Protective immunity to malaria: studies with cloned lines of rodent malaria in CBA/Ca mice. IV. The specificity of mechanisms resulting in crisis and resolution of the primary acute phase parasitaemia of. Plasmodium chabaudi chabaudi and P. yoelii yoelii

Low numbers of parasites from cloned lines of the rodent malaria parasites, Plasmodium chabaudi chabaudi AS and P. yoelii yoelii A, injected into CBA/Ca mice produce acute but usually self-limiting infections. During crisis, i.e. 1-2 days after peak parasitaemia, 'pre-immune' mice experiencing such 'background' infections were reinfected intravenously with homologous parasites or parasites of heterologous strains or species. P. c. chabaudi AS pre-immune mice controlled an AS challenge with essentially the same kinetics as the background infection. Reinfection of AS pre-immune mice with the heterologous (CB and IP-PCI) P. c. chabaudi strains or P. chabaudi adami DS had little effect on the initial growth of these parasites, although eventually the parasitaemia was controlled. In contrast, a partial inhibitory effect on the growth of P. vinckei lentum DS was evident. Challenge with the non-lethal (A) or lethal (YM) variants of P. y. yoelii resulted in an increase in both the growth and virulence of these parasites. P. y. yoelii A pre-immune mice controlled a homologous challenge, but were less effective at controlling the YM variant. In addition, they were unable to clear rapidly a P. c. chabaudi AS or P. v. lentum DS challenge. Both the multiplication and virulence of P. berghei ANKA were enhanced. These findings demonstrate that resolution of the primary acute parasitaemia in P. c. chabaudi AS- and P. y. yoelii A-infected mice is predominantly mediated by species- and strain-specific mechanisms.     

Stabilization of thymopentin and preservation of its pharmacological properties by 2-hydroxypropyl-β-cyclodextrin

Abstract— Thymopentin prepared in 5, 15, and 20% 2-hydroxypropyl-β-cyclodextrin (HPCD) was able to inhibit guinea-pig ileum contraction stimulated by anatoxin-a (3 × 10^?6 m ) after fourteen months of storage at room temperature. Thus, in contrast to the instability of thymopentin prepared without HPCD, the pharmacological activity was retained and could be stored in a ready-to-use solution for extended periods without refrigeration.     

Working alongside the general practitioner: a child psychiatric clinic in the general practice setting

A monthly child psychiatric clinic was established in a primary health care centre in order to offer a more accessible service to patients, and to improve liaison with primary health care professionals. Compared with the base child guidance unit, at the health centre there was a better first attendance rate, a much higher proportion of referrals from health professionals especially general practitioners, and an increased proportion of younger children referred. If further follow-up was necessary at the child guidance unit the attendance rate was very good. The service provided, although not reducing the need for a main multidisciplinary base, offered an acceptable and accessible opportunity for children with psychological problems to be assessed and treated, and for the referring professionals to have easy communication with the child psychiatrist.     

A single gene copy merozoite surface antigen and immune evasion?

During the course of chronic malaria infection antigenic variants of a parasite antigen are expressed and exposed on the surface of infected erythrocyte membranes. There also exists a number of apparently invariant single gene copy blood-stage antigens, exposed or non-exposed, which have been shown to afford immunity under experimental conditions. To determine why the host, presented with invariant 'protective' antigens, is unable to control infections effectively, immunity to a representative single gene copy antigen, the merozoite surface protein 1 (MSP1) was investigated in Plasmodium chabaudi chabaudi AS, a murine model of chronic malaria. Immunization with monoclonal antibody affinity purified native MSP1 resulted in enhanced control of parasitaemia on challenge, irrespective of the parasite inoculum size; challenge with a single parasite, however, suggested that expansion of resistant parasite subpopulations was not occurring. Challenge of mice immunized with recombinant fusion proteins encoding N- or C-terminal regions of the P.c. chabaudi AS MSP1 produced inconsistent effects, often parasitaemias were indistingishable from controls despite significant anti-MSP1 antibody responses. The not unlikely contamination of MSP1 native preparations with erythrocyte (E) components was considered. Immunization with a mixture of the MSP1 C-terminus recombinant polypeptide and a Triton X-100 solubilized lysate of normal E resulted in enhanced control of parasitaemia, however, no effect was seen after administration of either component on its own. Co-immunization of E with the N-terminus polypeptide reversed the inhibition seen, on this occasion with this construct alone.     

Aetiology of Acute Pharyngitis and Clinical Response to Empirical Therapy with Erythromycin Versus Amoxicillin

Guthrie R M, Ruoff G E, Rofman BA, Ginsberg D, Karp R R, BrownS M and Schulz GA. Aetiology of acute pharyngitis and clinicalresponse to empirical therapy with erythromycin versus amoxicillin.Family Practice 1988; 5: 29–35. One hundred and eighty-nine adults with acute pharyngitis hadculture and serological evaluation for groupA beta haemolyticstreptococci (GABHS), Mycoplasma pneumoniae, and Branhamellacatarrhalis. Sixteen patients had evidence for infection withGABHS, none for M. pneumoniae, and one for B. catarrhalis. Forthose with GABHS, there was no significant difference betweenempirical treatment by erythromycin or amoxicillin. For thosewithout GABHS, empirical treatment with erythromycin appearedto result in a statistically significant reduction in coughand a noticeable but less than significant reduction of othersymptoms when compared to empirical treatment with amoxicillin.The new formula tion of erythromycin utilized in this study(PCE) may be associated with a reduction in gastrointestinalintolerance from that reported with other erythromycin products.     

Lack of Delayed Neurotoxic Effect after Tri-o-cresyl Phosphate Treatment in Male Fischer 344 Rats: Biochemical, Neurobehavioral and Neuropathological Studies

Lack of Delayed Neurotoxic Effect after Tri-o-cresyl PhosphateTreatment in Male Fischer 344 Rats: Biochemical, Neurobehavioral,and Neuropathological Studies. SOMKUTI, S. G., TIL-SON, H. A.,BROWN, H. R., CAMPBELL, G. A., LAPADULA, D. M., AND ABOU-DONIA,M. B. (1988). Fundam. Appl. Toxicol. 10, 199-205. Tri-o-cresylphosphate (TOCP), which produces a delayed neurotoxic syndromein humans and some animal species, was given to Fischer 344(F344) male (18 week old) rats to determine if it causes biochemical,sensorimotor, and neuropathological effects. Animals were givenTOCP by gavage in doses ranging from 10 to 100 mg of TOCP/kgdaily for a period of 63 days. The rats were subjected to aseries of neurobehavioral tests including fore- and hindlimbgrip strength, motor activity, tremor, and latency to respondto a thermal stimulus. Central and peripheral nervous tissueswere examined for damage characteristic of organophosphorouscompound-induced delayed neurotoxicity (OPIDN). Brain neurotoxicesterase and acetylcholinesterase activities were inhibitedin a dose-dependent fashion. A group of three chickens treatedwith 100 mg of TOCP/kg/day for 18 days was included as the positivecontrol for enzymatic and histopathological alterations associatedwith OPIDN. Rats showed no consistent neurobehavioral changesor evidence of neuropathological damage in nervous tissues associatedwith treatment. In contrast, chickens treated with TOCP developeddelayed neurotoxicity characterized by ataxia, which progressedto paralysis. These neurological changes included swelling,fragmentation, and degeneration of the axon and myelin in bothcentral and peripheral nervous tissues. This study concludesthat the F344 rat is not sensitive to the delayed neurotoxiceffects of TOCP. When studying OPIDN in rats, care must be exercisedin choosing the experimental animal since some strains, e.g.,F344, are not sensitive.     

Molecular genetic characterization of XRCC4 function

XRCC4 is a generally expressed protein of 334 amino acids that is involved in the repair of DNA double-strand breaks and in V(D)J recombination, but its function is unknown. In this study, we have used a mutational approach and the yeast two-hybrid method to perform an initial characterization of this protein. We show that the XRCC4 protein is located in the nucleus. We also demonstrate that several potential phosphorylation sites are not required for XRCC4 function in a transient V(D)J recombination assay. In addition, we show that XRCC4 forms a homodimer in vivo with the homodimerization domain being located within amino acids 115-204. Finally, we define a core domain of XRCC4 that functions in V(D)J recombination and comprises amino acids 18-204. Potential functions of XRCC4 are discussed.      

Enumeration of Absolute Numbers of T and B Lymphocytes in Human Blood

A new immunofluorescence test permits the direct enumeration of T and B lymphocytes in unseparated blood. B cells were identified with antiimmunoglobulin sera and T cells by a rabbit anti-human brain serum rendered unreactive with B cells by sequential absorption with erythrocytes, liver, and either chronic lymphocytic leukaemia cells or a cell line, BRI-8, with B-cell surface characteristics. T and B cells were also enumerated with lymphocyte suspension purified by either Ficoll-lsopaque density sedimentation or by a two-step gelatin-polystyrene bead column method. T cells in Ficoll-purified suspension were also enumerated by rosette formation with sheep erythrocytes. Comparison of the T-B proportions evaluated with the different cell preparation showed that the cell separation procedures can give rise to a deviation in the T:B ratio in favour of B cells. The extent of this induced bias related inversely to lymphocyte yield. Staining of whole blood preparations or high-yield purified cells enables absolute numbers of T and B lymphocytes to be calculated. We consider this measurement considerably more informative than relative proportions of T and B cells.