Direct evidence of H7N7 avian influenza virus mutation from low to high virulence on a single poultry premises during an outbreak in free range chickens in the UK, 2008.

H5 and H7 subtypes of low pathogenicity avian influenza viruses (LPAIVs) have the potential to evolve into highly pathogenic avian influenza viruses (HPAIVs), causing high mortality in galliforme poultry with substantial economic losses for the poultry industry. This study provides direct evidence of H7N7 LPAIV mutation to HPAIV on a single poultry premises during an outbreak that occurred in June 2008 in free range laying hens in Oxfordshire, UK. We report the first detection of a rare di-basic cleavage site (CS) motif (PEIPKKRGLF), unique to galliformes, that has previously been associated with a LPAIV phenotype. Three distinct HPAIV CS sequences (PEIPKRKKRGLF, PEIPKKKKRGLF and PEIPKKKKKKRGLF) were identified in the infected sheds suggesting molecular evolution at the outbreak premises. Further evidence for H7N7 LPAIV preceding mutation to HPAIV was derived by examining clinical signs, epidemiological descriptions and analysing laboratory results on the timing and proportions of seroconversion and virus shedding at each infected shed on the premises. In addition to describing how the outbreak was diagnosed and managed via statutory laboratory testing, phylogenetic analysis revealed reassortant events during 2006-2008 that suggested likely incursion of a wild bird origin LPAIV precursor to the H7N7 HPAIV outbreak. Identifying a precursor LPAIV is important for understanding the molecular changes and mechanisms involved in the emergence of HPAIV. This information can lead to understanding how and why only some H7 LPAIVs appear to readily mutate to HPAIV.

Sonolysis promotes indirect Co-C bond cleavage of alkylcob(III)alamin bioconjugates.

Sonolysis of aqueous solutions produces H. and HO. that lead to Co-C bond cleavage in methylcob-(III)alamin (CH3-CblIII) and 2-[4-[4'-[bis(2-chloroethyl)amino]phenyl]butyroxy]ethylcob (III)alamin (Chl-HE-CblIII). Under anaerobic conditions, H. reduces CH3-CblIII to the unstable 19 e-CH3-CblII that dissociates to the alkane and CblII. Under aerobic conditions, O2 scavenges H. and Co-C bond cleavage occurs via a HO.-mediated process along with modification of the corrin ring by HO.. When H. and HO. are scavenged, there is no evidence of Co-C bond cleavage. This suggests no direct sonolysis of the Co-C bond occurs, in spite of the fact that the Co-C bond is 80 kcal/mol weaker than the H-OH bond. A bioconjugate of cob(III)alamin and the alkylating agent chlorambucil has been synthesized to give 2-[4-[4'-[bis(2-chloroethyl)amino]phenyl]butyroxy]ethylcob(I II)alamin. The chlorambucil-cobalamin complex also undergoes Co-C bond cleavage in a manner similar to that of methylcob-(III)alamin. Sonorelease of an active alkylating agent from the bioconjugate may provide a new method for the selective release of anticancer drugs and thus potentially reduce systemic toxicity.

Increased hospitalizations for asthma among children in the Washington, D.C. area during 1961-1981.

Hospital admissions for childhood asthma to three university affiliated hospitals in the Washington D.C. area (Children's Hospital National Medical Center, CHNMC, Prince George's General Hospital, PGGH, and Holy Cross Hospital, HCH) for the period 1961-1981 increased at least three to 18 fold. The over-all population of children less than or equal to 14 years of age increased, at most, only 1.5 fold by 1970, and thereafter decreased gradually until the end of the study. This increase in pediatric asthma hospitalizations has occurred despite significant improvements in the ambulatory management of the asthmatic child. In particular, the amount of specific anti-asthmatic medication prescribed for these patients has grown markedly. The increased hospitalization is most likely due to an increase in the occurrence of severe asthma in children, particularly black children.

Non-A, non-B hepatitis after experimental transmission of malaria by inoculation of blood.

In a 1969 prisoner volunteer study of malaria transmission by blood inoculation, six persons were subinoculated sequentially, and acute hepatitis occurred in the last four (sequential study). Subsequently, another 15 volunteers receiving malaria-rich blood from 14 different donors were followed prospectively (prospective study), and hepatitis developed in six. Incubation periods were shorter but serum transaminase levels were higher for the cases of hepatitis occurring in the sequential study than in the prospective study. Although the illnesses were clinically mild, elevations in transaminase levels persisted for more than six months in five and fluctuating transaminase activities were observed in nine of the 10 affected persons. In addition, an 11th prisoner developed sporadic hepatitis. Neither known human hepatitis viruses nor malaria could be implicated in these cases, which were classified as non-A, non-B (NANB) hepatitis. The data suggested that the viremia of short-incubation NANB hepatitis may begin within the first week after inoculation, confirmed that NANB hepatitis may be transmitted either percutaneously or nonpercutaneously, and provided further evidence that there is more than one NANB agent.

Airborne fungi and pollens of the Washington, D.C., metropolitan area.

Moulds and pollen allergies are common in the Washington, D.C., metropolitan area. In this survey airborne fungi and pollen grains were studied throughout 1977 by weekly sampling for determination of prevalence of types of fungi and pollens. Dominant pollen types were oak (April), pine (April) and ragweed (September), whereas those of fungi were Hormodendrum (June) and Aureobasidium (March).

Relationship of serum complement levels to events of the malarial paroxysm.

Malarial paroxysms due to Plasmodium vivax were studied for alterations in whole serum complement (C') and certain C' components. The objective was to relate C' values with events of the parasite cycle during schizogony and with the febrile pattern. Substantial decreases in C' were found in 9 of 18 paroxysms studied during relapse. In contrast, only one of 22 paroxysms occuring during the primary attack was associated with a striking depression in C', and this case exhibited certain characteristics of a relapse paroxysm. The mean change in C' levels during paroxysms in relapse (-23%) was significantly different from paroxysms of the primary attack (-2%). Depletion of C' was associated directly with degree of parasitemia and presence of complement-fixing (CF) antibody. Lowest levels of C' were found within a few hours after completion of schizont repture and peak fever. C4 levels reflected changes in whole serum C' and appeared to be a more sensitive indicator of C' alterations during malaria. While the alterations in C4 as well as C1 and C2 indicated that the classical C' pathway was involved, some preliminary results showed little or no depletion of late components, C3 and C6. Overall results are compatible with C' activation and depletion during or soon after schizont repture if parasite density is sufficiently high and if CF antibody is present.