Enteric Pathogens in Monkeys

From 1964 to 1967, 6,646 monkeys, representing 10 primate species, were examined for Shigella and Salmonella infections upon arrival at the National Center for Primate Biology. Of these animals, 12% were infected with Shigella, and 75% of the Shigella isolates were S. flexneri 4. The incidence of Salmonella infections decreased from 12 to 3% during the period of study. Epidemiological studies of animals in the colony for 90 days or more indicated no seasonal variation in the occurrence of Shigella and Salmonella. Many of the isolates from incoming monkeys as well as from laboratory-conditioned animals were resistant to chloramphenicol, dihydrostreptomycin, and tetracycline. The possible operation of drug-resistance factors in these infections is discussed.     

ADVANCED NEOPLASTIC DISEASE—Treatment with 5-Fluorouracil and Irradiation

One hundred and twelve patients with far advanced, inoperable neoplastic disease were treated by a method utilizing the simultaneous administration of the pyrimidine antagonist, 5-fluorouracil, and ionizing irradiation to an estimated tumor dose of 2,000 roentgen units. Seventy-seven of them had periods of objective regression of tumor of three months or more.The data presented suggest that either there may be an additive effect when the two modes of therapy are used simultaneously or one mode of therapy may potentiate the antitumor effect of the other.     

Lipid composition of human serum lipoproteins

1. The lipid compositions of the low-density lipoproteins, the high-density lipoproteins and the ultracentrifugal residue of human serum are presented, with emphasis on certain lipoprotein classes and lipid components not previously described. 2. Except for the lipoproteins with the lowest and highest densities, there is a trend for stepwise successive increase or, respectively, decrease in the relative amounts of the main constituents of lipoproteins. 3. High-density lipoprotein-2 and high-density lipoprotein-3 have different amounts of certain lipids; high-density lipoprotein-2 has relatively more free cholesterol and sphingomyelin; high-density lipoprotein-3 has more free fatty acids, diglycerides and ceramide monohexosides. 4. All the lipoproteins contain hydrocarbons of the alkane series. The greatest amount, which averages 4.4% of total lipid extracted, is in the ultracentrifugal residue; n-alkanes comprise 18-50% of the hydrocarbons. 5. All the lipoproteins contain ceramide monohexosides. The highest relative contents of these glycolipids are in high-density lipoprotein-3 and in the ultracentrifugal residue. 6. The ultracentrifugal residue contains 55% of the total quantity of free fatty acids present in serum. The remaining free fatty acids are distributed among the other lipoprotein classes. 7. The choline-containing phospholipids (phosphatidylcholine, lysophosphatidylcholine and sphingomyelin) comprise about 90% of the phospholipids in all the lipoprotein classes except the low-density lipoprotein-2, which contains about 80% of these phospholipids. 8. The presence of a large amount of lysophosphatidylcholine in the ultracentrifugal residue and the successive decrease of sphingomyelin from the low-density lipoprotein-1 to the ultracentrifugal residue was confirmed. 9. The low-density lipoprotein-2 and the ultracentrifugal residue are characterized by relatively high contents of the lower glycerides.     

Adoptive transfer of CD8+ T cells from immune animals does not transfer immunity to blood stage Plasmodium yoelii malaria

The malaria parasite, Plasmodium yoelii 17X, causes a self-limited, nonlethal infection characterized, in the blood stage, by preferential invasion of reticulocytes. Previous studies have suggested that immunity to the blood stage infection may be related to enhanced levels of class I MHC Ag on the parasitized reticulocyte surface and can be adoptively transferred to immunodeficient mice by immune CD8+ T cells in the absence of CD4+ T cells. To further examine the mechanisms of CD8+ T cell involvement in immunity to blood stage P. yoelii infection, we performed in vivo CD8 depletion and adoptive transfer experiments. Depletion of CD8+ T cells during primary blood stage infection in BALB/c mice did not diminish the ability of the mice to resolve their infections. Spleen cells from immune BALB/c and C57BL/10 mice were transferred to BALB/c-nu/nu and C57BL/10-nu/nu mice, respectively. The recipient mice were CD4 depleted in vivo to kill any transferred CD4+ T cells. The mice failed to control the infection. Populations of CD4-, CD8+ T cells were transferred from immune CBA/CaJ donors to in vivo CD4-depleted CBA/CaJ recipients. The mice were unable to control the infection. Although immune unfractionated spleen cells transferred rapid protection in all three mouse strains and immune CD4+ T cells transferred immunity in the two mouse strains studied, CD8+ T cells by themselves were neither protective nor did they enhance immunity.     

Relationship between tumor necrosis factor alpha and feline immunodeficiency virus expressions.

The presence of feline immunodeficiency virus (FIV) proviral DNA, expression of FIV p26 core protein, and production of tumor necrosis factor alpha (TNF-alpha) were assessed in sequential biopsies of spleen and lymph node sections, of mononuclear cells of the peripheral blood, and of the serum of specific-pathogen-free cats during the acute phase of FIV infection. A temporal relationship between TNF-alpha production and FIV p26 expression was noted. Two months following FIV infection, and preceding the detection of FIV viremia, levels of TNF-alpha in serum increased significantly (P = 0.04), and they remained elevated during FIV viremia in the third month postinfection. Immunoprecipitates representing expression of TNF-alpha and of FIV p26 were localized in common foci of lymph nodes of FIV-infected cats during this period of active viremia. With the advent of anti-FIV antibodies, circulating levels of TNF-alpha and p26 antigen and expression of TNF-alpha and p26 in the lymph nodes decreased during the fifth month postinfection, and p26 production became undetectable. With clearance of viremia, burden of proviral DNA in peripheral blood mononuclear cells became reduced (P = 0.041), with provirus remaining integrated principally within lymph nodes (P = 0.046). During aviremia, p26 expression was undetectable in any tissue but remained inducible in vitro. During acute FIV infection, TNF-alpha production and p26 expression are intimately linked.     

Interleukin-8 activates microtubule-associated protein 2 kinase (ERK1) in human neutrophils

The signal transduction initiated by the human cytokine interleukin-8 (IL-8), the main chemotactic cytokine for neutrophils, was investigated and found to encompass the stimulation of protein kinases. More specifically, IL-8 caused a transient, dose and time dependent activation of a Ser/Thr kinase activity towards myelin basic protein (MBP) and the MBP-derived peptide APRTPGGRR patterned after the specific concensus sequence in MBP for ERK enzymes. The activated MBP kinase was furthermore identified as an extracellular signal regulated kinase (ERK1) based on several criteria such as substrate specificity, molecular weight, activation-dependent mobility shift, and recognition by anti-ERK antibodies. For comparison, the chemotactic response of neutrophils to a stimulus of bacterial origin (fMet-Leu-Phe or fMLP) was also examined and found to involve the activation of a similar ERK enzyme. The present data clearly indicate that in terminally differentiated, non-proliferating human cells, the MBP kinase/ERK activity can serve other purposes than mitogenic signaling, and that processes such as chemotaxis, induced by bacterial peptides as well as by human cytokines like IL-8, involve the regulation of ERK enzyme.Abbreviations IL-8 interleukin-8 - fMLP fMet-Leu-Phe - MBP myelin basic protein - ERK extracellular signal regulated kinase - MAP2 microtubule-associated protein 2 - PK-A cAMP dependent protein kinase - PKI protein kinase inhibitor - PMSF phenyl-methanesulfonyl fluoride - PVDF poly-vinylidene difluoride - HBSF Hank's buffered salt solution - DAB 3,3-diaminobenzidine tetrahydrochloride - PNPP p-nitrophenyl-phosphate - HSA human serum albumin - EGTA [ethylenebis (oxyethylenenitrilo)]tetraacetic acid - SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis