Biomedical subjects
Publications and source records attributed to R Keller.
The consistently demonstrable antitumor effect of Corynebacterium parvum and BCG against a 7,12-dimethylbenz[a]anthracene-induced rat fibrosarcoma, growing either as a localized subcutaneous tumor or in ascites form, was abrogated by treatment of rats with antimacrophage agents such as silica or carrageenan.
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Cytomegalovirus (CMV) was isolated from the conjunctiva of a patient with mild unilateral catarrhal conjunctivitis associated with the typical clinical features of CMV mononucleosis syndrome in a previously healthy adult. The diagnosis was confirmed by a marked rise in the complement fixation antibody titers. Prospective studies are needed to determine the frequency of conjunctival involvement in CMV mononucleosis and the relation, if any, to sporadic cases of conjunctivitis.
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During prolonged starvation blood gas analyses on 24 lean and 78 obese subjects were performed. A statistically significant sex difference of acid-base status was found in that lean females were more acidotic after 4 - 6 days of fasting than lean males. This sex difference was abolished by severe and long-standing obesity, since females suffering from this condition were not significantly different from lean and obese males. Out of 78 obese patients fasted for 1 - 4 weeks 8 had one or more pH values below 7.30. It is concluded that regular blood gas analyses are indicated in all patients subjected to prolonged total fasting.
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This paper describes the identification of some of the contact-shifted resonances in the 1H NMR spectrum of low spin ferric cytochrome b5. In these experiments comparison with cytochrome b5 which had been reconstituted with deuteroheme IX played an important role. NMR techniques used include double resonance experiments, line width analyses, and studies of the pH-dependence of the 1H NMR chemical shifts. The electronic heme structure derived from these resonance assignments is characterized by a highly anisotropic spin density distribution. This anisotropy is most strikingly manifested in the resonances of the vinyl and propionic acid substituents of the protoheme IX. The experiments described in this paper further revealed the coexistence in aqueous solutions of two different molecular species of cytochrome b5, which can be simultaneously observed in the regions of the 1H NMR spectrum which contain the largely contact-shifted resonances.
The skin of congenitally athymic nu/nu mice is rich in mast cells which stain metachromatically, contain histamine and 5-hydroxytryptamine, and participate in the PCA reaction. Mast cells of athymic mice have thus the attributes of normal mast cells.
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Activated, nonimmune macrophages exerted profound effects on the proliferation and viability of eukaryotic target cells in vitro. Pronounced macrophage-mediated cytostasis was exerted on every rapidly proliferating cell line examined, irrespective of transformation, species derivation, cell type, or growth characteristics. However, the magnitude of cytostasis effected differed markedly among the 40 cell lines tested. There was no evident correlation between susceptibility to cytostasis and degree of transformation. Transformed cell lines with high and with low malignant attributes were affected equally. A comparable pattern was discerned for cytocidal effects of macrophages, in which the susceptibility of transformed targets was independent of the degree of malignancy.
Various attempts were made to assess the role of the mononuclear phagocyte system in tumor resistance of rats in vivo. The growth of sc inoculated, weakly immunogenic, carcinogen-induced, syngeneic tumor cells was modestly reduced by ip injection and, more impressively, by local injection of peptone-induced, activated, nonimmune macrophages. A single iv injection of silica particles or carrageenan on the day of sc tumor cell inoculation greatly enhanced tumor growth. When these agents had been given a few days before or after tumor cell inoculation, the tumor-promoting efficiency was distintly diminished or even cancelled. The enhancing effects of silica and carrageenan on tumor growth were nulified by the macrophage-stabilizing agent, poly-2-vinylpyridine N-oxide, To assess the in vivo consequences of silica administration, various cellular, biochemical, and functional macrophage parameters were determined at different intervals. Results indicated the complexity of events elicited after the mononuclear phagoycte system was damaged, which made the interpretation of such results difficult.
Recent work has indicated that macrophages can affect eukaryote cells in a variety of ways. The inhibitory or enhancing effects on target cell proliferation are mediated by soluble factors released from macrophages and appear to affect every replicating cells. Macrophages have also been shown to affect target cell viability and this destructive potential was initially considered to be tumor-specific. The present work further assesses these macrophage effects on targets by morphologic and fluorimetric methods. Morphologic analysis of the interaction between activated nonimmune macrophages (AM) and tumor cells attests to close cell-to-cell contact as an important factor in the mediation of target cell damage. All evidence suggests that damaged targets progressively disintegrate, and residues of target cell cytoplasma and/or nucleus are then engulfed as a secondary event. Analysis by impulse cytophotometry of the alterations in the DNA distribution occurring during interaction with AM revealed a marked decrease in the number of nuclei with higher DNA content. This effect was virtually identical irrespective of whether target cells were derived from normal or transformed tissues. Analysis of the consequences of AM/target cell interaction by cytofluorimetry showed that a large proportion of tumor cells lyse in the course of the interaction. However, no such killing occurred in recent explants derived from normal tissues interacted with AM; the majority of these targets were arrested in G1.
Cytomegalovirus was isolated from the PBBC from a patient with acute idiopathic polyneuritis. Viremia occurred during the early phase of the neurologic disease, preceding viruria, and was accompanied by specific CMV-IgM antibodies, which indicates a recently acquired infection. Complement fixing antibodies to CMV remained stable throughout the illness at a relatively low titer. Previously, CMV has been associated with acute idiopathic polyneuritis on the indirect evidence of rising or elevated titers of complement fixing antibodies or isolation of virus from urine or saliva or both. Our findings provide direct evidence for the causative role of CMV in acute idiopathic polyneuritis.
Cytomegalovirus- (CMV) infected cultured human fibroblasts incubated with normal human serum were shown to react with IgG by direct and indirect fluorescent antibody tests. The binding of IgG to infected cells was unrelated to the presence of anti-CMV complement fixing (CF) antibodies and was not observed with uninfected cells. The reaction was first observed 36 hours after infection as diffuse cytoplasmic staining which by 72 hr became localized into a dense perinuclear structure. The cytoplasmic fluorescence was not detected with anti-IgA or anti-IgM fluorescent conjugates. The reaction was seen with purified IgG and Fc fragments but was only minimally detectable with Fab fragments. It occurred in fibroblasts infected with three standard laboratory strains of CMV and seven recent CMV isolates from patients and was observed in six separate lots of human foreskin fibroblast cultures as well as in WI-38 cells. We conclude that CMV infection induces the formation of a IgG receptor in human fibroblasts.
Ascending radiculomyelitis in a 52-year-old woman was accompanied by transient marked hypoglycorrachia and polymorphonuclear pleocytosis of the CSF. Examination of the CSF later in the course of illness revealed albuminocytologic dissociation. This unusual sequence of findings was associated with serologic evidence of a recent cytomegalovirus (CMV) infection. In addition, the illness was associated with a nonthrombocytopenic purpuric rash. We proposed that the rash and neurologic disease were consequences of vasculitis caused by CMV infection.
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