Severe respiratory distress syndrome unresponsive to intensive care treatment--diagnostic and therapeutic considerations.

Respiratory Distress Syndrome (RDS) is a common complication in preterm neonates. If RDS is not responding to conventional treatment modalities (surfactant therapy, ventilatory support, etc.), an underlying pathology (pulmonary lymphangiectasia, capillary alveolar dysplasia, alpha-1 antitrypsin deficiency, etc.) other then prematurity should be taken into consideration.Here, we report on a preterm neonate with the unusual simultaneous occurrence of pulmonary and systemic lymphangiectasia and homozygous alpha-1 antitrypsin deficiency who developed severe RDS that was refractory to conventional treatment. The diagnostic and therapeutic approach in this patient is presented.

Congenital disorders of glycosylation type Ia as a cause of mirror syndrome.

Mirror syndrome (that is fetal hydrops with subsequent edema in the pregnant woman) is a rare condition. Early diagnosis is warranted, as maternal and fetal morbidity and mortality is increased if not diagnosed and treated properly. In most cases, the underlying cause remains unclear. We report a woman who has had two pregnancies complicated by mirror syndrome. Congenital disorder of glycosylation type Ia (CDG-Ia) was identified as the underlying fetal disease in both cases.

Fluorescent microsphere method is suitable for chronic bone blood flow measurement: a long-term study after meniscectomy in rabbits.

The fluorescent microsphere (FM) method is considered a reliable technique to determine regional bone blood flow (RBBF) in acute experiments. In this study, we verified the accuracy and validity of this technique for measurement of RBBF in a long-term experiment and examined RBBF after meniscectomy. Twenty-four anesthetized female New Zealand white rabbits (3 groups, each n = 8) received consecutive left ventricular injections of FM in defined time intervals after meniscectomy: group 1 from preoperation to 3 wk postoperation; group 2 from 3 to 7 wk postoperation; and group 3 from 7 to 11 wk postoperation. To test the precision of the FM method, two FM species were injected simultaneously at the first and last measurement. After the experiment, humeri, femora, tibiae, and reference organs (kidney, lung, brain) were removed and dissected according to standardized protocols. Fluorescence was determined in each reference blood and tissue sample, and blood flow values were calculated. Blood flow in kidney, lung, and brain revealed no significant difference between right and left side and remained unchanged during the observation period, thus excluding errors due to shunting and dislodging of spheres in our experiments. Comparison of relative bone blood flow values obtained by simultaneously injected FM showed an excellent correlation at the first and last injection, indicating valid RBBF measurements in long-term experiments. We found a significant increase in RBBF 3 wk after meniscectomy in the right tibial condyles compared with the nonoperated left side. Similar changes were found in the femoral condyles. RBBF in other regions of tibia, femur, and humerus revealed no significant differences between right- and left-sided bone samples of the same region. Our results demonstrate that the FM method is valid for measuring RBBF in long-term experiments. In addition, we were able to demonstrate that meniscectomy leads to an increase in RBBF in the tibial condyles at a very early stage. This increase might be caused by stress-induced alterations of the subchondral bone.

Anisotropy in judging the absolute direction of motion.

The angular dependence of precision measurements is well established as the oblique effect in motion perception. Recently, it has been shown that the visual system also exhibits anisotropic behaviour with respect to accuracy of the absolute direction of motion of random dot fields. This study aimed to investigate whether this angular dependent, directional bias is a general phenomenon of motion perception. Our results demonstrate, for single translating tilted lines viewed foveally, an extraordinary illusion with perceptual deviations of up to 35 degrees from veridical. Not only is the magnitude of these deviations substantially larger than that for random dots, but the general pattern of the illusion is also different from that found for dot fields. Significant differences in the bias, as a function of line tilt and line length, suggest that the illusion does not result from fixed inaccuracies of the visual system in the computation of direction of motion. Potential sources for these large biases are motion integration mechanisms. These were also found to be anisotropic. The anisotropic nature and the surprisingly large magnitude of the effect make it a necessary consideration in analyses of motion experiments and in modelling studies.

Effects of angiotensin II on adipose conversion and expression of genes of the renin-angiotensin system in human preadipocytes.

A complete functional renin-angiotensin system exists in human adipose tissue, but its regulation and the effects of angiotensin II on cells from this tissue are only beginning to be understood. In this study, we examined the effects of angiotensin II on changes in lipid accumulation, specific glycerol-3-phosphate dehydrogenase activity, and the expression of five genes of the renin-angiotensin system during the adipose conversion of human primary cultured preadipocytes. Angiotensin II leads to a distinct reduction in insulin-induced differentiation, but only has a marginal effect on the adipose conversion of cells stimulated with insulin, cortisol, and isobutyl methyl xanthine. During differentiation, angiotensinogen mRNA levels rise, renin mRNA levels decline, whereas renin-binding protein and angiotensin-converting enzyme levels are unaffected. Angiotensin II downregulates angiotensinogen and renin gene expression, but it does not affect renin-binding protein and angiotensin-converting enzyme levels. Angiotensin II thus prevents the development of adipocytes in contact with high insulin levels, while not inhibiting differentiation, which is further stimulated. Therefore, angiotensin II could be a protective factor against uncontrolled expansion of adipose tissue. Further studies are needed to find out whether the effects of angiotensin II on the renin-angiotensin system are direct feedback loops or secondary to changes in the differentiation program.

An inverse oblique effect in human vision.

In the classic oblique effect contrast detection thresholds, orientation discrimination thresholds, and other psychophysical measures are found to be smallest for vertical or horizontal stimuli and significantly higher for stimuli near the +/-45 degrees obliques. Here we report a novel inverse oblique effect in which thresholds for detecting translational structure in random dot patterns [Glass, L. (1969). Moiré effect from random dots. Nature, 223, 578-580] are lowest for obliquely oriented structure and higher for either horizontal or vertical structure. Area summation experiments provide evidence that this results from larger pooling areas for oblique orientations in these patterns. The results can be explained quantitatively by a model for complex cells in which the final filtering stage in a filter-rectify-filter sequence is of significantly larger area for oblique orientations.

Detecting shape deformation of moving patterns.

This study measured thresholds for the discrimination of rigidly and nonridgidly rotating patterns in two dimensions. The stimuli employed were closed contours created by the sum of two 'radial frequency' components and sensitivity to their deformation was measured as a function of the difference in the angular velocities of the components. Results show that thresholds do not depend on the specific shape of the pattern. To quantify the influence of local computations versus global pooling, thresholds were measured with parts of the pattern covered by (invisible) pie-shaped apertures. One finds thresholds are not simply a function of the total amount of pattern visible but exhibit a dependence on the number of apertures. Moreover, sensitivity to deformation could neither be fully explained on the basis of local computations nor by linear global summation. A simultaneous masking paradigm was employed to elucidate potential mechanisms involved in the computation of deformation. While 1D masks (horizontal gratings and translating random dots) only marginally elevate thresholds, rotating and expanding motion significantly impairs sensitivity. This indicates that detectors tuned to radial and circular motion are involved in the computation of shape deformation.

CDNA microarray gene expression analysis of B-cell chronic lymphocytic leukemia proposes potential new prognostic markers involved in lymphocyte trafficking.

Human cancer is characterized by complex molecular perturbations leading to variable clinical behavior, often even in single-disease entities. We performed a feasibility study systematically comparing large-scale gene expression profiles with clinical features in human B-cell chronic lymphocytic leukemia (B-CLL). cDNA microarrays were employed to determine the expression levels of 1,024 selected genes in 54 peripheral blood lymphocyte samples obtained from patients with B-CLL. Statistical analyses were applied to correlate the expression profiles with a number of clinical parameters including patient survival and disease staging. We were able to identify genes whose expression levels significantly correlated with patient survival and/or with clinical staging. Most of these genes code either for cell adhesion molecules (L-selectin, integrin-beta2) or for factors inducing cell adhesion molecules (IL-1beta, IL-8, EGR1), suggesting that prognosis of this disease may be related to a defect in lymphocyte trafficking. This report demonstrates the feasibility of a systematic integration of large-scale gene expression profiles with clinical data as a general approach for dissecting human diseases.

Biomass steam gasification--an extensive parametric modeling study.

A model for steam gasification of biomass was developed by applying thermodynamic equilibrium calculations. With this model, the simulation of a decentralized combined heat and power station based on a dual fluidized-bed steam gasifier was carried out. Fuel composition (ultimate analysis and moisture content) and the operating parameters, temperature and amount of gasification agent, were varied over a wide range. Their influences on amount, composition, and heating value of product gas and process efficiencies were evaluated. It was shown that the accuracy of an equilibrium model for the gas composition is sufficient for thermodynamic considerations. Net electric efficiency of about 20% can be expected with a rather simple process. Sensitivity analysis showed that gasification temperature and fuel oxygen content were the most significant parameters determining the chemical efficiency of the gasification.

Potential pathways and exposure to explain the human body burden of organochlorine compounds: a multivariate statistical analysis of human monitoring in Würzburg, Germany.

By means of multivariate statistical analysis of human monitoring in the vicinity of Würzburg it is examined whether the organochlorine levels in blood data of 309 persons can in part be explained by pollution from outdoor and/or indoor air. Although diet is the main source for intake this study concentrated on the remaining sources. Using 12 personal and geographical variables, which describe some aspects or components of indoor or outdoor exposure, the quantities of the different pathways for the intake are calculated and shown. Besides the impact of the indoor air, which can be pointed out for intake at the workplace for some PCB-congeners, also the hypothesis of the existence of an intake from outdoor air for some organochlorine compounds cannot be rejected. Here, the origin is the spatial variation of the pollution, which can be directly traced back to micro-climatic processes, local relief conditions, and the functional set-up of the town.

Conversion of dehydroepiandrosterone to downstream steroid hormones in macrophages.

Dehydroepiandrosterone (DHEA) is a ubiquitous adrenal hormone with immunomodulatory effects such as inhibition of the production of monokines. Whether DHEA itself or the downstream steroids are the immunomodulatory effector hormones in target cells is not known. In this study, we investigated the conversion of DHEA to downstream steroid hormones in target macrophages. Within 1 day of culture with radiolabeled DHEA, monocyte-derived macrophages converted DHEA to significant amounts of Delta5-derivatives such as 16OH-DHEA, 3beta, 17beta-androstenediol (A'diol), and 3beta,16alpha, 17beta-androstenetriol (A'triol). However, the production of Delta4-steroids (androstenedione (A'dione), testosterone (T), and 16OH-T) and estrogens (estrone, estradiol, and estriol) was relatively low. Further cultivation of macrophages for 5 days with radiolabeled DHEA resulted in a significant (P<0.05) increase of the molar amounts of A'triol (P=0.012), 16OH-T (P=0.008), and estriol (P=0.003). In contrast to monocyte-derived macrophages, monocytes did not express aromatase mRNA, which was demonstrated by RT-PCR (P<0.01). Furthermore, DHEA in macrophages significantly inhibited one of the downstream converting enzymes, the aromatase, which was not demonstrated in the presence of the typical macrophage activator, lipopolysaccharide (LPS) (P<0.01). In conclusion, conversion of DHEA to physiologically relevant amounts of Delta5- and Delta4-steroids and estrogens was demonstrated in monocyte-derived macrophages. The conversion depends on maturation of monocytes and local factors such as the presence of LPS. The conversion of DHEA leads to an increase of downstream effector hormones in target macrophages which may be an important factor for local immunomodulation.

Production of angiotensin II receptors type one (AT1) and type two (AT2) during the differentiation of 3T3-L1 preadipocytes.

During their development from progenitor cells, adipocytes not only express enzymatic activities necessary for the storage of triglycerides, but also achieve the capability to produce a number of endocrine factors such as leptin, tumor necrosis factor alpha (TNFalpha), complement factors, adiponectin/adipoQ, plasminogen activator inhibitor-1 (PAI-1), angiotensin II and others. Angiotensin II is produced from angiotensinogen by the proteolytic action of renin and angiotensin-converting enzyme; and several data point to the existence of a complete local renin-angiotensin system in adipose tissue, including angiotensin II receptors. In this study, we directly monitored the production of angiotensin II type one receptor (AT1) and angiotensin II type two receptor (AT2) proteins during the adipose conversion of murine 3T3-L1 preadipocytes by immunodetection with specific antibodies. AT1 receptors could be detected throughout the whole differentiation period. The strong AT2 signal in preadipocytes however was completely lost during the course of differentiation, which suggests that expression of AT2 receptors is inversely correlated to the adipose conversion program.

Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-alpha on intracellular amount and secretion of apM1 in differentiating primary human preadipocytes.

3T3-L1-adipocytes produce the adipocyte complement related protein of 30 kD (Acrp30), which is also designated as AdipoQ. In order to study the expression and secretion of the human homologue of this protein, apM1 (adipose Most abundant gene transcript 1, also named gelatin-binding protein of 28 kD [GBP28] or adiponectin), a polyclonal antibody was produced. Both expression and secretion can be detected beginning with day 4 after induction of differentiation. The amount of expressed apM1 correlates with the specific activity of the differentiation marker glycerol-3-phosphate dehydrogenase. Secretion of apM1 is increased by the addition of ionomycin. Both the nonhydrolysable dibutyryl-cycloAMP and tumour necrosis factor alpha reduce the expression and secretion of apM1.

[Complicated malaria tropica in an infant]. / Komplizierte Malaria tropica bei einem Säugling.

We report on a five month-old infant from Cameroon, who was admitted because of febrile gastroenteritis after living in Germany for two weeks. Since the patient was somnolent, had a parasitaemia of Plasmodium falciparum of 230,000/microliter, a haemoglobin concentration of 5.3 g/dl and a thrombocytopenia, a complicated falciparum malaria was diagnosed. Treatment was started immediately with intravenous 20 mg quinine/kg bw as a loading dose, followed by 10 mg/kg bw every 12 hours, combined with intravenous clindamycin 10 mg/kg bw bd. Red blood cells were transfused once. The parasitaemia dropped to 2000 trophozoites/microliter within 48 hours. No asexual stages were detectable from the third day of treatment on. Weekly controls for the following four weeks remained negative. The mortality rate of complicated malaria is 50% in the first year of life, which can be reduced by early treatment. We present this case to draw attention to therapeutic options in infants.

Computing feature motion without feature detectors: a model for terminator motion without end-stopped cells.

Pointlike object features such as line-endings, have a privileged position in the computation of the veridical direction of object motion. Experiments confirm that the human visual system relies heavily on such features if they are present. It has been proposed that units such as end-stopped cells might be necessary for the computation of feature motion instead of the simple cells used in plaid motion models. Conventional plaid motion models have not been applied to feature motion. We present here a model, based on ordinary simple cells, using two parallel pathways (Fourier and non-Fourier) for the computation of the direction of two dimensional motion. Although similar in structure to popular models of plaid motion, our model includes a novel scheme for contrast normalisation and incorporates spatial pooling at the level of MT cells. The model predictions are consistent with psychophysical results for plaids. Furthermore, it computes directions within 5 degrees of the physical motion of line-endings. It is shown that the non-Fourier signal is necessary for the computation of veridical motion.

Evidence for a local renin angiotensin system in primary cultured human preadipocytes.

OBJECTIVE: To investigate whether human preadipocytes possess a complete functional renin angiotensin system. MEASUREMENTS: Gene expression of angiotensinogen, renin, renin binding protein, angiotensin converting enzyme (ACE) and angiotensin II (ang II) receptor type 1 in human preadipocytes; ACE protein and ang II production of human adipose tissue stromal cells differentiated or not in primary culture. RESULTS: All genes mentioned above were found to be expressed in human preadipocytes. ACE was translated into protein as detected by western blot. Ang II was secreted both by undifferentiated preadipocytes and immature adipocytes, and its production was significantly elevated in differentiated cells. CONCLUSIONS: Preadipocytes from human adipose tissue express a functional renin angiotensin system (RAS).

The role of PDGF-dependent suppression of apoptosis in differentiating 3T3-L1 preadipocytes.

In a chemically defined serum-free culture system, platelet-derived growth factor (PDGF) as the only externally applied growth factor, in concert with corticosterone, 3-isobutyl-1-methylxanthine (IBMX) and low insulin (1nM), stimulates adipose conversion of 3T3-L1 preadipocytes. Omission of PDGF during the induction period results in loss of differentiation competence and apoptotic cell death. Induction of apoptosis is shown to be clearly mediated by PDGF withdrawal, since neither corticosterone nor IBMX affect the apoptotic behaviour of 3T3-L1 cells. Cell viability in the absence of the survival factor PDGF could be achieved by application of high insulin (1 microM) or ectopical expression of the anti-apoptotic proto-oncogene Bcl-2. However, PDGF-independent suppression of cell death does not trigger adipose conversion in the presence of corticosterone and IBMX. Therefore, we conclude that suppression of apoptosis per se is not permissive for differentiation of 3T3-L1 preadipocytes and PDGF might exert some additional differentiation-promoting effect(s).

Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts.

In fibroblasts derived from human adipose tissue, aromatase induction is observed after exposure to 1 microM cortisol in the presence of serum or platelet-derived growth factor (PDGF). Progesterone suppresses this induction in a dose-dependent manner, 10 microM resulting in complete inhibition. A reduced cortisol concentration (0.1 microM) concomitantly reduces the progesterone concentration required for effective inhibition (10-100 nM). This effect of progesterone is specific, as neither the release of cellular enzymes nor aromatase induction by dibutyryl-cAMP, which acts independently from cortisol, are affected. However, the inhibitory effect of progesterone requires its presence throughout the induction period. Kinetic studies in intact cells reveal a reduced number of aromatase active sites upon progesterone treatment, whereas progesterone at near-physiological concentration (100 nM) does not inhibit aromatase activity in isolated microsomes. Semi-quantitative reverse transcriptase PCR analysis shows reduced amounts of aromatase mRNA in progesterone-treated cells, indicating specific inhibition of the glucocorticoid-dependent pathway of aromatase induction. The inhibitory effect of progesterone is not blocked by the anti-progestin ZK114043, excluding action via progesterone receptors and indicating competition for the glucocorticoid receptor. Progesterone must be considered a potential physiological inhibitor of glucocorticoid-dependent aromatase induction in adipose tissue. It is proposed that it is a suppressor of aromatase induction in adipose tissue in premenopausal women.