Postpsychiatry: a new direction for mental health.
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Biomedical subjects
Publications and source records attributed to P Bracken.
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Infection with the parasitic nematode Trichinella spiralis is initiated when the L1 larva invades host intestinal epithelial cells. Monoclonal antibodies specific for glycans on the larval surface and secreted glycoproteins protect the intestine against infection. Protective antibodies recognize tyvelose which caps the target glycan. In this study, we used an in vitro model of invasion to further examine the mechanism(s) by which tyvelose-specific antibodies protect epithelial cells against T. spiralis. Using cell lines that vary in susceptibility to invasion, we confirmed and clarified the results of our in vivo studies by documenting three modes of interference: exclusion of larvae from cells, encumbrance of larvae as they migrated within epithelial monolayers, and inhibition of parasite development. Excluded larvae bear cephalic caps (C. S. McVay et al., Infect. Immun. 66:1941-1945, 1998) of immune complexes that may physically block invasion or may interfere with sensory reception. Monovalent Fab fragments prepared from a tyvelose-specific antibody also excluded larvae from cells, demonstrating that antibody binding can inhibit the parasite in the absence of antigen aggregation and cap formation. In contrast, encumbered larvae caused extensive damage to the monolayer yet were not successful in establishing a niche, as reflected by their failure to molt. These results show that antibodies to tyvelose exhibit multiple modes of inhibitory activity, further implicating tyvelose-bearing glycoproteins as mediators of invasion and niche establishment by T. spiralis.
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The importance of the donated organ as a source of CMV was assessed in 120 patients following orthotopic liver transplant and the CMV infections that developed in these patients were graded by severity. Forty-four recipients were CMV antibody negative pre-transplant. Eighteen of these received organs from CMV antibody positive donors and 15 (83%) developed primary CMV infections, 13 (87%) of which were symptomatic. Twenty-six received organs from CMV antibody negative donors and only 2 (8%) became CMV positive post transplant (P less than 0.001). These data suggest that there would be a considerable advantage in matching CMV antibody negative recipients with negative donors. Forty-five percent of secondary infections were asymptomatic compared with 12% of primary infections, and only 11% became disseminated compared with 53% of primary infections. The secondary infections that followed transplantation of an organ from a CMV antibody positive donor were more likely to be symptomatic and were more severe than those in patients who received seronegative livers.
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A case of mania subsequent to head injury is presented. The literature reporting cases of mania after head injury is reviewed. It is suggested that the concept of Secondary Mania be broadened to include cases occurring after head injury. It is also suggested that a true bipolar illness can be secondary.
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Rat hepatocytes were incubated in monolayer culture, under serum free conditions, for 8 h. Glucagon (10 nM), 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (100 microM) and dexamethasone (100 nM) increased the activity of phosphatidate phosphohydrolase by approx. 2-, 3.6- and 3.3-fold, respectively. Spermine alone had no significant effect. Spermine (2.5 mM) almost completely inhibited the glucagon induced increase in phosphohydrolase activity. It only partially inhibited the dexamethasone and cyclic AMP mediated inductions. Spermidine had no significant effect in this respect. The results are discussed in relation to the known effects of polyamines on glycerolipid synthesis, in particular, and on intermediary metabolism.
Rat hepatocytes were incubated in monolayer culture, under serum-free conditions for 8 h. Rat growth hormone (up to 100 nM) increased the activity of phosphatidate phosphohydrolase by up to 47%. Insulin (500 pM or 35 nM), cycloheximide or actinomycin D reversed this effect. The ability of growth hormone to modify the effects of insulin is discussed in relation to the control of the phosphohydrolase activity and glycerolipid synthesis.
The clarification of turbid AA-amyloid-fibril-containing agarose gels by serum has been ascribed to degradation of the fibrils and designated as 'amyloid degrading factor'. In the present study, sera of 32 healthy blood donors and 32 patients with rheumatoid arthritis all showed 'degrading factor activity' against both AA amyloid fibrils and a non-fibrillar reticulin preparation of normal liver in an agarose plate assay. AL amyloid fibrils were not affected. The 'degrading activity' of serum was correlated with the serum albumin concentration, and the effect was also given by purified human and bovine serum albumin, although it was not seen with other serum proteins. The 'degrading activity' of serum against AA amyloid and reticulin was significantly correlated: both substrates showed low levels in a chronic disease such as rheumatoid arthritis, and reticulin inhibited 'degrading activity' against AA amyloid and vice versa. These results suggest the same process involves both substrates. 'Degrading activity' was also given by EDTA and a specific calcium chelator, and was inhibited by calcium and magnesium. An enzyme inhibitor showed only partial inhibition of the 'degrading activity' of serum, purified albumin, and EDTA. These results suggest that serum 'degrading factor activity' is a non-specific calcium-mediated effect against AA amyloid and reticulin preparations dispersed in agarose. It may represent a change in the degree of aggregation of these proteins rather than being an effect of proteolytic degradation. This confirms the conclusions of other workers that amyloid 'degrading factor activity' is an phenomenon in vitro of doubtful pathophysiological significance.
The autosomal recessive disorder homocystinuria involves, in all its subgroups, an abnormality of methionine metabolism. The metabolism of methionine has been a central focus of interest for those who propose the transmethylation hypothesis of schizophrenia. The "methionine effect," as described in the research literature, is thus a theoretical link between these two disorders. The authors review the literature and describe those cases where both have occurred in the same patient. They indicate that whereas many patients with homocystinuria have been psychotic, few have been actually labeled schizophrenic. A patient with homocystinuria, mental retardation, and episodic psychosis is described and this case is used to point to the difficulties in making a definite psychiatric diagnosis in these patients. A relationship between the two syndromes is suggested.
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