Induction of protective immunity to monoclonal-antibody-defined Plasmodium falciparum antigens requires strong adjuvant in Aotus monkeys.

Monoclonal antibodies to the major Plasmodium falciparum merozoite surface coat and rhoptry antigens were produced. A combination of the affinity-purified polypeptides with Freund complete adjuvant which was given three times completely protected an Aotus lemurinus azure (karotype VI) monkey against homologous challenge; however, immunization with the same polypeptides with a muramyl dipeptide derivative [MDP-Lys(L18)] did not protect a second Aotus monkey, even though comparable high antibody titers were induced.     

Activation of μ-opiate receptors as a factor of regulation of heart resistance to ischemia-reperfusion and oxidative stress

Intravenous injection of the selective μ-opiate receptor agonist DAMGO (0.1 mg/kg, 15 min before isolation of the heart) improved resistance of isolated perfused rat heart to ischemia (45 min) and reperfusion (60 min) damages.In vivo administration of DAMGO prevented reperfusion-induced damages to cardiomyocytes and decreased the content of conjugated dienes in the myocardium during ischemia-reperfusionin vitro. Furthermore, stimulation of μ-opiate receptors promoted recovery of myocardial contractility during reoxygenation, but had no effect on heart resistance to free radical-induced damages during perfusion of isolated heart with a solution containing Fe²⁺ and ascorbic acid. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 163–167, August, 2000     

Concurrent and consecutive infection and immunisation with yellow fever and UGMP-359 viruses

Concurrent and consecutive infection and immunisation with yellow fever virus and UGMP-359 virus was investigated in mice, using identical doses of both viruses. In double infection it was shown that both viruses could multiply independently of one another, when both were inoculated simultaneously by the intracerebral route. On the other hand, there was mutual exclusion between them when the inoculation of one antedated the other, by the same intracerebral route. Both viruses multiplied to similar titres, in single infection, in the target organ (brain). By the intraperitoneal route, the outcome was influenced byhe relative sensitivity of this route of inoculation to support and sustain the replication of either virus. Thus, because yellow fever virus replicated more than UGMP-359 after intraperitoneal inoculation, the latter is always excluded, even when the inoculation ofUGMP-359 preceded that of yellow fever. In the double immunization studies it was shown that comparative specific antibody titres to both viruses were obtained either when both viruses, as immunogens, were given simultaneously, or when the inoculation of one was alternated, at weekly intervals, with the other.     

Relative Immunogenicity and Tolerogenicity of Individual Regions or Segments of the MHC

Mixed lymphocyte culture (MIX) reactivity, induction of cytotoxicity in vitro, survival of skin allografts, and induction of neonatal transplantation tolerance were compared in mice of the strain combinations differing in the entire H-2 complex or in individual segments of it. The results showed that antigenic products of the K end of the H-2 complex were more immunogenic and also more resistant to tolerance induction than the products of the D end of H-2. I-region products that elicited transplantation reactions of variable strength, depending on the detection system, were relatively easier to overcome in tolerance induction and could, at least in some combinations, contribute to tolerance induction across the barrier represented by the products of the K region of the H-2 complex.     

Growth sensitivity of a recombinant simian virus 5 P/V mutant to type I interferon differs between tumor cell lines and normal primary cells

A paramyxovirus SV5 mutant (rSV5-P/V-CPI-) that encodes 6 naturally-occurring P/V gene substitutions is a potent inducer of type I interferon (IFN) and is restricted for low moi growth, two phenotypes not seen with WT SV5. In this study, we have compared the IFN sensitivity of WT SV5 and the rSV5-P/V-CPI- mutant in tumor cell lines and in cultures of normal primary cells. We have tested the hypothesis that differences in IFN induction elicited by WT rSV5 and rSV5-P/V-CPI- are responsible for differences in low moi growth and spread. In contrast to WT SV5, low moi infection of A549 lung carcinoma cells with rSV5-P/V-CPI- resulted in a plateau of virus production by 24-48 h pi when secreted IFN levels were between approximately 100 and 1000 U/ml. Gene microarray and RT-PCR analyses identified IFN genes and IFN-stimulated genes whose expression were increased by infection of A549 cells with WT and P/V mutant viruses. Restricted low moi growth and spread of rSV5-P/V-CPI- in A549 cells was relieved in the presence of neutralizing antibodies to IFN-beta but not TNF-alpha. When A549 or MDA-MB-435 breast tumor cells were pretreated with IFN, both WT and P/V mutant viruses showed delayed spread and approximately 10-fold reduction in virus yield, but infections were not eliminated. Using normal primary human epithelial cells that have undergone limited passage in culture, WT rSV5 and rSV5-P/V-CPI- displayed high moi growth properties that were similar to that seen in A549 cells. However, IFN pretreatment of these primary cells as well as normal human lung cells eliminated low moi spread of both mutant and WT rSV5 infections. Together, these data demonstrate that SV5 growth in normal primary human cells is highly sensitive to IFN compared to growth in some tumor cell lines, regardless of whether the P/V gene is WT or mutant. These results suggest a model in which spread of WT SV5 in normal human cells is dependent on the ability of the virus to prevent IFN synthesis. The implications of these results for the use of recombinant paramyxoviruses as vectors are discussed.     

The Effect of Anti-Lymphocytic Serum on Infection by Congo Virus (Crimean Haemorrhagic Fever Virus Related) and Mokola Virus (Rabies Virus Related)

Antilymphocytic serum (ALS) raised in white New Zealand rabbits with Swiss albino mice thymocytes significantly protected mice challenged with Congo virus (Crimean haemorrhagic fever virus related) from the lethal episodes of the infection. There was a delaying as well as a sparing effect on morbidity and mortality, which was particularly striking in adult mice. Histopathological examination of brain sections of treated mice showed a complete suppression of the characteristic inflammatory tissue reactions, which marked similar sections prepared from mice treated with normal rabbit serum (NRS) or from the virus control group. Unlike Congo virus infection, ALS did not have a demonstrable effect on Mokola virus (rabies virus related) infection. A comparison of the effect of ALS on Congo virus infection and its effect on murine lymphocytic choriomeningitis is made.It was observed that a constant feature of ALS treatment was gross splenic enlargement in the animals. It is suggested that this might have been due, at least in part, to a gross sequestration of sensitized red blood cells, as revealed by the histopathology of the organ. Other possible causes of splenomegaly in immunosuppressed mice are also discussed.     

Electron microscopic studies on the development of vesicular stomatitis virus

Summary The development of vesicular stomatitis virus in chick embryo fibroblasts has been studied. Infectivity titres were correlated with electron microscopic observations. The demonstration of virus particles in both ultrathin sections of infected cells and in the culture fluid coincided with a rise in virus titre. Intracytoplasmic crystalline arrays, presumably progeny virus materials, were demonstrated in infected but not in noninfected cells. The individual units of the crystals measure about 61-61 m. across. Virus matures both at the cell surface and at vacuolar membranes in finger-like projections. The typical mature virus particle is essentially bullet-shaped, with average dimensions of 176×71 m. While virus synthesis seems to occur exclusively in the cytoplasm with probably no participation of the cell nucleus, free virus particles were not observed in the cytoplasm. Evidence for a close similarity between the morphology and the development of vesicular stomatitis virus and rabies virus are given. It is suggested that both these viruses and other similar animal viruses showing the characteristic structural polarity may be taxonomically related.A visiting scientist from the Nigerian Federal Government.     

Specific biochemical markers of bone metabolism and cytokine study confirm the diagnosis of malignant infantile osteopetrosis at birth using cord blood sample

AIMS: To investigate the serum creatine kinase isoenzyme pattern, specific biochemical markers of bone metabolism, and cytokines in a Chinese family with osteopetrosis, and correlate abnormalities with the pathophysiology of this condition. METHODS: A Chinese female baby was diagnosed with malignant infantile osteopetrosis at the age of 3 weeks by clinical history and biochemical investigations. We studied the laboratory and radiological manifestations of this index case and her family members. RESULTS: Serum CK-BB fraction of our index patient was elevated to 18.0% (normal 1.6-7.6%). Her biochemical markers of bone resorption including serum C-terminal telopeptide concentration and urine N-terminal telopeptide to creatinine ratio were decreased to 0.54 microg/L (normal 0.72-1.56 microg/L) and 159 x 10(-6) (normal 372-900 x 10(-6)), respectively. Serum cytokines including soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) concentration was suppressed to 0.11 pmol/L (normal 0.23-0.82 pmol/L) and osteoprotegerin (OPG) concentration was 4.9 pmol/L (normal 2.8-4.9 pmol/L), resulting in an elevated OPG to sRANKL ratio of 44.5 (normal 3.8-19.4) in favour of bone formation. CONCLUSIONS: If left untreated, this condition is usually fatal within the first year of life. With early diagnosis, management including bone marrow transplantation can be planned ahead and will result in a better survival.