Palliative medicine: a change in emphasis?
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Biomedical subjects
Publications and source records attributed to R MacLeod.
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An ultrastructural examination of various tissues from CFW/D mice, neonatally injected with Moloney murine leukaemia virus (Mo-MuLV) revealed the presence of type C virus particles budding from the membranes of various bone marrow-derived cells, pancreatic acinar cells, beta cells, and submandibular gland acinar cells. These observations indicate that Mo-MuLV has the potential to replicate in non-lymphoid cell types even when acquired post-partum. In the pancreas, a large accumulation of immature and mature viral particles was observed between the cell membranes of the acinar cells and the basal lamina. A similar accumulation of viral particles was observed in the lumina of the acinus of submandibular glands. The role of murine leukaemia viruses as potential mediators of aberrations of non-haemopoietic tissues and an alternative mode of viral transmission are discussed.
A group of temperature sensitive mutants of Moloney murine leukemia virus (MoMuLV) designated as ts1, ts7, and ts11 rapidly and invariably induce hind-limb paralysis ranging from 28 to 52 days postinjection of neonatal CFW/D mice. These temperature-sensitive mutants are defective in the processing of the precursor of the env protein, gPr80env in infected cells, resulting in the accumulation of gPr80env in the infected cell and production of virions with reduced amounts of gp70, p15E, and p12E when compared to that of the wild-type virion. In contrast, two nonparalytogenic ts mutants, ts3 and ts10, like the wild-type virus, show normal processing of gPr80env in infected cells and production of virions with a similar amount of env proteins to that of the wild-type virion.
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Several procedures were utilized to study the effects of prolactin on dopamine synthesis in the medial basal hypothalamus of the rat. Elevation of serum prolactin was produced by the administration of trifluoperazine (5 mg/kg, i.p.) and resulted in a significant increase in the conversion of [3',5'-3H]tyrosine to dopamine when measured in slices of medial basal hypothalamus and striatum. Hypophysectomy abolished this effect of trifluoperazine in the medial basal hypothalamus but not in the striatum. In addition, the synthesis of dopamine was significantly elevated in slices of medial basal hypothalamus obtained from rats bearing pituitary tumor implants that secreted microgram quantities of prolactin. In contrast, the in vitro synthesis of dopamine in the striatum of such rats was increased by the secretory products in one tumor line but decreased in another compared to that observed in control animals. It is suggested that the ability of prolactin to accelerate the synthesis of dopamine in the medial basal hypothalamus might constitute a short loop feedback system that finely regulates prolactin secretion.
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The mode of action of interferon in de novo Moloney murine leukemia virus (Mo-MuLV) infection of mouse bone marrow/thymus (TB) cells was studied. Our results indicate that in interferon-treated cells, there is approximately a 2000 fold decrease in the production of infectious MuLV, but only a 10-20 fold decrease in the level of viral specific extracellular reverse transcriptase activity, and only about a 2 fold difference in the number of virus particles observed on the cell membrane as determined by scanning electron microscopic (SEM) studies. Transmission electron microscopic (TEM) studies showed that the proportion of early budding virions, which have shallow crescent-shaped ribonucleoprotein cores (Figure 3A), to virions in later stages of assembly (Figures 3B-3D) is relatively higher in interferon-treated cells than in the untreated controls. From a temperature shift-down experiment on a temperature-sensitive mutant of MuLV, ts 3, which produces viral particles that fail to dissociate from the cell surface at the nonpermissive temperature, we demonstrated that ts 3 virions partially assembled on the cell membrane prior to the addition of interferon are able to complete assembly and to dissociate from the cell membrane on temperature shift-down in the presence of interferon action. Our data suggest that interferon neither inhibits the late stages of virion assembly at which ts 3 virions are arrested at the nonpermissive temperature nor prevents release of the virions. Our findings also indicate that in interferon-treated cells, most of the extracellular virions are noninfectious.
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The wild-type New Jersey serotype of vesicular stomatitis virus generated two types of defective interfering T-particles. The physical properties of these particles and the wild-type virion were determined by laser light scattering spectroscopy, sedimentation measurements, and electron microscopy.
The scanning electron microscope was used to study the budding process of the wild-type Moloney murine leukemia virus and one of its temperature-sensitive mutants, designated ts 3. A considerably larger number of budding particles was observed on TB cells infected with ts 3 at the nonpermissive temperature (39 C) than at the permissive temperature (34 C). No apparent difference was noted between the number of particles on ts 3-infected cells at (34 C) and wild-type-infected cells at 34 or 39 C. Virions were detected at the cell membrane of ts 3-infected cells at 39 C as early as 8 h postinfection. Virion density increased progressively up to 48 h after which no increase was observed. An average of 1,600 virus particles was observed at the cell surface at the peak of virus production. The distribution of these on the cell membrane appeared to be random. The maximum proportion of the cell surface occupied by the viral particles did not exceed 10%. After temperature shift from 39 to 34 C, approximately 90% of the particles had dissociated from the cell membrane within 1 h.
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A simple alphabetical classification is offered as a means to codify the proteins of rhabdoviruses, using vesicular stomatitis virus as the prototype.
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