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The protozoan parasite Toxoplasma gondii secretes a family of serine-threonine protein kinases into its host cell in order to disrupt signaling and alter immune responses. One prominent secretory effector is the rhoptry protein 18 (ROP18), a serine-threonine kinase that phosphorylates immunity related GTPases (IRGs) and hence blocks interferon gamma-mediated responses in rodent cells. Previous genetic studies show that ROP18 is a major virulence component of T. gondii strains from North and South America. Here, we implemented a high throughput screen to identify small molecule inhibitors of ROP18 in vitro and subsequently validated their specificity within infected cells. Although ROP18 was not susceptible to many kinase-directed inhibitors that affect mammalian kinases, the screen identified several sub micromolar inhibitors that belong to three chemical scaffolds: oxindoles, 6-azaquinazolines, and pyrazolopyridines. Treatment of interferon gamma-activated cells with one of these inhibitors enhanced immunity related GTPase recruitment to wild type parasites, recapitulating the defect of Δrop18 mutant parasites, consistent with targeting ROP18 within infected cells. These compounds provide useful starting points for chemical biology experiments or as leads for therapeutic interventions designed to reduce parasite virulence.

The Behavior Prediction Scale is a questionnaire by which a respondent's sensitivity to the following components of the ethical-risk situation might be measured: expectancy that gain will result from the unethical act, the magnitude of that gain, the likelihood of punishment, and the severity of punishment. When 15 psychopathic and 15 non-psychopathic prisoners were contrasted, only the psychopaths were sensitive to the expectation of gain. Neither group was sensitive to either the magnitude of gain or the likelihood of punishment; both were sensitive to the magnitude of punishment, however. These results differ markedly from the finding that “normal” populations exhibit sensitivity to all of these components.

Between Jan 15 and March 15, 1971, forty-eight grade-school patients living in western Chicago were hospitalized with an encephalopathic illness. Fourteen of these children had illnesses compatible with Reye syndrome (encephalopathy with liver impairment). Most of the children showed evidence of central nervous system (CNS) dysfunction within ten days after onset of a febrile upper respiratory tract illness. Seizures developed in 11 of the 48 patients (including 4 of the 14 with Reye syndrome). Eight of the encephalopathic patients, including 6 of the 14 with Reye syndrome, died. Two children without Reye syndrome had abnormalities of liver enzymes coincident with cerebrospinal fluid pleocytosis. Sixteen of the 24 patients tested had titer rises in serum against influenza type B only; influenza type B was isolated from throat cultures of 2 patients. This, the seventh report of CNS complications (Reye syndrome) associated with influenza type B, suggests that surveillance for neurologic sequelae should become part of the epidemiologic evaluation of influenza epidemics. ( JAMA 231:817-821, 1975)

Delegation of discretionary authority to subordinate agencies and tribunals is an increasingly necessary and frequent element of the administrative process. One example of delegated discretion is the power given to the Immigration Appeal Board under Section 15 of the Immigration Appeal Board Act; the Board may stay or quash deportation orders on grounds stipulated in the section. The authors critically examine the Board's interpretation of the enumerated grounds in order to establish the nature of the Board's policy in applying the section. Their analysis of recent Board decisions with respect to Section 15 reveals that under Sections 15(l)(a) and 15(l)(b)(ii) the Board has "evolved impressive guidelines", but that their decisions under Section 15(l)(b)(i) are open to some criticism. The authors suggest that the Board's interpretation of Section 15(l)(b)(i) may actually have "thwarted the inten tion of Parliament." In this connection, they question the Board's preoccupa tion with its own image as court. However, they conclude that, on the whole, the Board has exercised its discretion in line with the intention of Parliament that humanitarian and compassionate consideration be applied to specific cases, and has evolved guidelines which enable it to carry out this intention.