Epithelial marker genes are expressed in cultured embryonic rat lung and in vivo with similar spatial and temporal patterns

Explants of embryonic lung are often used to characterize lung growth, bronchial tree pattern, and cell differentiation. Most investigators culture lungs for 3-7 days in defined media lacking, e.g., added growth factors or hormones. If growth and differentiation are comparable to that in vivo, these cultures show considerable promise for identifying developmental regulatory molecules and target genes, and for elucidating molecular responses. We used in situ hybridization and RT-PCR to compare times and sites of expression of mRNAs of six epithelial genes in cultured and uncultured fetal rat lungs. These genes, expressed in distal lung of adult rats, are surfactant proteins (SP) A, B, and C; LAR, a receptor-type tyrosine phosphatase; Clara cell secretory protein (CC10, CCSP); and T1alpha. SP-A, SF-B, LAR, and CC10 are expressed by both Clara and Type II cells in adult animals. SP-C and T1alpha are unique markers for Type II and Type I cells, respectively. SP-C, LAR, and T1alpha are expressed before the lung is explanted (Day 13.5); SP-A, -B, and CC10 mRNAs are first detected later. The onset of expression is similar in vivo and in vitro. Although the patterns of expression differ for each mRNA, their sites of expression in culture match those in vivo relative to the bronchial tree. The explanted embryonic lung appears to be an excellent experimental model.     

Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses

On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship.     

An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients

A prospective study was performed to assess the potential value of interleukin (IL)-8, IL-6, and C-reactive protein (CRP) serum levels to predict fever, gram-negative bacteremia and complicated infection in neutropenic patients with cancer. Serum samples were obtained three times a week during 208 neutropenic episodes following cytotoxic chemotherapy. Fever of any cause developed during 104 out of 191 evaluable episodes. Serum levels of neither cytokine nor CRP were predictive of fever within more than 24 h before its onset. Unlike CRP, both IL-6 and IL-8 serum levels were significantly different between microbiologically documented infections and unexplained fevers. The highest values of IL-6 and IL-8 were observed in episodes of gram-negative bacteremia. Using receiver-operating-characteristic curves, the analysis of cytokine levels measured around the onset of fever indicated that IL-8 is potentially useful for predicting gram-negative bacteremia, with a high negative predictive value of > 90% and a moderate positive predictive value of 50% (sensitivity, 70%; specificity, 91%). In patients with persistent fever, predictions of further clinical complications, defined as prolonged fever of more than 7 days' duration, pneumonia, shock and/or death due to infection, were best predicted by IL-6. With an IL-6 cutoff value of 250 pg/ml in samples obtained 8 to 32 h after onset of fever, the positive predictive value was 92%, the negative predictive value 91% (sensitivity, 85%; specificity, 95%). The positive predictive value of IL-6 in samples obtained another 24 h later from patients still febrile remained > 90%, but the negative predictive value dropped to 47%. In any of the analyses, the predictive values of CRP levels were poor and inferior to either cytokine. These findings may have clinical value in identifying subgroups of patients requiring different therapeutic approaches.     

From information to probability: An axiomatic approach—Inference is information processing

We define the very rich language of composed conditionals on a three‐valued logic and use this language as the communication tool between man and machine. Communication takes place for three reasons: knowledge acquisition, query, and response. Learning, thinking, and answering questions are of a pure information theoretical nature. The pivot of this knowledge processing concept is the amount of information (bit) we receive if a conditional becomes true. We follow an axiomatic approach to information theory rather than the classical probabilistic approach of Shannon; information comes first, and then comes probability. In the light of this philosophy, query and response experience new interpretations. Both, acquisition and response are realized by maximizing entropy and minimizing relative entropy, respectively. The iterative solution of these mathematical optimization problems gives new insights into the adaptation of prior knowledge to new information. Our expert system shell SPIRIT supports this kind of knowledge processing, which will be established by suitable examples. © 2003 Wiley Periodicals, Inc.     

Perfluorocarbons are effective oxygen carriers in cardiopulmonary bypass

Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1, 2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group 1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/- 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus 1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.     

Hormonal secretion during nighttime sleep indicating stress of daytime exercise

We tested the hypothesis that long-duration exercise (LDE) of moderate intensity, but not LDE of low intensity, during the daytime changes the typical temporal patterns of hormone release during subsequent nocturnal sleep. Ten trained healthy men participated in a balanced crossover study including three conditions: 1) no exercise, 2) LDE of low intensity (biking 40 km; 1800-2030), and 3) LDE of moderate intensity (biking 120-150 km; 1600-2030). During the subsequent night (2300-0700), somnopolygraphic sleep recordings were obtained, and concentrations of cortisol, growth hormone (GH), and testosterone were measured every 15 min. During the no exercise nights, the typical secretory patterns were present with peak concentrations of GH but nadir concentrations of cortisol during the first half of sleep but increased cortisol levels and minimum GH levels during the second part of sleep. Testosterone concentrations increased during the second half of sleep. LDE of moderate intensity reduced rapid-eye-movement sleep [13.9 vs. 16.9% (no exercise); P < 0.01]. Levels of testosterone decreased with increasing intensity of daytime exercise (P < 0.05). Moderate-, but not low-intensity, LDE decreased GH levels in the first half (P < 0.05) and increased GH levels in the second half (P < 0.005) of sleep. Also, LDE of moderate intensity but not LDE of low intensity increased cortisol levels during the first half (P < 0.005) and decreased cortisol secretion during the second half (P < 0.05) of sleep. Results suggest that nocturnal profiles of GH and cortisol concentrations may serve to indicate the disturbance of normal anabolic functions of sleep due to daytime exercise.     

Analysis of grain boundary movement analogous to dislocation movement – both with a matrix having precipitates

In the present investigation it has been shown exemplarily for an austenite microstructure containing carbonitrides that the specific restraining force of a grain boundary due to the distribution of precipitates can be described by a modified Orowan's law, so that the grain boundary movement is considered to be analogous to the dislocation movement. This is achieved by using a modified restraining force F_r (corresponding to the cubic geometry of the particles), a detailed thermodynamic analysis of the precipitates (in this case, carbonitrides) and selected relation for the interparticle spacing L_a. The specific restraining force and the interparticle spacing depend on temperature within the austenite range. Each temperature is attached to a couple (F_r/L_a). The plot F_r against shows straight lines for each steel and from their average slope, a shear module G' of grain boundaries, which is about 64300 N·cm^?2, is obtained. Hence, it is possible to describe the specific restraining force of a grain boundary with the help of Orowan's law or as it is conventionally done by using Zener's modell. At a critical temperature T*, which is different for each steel, the specific restraining force is equal to the driving force of the grain boundary. The corresponding values of L_a are also different for each steel and the steel which is the most resistant to grain coarsening is allowed to have the greatest value of L_a which still retains the capacity of impeding grain coarsening.