Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers.

Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema. A total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance). Emphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV(1)), FEV(1)/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George's Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution. Distribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.

Insulin-like growth factor 2 and insulin-like growth factor binding protein 2 expression in hepatoblastoma.

The expression of insulin-like growth factor 2 (IGF2) and insulin-like growth factor binding protein 2 (IGFBP2) in 11 cases of hepatoblastoma was studied by means of in situ mRNA hybridization using digoxigenin (DIG)-labeled riboprobes. The results showed that both IGF2 and IGFBP2 transcripts are present in hepatoblastoma and that their expression is inversely correlated with the degree of tumor cell differentiation. The data suggested that IGF2 and IGFBP2 gene expression could be regarded as a marker for assessment of the degree of differentiation in hepatoblastoma.

Modeling and artificial intelligence approaches to enzyme systems.

Modeling is a means of formulating and testing complex hypotheses. Useful modeling is now possible with biological laboratory microcomputers with which experimenters feel comfortable. Artificial intelligence (AI) is sufficiently similar to modeling that AI techniques, now becoming usable on microcomputers, are applicable to modeling. Microcomputer and AI applications to physiological system studies with multienzyme models and with kinetic models of isolated enzymes are described. Using an IBM PC microcomputer, we have been able to fit kinetic enzyme models; to extend this process to design kinetic experiments by determining the optimal conditions; and to construct an enzyme (hexokinase) kinetics data base. We have also used a PC to do most of the constructing of complex multienzyme models, initially with small simple BASIC programs; alternative methods with standard spreadsheet or data base programs have been defined. Formulating and solving differential equations in appropriate representational languages, and sensitivity analysis, are soon likely to be feasible with PCs. Much of the modeling process can be stated in terms of AI expert systems, using sets of rules for fitting and evaluating models and designing further experiments. AI techniques also permit critiquing and evaluating the data, experiments, and hypotheses being modeled, and can be extended to supervise the calculations involved.

Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. I. Lesions associated with mesangial IgM deposits.

The present studies examined the pathogenesis of focal glomerular sclerosis in aging rats. A marked difference in development of the lesion was noted between males and females, and strain variability was an important factor. Increased glomerular basement membrane permeability with loss of selectivity unrelated to changes in glomerular sialoprotein occurred with aging and was accompanied by increasing proteinuria. Noncomplement-fixing mesangial deposits of rat IgM were present after 1 month of age and were also found in lesser amounts in germfree rats. Fluoresceinated eluates of rat kidneys did not have antibody activity against rat serum or tissue antigens. There was no evidence for a pathogenetic role of IgM deposits. Rat IgG, IgA, IgE, C3, and fibrin were occasionally found in sclerotic areas. Analysis of multiple histologic sections revealed a close correlation between aging and glomerular pathology, with a poor correlation between tubular damage and aging. Glomerular damage appeared to be the initial event leading to tubular damage. Indirect evidence suggests that a relative thymic deficiency may play an important role in the pathogenesis of the lesion.