Butyrate increases production of human chimeric IgG in CHO-K1 cells whilst maintaining function and glycoform profile

The influence of sodium butyrate on the production and glycosylation of recombinant mouse/human chimeric antibody by transfected CHO-K1 cells was investigated. We selected cells expressing 'wild-type' antibody with a human IgG3 heavy chain and a mutant of this molecule in which Phe 243 is replaced by Ala. These proteins have previously been shown to exhibit very different glycoform profiles with the mutant IgG being comprised of glycoforms having a high galactose and sialic acid content. Cell culture with 0-5 mM butyrate was shown to effect a 2-4-fold increase in antibody production whilst the induction of apoptosis was observed in a dose-dependent manner. The optimal butyrate concentration was observed to be 2 mM. The glycoform profile of each antibody produced in the presence of butyrate was analyzed by HPAEC-PAD and shown to be unchanged, relative to that produced in the absence of butyrate. Biological activity was evaluated by the ability of the antibodies to trigger superoxide generation, through Fc gamma RI, and shown to be independent of production in the presence or absence of butyrate. A similar increase in production was observed for a high antibody-producing cell line when expanded in a hollow fibre bioreactor under low-serum conditions (1%). These results demonstrated that butyrate is of value for increasing the productivity of CHO-K1 for recombinant IgG and does not compromise either glycosylation or biological activity.     

Immunological mechanisms in the maintenance of pregnancy

Mmammalian pregnancy involves prolonged, intimate interactions between genetically dissimilar organisms. This dissimilarity evokes an immunological response in the gravida which promotes placental implantation and fetal viability. The nature of the immunological reactions, the factors moderating these responses and the signficance of abnormalities in the responses are discussed.     

Do dysfunctional cognitions mediate the relationship between risk factors and postnatal depression symptomatology?

BACKGROUND: This study investigated the mediating role of general and maternal-specific dysfunctional cognitions, in the relationship between non-cognitive risk factors and postnatal depressive symptomatology. METHODS: An Australian community sample comprising 406 postnatal women responded to the Dysfunctional Attitude Scale (DAS), the Maternal Attitudes Questionnaire (MAQ), the Vulnerable Personality Style Questionnaire (VPSQ) and the Edinburgh Postnatal Depression Scale (EPDS). They also responded to several questions related to perinatal and postnatal experiences. RESULTS: Path analysis demonstrated that different mediational pathways operated for different risk factors. The relationship between having a difficult baby and postnatal depression was fully mediated by maternal-specific dysfunctional cognitions (MAQ scores), whereas the relationship between past history of depression and postnatal depression was partially mediated by general dysfunctional cognitions (DAS scores). Finally, the relationship between a vulnerable personality and depressive symptomatology was mediated by both DAS and MAQ scores. LIMITATIONS: The study employed a correlational design. Thus, all inferences regarding possible causal pathways are tentative. In addition, the generalisability of these findings to other populations needs to be demonstrated in future research. CONCLUSIONS: The results of the study are consistent with the view that risk factors may influence postnatal depression indirectly through at least two distinct cognitive mediators (dysfunctional maternal and general cognitions). It may be possible to target therapies more effectively by identifying the relevant mediating mechanism(s) for individuals with different risk profiles.     

Oxatomide: Inhibition and stimulation of histamine release from human lung and leucocytes in vitro

Oxatomide is a very potent inhibitor of histamine release induced by anti-1gE and Timothy pollen extract in passively sensitized human lung fragments and that induced by anti-1gE from human leucocytes. Its spectrum of activity is different from sodium cromoglycate-like drugs.In high concentrations oxatomide, like other antihistamines and related structures, induced histamine release from both lung and leucocytes. However, oxatomide induced histamine release far more effectively from sensitized lung than non-sensitized lung.Inhibition of immunologically induced histamine release by oxatomide may play a part in its action as an anti-hay fever and, possibly, an anti-asthmatic drug.     

Silo gas exposure in New York state following the dry growing season of 1995

Exposure to silo gas is a recognized agricultural hazard. Silo gas produced from corn fermentation may consist of oxides of nitrogen and carbon dioxide. The presence of potentially lethal concentrations of nitrogen dioxide (NO2) within vertical silos has been well documented. The risk of silo gas exposure from other silage storage methodologies--including horizontal "ag-bags" and concrete bunkers--has been less well characterized. A dry growing season is known to be a factor for elevating nitrate levels in corn plants and can result in increased NO2 production. Farms in the northeastern United States faced drought conditions during the 1995 growing season. The New York State (NYS) Department of Health (DOH) and the New York Center for Agricultural Medicine and Health (NYCAMH) investigated four exposure incidents involving six farmworkers during September/October 1995. Four of these workers were hospitalized for multiple days, with two workers receiving treatment in intensive care units. The remaining two workers were treated in hospital emergency departments; one refused admission and left against medical advice. We monitored NO2 levels from "ag-bags" at several New York farms. For four days, outdoor concentrations of NO2 at one site remained in excess of the National Institute for Occupational Safety and Health's (NIOSH) immediately dangerous to life and health value (IDLH) of 20 ppm. As a result of the clinical and industrial hygiene data, and the growing season's abnormal weather conditions, DOH and NYCAMH issued statewide health hazard alerts and conducted educational activities to warn farmers and their families. The findings of this study reinforce the potential hazards associated with silo gas exposure and identify the use of ag-bags as a relatively new avenue for significant worker exposure.     

Using the Internet for postgraduate medical education.

Obtaining information from the Internet can be fun. As the Internet is unregulated, the quality of this information can vary enormously and time can be wasted searching poor quality websites. Despite this, use of the Internet for postgraduate medical education is increasing.     

The differential effects of haloperidol and methamphetamine on time estimation in the rat

Forty rats were trained to make a left lever response if a signal (white noise) was 2.5s and to make a right lever response if the signal was 6.3s. When seven intermediate signal durations, to which responses were not reinforced, were randomly interspersed the probability of a right-lever (long) response increased as a function of signal duration. Methamphetamine shifted this psychometric function leftward and decreased its slope: haloperidol also decreased the slope but shifted the function rightward. A combination of haloperidol and methamphetamine led to a function similar to the saline control function. The leftward shift probably reflects an increase in the speed of an internal clock, and the rightward shift probably reflects a decrease in its speed. Since methamphetamine releases several catecholamines, including dopamine, and haloperidol blocks dopamine receptors, it is plausible that the horizontal location of the psychometric function (the speed of the clock) is related to the effective level of dopamine.     

Temporal pattern dependence of neuronal peptide transmitter release: models and experiments.

In this paper we construct, on the basis of existing experimental data, a mathematical model of firing-elicited release of peptide transmitters from motor neuron B15 in the accessory radula closer neuromuscular system of Aplysia. The model consists of a slow "mobilizing" reaction and the fast release reaction itself. Experimentally, however, it was possible to measure only the mean, heavily averaged release, lacking fast kinetic information. Considered in the conventional way, the data were insufficient to completely specify the details of the model, in particular the relative properties of the slow and the unobservable fast reaction. We illustrate here, with our model and with additional experiments, how to approach such a problem by considering another dimension of release, namely its pattern dependence. The mean release is sensitive to the temporal pattern of firing, even to pattern on time scales much faster than the time scale on which the release is averaged. The mean release varies with the time scale and magnitude of the pattern, relative to the time scale and nonlinearity of the release reactions with which the pattern interacts. The type and magnitude of pattern dependence, especially when correlated systematically over a range of patterns, can therefore yield information about the properties of the release reactions. Thus, temporal pattern can be used as a probe of the release process, even of its fast, directly unobservable components. More generally, the analysis provides insights into the possible ways in which such pattern dependence, widespread especially in neuropeptide- and hormone-releasing systems, might arise from the properties of the underlying cellular reactions.