endoplasmic reticulum (ER). Interestingly, the ER localization of cathepsin W was also found in NK cells, in which colocalization studies revealed an overlapping staining of cathepsin W and Con A, an ER-specific lectin. Furthermore, subcellular fractionation of cathepsin W-expressing cells confirmed the ER localization and showed that cathepsin W is membrane associated. Based on the results of this study, cathepsin W might represent a putative component of the ER-resident proteolytic machinery. The constitutive expression in NK cells and the stronger up-regulation of cathepsin W by IL-2 in NK cells than CTLs suggest that cathepsin W is not just a marker of cytotoxic cells but is, rather, specifically expressed in NK cells.
Antibodies, Monoclonal↗
Structural organisation of the head-to-tail interface of a bacterial virus.
In tailed icosahedral bacteriophages the connection between the 5-fold symmetric environment of the portal vertex in the capsid and the 6-fold symmetric phage tail is formed by a complex interface structure. The current study provides the detailed analysis of the assembly and structural organisation of such an interface within a phage having a long tail. The region of the interface assembled as part of the viral capsid (connector) was purified from DNA-filled capsids of the Bacillus subtilis bacteriophage SPP1. It is composed of oligomers of gp6, the SPP1 portal protein, of gp15, and of gp16. The SPP1 connector structure is formed by a mushroom-like portal protein whose cap faces the interior of the viral capsid in intact virions, an annular structure below the stem of the mushroom, and a second narrower annulus that is in direct contact with the helical tail extremity. The layered arrangement correlates to the stacking of gp6, gp15, and gp16 on top of the tail. The gp16 ring is exposed to the virion outside. During SPP1 morphogenesis, gp6 participates in the procapsid assembly reaction, an early step in the assembly pathway, while gp15 and gp16 bind to the capsid portal vertex after viral chromosome encapsidation. gp16 is processed during or after tail attachment to the connector region. The portal protein gp6 has 12-fold cyclical symmetry in the connector structure, whereas assembly-naïve gp6 exhibits 13-fold symmetry. We propose that it is the interaction of gp6 with other viral morphogenetic proteins that drives its assembly into the 12-mer state.
Bacillus subtilis↗
Potentiometric polymeric membrane electrodes for measurement of environmental samples at trace levels: new requirements for selectivities and measuring protocols, and comparison with ICPMS.
It is here established that potentiometric polymeric membrane electrodes based on electrically neutral ionophores are useful analytical tools for heavy metal ion determinations in drinking water at nanomolar total concentrations. This means that they can compete with the most sophisticated techniques of instrumental analysis. With optimized ion-selective membranes based on the lead-selective ionophore 4-tert-butylcalix[4]arenetetrakis(thioacetic acid dimethylamide) as model example, a number of native and spiked drinking water samples are potentiometrically assessed for lead, and the results compared with ICPMS measurements. The goal of this work is to demonstrate that detection limits in real world samples are routinely achieved that are, with 1.5 ppb, at least 10-fold lower than the lead action limit imposed by the U.S. Environmental Protection Agency (15 ppb). In contrast to earlier reports, different conditioning and measuring protocols are followed, and membranes and inner filling solution of optimized composition are used. The sensors are shown to be useful for the speciation analysis of lead in water as well. Typical water samples are acidified to pH 4 to assess total lead rather than free, uncomplexed lead. For lead concentrations above 2 ppb, the values compare very well with ICPMS. Main interferences are found to be H+ and Cu2+, although Cu2+ only shows significant interference at levels around or above its own action limit (1.3 ppm), in which case the water sample would anyway show quality problems. An explicit, simplified flux model targeted to the practical use of these sensors explains the extent of expected interference. Sensors are shown to require a higher selectivity than predicted by models not considering ion fluxes, since in dilute samples, the counterdiffusion flux of lead from the membrane into the sample becomes potential determining. The model and experiments shown here are a foundation for future trace level applications of potentiometric polymeric membrane electrodes.
Algorithms↗
Experimental evidence for the formation of doubly charged oxide and hydroxide ions in inductively coupled plasma mass spectrometry.
The formation of doubly charged polyatomic ions in inductively coupled plasma mass spectrometers was investigated using commercially available instruments. The species observed were ThO2+ and ThOH2+, which were found in similar amounts with the different instruments used in this study, when operated under routine analytical conditions. The signal ratios for ThO2+ were between 1.8 x 10(-4) and 4.2 x 10(-4) relative to the singly charged elemental ion and between 1.4 x 10(-2) and 2.2 x 10(-2) relative to the doubly charged elemental ion. The formation of ThOH2+, was between 1.1 x 10(-4) and 2.8 x 10(-4) relative to the singly charged elemental ion and between 0.72 x 10(-2) and 1.3 x 10(-2) relative to the doubly charged elemental ion. A mechanism is proposed for the formation of the doubly charged oxide and hydroxide ions that is based on the condensation of the doubly charged elemental ion with water or oxygen molecules in the interface region of the mass spectrometer.
Journal Article↗
Splice variants of human cathepsin L mRNA show different expression rates.
Human cathepsin L (hCATL) mRNA occurs in vivo in at least three splice variants. They differ in the length of exon 1, which comprises 278 nucleotides (hCATL-A), 188 nucleotides (hCATL-A2) and 132 nucleotides (hCATL-A3), respectively. We describe here the shortest variant for the first time. This form is predominant in all tissues and cells examined so far, including malignant tumors. We studied the expression rate of the three mRNA variants in order to explain why malignant kidney tumors show low cathepsin L activity despite of high mRNA levels. The variant hCATL-A3 showed the highest expression rate in vitro and in vivo. Based on these results, we suggest a cis-acting element on human cathepsin L mRNA which can be bound by a negative trans-acting regulator, thus leading to reduced expression rates.
Cathepsin L↗
Targeting of the pro-apoptotic VDAC-like porin (PorB) of Neisseria gonorrhoeae to mitochondria of infected cells.
Infection of cell cultures with Neisseria gonorrhoeae results in apoptosis that is mediated by the PorB porin. During the infection process porin translocates from the outer bacterial membrane into host cell membranes where its channel activity is regulated by nucleotide binding and voltage-dependent gating, features that are shared by the mitochondrial voltage-dependent anion channel (VDAC). Here we show that porin is selectively and efficiently transported to mitochondria of infected cells. Prevention of porin translocation also blocked the induction of apoptosis. Mitochondria of cells treated with porin both in vitro and in vivo were depleted of cytochrome c and underwent permeability transition. Overexpression of Bcl-2 blocked porin-induced apoptosis. The release of cytochrome c occurred independently of active caspases but was completely prevented by Bcl-2. Our data suggest that the Neisseria porin can, like its eukaryotic homologue, function at the mitochondrial checkpoint to mediate apoptosis.
Apoptosis↗
Influence of proliferation, differentiation and dedifferentiation factors on the expression of the lysosomal cysteine proteinase cathepsin L (CL) in thyroid cancer cell lines.
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Adenocarcinoma, Follicular↗
Recent trends and developments in laser ablation-ICP-mass spectrometry.
The increased interest in laser technology (e.g. for micro-machining, for medical applications, light shows, CD-players) is a tremendous driving force for the development of new laser types and optical set-ups. This directly influences their use in analytical chemistry. For direct analysis of the elemental composition of solids, mostly solid state lasers, such as Nd:YAG laser systems operating at 1064 nm (fundamental wavelength), 266 nm (frequency quadrupled) and even 213 nm (frequency quintupled) have been investigated in combination with all available inductively coupled plasma mass spectrometers. The trend towards shorter wavelengths (1064 nm - 157 nm) was initiated by access to high quality optical materials which led to the incorporation of UV gas lasers, such as excimer lasers (XeCl 308 nm, KrF 248 nm, ArF 193 nm, and F2 157 nm) into laser ablation set-ups. The flexibility in laser wavelengths, output energy, repetition rate, and spatial resolution allows qualitative and quantitative local and bulk elemental analysis as well as the determination of isotope ratios. However, the ablation process and the ablation behavior of various solid samples are different and no laser wavelength was found suitable for all types of solid samples. This article highlights some of the successfully applied systems in LA-ICP-MS. The current fields of applications are explained on selected examples using 266 nm and 193 nm laser ablation systems.
Journal Article↗
Optimization of a laser ablation-inductively coupled plasma "time of flight" mass spectrometry system for short transient signal acquisition.
Simultaneous ion sampling and sequential detection offered by inductively coupled plasma 'time of flight' mass spectrometry (ICP-TOFMS) provides advantages for the analysis of short transient concentration-variable signals as produced in laser ablation. In order to investigate the capabilities of ICP-TOFMS in combination with an excimer laser ablation system, ablation studies on reference materials and geological samples were carried out. Various ICP-TOFMS parameters were optimized for laser-induced aerosols. Transverse rejection ion pulse was used to extend the dynamic range in concentration. A reduced volume ablation cell was designed and used in order to increase the sample density in the ICP. Results for 63 simultaneously measured isotopes (SRM 610 from NIST) lead to limits of detection in the 1-100 microg/g range for a 80 microm crater diameter (10 Hz, 1.2 mJ pulse energy). The reproducibility of signal ratios was determined to be better than 2% RSD for transient signals using 102 ms integration time. These optimized parameters were then used for the analysis of tin-rich fluid inclusions. Preliminary results of multielement analysis and isotopic ratio determinations on individual fluid inclusions (63 isotopes, 102 ms integration time) demonstrate the capabilities of ICP-TOFMS in combination with laser ablation.
Journal Article↗
Neisseria gonorrhoeae porin modifies the oxidative burst of human professional phagocytes.
A hallmark of infection with the gram-negative bacterium Neisseria gonorrhoeae is the local infiltration and subsequent activation of polymorphonuclear neutrophils. Several gonococcal outer membrane proteins are involved in the interaction with and the activation of these phagocytes, including gonococcal porin, the most abundant protein in the outer membrane. Previous work suggests that this porin plays a role in various cellular processes, including inhibiting neutrophils activation and phagosome maturation in professional phagocytes. Here we investigated the ability of porin to modify the oxidative metabolism of human peripheral blood neutrophils and monocytes in response to particulate stimuli (including live gonococci) and soluble agents. The activation of the oxidative metabolism was determined by chemiluminescence amplified with either luminol or lucigenin. We found that treatment of the phagocytes with porin inhibits the release of reactive oxygen species measured as luminol-enhanced chemiluminescence in response to zymosan, latex particles, and gonococci. The engulfment of these particles was not, however, affected by porin treatment. Similar effects of porin on the chemiluminescence response were observed in cytochalasin B-treated neutrophils exposed to the soluble chemotactic peptide N-formylmethionyl-leucyl-phenylalanine. This indicates that porin selectively inhibits granule fusion with those cellular membranes that are in direct contact with porin, namely, the phagosomal and plasma membranes. This porin-induced downregulation of oxidative metabolism may be a potent mechanism by which gonococci modulate oxygen-dependent reactions by activated phagocytes at inflammation sites.
Diglycerides↗
Unexpected findings in the investigation of an airplane crash.
We report on the discovery at autopsy of an unexpected cause of a crash during landing of a small sports plane with four people on board. Surprisingly, an intact bullet and fragments of the casing were found in the body of the pilot. As expected, autopsy of the other passengers predominantly revealed signs of polytraumatization. In addition, one passenger had a tunnel wound to the left hand and another, a soft tissue tear between the thumb and forefinger of the right hand. These wounds were considered to be associated with a shooting incident in the cabin. The autopsy findings and additional gunpowder trace investigations suggested that the pilot had been incapacitated by a shot from behind, resulting in the plane crash. The present findings underscore the importance of conducting autopsies on all air crash victims.
Accidents, Aviation↗
Neisserial porin (PorB) causes rapid calcium influx in target cells and induces apoptosis by the activation of cysteine proteases.
The porin (PorB) of Neisseria gonorrhoeae is an intriguing bacterial factor owing to its ability to translocate from the outer bacterial membrane into host cell membranes where it modulates the infection process. Here we report on the induction of programmed cell death after prolonged infection of epithelial cells with pathogenic Neisseria species. The underlying mechanism we propose includes translocation of the porin, a transient increase in cytosolic Ca2+ and subsequent activation of the Ca2+ dependent protease calpain as well as proteases of the caspase family. Blocking the porin channel by ATP eliminates the Ca2+ signal and also abolishes its pro-apoptotic function. The neisserial porins share structural and functional homologies with the mitochondrial voltage-dependent anion channels (VDAC). The neisserial porin may be an analogue or precursor of the ancient permeability transition pore, the putative central regulator of apoptosis.
Adenosine Triphosphate↗
[Improvement of physical performance and aerobic capacity mediated by a novel 4--week ambulatory cardiac rehabilitation program].
During a 4-week ambulatory cardiac rehabilitation program, 262 patients with coronary artery disease (CAD), 235 men and 27 women, 53.6 +/- 10.2 years, performed 30.5 +/- 2.9 exercise units. Before and after the rehabilitation program exercise, capacity was assessed by bicycle ergometry. There was a significant (p < 0.001) increase in the maximum exercise capacity at the end of the program (105.3 +/- 32.3 vs. 121.9 +/- 37.3 W). Physical work capacity on the 2.0 mmol lactate level improved (p < 0.001) from 72.2 +/- 23.5 to 86.4 +/- 25.8 W, on the 2.5 mmol/l level (p < 0.001) from 83.5 +/- 23.2 to 97.4 +/- 26.4 W, and on the 3.0 mmol/l level (p < 0.001) from 93.1 +/- 23.0 to 106.6 +/- 26.1 W. Despite enhanced performance, heart rate remained unaltered on the 2.0, 2.5, and 3.0 mmol/l lactate level. Furthermore, ergometric performance on predefined heart rate levels was significantly (p < 0.001) increased: 85/min: from 56.0 +/- 24.1 to 65.8 +/- 24.5 W, 90/min: from 62.0 +/- 27.3 to 71.2 +/- 26 W; 95/min: from 67.2 +/- 26.4 to 77.5 +/- 27.6 W; 100/min: from 71.1 +/- 29.6 to 80.6 +/- 28.1 W; 105/min: from 69.8 +/- 26.2 to 81.9 +/- 28.2 W and 110/min: from 73.6 +/- 28.9 to 90.4 +/- 29.4 W. The results demonstrate that physical performance in patients with CAD was improved by our novel ambulatory cardiac rehabilitation program. This improvement included an increase in maximum as well as endurance work capacity; furthermore, this increase was accompanied by a decrease in resting and exercise heart rates. The results demonstrate an absolute increase of physical performance, more importantly an increase of physical performance at defined lactate levels in the presence of unchanged heart rates mediated by the rehabilitation program. Thus, this increase was independent of motivational factors in the patients and/or the investigators during the re-exercise test. On the contrary, our data demonstrate that it is based on an improvement of aerobic endurance capacity associated with a therapeutically beneficial significant decrease of heart rate for a defined workload. The effects were independent of pharmacological influences (e.g., beta-receptor antagonists). These findings are of clinical importance with respect to reduction of myocardial oxygen consumption in patients with CAD.
Coronary Disease↗