Modulation of cell proliferation by human recombinant interleukin-1 and immune interferon

The growth-modulating effects of recombinant alpha- and beta-forms of human interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) were examined with several human cell lines. Exposure to combinations of IL-1 and IFN-gamma resulted in three categories of cell response. The first was cell lines in which IL-1 stimulated growth and offset the growth inhibitory effects of IFN-gamma. These lines included the lung carcinoma CALU-1 and the colon carcinoma SW-48. The second was some of the cell lines that were refractory to IL-1 and that were inhibited by IFN-gamma alone. These included the cervical carcinoma HeLa, the transformed milk line HBL-100, and the myelogenous leukemia K562. The third group consisted of cells in which growth inhibition by IL-1 and IFN-gamma was additive. These included the mammary carcinomas MCF-7 and MDA-MB-415. The exception to this latter group was ME-180 in which significant additive inhibitory effects could not be demonstrated. IL-1 alone primarily induced a cytostatic effect in growth-inhibited cell lines. The cytolytic effect induced by IFN-gamma was increased in the presence of IL-1. The data support the conclusion that the effects on growth of IL-1 and IFN-gamma are mediated by different mechanisms.     

Syme amputation. An evaluation of the physical and psychological function in young patients

Twenty-one patients who had had twenty-three Syme amputations at an average age of four years and eleven months were studied to assess their physical and psychological functional status. Physical evaluation was based on a timed fifty-yard (45.7-meter) dash, Cybex testing of quadriceps and hamstring function, and history of sports participation. Psychological function was based on four psychological tests. Quadriceps power correlated closely with athletic function. Excessive genu valgum caused a noticeable abnormality of gait. Migration of the heel pad did not cause problems with gait. Better psychological function correlated with better orthopaedic function. The level of family stress was the predominant factor that influenced test results relative to behavior, self-concept, and intelligence quotient. As a result of this study, we believe that a Syme amputation in a young patient may be compatible with athletic and psychological function closely approaching that of a non-handicapped child of the same age.     

Neuroimaging in child and adolescent psychiatry

Although less well studied in child and adolescent psychiatry than in adult psychiatry, brain imaging has significantly altered psychiatric research and practice. This review focuses on the modalities that are used to image the brain. These include structural imaging techniques of computer tomography (CT) and magnetic resonance imaging (MRI), as well as functional imaging techniques of computed electroencephalography (CEEG), positron emission tomography (PET), and single photon emission computed tomography (SPECT). The technologies are reviewed, strengths and weaknesses of modalities discussed, and research progress reported.     

Studies on the mechanism of binding of serpins and serine proteases.

The serpin family of inhibitors have an important role in the control of coagulation and fibrinolysis. For a full understanding of how these pathways operate in vivo and correct measurement of enzyme and inhibitor activity, in vitro knowledge of the mechanism of action of serpins is essential. Using alpha 2-antiplasmin as a model inhibitor we find, in contrast to most previous reports, a reversible mechanism: E + I in equilibrium with EI in equilibrium with EI', where complex formation is two stepped, but both steps are reversible. Our work with plasmin in the presence of 50 mM aminohexanoic acid shows that binding of alpha 2-antiplasmin is very tight (but reversible) with an overall Ki (Ki final) = 4.0 pM. With chymotrypsin (a model serine protease) Ki final = 100 pM, so as expected binding of alpha 2-antiplasmin is weaker with chymotrypsin. However, analysis of the individual rate constants shows that the difference in strength of binding is accounted for by the dissociation rate constant for the second step (k-2) = 1.9 x 10(-6) s-1 for plasmin and 1.1 x 10(-4) s-1 for chymotrypsin. Thus k-2, the rate constant previously ignored, explains the different affinities of alpha 2-antiplasmin for these two enzymes. Furthermore, this model of two (or more) step, reversible binding is accepted for protease inhibitors of other families. With one of these, aprotinin (a Kunitz inhibitor) with plasmin we also obtain a two-stage reversible mechanism with a Ki final = 200 pM and the strength of inhibition is also largely determined by k-2 = 3.5 x 10(-5) s-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leukaemia inhibitory factor is over-expressed by ischaemic brain tissue concomitant with reduced plasma expression following acute stroke

Leukaemia inhibitory factor (LIF) is a glycoprotein of the interleukin-6 family, which has potent pro-inflammatory properties and is involved in regulation of neuronal differentiation. We have previously identified its upregulation in gene microarrays following acute ischaemic stroke in man. LIF expression and localization was measured in human ischaemic stroke autopsy specimens, in a rat model of middle cerebral artery occlusion (MCAO) and in human foetal neural cell cultures following oxygen-glucose deprivation (OGD) by Western blotting and immunohistochemistry. Circulating LIF was determined in the plasma of patients in the hyper-acute stroke phase using a multiplex enzyme-linked-immunosorbent serologic assay system. Patients demonstrated an increase in LIF expression in peri-infarcted regions with localization in neurons and endothelial cells of microvessels surrounding the infarcted core. The rat MCAO model showed similar upregulation in neurons with a peak increase at 90 min. Circulating serum LIF expression was significantly decreased in the hyper-acute phase of stroke. Brain-derived neurons and glia cultured in vitro demonstrated an increase in gene/protein and protein expression respectively following exposure to OGD. Increased LIF expression in peri-infarcted regions and sequestration from the peripheral circulation in acute stroke patients characteristic of the pathobiological response to ischaemia and tissue damage.     

Renal actions of oxyphenbutazone.

Oxyphenbutazone decreased the renal excretion of sodium and water in anesthetized dogs. As these excretions decreased, the drug also produced a decrease in renal blood flow and in the glomerular filtration rate. Blood pressure increased slightly. These changes are consistent with an inhibition of renal prostaglandin synthesis and could explain why oxyphenbutazone is reported to produce weight gain and edema when used clinically.