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Biomedical subjects

M Brauer

Publications and source records attributed to M Brauer.

At least 19 recordsLinked to original sources

[Respiratory failure and pulmonary fibrosis as a late side-effect after chemotherapy-induced by oxygen administration].

Pulmonary fibrosis (PF) may develop following successful chemotherapy for malignancy, even if such therapy is not combined with radiotherapy. Bleomycin, which is known to induce acute pneumonitis and lung fibrosis, is especially associated with chemotherapy-induced PF, and bleomycin-induced pulmonary fibrosis can occur more than five years after such therapy. Additionally, supplemental oxygen therapy can trigger the onset of pneumonitis and lethal PF in patients who have previously received bleomycin therapy. Careful assessment of lung function via spiroergometry and arterial blood gas analysis during exercise are required if the administration of supplemental oxygen is considered. Two case reports reveal the potential lethal risk of oxygen for patients who have been treated with bleomycin: (1) a patient with successfully resected and treated basal tongue carcinoma and (2) a patient in remission after being treated for non-Hodgkin lymphoma. Single and double lung transplantation is the only therapeutic option for patients with severe, oxygen-induced PF and should be included as an indication for lung transplantation. Early recognition of pulmonary diffusion abnormalities and establishing a risk profile, as well as consequent monitoring of pulmonary function, may help to avoid or at least reduce the risk of PF induced by oxygen therapy when administered to patients who have previously been given bleomycin.

Adult↗

Exposure to traffic related air pollutants: self reported traffic intensity versus GIS modelled exposure.

BACKGROUND: In epidemiological studies of the potential health effects of traffic related air pollution, self reported traffic intensity is a commonly used, but rarely validated, exposure variable. METHODS: As part of a study on the impact of Traffic Related Air Pollution on Childhood Asthma (TRAPCA), data from 2633 and 673 infants from the Dutch and the German-Munich cohorts, respectively, were available. Parents subjectively assessed traffic intensity at the home address. Objective exposures were estimated by a combination of spatial air pollution measurements and geographic information system (GIS) based modelling using an identical method for both cohorts. RESULTS: The agreement rates between self reported and GIS modelled exposure--accumulated over the three strata of self assessed traffic intensity--were 55-58% for PM(2.5), filter absorbance (PM(2.5) abs), and nitrogen dioxide in Munich and 39-40% in the Netherlands. Of the self reported low traffic exposed group, 71-73% in Munich and 45-47% in the Netherlands had low modelled exposure to these three air pollutants. Of the self assessed high exposed subgroups in Munich (15% of the total population) and the Netherlands (22% of the total population), only 22-33% and 30-32% respectively had high modelled exposure to the three air pollutants. The subjective assessments tend to overestimate the modelled estimates for PM(2.5) and NO2 in both study areas. When analysis was restricted to the portion of the Dutch cohort living in non-urban areas, the agreement rates were even lower. CONCLUSIONS: Self reported and modelled assessment of exposure to air pollutants are only weakly associated.

Adult↗

[Effect of enteral naloxone on the incidence of gastritis and esophagitis in mechanically ventilated patients].

BACKGROUND: Gastrtis and esophagitis are frequent and severe complications in intensive care patients, mainly caused by increased duodenogastral reflux. Opioids, commonly used in intensive care, are known to impair gastrointestinal (GI) motility which increases retrograd flow of gastric content. In a previous study, we showed that enteral administered naloxone reduces gastric reflux by selectively blocking GI opioid receptors. Therefore, in a subpopulation of these patients we studied the effect of enteral naloxone on the incidence of mucosal injury in opioid-treated, mechanically ventilated patients. METHODS: After IRB approval, mechanically ventilated, fentanyl-treated patients without gastrointestinal surgery or diseases were assigned to receive 8 mg naloxone or placebo four times daily via a gastric tube. Additional inclusion criteria were opioid treatment for at least three days and endoscopy of the upper GI tract. Frequency of gastritis and esophagitis was quantified according to the Savary-Miller Score, and further parameter of GI motility (frequency of propulsive medication, amount of enteral feeding) were measured. RESULTS: In four of seventeen patients of the naloxone group (24 %) and 14 of 22 patients of the placebo group (64 %; p = 0.02), esophageal or gastral mucosal injuries were detected. In the naloxone group, gastral reflux as well as need for propulsive medication were significantly lower. Volume of enteral feeding showed an increasing trend in the second half of the study. CONCLUSION: Reduction of esophagogastral mucosal injury and reduced need for procinetic medication suggests an improvement of GI motility by enteral naloxone in fentanyl-treated, mechanically ventilated patients.

Adult↗

[Association between amniotic fluid insulin in the second trimester, maternal glucose tolerance and fetal malformations].

INTRODUCTION: Maternal hyperglycemia during gestational diabetes leads to fetal hyperinsulinemia, which is associated with increased perinatal morbidity and mortality. Amniotic fluid insulin levels are therefore considered by some researchers to be ideal parameters to use in diagnosing gestational diabetes and making decisions about correct therapy. There are various recommendations about determining gestational diabetes early in pregnancy (< 24 weeks) by measuring amniotic fluid insulin. This study tests this association -- taking additional risk factors into account -- in a group of pregnant women who had genetic indications requesting for amniocentesis (AC). MATERIALS AND METHODS: All pregnant women who came to our clinic for genetically-determined amniocentesis from April 10, 1995 - Jan. 31, 2000 and who were between 12 and 24 weeks were included in our study. After a sample of amniotic fluid was taken, the laboratory performed a competitive radio-immuno-assay to determine the insulin concentration. O'Sullivan's cut-off values were used in diagnosing gestational diabetes. Since not all pregnant woman in our clinic were screened for gestational diabetes, we gathered our data retrospectively by checking all birth records; these were available in our clinic's data archive. RESULTS: A total of 483 pregnant women were included in our study. 22 (4.6 %) of them were classified as gestational diabetics. The average value for amniotic fluid insulin was 1.21 mU/L +/- 0.89. The insulin values for the entire study population exhibited a weekly increase of 0.1 mU/L from the 12th through the 24th week. The insulin concentrations for the 22 gestational diabetics were not significantly higher than those of the non-diabetics (1.05 mU/L vs. 1.0 mU/L; p = 0.34). In the 90 (th) percentile and above of the amniotic fluid insulin levels (2.2 mU/L) for the entire study population, the rate of gestational diabetics was at 11.8 % three times that of the non-diabetics, at 3.7 % (p = 0.021). Among the risk factors for gestational diabetes, an increased body mass index (BMI) value correlated significantly with increased insulin concentration (p < 0.001). The patients at and above the 90th percentile also had significantly higher BMI values (p = 0.002). In the multivariate analysis, the following influences were determined to be significant: maternal body mass index (p < 0.001) and the gestational age (p < 0,001), not the mere diagnosis of "gestational diabetes". A significant association was not found between elevated insulin values in amniotic fluid and the child's birth weight, APGAR values, pH-levels and blood glucose values. However, a significant association was found regarding fetal malformations and chromosome abnormalities. CONCLUSION: Even very low concentrations of insulin can be identified in amniotic fluid early in the pregnancy. The values increase during the course of the pregnancy. There is a positive correlation between maternal weight (BMI) and insulin levels in the amniotic fluid. Pregnant women with gestational diabetes have higher insulin levels in their amniotic fluid. The multivariant analysis shows, however, that this association can be traced to the maternal BMI and the time point during the pregnancy when the AC was performed. Malformations, especially those with a neural tube defect, are an additional cause for elevated insulin values in amniotic fluid.

Adult↗

A field comparison of four samplers for enumerating fungal aerosols I. Sampling characteristics.

UNLABELLED: This study compared the performance of four bioaerosol samplers, the Reuter Centrifugal Air Sampler, the Andersen N6 single stage, the Surface Air System 90, and the Air-o-Cell, in measurements for airborne fungal propagules collected in 75 public building sites without prior knowledge of water damage or mold problems in British Columbia, Canada. The samplers had differences in detection limits, reproducibility, and overall yield. However, high and significant correlations between samplers (indoor samples: Pearson r = 0.60-0.85, P < 0.001) suggest that relative performances between samplers were reasonably consistent. These results indicate that fungal airborne concentration data are dependent on the methods used for assessment, and introduce additional variability in exposure assessment studies. PRACTICAL IMPLICATIONS: In the absence of a standard protocol for sampling bioaerosols, the interpretation of aerosol data reported in indoor air quality studies is entirely dependent on an appreciation of the sampling characteristics of commonly used instrumentation. Although a number of comparative studies have been undertaken in the laboratory, only a few studies have made reported comparison data under field conditions. This study compared three culturable sampling devices, the Andersen N6, SAS 90, and RCS, and one particulate sampling device, the Air-o-Cell, in offices and public areas in a variety of buildings, under conditions of forced air or natural ventilation. The concentrations of fungal aerosols collected during simultaneous sample collection were highly correlated, yet varied by orders of magnitude. The performance of these devices must be carefully considered before a standard protocol can be promulgated.

Air Microbiology↗

A field comparison of four fungal aerosol sampling instruments: inter-sampler calibrations and caveats.

UNLABELLED: Four bioaerosol samplers (Reuter Centrifugal, Andersen N6 Single Stage, Surface Air System Super 90, and Air-o-Cell) were used to take c. 300 side-by-side measurements at 75 public building sites. Regression models were developed to examine the relationships between each method pair. The models demonstrate that measurements from these instruments are not directly comparable, requiring inter-instrument calibration. Sampling location (indoor vs. outdoor) was a confounder in all the pairwise comparisons between samplers. In addition, the slopes of the relationships between all method pairs except one differed in indoor vs. outdoor locations. These results emphasize that direct comparisons between methods should not be undergone without prior calibration. Where measurement circumstances are similar to those of this study, the regression models might serve as a basis to convert measurements made with one instrument to those made with another. However, the robustness and generalizability of the models in different measurement settings needs to be assessed. PRACTICAL IMPLICATIONS: Many different bioaerosol sampling devices are in common use for indoor air quality studies. If data from research studies are to be compared, an approximation of the relationships between the equipment would be useful. A comparison of three culturable sampling devices (Andersen N6, SAS 90, RCS) and one particulate sampling device (Air-o-Cell) collecting simultaneous samples under field conditions showed high linear correlations between methods. However, while direct comparisons between sampling data were not possible, the regression models reported here explained 60-85% of the variance in fungal concentrations, and underscored the importance of the effect of environment on measurement.

Air Microbiology↗

Point-of-sale glass bottle recycling: indoor airborne exposures and symptoms among employees.

AIMS: To assess the impact of newly introduced point-of-sale glass bottle recycling on indoor air quality and employee health. METHODS: Airborne exposures and both chronic and acute respiratory and somatic symptoms were surveyed among 226 employees at 36 randomly selected liquor stores with bottle recycling and in-house glass breaking. Each store was visited twice; between visits glass breaking was discontinued for one month in half the stores (selected at random), although bottles were still collected and stored on site. Rates of chronic symptoms were compared to an external, unexposed control population. RESULTS: Geometric mean exposure levels were 0.18 mg/m3 for inhalable particulate matter and 3.6 EU/m3 for endotoxin (270 personal samples); 1064 CFU/m3 for viable fungi (648 area samples). Fungal levels were associated with visibly mouldy bottles being broken, outdoor fungal counts, and uncovered glass bins. Exposures were not altered by the intervention of shutting down glass breaking machinery. Compared to controls, employees reported more work related chronic chest tightness and chronic nasal symptoms. Acute chest symptoms were associated with breaking visibly mouldy bottles, but not with measured fungal counts. Inhalable particulate matter levels >0.2 mg/m3 were associated with acute upper airway irritation. Somatic symptoms were associated with measures of psychosocial job strain. CONCLUSION: Results suggest that this type of recycling programme may generate fungal exposures sufficient to elicit upper airway and chest symptoms.

Acute Disease↗

Wood smoke exposure and lung adenocarcinoma in non-smoking Mexican women.

OBJECTIVE: To determine the association between long-term exposure to wood smoke from cooking and lung adenocarcinoma in non-smoking Mexican women. METHODS: We reviewed records of hospitalized patients at a chest referral hospital in Mexico City and identified 113 histologically proven lung adenocarcinoma cases in non-smoking women. Four control groups of non-smoking women were also selected: 99 patients with pulmonary tuberculosis (PTB), 110 with interstitial lung disease (ILD), 64 with miscellaneous pulmonary conditions (MISC), and the three control groups combined (COMB) (n = 273). RESULTS: Exposure was assessed on the basis of questionnaire responses at the time of hospital admission. Exposure to wood smoke for more than 50 years, but not for shorter periods, was associated with lung cancer after adjusting for age, education, socio-economic status and environmental tobacco smoke (ETS) exposure. Adjusted odds ratios from the multivariable logistic regression models were 1.4 (95%CI 0.6-2.0) for cases vs. TB controls, 1.9 (95%CI 0.9-4.0) for cases vs. ILD controls, 2.6 (95%CI 1.0-6.3) for cases vs. MISC controls and 1.9 (95%CI 1.1-3.5) for cases vs. COMB controls. CONCLUSION: These findings suggest that long-term exposure to wood smoke from cooking may contribute to the development of lung cancer.

Adenocarcinoma↗

Secular trends in neonatal macrosomia in Berlin: influences of potential determinants.

To investigate the trend in the prevalence of neonatal macrosomia and to evaluate the influences of potential determinants, key features of 206 308 hospital deliveries (97% of all) in Berlin in the years 1993-99, collected by the Berlin Medical Board, were analysed using SPSS 10.0. After exclusion of multiple births and preterm infants, there was a significant increase over 7 years (P < 0.01) in the prevalence of birthweights >or= 4000 g, maternal age >or= 30 years, height of >or= 165 cm, prepregnancy BMI (body mass index) >or= 26 kg/m2 and pregnancy weight gain> 16 kg, but no substantial trend in the prevalence of recognised diabetes or maternal smoking. The adjusted model (OR [95% CI]) for delivering a newborn >or= 4000 g was statistically significant for post-term delivery (2.56 [2.39, 2.75]), women aged >or= 30 years (1.06 [1.02-1.11]), >or= 165 cm tall (1.94 [1.87,2.01]), multiparae (1.98 [1.91, 2.05]), not smoking in pregnancy (2.03 [1.93, 2.14]), prepregnancy BMI >or= 26 compared with < 20 (4.01 [3.77, 4.26]), pregnancy weight gain >or= 16 kg compared with < 10 kg (3.37.[3.22, 3.53]) and for recognised diabetes (1.85.[1.69, 2.04]). It is speculated that this increase in the prevalence of neonatal macrosomia may contribute to the secular trend of overweight and obesity under affluent living conditions.

Berlin↗

Amniotic fluid insulin levels and fetal abdominal circumference at time of amniocentesis in pregnancies with diabetes.

AIMS: Fetal hyperinsulinism is a strong predictor for excessive growth and fetopathy in pregnancies complicated by diabetes. We examined (i). the relationship between measurements of amniotic fluid insulin (AF insulin) and fetal abdominal circumference (AC) at the time of amniocentesis, and (ii). whether there is a threshold for fetal AC percentiles which can identify low vs. high-risk levels of AF insulin without performing an amniocentesis. METHODS: In a retrospective study, AF insulin from 121 pregnant diabetic women (32 pregestational; 89 gestational) was measured during the 3rd trimester as part of a diabetes management protocol. AC measurements were transformed into a continuous variable of percentile growth for gestational age (Hadlock). Division of the cohort according to deciles or quartiles of AC percentiles was performed to identify a threshold AC with a significant increase in elevated AF insulin, previously defined as AF insulin >or= 7 microU/ml. A receiver operator characteristic (ROC) curve was created and the negative predictive value (NPV) of the determined threshold was calculated. RESULTS: AF insulin levels were significantly correlated with the AC percentiles (r = 0.3, P = 0.0005) by linear regression. No AC threshold could reliably identify a moderate elevated AF insulin >or= 7 microU/ml (NPV 77.2%), but an AC threshold >or= 75th percentile could identify with fetal hyperinsulinism with an AF insulin >or= 16 microU/ml. All 10 cases of AF insulin >or= 16 microU/ml were identified with a NPV of 100% (74/74). CONCLUSIONS: Our data indicate that an AC >or= 75th percentile determined by a 3rd trimester ultrasound examination may discriminate between pregnancies at low vs. high risk for AF insulin >or= 16 microU/ml. This AF insulin concentration corresponds to a level of hyperinsulinism reported to be associated with considerable neonatal and long term morbidity.

Adult↗

Exposure misclassification and threshold concentrations in time series analyses of air pollution health effects.

Linear, no-threshold relationships are typically reported for time series studies of air pollution and mortality. Since regulatory standards and economic valuations typically assume some threshold level, we evaluated the fundamental question of the impact of exposure misclassification on the persistence of underlying personal-level thresholds when personal data are aggregated to the population level in the assessment of exposure-response relationships. As an example, we measured personal exposures to two particle metrics, PM2.5 and sulfate (SO4(2-)), for a sample of lung disease patients and compared these with exposures estimated from ambient measurements Previous work has shown that ambient:personal correlations for PM2.5 are much lower than for SO4(2-), suggesting that ambient PM2.5 measurements misclassify exposures to PM2.5. We then developed a method by which the measured:estimated exposure relationships for these patients were used to simulate personal exposures for a larger population and then to estimate individual-level mortality risks under different threshold assumptions. These individual risks were combined to obtain the population risk of death, thereby exhibiting the prominence (and the value) of the threshold in the relationship between risk and estimated exposure. Our results indicated that for poorly classified exposures (PM2.5 in this example) population-level thresholds were apparent at lower ambient concentrations than specified common personal thresholds, while for well-classified exposures (e.g., SO4(2-)), the apparent thresholds were similar to these underlying personal thresholds. These results demonstrate that surrogate metrics that are not highly correlated with personal exposures obscure the presence of thresholds in epidemiological studies of larger populations, while exposure indicators that are highly correlated with personal exposures can accurately reflect underlying personal thresholds.

Air Pollution↗

Increased F2 isoprostanes in the acute chest syndrome of sickle cell disease as a marker of oxidative stress.

Nitric oxide metabolism is altered during the acute chest syndrome of sickle cell disease. In the presence of oxygen and oxygen-related molecules, nitric oxide can preferentially form the powerful oxidants nitrite, nitrate, and peroxynitrite. We hypothesized that increased oxidative stress may contribute to the pathogenesis of acute chest syndrome and measured F2 isoprostanes, a nonenzymatically generated molecule resulting from free radical catalyzed lipid peroxidation in patients with sickle cell disease in various stages of disease. Plasma samples were obtained from nineteen patients with sickle cell disease during acute chest syndrome (pre- and postexchange transfusion), vasoocclusive crisis, and/or at baseline; 12 normal volunteers served as controls. F2 isoprostanes were measured by gas chromatography/mass spectrophotometry. There was a 9-fold increase in F2 isoprostanes in patients with acute chest syndrome as compared with normal volunteers. There was approximately a 50-60% decline in isoprostanes postexchange transfusion to a level similar to that of patients with sickle cell disease at baseline. There was no difference in isoprostanes between vasoocclusive crisis and patients with sickle cell disease at baseline. Increased oxidative stress, measured by generation of F2 isoprostanes, occurs during acute chest syndrome and may have an important role in the pathogenesis of this disease process.

Acute Disease↗

The communication of social stereotypes: the effects of group discussion and information distribution on stereotypic appraisals.

Stereotypes are fundamentally social constructs, formulated and modified through discussion and interaction with others. The present studies examined the impact of group discussion on stereotypes. In both studies, groups of participants discussed their impressions about a hypothetical target group after having read behaviors performed by target group members. These behaviors included both stereotypic and counterstereotypic examples, and the distribution of these behaviors varied across discussion group members. In some groups only 1 member knew of the counterstereotypic behaviors; in other groups this information was distributed across all group members. In general, discussion led to a polarization of the target group stereotypes, but this effect was lessened when the counterstereotypic behaviors were concentrated in 1 group member. In this case, these counterstereotypic behaviors were discussed more and retained better.

Adult↗

Familial recurrence of spontaneous fetal intracranial hemorrhage: ultrasonographic diagnosis and postnatal magnetic resonance imaging (MRI).

We report fetal intracranial hemorrhage in term siblings from consanguineous parents, spontaneously occurring in the third trimester of pregnancy. Prenatal ultrasound in one case and postnatal MRI in both demonstrated massive parenchymal bleeding involving large areas of the cerebral cortex, white and gray matter. Vasculopathies, vascular malformations, coagulopathies, thrombocytopenia and relevant metabolic disorders could be excluded.

Brain↗

Air pollution and retained particles in the lung.

Epidemiologic evidence associates particulate air pollution with cardiopulmonary morbidity and mortality. The biological mechanisms underlying these associations and the relationship between ambient levels and retained particles in the lung remain uncertain. We examined the parenchymal particle content of 11 autopsy lungs from never-smoking female residents of Mexico City, a region with high ambient particle levels [3-year mean PM(10) (particulate matter < or = 10 microm in aerodynamic diameter)= 66 microg/m(3)], and 11 control residents of Vancouver, British Columbia, Canada, a region with relatively low levels (3-year mean PM(10) = 14 microg/m(3). Autopsy lungs were dissolved in bleach and particles were identified and counted by analytical electron microscopy. Total particle concentrations in the Mexico City lungs were significantly higher [geometric mean = 2,055 (geometric SD = 3.9) x 10(6) particles/g dry lung vs. 279 (1.8) x 10(6) particles/g dry lung] than in lungs from Vancouver residents. Lungs from Mexico City contained numerous chain-aggregated masses of ultrafine carbonaceous spheres, some of which contained sulfur, and aggregates of ultrafine aluminum silicate. These aggregates made up an average of 25% of the total particles by count in the lungs from Mexico City, but were only rarely seen in lungs from Vancouver. These observations indicate for the first time that residence in a region with high levels of ambient particles results in pulmonary retention of large quantities of fine and ultrafine particle aggregates, some of which appear to be combustion products.

Aged↗

Air quality in postunification Erfurt, East Germany: associating changes in pollutant concentrations with changes in emissions.

The unification of East and West Germany in 1990 resulted in sharp decreases in emissions of major air pollutants. This change in air quality has provided an opportunity for a natural experiment to evaluate the health impacts of air pollution. We evaluated airborne particle size distribution and gaseous co-pollutant data collected in Erfurt, Germany, throughout the 1990s and assessed the extent to which the observed changes are associated with changes in the two major emission sources: coal burning for power production and residential heating, and motor vehicles. Continuous data for sulfur dioxide, total suspended particulates (TSP), nitric oxide, carbon monoxide, and meteorologic parameters were available for 1990-1999, and size-selective particle number and mass concentration measurements were made during winters of 1991 and 1998. We used hourly profiles of pollutants and linear regression analyses, stratified by year, weekday/weekend, and hour, using NO and SO(2) as markers of traffic- and heating-related combustion sources, respectively, to study the patterns of various particle size fractions. Supplementary data on traffic and heating-related sources were gathered to support hypotheses linking these sources with observed changes in ambient air pollution levels. Substantially decreased (19-91%) concentrations were observed for all pollutants, with the exception of particles in the 0.01-0.03 microm size range (representing the smallest ultrafine particles that were measured). The number concentration for these particles increased by 115% between 1991 and 1998. The ratio of these ultrafine particles to TSP also increased by more than 500%, indicating a dramatic change in the size distribution of airborne particles. Analysis of hourly concentration patterns indicated that in 1991, concentrations of SO(2) and larger particle sizes were related to residential heating with coal. These peaks were no longer evident in 1998 due to decreases in coal consumption and consequent decreased emissions of SO(2) and larger particles. These decreases in coal combustion and the decreased concentrations of SO(2) and particles of larger size classes may have led to decreased particle scavenging and may be partially responsible for the observed increases in ultrafine particles. Traffic-related changes, such as increased numbers of trucks and increased use of diesel vehicles in Erfurt, were also associated with increased number concentrations of ultrafine particles. Morning particle peaks of all sizes were associated with NO and CO (markers for traffic) in both the 1991 and 1998 periods. There were significant differences in the ultrafine particle levels for morning hours between 1991 and 1998, suggesting that traffic was the cause of this increase.

Air Pollutants↗

Fixation of heterocumulenes. 1. A theoretical study on the irreversible reaction of CO(2) with a 2-lithio-1,3-dithiane

The mechanism of electrophilic addition of CO(2) to 2-lithio-2-phenyl-1, 3-dithiane-tetrahydrofuran-tetramethylethylendiamine, a Corey-Seebach "umpolungs" reagent for nucleophilic acylation, was investigated at the B3YLP/6-311+G//HF/6-31+G level of theory with specific solvation effects being included in the study. The overall reaction is exothermic by 18.8 kcal/mol and proceeds via precomplexation of the CO(2) (necessary for activation). The reaction barrier is calculated to be 11.9 kcal/mol (relative to the precomplex 2a) and represents a lower boundary for the activation energy. The reaction barrier is shown to originate from specific solvent effects. A detailed survey of the electronic effects governing the reaction is given. The ab initio results were then compared with semiempirical PM3 calculations, which were extended to include the heterocumulenes COS and CS(2). As expected, the reduced electrophilicity of these molecules leads to a higher activation barrier by retention of the same reaction mechanism.

Journal Article↗

Assessing lymphocyte functions in neonates for revealing abnormal prenatal development of the immune system.

Because it is difficult to assess prenatally induced functional deficits of the human immune system, we developed an ex vivo method for differentiation and maturation of peripheral lymphocytes of newborn, preferentially using umbilical cord blood. Many lymphocyte subsets of newborn infants are "immature" with respect to defined surface receptors. An example of such an immaturity is the almost complete lack of "memory"-type helper T cells (also designated as helper-inducer cells), characterized by expressing the surface receptors: CD4(+)CD45R0(+)CD45RA(-)CD29(high). On the other hand, umbilical cord blood contains many "naive"-type helper T cells (often designated as suppressor-inducer cells), with the receptors: CD4(+)CD45R0(-)CD45RA(+)CD29(low). In this report, we demonstrate that the immature helper lymphocyte population of umbilical cord blood is capable of differentiating to mature cells following stimulation with pokeweed mitogen (PWM) and other stimulants ex vivo. The obtained receptor pattern is virtually indistinguishable from the one observed on the mature cells of adults. Such an extensive differentiation can only be achieved with cells of newborns. As intermediates during differentiation in culture, CD45R0(+)CD45RA(+) cells may be observed which are rather rare in vivo. Additionally, the appearance of several activation (CD25, CD69, HLA-DR) and adhesion (CD11a, CD11b, CD11c, CD18, CD49b, CD49d, CD54) receptors on CD4 cells were analyzed. With this model system evidence for the sequence of events during differentiation and maturation may be obtained. This ex vivo-model is capable of studying the capacity of lymphocytes for differentiation and activation processes barely accessible in vivo. It may also be expected to represent an interesting tool for measuring the capacity for maturation and differentiation in the blood of children of different ages under normal and pathological conditions ex vivo. In addition, substance-induced effects may be studied in vitro with this approach on immature cells from newborn, or infants during culturing. Teratogenesis Carcinog. Mutagen. 20:171-193, 2000.

Antigens, CD20↗