Orientation-dependent enhancement by H-NS of the activity of the type 1 fimbrial phase switch promoter in Escherichia coli

The role of 4-hydroxynonenal (HNE), a major lipid peroxidation product, in oxidative damage to mitochondrial cytochrome c oxidase (COX) was examined. Oxidative stress was induced in mitochondria isolated from livers of male Sprague-Dawley rats by tert-butylhydroperoxide (t-BHP). COX activity was inhibited, with a concomitant increase in endogenous HNE level in mitochondria. COX activity was also inhibited following incubation of mitochondria with 50-450 microM HNE. Blocking HNE degradation intensified COX inhibition by HNE and by t-BHP-induced oxidative stress, the latter accompanied by a simultaneous increase in endogenous HNE production. On the other hand, COX inhibition by HNE was markedly reduced by potentiating HNE degradation via enhancing conjugation of HNE with reduced glutathione (GSH). Incubation of purified COX with 10-400 microM HNE resulted in HNE adduct formation with specific subunits of COX, correlated with inhibition of the enzyme activity. These data suggest that HNE may inhibit mitochondrial COX by forming adducts with the enzyme, and that this could be one mechanism underlying mitochondrial damage caused by oxidative stress. The findings also illustrate a role for GSH in protecting mitochondria from the deleterious effects of HNE.     

Prothymosin alpha modulates the interaction of histone H1 with chromatin

Prothymosin alpha (ProTalpha) is an abundant acidic nuclear protein that may be involved in cell proliferation. In our search for its cellular partners, we have recently found that ProTalpha binds to linker histone H1. We now provide further evidence for the physiological relevance of this interaction by immunoisolation of a histone H1-ProTalpha complex from NIH 3T3 cell extracts. A detailed analysis of the interaction between the two proteins suggests contacts between the acidic region of ProTalpha and histone H1. In the context of a physiological chromatin reconstitution reaction, the presence of ProTalpha does not affect incorporation of an amount of histone H1 sufficient to increase the nucleosome repeat length by 20 bp, but prevents association of all further H1. Consistent with this finding, a fraction of histone H1 is released when H1-containing chromatin is challenged with ProTalpha. These results imply at least two different interaction modes of H1 with chromatin, which can be distinguished by their sensitivity to ProTalpha. The properties of ProTalpha suggest a role in fine tuning the stoichiometry and/or mode of interaction of H1 with chromatin.     

Mullerian adenosarcoma of the uterine corpus associated with tamoxifen therapy: a report of six cases and a review of tamoxifen-associated endometrial lesions

Six consultation cases of mullerian adenosarcoma of the uterus were encountered in women who were receiving adjuvant tamoxifen therapy for carcinoma of the breast. To our knowledge, only one previous similar case has been reported. The women, who were 48-76 years of age, had received tamoxifen for periods of 6 months to 4 years (mean 2.7 years) in five of the cases; the duration of tamoxifen therapy in the sixth case is unknown. All of the tumors were polypoid endometrial masses that superficially invaded the myometrium in two cases. The microscopic appearance of the tumors was similar to that of previously described uterine mullerian adenosarcomas. These and other recent observations indicate that tamoxifen treatment may be complicated by uterine neoplasms other than endometrial adenocarcinoma. These findings also support previous observations that prolonged exogenous or endogenous hyperestrinism may lead to the development of mesenchymal and mixed epithelial-mesenchymal tumors of the uterus.     

Influence of cell polarity on retrovirus-mediated gene transfer to differentiated human airway epithelia

Gene transfer with recombinant murine leukemia viruses (MuLV) provides the potential to permanently correct inherited lung diseases, such as cystic fibrosis (CF). Several problems prevent the application of MuLV-based recombinant retroviruses to lung gene therapy: (i) the lack of cell proliferation in mature pulmonary epithelia, (ii) inefficient gene transfer with a vector applied to the apical surface, and (iii) low titers of many retroviral preparations. We found that keratinocyte growth factor (KGF) stimulated proliferation of differentiated human tracheal and bronchial epithelia. Approximately 50% of epithelia divided in response to KGF as assessed by bromodeoxyuridine histochemistry. In airway epithelia stimulated to divide with KGF, high-titer ampho- and xenotropic enveloped vectors preferentially infected cells from the basal side. However, treatment with hypotonic shock or EGTA transiently increased transepithelial permeability, enhancing gene transfer with the vector applied to the mucosal surfaces of KGF-stimulated epithelia. Up to 35% of cells expressed the transgene after gene transfer. By using this approach, cells throughout the epithelial sheet, including basal cells, were targeted. Moreover, the Cl- transport defect in differentiated CF airway epithelia was corrected. These findings suggest that barriers to apical infection with MuLV can be overcome.     

The DNA extruded by rat spleen cells in culture

1. Part of the DNA extruded by cultured rat spleen cells occurs in the form of a low density lipid complex. 2. The present work indicates that this complex is also associated with protein but not with RNA and its elementary properties have been studied. 3. For example, it is destroyed by freezing and thawing or by deoxycholate treatment and small quantities of copper salts added to the medium may either inhibit or stimulate its release depending on the conditions.     

Intra-arterial bolus of 125I labeled meglumine diatrizoate. Early extravascular distribution

A mixture of 125I labeled meglumine diatrizoate and 131I labeled human serum albumin was injected into the lower abdominal aorta of 30 anesthetized, laparotomized male rats. Measurements of the activities in cardiac blood and in different tissues of the hindlimbs and tests were perfomed at six time intervals ranging from 5 seconds to 2 minutes after injection, the determine early uptake and distribution volumes of diatrizoate. Concentrations and distribution volumes were initially much greater than values obtained after intravenous injection, but these differences had considerably decreased or disappeared by 2 minutes.     

Nonlinear system identification using wavelet networks

A novel identification scheme using wavelet networks is presented for nonlinear dynamical systems. Based on fixed wavelet networks, parameter adaptation laws are developed using a Lyapunov synthesis approach. This guarantees the stability of the overall identification scheme and the convergence of both the parameters and the state errors, even in the presence of modelling errors. Using the decomposition and reconstruction techniques of multiresolution decompositions, variable wavelet networks are introduced to achieve a desired estimation accuracy and a suitable sized network, and to adapt to variations of the characteristics and operating points in nonlinear systems. B-spline wavelets are used to form the wavelet networks and the identification scheme is illustrated using a simulated example.     

A new direct approach of computing multi-step ahead predictions for non-linear models

A new direct approach of computing multi-step ahead predictions for non-linear time series is introduced. The covariance of the parameter estimates associated with, and the mean squared k -step ahead prediction errors of the new direct approach are smaller than those obtained using the conventional direct approach. Numerical examples are included to illustrate the application of the new direct approach.     

Non-linear output frequency response functions for multi-input non-linear Volterra systems

The concept of non-linear output frequency response functions (NOFRFs) is extended to the non-linear systems that can be described by a multi-input Volterra series model. A new algorithm is also developed to determine the output frequency range of non-linear systems from the frequency range of the inputs. These results allow the concept of NOFRFs to be applied to a wide range of engineering systems. The phenomenon of the energy transfer in a two degree of freedom non-linear system is studied using the new concepts to demonstrate the significance of the new results.