Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP119) induces protective immunity to blood stage malaria infection in mice

Variable protection against malaria blood-stage infection has been demonstrated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP1₁₉) using CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C mice with yeast expressed Plasmodium yoelii MSP1₁₉ plus a mixture of native and recombinant cholera toxin B subunit, could induce serum MSP1₁₉-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunization led to protection following challenge (peak parasitaemia < 1%) in mice with the highest MSP1₁₉-specific titre (≥ 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%–1% was followed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell, following the detection of parasites in the peripheral blood. CD4⁺ T cell-depletion abrogated the ability of the mice to boost their antibody response following challenge. These data demonstrate the potential for intranasal immunization with MSP1₁₉ to protect against malaria .     

Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.     

THE NATURE OF ARTHRITIS PAIN

A modified version of the McGill Pain Questionnaire in visualanalogue format was used to evaluate the sensory, affectiveand evaluative intensities of pain experienced by 40 patientswith rheumatoid arthritis and 20 patients with degenerativearthritis. The affective component of the pain was found tobe more intense than the sensory component in all patients indicatingthe importance of emotional factors in the pain experience.The sensory aspects of the pain were more complex than the affectiveones reflecting the varied sources and combinations of somaticpathology. There were no significant differences found in theoverall pain experience between rheumatoid and degenerativearthritis. No differences were noted in the evaluative categoryof pain. Overall pain intensity increased with disease durationin both rheumatoid and degenerative arthritis. The relationshipof affective and sensory components of the pain experience didnot alter with duration of disease. KEY WORDS: Arthritis, Pain     

BRUCELLOSIS COMPLICATED BY AORTIC VALVE ENDOCARDITIS

A 30 year old veterinary surgeon developed a febrile illness with serological evidence of Brucellosis. He was known to have aortic valve disease and during the course of the illness, the clinical features of endocarditis became evident, with a vegetation visible echocardiographically on the aortic valve. Because of persisting fever despite appropriate antibiotic therapy, aortic valve replacement with a viable cryopreserved allograft aortic valve was undertaken. Organisms consistent with Brucella species were demonstrated in the excised vegetation. The patient received a six week course of antibiotics and his post-operative course was uneventful.     

THE SIGNIFICANCE OF B-CELL CLONALITY IN GASTRIC LYMPHOID INFILTRATES

The significance of the demonstration of a clonal B-cell population in gastric lymphoid infiltrates was investigated by analysis of immunoglobulin heavy chain (IgH) gene rearrangements using sensitive polymerase chain reactions, employing fluorescently labelled primers to target the FR3 and FR1 regions. Tissue blocks were studied showing different histological features (high-grade lymphoma, low-grade lymphoma, and chronic gastritis) from 12 gastrectomies for primary gastric lymphoma, together with blocks showing chronic gastritis from 13 cases of gastric adenocarcinoma and biopsies from 33 patients with active Helicobacter -associated chronic gastritis. Clonal IgH gene rearrangements were detected in lymphoma samples from eight of the gastrectomies for lymphoma (67 per cent). In four of these eight specimens, clonal rearrangements were also detectable in the samples showing only chronic gastritis. Three of 28 (11 per cent) informative biopsies showing active Helicobacter -associated chronic gastritis had detectable clonal populations. Clonal rearrangements were also demonstrated in two of eight (25 per cent) informative blocks showing chronic gastritis from eight gastrectomies for adenocarcinoma. It is concluded that the detection of a clonal population in a suspicious lymphoid infiltrate does not confirm the diagnosis of lymphoma, nor does the absence of such a population imply benignity.     

An unusual pattern of metastases from Merkel cell carcinoma

An unusual case of Merkel cell carcinoma is presented in which the time course to development of nodal and haematogenous metastases was protracted and the predominant site of metastatic disease was small bowel.     

Aetiology of non-immune hydrops: the value of echocardiography

Summary. Forty-eight pregnancies, five of them multiple, were referred for fetal cardiac assessment following the detection of non-immune hydrops fetalis; there were 52 hydropic fetuses in total. A cardiovascular aetiology was found in 21 of these 52 (40%); structural heart disease was present in 13, tachyarrhythmia in the remaining eight. The accurate delineation of these causes was possible using fetal echo-cardiography, and enabled rational management to be instituted. This included termination of pregnancy, pharmacological control of arrhythmias and appropriate timing of delivery.