A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion

Mucus hypersecretion and plugging of lower respiratory tract airways contributes to the morbidity and mortality associated with asthma. Interleukin (IL)-4 plays a putative role in some forms of asthma. Thus, transgenic mice that overexpress murine IL-4 selectively within the lung were used to study the effect of IL-4 on mucus glycoprotein gene expression and mucin release. Histologic examination of lung sections from IL-4 mice revealed that nonciliated epithelial cells from conducting airways were hypertrophic, due at least in part to the accumulation of mucus glycoprotein. The cytoplasm of these cells stained positively for glycoproteins using mucicarmine, alcian blue (AB), and periodic acid-Schiff (PAS). Ciliated cells were also enlarged but did not show any mucin-specific staining. Inclusion granules typically found in nonciliated (Clara) cells of control mice were absent in the IL-4 transgenic mice. Northern blot analysis of total RNA from lung tissue revealed that the expression of the MUC5AC, but not MUC2, mucin gene was distinctly upgraded in IL-4 transgenic mice compared to transgene-negative controls. In addition, a 5- to 10-fold increase in AB- and PAS-positive material was found in lavage fluid from IL-4 overexpressing mice compared to transgene-negative controls. Thus, the overexpression of IL-4 locally within the lung enhances mucus glycoprotein synthesis by altering gene expression, results in the accumulation of mucus glycoprotein in nonciliated epithelial cells, and induces the release of mucus into the airway lumen. We therefore hypothesize that the overproduction of mucus seen in some patients with asthma may be a direct result of the action of IL-4 within the inflamed lung.     

Unusual fatty acid compositions of the hyperthermophilic archaeon Pyrococcus furiosus and the bacterium Thermotoga maritima

The fatty acid compositions of the hyperthermophilic microorganisms Thermotoga maritima and Pyrococcus furiosus were studied and compared. A total of 37 different fatty acids were identified in T. maritima, including the novel 13,14-dimethyloctacosanedioic acid. In contrast, a total of 18 different fatty acids were characterized, as minor components, in P. furiosus, and these included saturated, monounsaturated, and dicarboxylic acids. This is the first report of fatty acids from an archaeon.     

Peptide growth factors in normal and hypertrophied bladder

The pharmacokinetics of oral zidovudine in HIV-infected children and adults are reported. Fourty-six patients were investigated. For data analysis three groups of similar size were formed: young children 4 months-4 years, n = 15 (group 1), older children up to 13 years, n = 16 (group 2) and young adults, n = 15 (group 3). After a single oral dose repeated blood samples were taken 1/2 hourly during a period of 4 hours and zidovudine concentrations in plasma were determined by high performance liquid chromatography. For better comparison of dose dependent parameters peak concentrations (Cmax) and the area under the time-concentration curves (AUC) were normalized either to the dose/body weight (bw) or the dose/body surface area (bs), respectively. Time to reach peak concentrations and mean terminal elimination half-life times (t1/2 beta = 63.4 +/- 47.6, 74.9 +/- 54.9 and 56.9 +/- 16.4 min in group 1, 2 and 3, respectively, mean +/- SD) were not significantly different between the three groups. With normalization to dose/bw young children in comparison to adults had significantly lower Cmax (2.7 +/- 1.3 vs. 4.6 +/- 2.4 mumol/l, p = 0.016) and AUC (226 +/- 108 vs. 373 +/- 224 mumol.min/l, p = 0.038). Group 2 gave intermediate values. However, with normalization to dose/bs differences in Cmax (6.5 +/- 3.3, 7.3 +/- 4.2 and 6.8 +/- 3.6 mumol/l, in group 1, 2, and 3, respectively) and AUC (563 +/- 313, 691 +/- 351 and 555 +/- 342 mumol.min/l, in group 1, 2 and 3) were not significant between the three groups. It is likely that changes in body water content with age may account for most of these differences observed. In conclusion, a similar pharmacokinetic profile was found in children older than 3 months as compared to older children or adults.     

Visual recognition based on temporal cortex cells: viewer-centred processing of pattern configuration

A model of recognition is described based on cell properties in the ventral cortical stream of visual processing in the primate brain. At a critical intermediate stage in this system, 'Elaborate' feature sensitive cells respond selectively to visual features in a way that depends on size (+/- 1 octave), orientation (+/- 45 degrees) but does not depend on position within central vision (+/- 5 degrees). These features are simple conjunctions of 2-D elements (e.g. a horizontal dark area above a dark smoothly convex area). They can arise either as elements of an object's surface pattern or as a 3-D component bounded by an object's external contour. By requiring a combination of several such features without regard to their position within the central region of the visual image, 'Pattern' sensitive cells at higher levels can exhibit selectivity for complex configurations that typify objects seen under particular viewing conditions. Given that input features to such Pattern sensitive cells are specified in approximate size and orientation, initial cellular 'representations' of the visual appearance of object type (or object example) are also selective for orientation and size. At this level, sensitivity to object view (+/- 60 degrees) arises because visual features disappear as objects are rotated in perspective. Processing is thus viewer-centred and the neurones only respond to objects seen from particular viewing conditions or 'object instances'. Combined sensitivity to multiple features (conjunctions of elements) independent of their position, establishes selectivity for the configurations of object parts (from one view) because rearranged configurations of the same parts yield images lacking some of the 2-D visual features present in the normal configuration. Different neural populations appear to be selectively tuned to particular components of the same biological object (e.g. face, eyes, hands, legs), perhaps because the independent articulation of these components gives rise to correlated activity in different sets of input visual features. Generalisation over viewing conditions for a given object can be established by hierarchically pooling outputs of view-condition specific cells with pooling operations dependent on the continuity in experience across viewing conditions. Different object parts are seen together and different views are seen in succession when the observer walks around the object. The view specific coding that characterises the selectivity of cells in the temporal lobe can be seen as a natural consequence of selective experience of objects from particular vantage points. View specific coding for the face and body also has great utility in understanding complex social signals, a property that may not be feasible with object-centred processing.