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Introduction: The murine model is a well-established surrogate for studying human cranial suture biology. In mice, all sutures with the exception of the posterior frontal (PF) suture remain patent throughout life. Histology is regarded as the gold standard for analyzing sutures. On this basis, PF suture fusion begins on day of life 25 and is complete by day 45. Cranial suture histology, however, requires sacrifice of the animal to obtain tissue for analysis. As a result, knowledge of the kinetics of cranial suture fusion is based on a patchwork analysis of many sutures from many different animals. The behavior of a single suture through time is unknown. Our goal is to develop a noninvasive means to repeatedly image mouse cranial sutures in vivo. As a first step, the present study was performed to evaluate microfocal computer tomography (micro-CT) technology for the use of capturing images of a mouse cranium in situ., Methods: The micro-CT system consists of a microfocal X-ray source and a large format CCD camera optically coupled to a high-resolution X-ray image intensifier, digitally linked to a computer. The PF and sagittal sutures lie in continuity along the midline of the skull. Holes were drilled in the calvaria on both sides of the PF and sagittal sutures of a 45-day-old euthanized mouse. A micro-CT scan of this animal was performed and hundreds of cross-sectional images were generated for the cranium. These images were used to reconstruct three-dimensional volumetric images of the entire cranium. Comparisons were made between (1). the gross specimen and the three dimensional reconstructions; (2). two-dimensional coronal images obtained by micro-CT and those obtained by histology., Results: Analysis of PF and sagittal sutures demonstrated the following: (1). The drilled holes were accurately rendered by micro-CT, when compared to both the gross specimen and the histology. (2). The sagittal suture was found to be patent by both micro-CT and histology. (3). The PF suture is fused by histology, but unexpectedly, the PF suture appears incompletely fused by micro-CT. By micro-CT, however, the anterior and endocranial regions appear more extensively fused than the remainder of the PF suture, a finding consistent with published histologic analysis., Conclusions: We successfully imaged 45-day-old mouse cranial sutures in situ using micro-CT technology. Precise correlation between histologic sections and radiologic images is difficult, but convincing similarities exist between the gross specimen and images from micro-CT and histology. PF suture fusion in a 45-day-old animal appears different by micro-CT than by histology. One possible explanation for this apparent discrepancy is that suture fusion in histology is determined based on the appearance of bone morphology and not tissue density, as the specimens are necessarily decalcified to section the bone. Micro-CT, on the other hand, distinguishes tissues on the basis of density. Newly forming bone may require bone matrix formation prior to complete calcification; PF suture in 45-day-old mice may be morphologically complete but incompletely ossified. Studies correlating histologic and micro-CT assessment of suture development are underway. Micro-CT appears to be a promising method for noninvasive imaging of mouse cranial suture.

Aspergillus fumigatus an opportunistic fungus is associated with a number of diseases in humans. Allergy resulting from exposure to the A. fumigatus allergens has been recognized frequently. The damage caused by the disease is very striking in patients with atopy and those with cystic fibrosis. Avoidance to exposure is not feasible because A. fumigatus spores are ubiquitously distributed in the environment. Hence, immunotherapeutic regimens in severe forms of A. fumigatus allergy may have a high potential. However, before such forms of therapy can be envisaged, it is essential to understand the immunopathogenesis. In the present study, we investigated the role of purified A. fumigatus allergens in the development of allergic asthma in mice. We have used four major recombinant A. fumigatus allergens in the murine model. Mice exposed to Asp f 1, f 3, and f 4 showed inflammatory changes in the lungs and airway hyperreactivity. The immune responses, including elevated serum IgE, enhanced eosinophils, recruitment in the peripheral blood and lungs, and expression of regulatory cytokines, are characteristic of a Th2 response. Asp f 6 demonstrated only a reduced response in these animals. The results suggest that the pathology induced by crude A. fumigatus extract results from the cumulative effects of the allergens and the individual responses varied considerably with different purified antigens., (Copyright 2001 Academic Press.)

Inhalation of Aspergillus fumigatus, a ubiquitous fungus, results in the development of allergic bronchopulmonary aspergillosis, a disabling allergic lung disease. For better patient management early diagnosis is essential, and understanding of the immune mechanism is important in achieving this goal. Although animal model studies have contributed to the understanding of the disease mechanism, details on the immunopathogenesis are still lacking. In the present study, we have developed an allergic aspergillosis model in wild-type and IL-4 knockout mice and studied the immune and airway responses. The results indicate that the immune response, pulmonary pathology, and airway reactivity comparable to allergic bronchopulmonary aspergillosis are reproducible in wild mice. IL-4 knockout mice showed similar pulmonary pathology, but no increase in airway resistance, suggesting that IgE and hence IL-4 may be important in eliciting the airway response, while other factors may be involved in the inflammatory process., (Copyright 1999 Academic Press.)

The arterial and venous pressure curves obtained after occluding the venous outflow from a dog lung lobe perfused with constant flow contain information about the intralobar longitudinal distribution of vascular resistance (R) and compliance (C). To utilize this information, a lumped model consisting of four parallel C's separated by three serial R's was used. Solutions of the governing differential equations yield a nonlinear system of four algebraic equations in the seven unknowns and the measured data. Three of the equations form a linear subsystem in which the unknowns are the three R's and the coefficients are functions of the four C's. This is an underdetermined system, but when nonnegativity and boundedness constraints are adjoined, the solution set falls within a narrow band of distributions of cumulative R relative to cumulative C. The shape of this band changes when data are obtained from lobes influenced by various vasoactive stimuli revealing the changes in the longitudinal distribution of the vascular resistance relative to the vascular compliance.

Rapid occlusion of the venous outflow from a lung lobe perfused with constant flow causes the arterial and venous pressure to increase with time. Pressure values obtained by linear extrapolation of the nearly linear portions of the resulting arterial and venous pressure versus time curves back to the instant of occlusion provide data which can be used to place limits on the actual unknown distribution of resistance versus compliance. This has been proven deductively for the case of compartmental models having a small number of resistances and compliances. For compartmental models having a large number of resistances and compliances approaching a continuous distribution, an inductive approach was used in which a large number of simulations indicated that the actual continuous distribution is confined by the experimental data to the same limits as those for the small number of resistances and compliances.