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.     

Creep and Creep Rupture of an Advanced Silicon Nitride Ceramic

Creep and creep rupture behavior of an advanced silicon nitride ceramic were systematically characterized in the temperature range 1150° to 1300°C using uniaxial tensile creep tests. Absence of tertiary creep and the order-of-magnitude breaks in both creep rate and rupture lifetime at certain threshold combinations of stress and temperature were two characteristic features of the creep behavior observed. Thermal annealing was found to have enhanced both subsequent creep resistance and creep rupture life. The stress exponent (n) and the activation energy (Q) defined in the Norton relation were found to be 12.6 and 1645 kJ/mol for the material investigated. Both values appear to fall in the general range of those reported for other but similar types of Si₃N₄ ceramic materials. The stress exponent, m , equivalent to the slope of the Larson–Miller equation was found to be in the range 13 to 14.4, and that defined as p in the Monkman–Grant relation to be 0.91, based on the available experimental data. The values of m , n , and p obtained above approximately support the interrelationship of the three exponents given by p = m/n.     

Reversible Disorder in a Room Temperature Ferromagnet

Random magnetic fields, varying from site to site in a magnetic material, are a form of disorder that can determine the local architecture and stability of the magnetic state. In a ferromagnet, the application of an external magnetic field can amplify the effects of the internal random fields and, in principle, harden a magnetic domain, without changing temperature and only for as long as the external field is present. Here, the rare‐earth compound Nd₂Fe₁₄B, formed with a granular morphology of random‐packed, elongated grains, is an experimental realization of the Random Field Ising Model in a room temperature ferromagnet. The application of magnetic fields transverse to the easy axis tunes the coupling between the structural disorder and the magnetic pinning properties. This material both illuminates the intricacies of tunable disorder and serves as a guidepost along the way to developing increased‐density magnetic storage media.     

''Dual positivity'' for neural tube defects and down syndrome at maternal serum screening: gestational outcome

The pattern of anatomical features of the brain revealed by magnetic resonance imaging (MRI) is described in six patients incidentally identified as having acallosal brains. The complex of morphological features associated with complete agenesis of the corpus callosum included lateral displacement of slitlike anterior horns of the lateral ventricles (bullhorn-like shape), dilatation of the posterior horns of the lateral ventricles, absence of the septum pellucidum, lateral displacement of the cingulate gyri, complete separation of fornices and the presence of the anterior commissure and longitudinal callosal bundles (Probst's bundles). No compensatory enlargement of the anterior commissure was seen in the patients. The planimetrically measured cross-sectional areas of the anterior commissures were between 2.0 and 4.2 mm2 (mean 3.1) (in ten normal subjects they were 4.5, SD 0.4; range 3.8-5.2 mm2) and were reduced in four and normal in two patients. Inconstant morphological features were an absence of the posterior commissure and a radial pattern of the sulci and gyri on the medial aspect of the hemispheres. Conventional clinical testing revealed no abnormalities except a slight impairment of walking heel-to-toe in two patients. None of the patients had subjective restrictions of activities of daily life, which shows the efficacy of unknown compensatory processes.     

Diagnosis and therapy of diarrhea

Diarrhea is still one of the most frequent causes of death and poses many diagnostic and therapeutic problems. Whereas the etiology of acute diarrhea is mainly infectious, the cause of chronic diarrhea is much more multifarious and thus more difficult to diagnose. The etiology of acute diarrhea as well as the sense and nonsense of diagnostic procedures and therapeutic possibilities are discussed. A rational and practical concept for evaluation of chronic diarrhea is presented.     

Primary sclerosing cholangitis--an ulcerative colitis-associated illness with surgical consequences

Primary sclerosing cholangitis (PSC) is generally associated with ulcerative colitis (UC). The disease typically progresses slowly, but ultimately, and leads to cirrhosis, liver failure or bile duct cancer. PSC patients with simultaneous ulcerative colitis are also at higher risk for colorectal cancer. At the present time, there is no effective treatment for PSC, although preliminary data show encouraging results after treatment with ursodeoxycholic acid. However, there are no data concerning the delay or prevention of progress of the disease with this drug, because follow-up time is not yet long enough. Isolated bile duct strictures should be treated endoscopically. The possible effect of proctocolectomy on the course of PSC is controversial. Liver transplantation is the therapy of choice for PSC in its final stage. The 5-year survival rate (89%) is significantly better than after transplantation for other indications. Patients with ulcerative colitis have to be followed up by lifelong colonoscopy. Although the course of UC after transplantation is mostly asymptomatic, these patients are at higher risk for colorectal cancer.     

At-line solid-phase extraction for capillary electrophoresis: application to negatively charged solutes

The molecular karyotype of a series of Giardia lamblia isolates representing the two major genotypes (Groups 1 and 3) was generated by assigning 13 genetic markers to chromosomes separated by pulsed-field gel electrophoresis. The co-localization identified five linked groups of genetic markers in Group 1 isolates. For each of the five linkage groups, there were up to four size variants that hybridized with the same genetic markers. Long range physical maps of the regions flanking the low copy number genetic markers indicated that these size variants were homologous chromosomes. The linkage groups were similar in Group 1 and 3 isolates. The core of each chromosome was stable while the subtelomeres were variable. The location of the ribosomal DNA repeats was variable among the different isolates and they were found in the subtelomeric regions of any of the five linkage groups. The data suggest a functional ploidy of at least four. Hypervariable subtelomeric regions of homologous chromosomes provide the structural basis of the chromosome size heterogeneity that is characteristic of G. lamblia.