Biomedical subjects

M Ernst

Publications and source records attributed to M Ernst.

At least 37 records · Page 2Linked to original sources

PubMed2001

Identification of a novel dendritic cell-like subset of CD64(+) / CD16(+) blood monocytes.

Human monocytes (Mo) consist of a major subset of Fcgamma-receptor I (CD64)-positive typical low accessory phagocytes, and a minor CD64(-) DC-like subset with high T cell-accessory and IFN-alpha-releasing activity. Both populations also differentially express CD16 (Fcgamma-receptor III). Double labeling with anti-CD64 and anti-CD16 mAb, as performed here, identified four different subsets. The CD64(-) subset consists of CD64(-) / 16(+) cells with high antigen-presenting cell (APC) function and macrophage-like phenotype, and a CD64(-) / 16(-) subset of less active APC but which exhibits a higher mixed lymphocyte reaction (MLR) stimulating and IFN-alpha-producing capacity, possibly resembling plasmacytoid dendritic cell type II (DC2) blood precursors. As well as the majority of CD64(+) cells that appeared CD64(+) / 16(-) and represent typical low-accessory, CD14(high) Mo, we could identify and describe a novel minor subset of CD64(+) / 16(+) cells which is unique in combining typical DC and Mo characteristics in the same cell. These are high IL-12 production, high accessory capacity for antigen- or allogen-activated lymphocytes, and high expression of HLA-DR, CD86, and CD11c.

Antigen-Presenting Cells↗

PubMed2001

Adiabatic dipolar recoupling in solid-state NMR: the DREAM scheme.

A theoretical treatment of the DREAM adiabatic homonuclear recoupling experiment is given using Floquet theory. An effective Hamiltonian is derived analytically and the time evolution of the density operator in the adiabatic limit is described. Shape cycles are proposed and characterized experimentally. Application to spin-pair filtering and as a mixing period in a 2D correlation experiment is explored and the experimental results are compared to theoretical predictions and exact numerical simulations.

Journal Article↗

PubMed2001

Membrane filtration of two sulphonamides in tertiary effluents and subsequent adsorption on activated carbon.

The adsorption behaviour of two polar organic micropollutants (N-n-butylbenzenesulphonamide and sulphmethoxazole) onto powdered activated carbon (PAC) under competitive conditions prior to and after filtration with a tight ultrafiltration membrane was examined. The sulphonamides were spiked into microfiltered tertiary municipal effluent in microg L(-1) quantities. Ultrafiltration of these effluents resulted in better adsorbability for both the micropollutants and the background organic matter in the permeates compared to the feed waters. This behaviour seems to be caused by a reduced blocking of micropores by lower concentrations of high molecular weight compounds in membrane filtrates. A combined treatment of ultrafiltration prior to adsorption can therefore reduce the carbon demand for potentially harmful micropollutants in effluents.

Adsorption↗

PubMed2001

Smoking history and nicotine effects on cognitive performance.

This study examined the effects of abstinence from smoking, of smoking history, and of nicotine administration on visual attention (2-Letter Search Task), verbal information processing (Logical Reasoning Task), and working memory (N-Back Tasks). Fourteen smokers, 15 ex-smokers, and 9 never-smokers took part. All subjects participated in a training session (when smokers had been smoking ad libitum) and in two subsequent test sessions after administration of 4 mg nicotine gum or placebo, respectively. Smokers were 12-h abstinent when they received gum. An effect of acute nicotine administration (independent of smoking history) was seen only with respect to reaction time on the 2-Letter Search Task. Working memory performance was related to smoking history (smokers performed most poorly and never-smokers best). The Logical Reasoning Task showed no effects of either acute or chronic nicotine exposure. The findings indicate that nicotine may influence focusing of attention in smokers as well as nonsmokers, and that trait-like differences in some cognitive domains, such as working memory, may be either long-term effects or etiological factors related to smoking.

Administration, Cutaneous↗

PubMed2001

Effects of triazolam on brain activity during episodic memory encoding: a PET study.

It is well documented that acute administration of the benzodiazepine hypnotic drug triazolam (Halcion) impairs episodic memory encoding. We examined the neuroanatomical substrates of this effect in healthy adult volunteers using a double-blind, within-subject design. Following oral capsule administration (0.25 mg/70 kg triazolam or placebo), regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) with 15O-H(2)O during the performance of semantic categorization, orthographic categorization, and visual fixation (resting) tasks. rCBF associated with episodic memory encoding was measured by the difference in rCBF during the orthographic categorization task relative to that during the semantic categorization task. Results in the placebo condition (n = 9) replicated those of previous nonpharmacological encoding studies (activation in the left prefrontal cortex, cerebellum, anterior cingulate cortex, temporal cortex, and occipital cortex). Relative to placebo, results in the triazolam condition (n = 6) revealed significantly impaired memory performance, and deactivation during encoding in a subset of areas shown previously to be associated with encoding (anterior cingulate cortex, cerebellum, and precuneus). Results are discussed in relation to triazolam's effects on mnemonic versus attentional processes.

Adult↗

PubMed2001

Methods for sequential resonance assignment in solid, uniformly 13C, 15N labelled peptides: quantification and application to antamanide.

The application of adiabatic polarization-transfer experiments to resonance assignment in solid, uniformly 13C-15N-labelled polypeptides is demonstrated for the cyclic decapeptide antamanide. A homonuclear correlation experiment employing the DREAM sequence for adiabatic dipolar transfer yields a complete assignment of the C(alpha) and aliphatic side-chain 13C resonances to amino acid types. The same information can be obtained from a TOBSY experiment using the recently introduced P9(12)1 TOBSY sequence, which employs the J couplings as a transfer mechanism. A comparison of the two methods is presented. Except for some aromatic phenylalanine resonances, a complete sequence-specific assignment of the 13C and 15N resonances in antamanide is achieved by a series of selective or broadband adiabatic triple-resonance experiments. Heteronuclear transfer by adiabatic-passage Hartmann-Hahn cross polarization is combined with adiabatic homonuclear transfer by the DREAM and rotational-resonance tickling sequences into two- and three-dimensional experiments. The performance of these experiments is evaluated quantitatively.

Amino Acids↗

PubMed2001

A D(V)-like phenotype is obliterated by A226P in the partial D DBS.

BACKGROUND: In D category V types, the RHD exon 5 or parts thereof are replaced by the corresponding RHCE DNA segments. In D category V types I and II, the amino acid at position 226 is alanine, which is typical of the prevalent RHD allele and is observed in all RHCE alleles encoding the antigen e. A proline at position 226 in RHCE encodes the antigen E. STUDY DESIGN AND METHODS: A blood sample of ccDEe phenotype was referred as suspected D category VI. The RHD nucleotide sequence and the D epitope pattern were determined. RESULTS: A new partial D, DBS, encoded by an RHD-RHcE(5)-RHD hybrid allele, was found. Although it differed from D(Va) type II by an A226P substitution only, it lacked epitopes epD4, epD12, epD17, epD18, and epD22 that were present in D(Va). The 5' breakpoint region was located between the deletion in RHD intron 4 and the first polymorphic nucleotide of DBS exon 5. CONCLUSION: The phenotypes of RHD alleles with gene conversions limited to exon 5 depended critically on the amino acid at position 226. If alanine was present at this position, gene conversions involving E233Q led to a D(Va)-like phenotype. If proline was present, many additional epitopes were lost, and the phenotype became reminiscent of DFR. The 5' breakpoint region is shared by 10 alleles and may represent the most active "hot spot" for gene conversions known in RH.

Adult↗

PubMed2001

[Non-tubercular mycobacterial infection of the lungs due to Mycobacterium smegmatis].

Nontuberculous mycobacteriosis due to M. smegmatis is a rarity. We report on the case of a 51 year old male HIV-seronegative patient without predisposing bronchopulmonary disease, but with a state after gastrectomy and splenectomy who developed unproductive cough, night sweat and weight loss. The chest radiograph and thoracic CT showed wide-spread bilateral patchy infiltrations. Histological examination of transbronchial biopsies revealed chronic carnificating pneumonia. A perhoracic fine-needle biopsy showed caseating epitheloid cell granulomas with acid fast bacilli. These were identified as M. smegmatis by PCR with subsequent sequencing. Acid fast bacilli could not be detected microscopically neither in sputum nor in bronchial secretions, however M. smegmatis has been repeatedly detected by culture in these materials. In neither material tubercle bacilli have been detected by nucleic acid amplification (NAT) or culture. Immunologic investigations revealed a reduced number of CD4+ lymphocytes and a reduction of interferon alpha- and -gamma-synthesis by peripheral blood mononuclear cells. Treatment with Rifabutin, Ethambutol, Clarithromycin and Ofloxacin resulted in complete clinical and roentgenological resolution.

CD4-Positive T-Lymphocytes↗

PubMed2001

[Mycotic aneurysms--A retrospective analysis].

12 patients (10 males and 2 females, average age 53 years) were operated upon in our hospital between 1994 and 1999 for mycotic aneurysms. The aneurysms were located in 7 patients in the aorto-iliac segment, 5 patients were treated for peripheral or visceral aneurysms. Two of these patients suffered from multiple aneurysms. When peripheral arteries were affected, a pulsatile tumour was felt. Most of these tumours developed in a relatively short period of time and sometimes a perivascular inflammation occurred. This was not the case when central arteries were attacked. A septic process or an infection, for example salmonella-enteritis, often preceded shortly the development of a mycotic aneurysm. In the case of an aneurysm of the aorto-iliac section we consider an in situ reconstruction with alloplastic material in combination with a perivascular debridement, lavage and omentum majus plastic as the treatment of choice. In peripheral arteries reconstruction should be performed with autologous vessels. Depending on the local findings, a perivascular debridement should also be performed in these cases. The reconstruction always should be combined with a calculated antibiotic therapy. Two of our patients died perioperatively. During follow up, 8 patients showed patent reconstructions and no signs of infection. The urgency of surgery depends on the level of inflammation and the existence of any secondary complications.

Adult↗

PubMed2001

p16(INK4a) alterations in chronic pancreatitis-indicator for high-risk lesions for pancreatic cancer.

BACKGROUND: p16(INK4a) alterations are considered to be an early event in pancreatic tumorigenesis and have been described in duct lesions adjacent to pancreatic cancers. This study evaluates whether duct lesions in chronic pancreatitis tissues of patients without pancreatic cancer also harbor genetic alterations in the p16(INK4a) tumor-suppressor gene, and thus represent high-risk precursors for pancreatic cancer. METHODS: Tissues were obtained from 20 pancreatic specimens taken from patients operated on for histologically verified chronic pancreatitis. Pancreatic intraductal neoplasias (PanIN) were identified in hematoxylin-and-eosin-stained slides. p16 protein expression was investigated immunohistochemically in all specimens. DNA from PanIN and non-PanIN tissue was analyzed genetically for p16(INK4a) mutations by single-strand conformation variation analysis and direct sequencing of the encoding region. Additionally, p16(INK4a) promoter methylation was analyzed by a methylation specific polymerase test. RESULTS: PanIN-1a lesions were identified in 10 of the 20 chronic pancreatitis specimens. Four of these 10 PanIN specimens (40%), but none of the 20 non-PanIN tissues, revealed a loss of p16 expression in immunohistochemistry. The mutational analysis of the p16(INK4a) gene showed 1 known polymorphism (c.442G > A; A148T) but no mutations. Two of the 10 specimens with PanIN revealed an inactivating hypermethylation of the p16(INK4a) promoter. CONCLUSIONS: This study shows for the first time that p16(INK4a) alterations can be observed in a considerable number of PanIN1 in chronic pancreatitis tissues not associated with pancreatic cancer. Therefore, p16(INK4a) alterations, especially promoter methylation, might indicate high-risk precursors in chronic pancreatitis that might progress to cancer.

Adult↗

PubMed2001

Behavioral and neural consequences of prenatal exposure to nicotine.

OBJECTIVE: To review evidence for the neurodevelopmental effects of in utero exposure to nicotine. Concerns about long-term cognitive and behavioral effects of prenatal exposure to nicotine arise from reports of increased rates of disruptive behavioral disorders in children whose mothers smoked during pregnancy. The relatively high rate of tobacco smoking among pregnant women (25% of all pregnancies in the U.S.) underlines the seriousness of these concerns. METHOD: This review examines the largest and most recent epidemiological and clinical studies that investigated the association of prenatal nicotine exposure with health, behavioral, and cognitive problems. Because of the numerous potential confounding variables in human research, findings from animal studies, in which environmental factors are strictly controlled, are also discussed. Finally, neural and molecular mechanisms that are likely to underlie neurodevelopmental disruptions produced by prenatal nicotine exposure are outlined. RESULTS: A dose-response relationship between maternal smoking rates and low birth weight (potentially associated with lower cognitive ability) and spontaneous abortion is consistently found, whereas long-term developmental and behavioral effects in the offspring are still controversial, perhaps because of the difficulty of separating them from other genetic and environmental factors. Despite the wide variability of experimental paradigms used in animal studies, common physical and behavioral effects of prenatal exposure to nicotine have been observed, including low birth weight, enhanced locomotor activity, and cognitive impairment. Finally, disturbances in neuronal pathfinding, abnormalities in cell proliferation and differentiation, and disruptions in the development of the cholinergic and catecholaminergic systems all have been reported in molecular animal studies of in utero exposure to nicotine. CONCLUSIONS: Prenatal exposure to nicotine may lead to dysregulation in neurodevelopment and can indicate higher risk for psychiatric problems, including substance abuse. Knowledge of prenatal exposure to nicotine should prompt child psychiatrists to closely monitor at-risk patients.

Animals↗

PubMed2001

Fas (CD95)-Fas ligand interactions are responsible for monocyte apoptosis occurring as a result of phagocytosis and killing of Staphylococcus aureus.

Human peripheral blood monocytes become apoptotic following phagocytosis of Staphylococcus aureus. In this study, we investigated the mechanisms involved in this phenomenon. Cells exposed to bacteria were examined for the surface expression of Fas and Fas ligand (FasL). The level of soluble form of FasL was also measured in the culture supernatants. As Fas-mediated apoptosis involves the activation of caspases, the activities of caspase-8 and caspase-3 were determined. Finally, the involvement of oxidative stress in apoptosis of infected monocytes was investigated. The data indicated that as a consequence of phagocytosis of S. aureus, FasL is released from the monocyte surface and induces apoptosis of phagocytic monocytes and to some extent the bystander cells. The importance of this mechanism was confirmed by demonstrating that blockage of CD95 prevents S. aureus-induced apoptosis of monocytes. Cell death occurring after phagocytosis of S. aureus involves the activation of caspase-3-like proteases, as the specific caspase-3 inhibitor suppressed apoptosis of infected cells. The generation of reactive oxygen intermediates by phagocytic monocytes by itself is not sufficient as a death signal but rather acts in up-regulating FasL shedding and possibly in modulating caspase activity.

Antioxidants↗

PubMed2001

Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leucomalacia.

AIMS: To compare the ultrasound (US) evolution and neurodevelopmental outcome of infants with localised (grade II) and extensive (grade III) cystic periventricular leucomalacia (c-PVL). METHODS: Over a nine year period, c-PVL was diagnosed in 96/3451 (2.8%) infants in two hospital cohorts. Eighteen were excluded from the study. Thirty nine infants with grade II PVL were compared with 39 infants with grade III PVL. RESULTS: The two populations were comparable for gestational age and birth weight. In infants with grade II PVL, cysts were noted to develop more often after the first month of life (53%) in contrast with grade III PVL (22%) (odds ratio (OR) 3.81 (95% confidence interval (CI) 1.19 to 12.63)). Cysts were also more often unilateral in grade II (54%) than in grade III PVL (0%) (OR indefinite; RR 3.17 (95% CI 2.16 to 4.64)). At 40 weeks postmenstrual age (PMA), cysts were no longer seen on US in 13/38 infants with grade II PVL, with ventriculomegaly being the only visible sequel in nine cases. In grade III PVL, cysts were still present in 25 of the 27 surviving infants. Nine infants with grade II PVL were free of motor sequelae at follow up compared with one infant with grade III PVL (OR 8.07 (95% CI 0.92 to 181.66)). Twenty two out of 29 children with grade II PVL who developed cerebral palsy achieved independent walking compared with 3/26 with grade III PVL (OR 75 (95% CI 11.4 to 662)). CONCLUSIONS: In the cohort studied, 50% of the infants with c-PVL had a more localised form (grade II). In grade II PVL, the cysts developed beyond the first month of life in more than half of the cases and were often no longer visible, on US, at 40 weeks PMA. In order not to miss this diagnosis, sequential US should also be performed beyond the first month of life. Mild ventriculomegaly noted at term can sometimes be due to grade II c-PVL. Cerebral palsy was slightly less common and tended to be less severe in infants with grade II PVL than in those with grade III PVL.

Age of Onset↗

PubMed2001

Absence of cytokine response to bacterial challenge in human tubuloepithelial cells.

In acute bacterial renal infections, which are most frequently caused by Escherichia coli, tubuloepithelial cells are involved with respect to bacterial adherence, invasion and cytotoxicity. In addition, cytokines expressed by tubuloepithelial cells may be relevant for the recruitment of inflammatory cells and tissue damage in bacterial interstitial nephritis. We asked which inflammatory cytokines are produced by primary human tubuloepithelial cells following in vitro exposure to E. coli and found no release of IL-6, IL-8 and TNF-alpha by tubular cells challenged by bacteria. Purified virulence factors (fimbriae, lipopolysaccharide) from E. coli were also without effects on cytokine release by tubular cells. Since lymphocytic infiltration is a characteristic feature in the chronic form of interstitial nephritis, MHC class II expression by tubular cells in response to bacterial coincubation was analyzed. Exposure to both IFN-gamma and E. coli enhanced MHC class II expression on tubuloepithelial cells. In conclusion, tubuloepithelial cells may play an active role in the local defense against bacteria, e.g. by expressing MHC class II molecules. However, in vitro inflammatory cytokines are not induced by E. coli in this cell population.

Bacterial Proteins↗

PubMed2001

Interleukin-12 as successful adjuvant in tuberculosis treatment.

Interleukin-12 (IL-12) proved to be an effective and successful adjuvant to a standard antituberculotic medication in a patient suffering from progressive clinical tuberculosis (TB). IL-12 is a potent enhancer of interferon-gamma production which is necessary for killing intracellular bacteria like mycobacteria. This patient's TB was progressive, although sensitivity to first-line antituberculotics was proven and medication was given as directly observed therapy over more than 8 months. The 3-month adjuvant therapy with IL-12 significantly and convincingly improved results. It is believed that this case, the first in the literature to describe adjuvant interleukin-12 therapy in tuberculosis, strongly encourages the study of adjuvant interleukin-12 therapy on a more systematic basis.

AIDS-Related Opportunistic Infections↗

PubMed2001

Dehydroepiandrosterone supplementation in healthy men with an age-related decline of dehydroepiandrosterone secretion.

Serum dehydroepiandrosterone declines with age. Whether this represents a harmful deficiency or an age-related adaptation is not known. Dehydroepiandrosterone replacement in adrenal insufficiency, a state of pathological loss of dehydroepiandrosterone production, improves well-being, mood, and sexuality. To determine the effects of dehydroepiandrosterone in healthy men with a physiological, age-related decline in serum dehydroepiandrosterone sulfate, we conducted a double blind cross-over study in 22 healthy male volunteers (age range, 50-69 yr) with endogenous dehydroepiandrosterone sulfate levels below 4.1 micromol/liter (1500 ng/ml) receiving 4 months of dehydroepiandrosterone (50 mg/d) and 4 months of placebo treatment in random order, with a 1-month washout period. Dehydroepiandrosterone treatment increased serum dehydroepiandrosterone and dehydroepiandrosterone sulfate to concentrations usually found in young men. Circulating androgen levels did not change; however, androgen metabolites increased, indicating enhanced peripheral androgen synthesis. At baseline, psychometric assessment revealed normal well-being and sexuality scores. After 4 months of dehydroepiandrosterone, no effect on sexuality was observed, whereas some mood scores improved slightly, but were not significantly different from scores after placebo. Compared with placebo, dehydroepiandrosterone had no effect on serum lipids, bone markers, body composition, or exercise capacity. Thus, in contrast to previous findings in adrenal insufficiency, we found no obvious benefit of 4 months of dehydroepiandrosterone supplementation in healthy men with a physiological decline of dehydroepiandrosterone production.

Affect↗

PubMed2001

Heterogeneity of human peripheral blood monocyte subsets.

In recent years the number of reports describing phenotypically and functionally distinct subsets of human blood leukocytes, and in particular of subtypes of antigen-presenting cells has continuously increased. A great diversity was described not only for dendritic cells (DC), but also for human blood monocytes (Mo) and macrophages (Mac). Similar to DC, the different types of Mo subsets could be defined by distinct phenotypes and immunoregulatory functions. The characterization of blood Mo subpopulations revealed that some of them exhibit common features with myeloid or lymphoid DC and tissue Mac, but also demonstrate the existence of novel unique cell populations. The generation of lymphoid and myeloid DC and their heterogeneity has been the subject of recent reviews. Here we focus on Mo from human peripheral blood and summarize the data (including our own) dealing with their phenotypic and functional, in particular immunoregulatory properties.

Antigen Presentation↗

PubMed2001

[Continuous measurement of baseline atmospheric carbon monoxide in western China].

In-situ custom-designed gas chromatography(GC)-HgO system was established for the continuous measurement of atmospheric CO at Waliguan Baseline Station(36 degrees 17' N, 100 degrees 54' E, 3816 m asl) in western China. The system's assembling, testing, running and calibration indicated that the chromatographic method has stable baseline and high separation efficiency, as well as reliable detection method. This system adopted high automatic operating techniques and followed strict quality control. It is up to the standard of WMO's baseline watch on global atmosphere. According to the flask sampling results of in-situ CO variation at Waliguan, CO standards in clean dry air under international comparison were used to determine the adjustable working standard curves, so as to calculate the ambient CO mixing ratios based on peak height. This system's detection limit for CO is around 1 x 10(-9) (V/V), the precision is below 0.1% and accuracy in +/- 0.05%, it can provide continuous and accurate surface CO mixing ratios in baseline areas of China.

Air↗