Biomedical subjects
Publications and source records attributed to D C Burke.
Brain abscess is an uncommon complication of the insertion of skull tongs. The two cases reported demonstrate the difficulty that may occur in diagnosis and the high mortality associated with this complication.
NIH 3T3 mouse cells were infected at very high multiplicity with murine sarcoma/leukaemia virus (MSV/MLV) and then cloned. All of the 48 clones obtained were morphologically transformed, all but one showed anchorage-independence of growth, typical of MSV-transformed NIH 3T3 cells and most (91%) produced MSV/MLV. When cells which had been pre-treated with 10(4) units/ml of purified interferon (IF) were infected under the same conditions and then cloned in the presence of the same amount of IF, only 6 of a total of 63 clones were morphologically transformed. All but these 6 showed a degree of anchorage-independence typical of the uninfected parental cells and very few (2.4%) produced virus. Furthermore, the MSV genome could not be rescued in any of the 23 clones tested and only 1 out of 10 clones produced tumours. The properties of these clones remained stable over a period of 10 to 20 passages in the absence of interferon. We conclude that interferon can irreversibly block an early step in the MSV/MLV infectious process.
When L929 cells were treated with interferon and subsequently with poly(rI).poly(rC), there was a pronounced toxic effect. Most of the cells lysed, but some survived and grew at the same rate as control cells to yield cells which were as sensitive to the effects of interferon and poly(rI).poly(rC) as the original population. The proportion of surviving cells did not vary with either the cell cycle or the cell density. The treated cells produced interferon and some of the interferon was produced by the resistant cells. Cells which had been X-irradiated before treatment with interferon and poly(rI).poly(rC) behaved similarly so cell division was not necessary for the development of toxicity. The toxic effect also developed when cells were enucleated with the aid of cytochalas in B after treatment with interferon, but not if they were enucleated before treatment. It is concluded that the nucleus is essential for interferon to exert its effect on the cells, but not for the development of cytotoxicity after the addition of poly(rI).poly(rC).
After treatment with Sendai virus, Namalwa cells form large amounts of interferon. RNA extracted from treated whole cells or from their polysomes was injected into Xenopus laevis oocytes and the interferon formed was titrated. The results show that the amount of interferon mRNA was maximal by 9 h after treatment of the cells with Sendai virus and then declined. Sucrose gradient centrifugation of the mRNA gave substantial purification and showed that its size was 12 S.
5-Bromodeoxyuridine (BrdUrd) increased interferon production by the Namalwa line of human lymphoblastoid cells treated with Sendai virus, but inhibited their growth. Thymidine, which also inhibited cell growth had no effect on interferon production, so that growth inhibition per se was not the cause of the stimulation. BrdUrd was incorporated into cellular DNA; 5-chlorodeoxyuridine and 5-iododeoxyuridine (which are also incorporated) increased the interferon yield, but 5-fluorodeoxyuridine (which is not incorporated) did not. Thymidine reduced both the incorporation of BrdUrd and its stimulatory effect on interferon production. Deoxycytidine (which prevents the cytotoxic effects of BrdUrd) had no effect on the stimulation. BrdUrd also stimulated interferon production in response to poly(rI) . poly(rC) in growing human diploid fibroblasts but not in SV40 virus-transformed human cells. Since BrdUrd was incorporated into the DNA of all these cells, we concluded that incorporation is necessary, but not sufficient for the stimulation of interferon formation.
Forty-two primary human-mouse cell hybrids, derived in two separate experiments, were treated with Newcastle disease virus (NDV): eight hybrids were found to produce human interferon and this was shown in every case to be predominantly of the fibroblast type. An extensive analysis was made in terms of karyotype and marker enzymes on all the eight hybrids producing interferon and also on five hybrids which did not produce interferon, five randomly selected hybrids and eleven subclones resistant to diphtheria toxin. The results suggest that, contrary to previous reports, a gene on chromosome 5 is not involved in production of human interferon. Its production was however correlated with the presence of chromosome 9 in the hybrids. Analyses of two sets of human-Chinese hamster hybrid subclones from two different crosses were also consistent with the assignment of a human interferon gene to chromosome 9.
A correct and accurate diagnosis of paraplegia or tetraplegia due to a spinal cord injury is an important first step in the treatment. A simplified method of performing such an examination is presented to help overcome a diagnostic blind spot of many medical practitioners. Some of the traps and subtleties of diagnosis are discussed.
This paper reviews the medical records of 100 consecutive patients with tetraplegia owing to diving injury. Their high survival characteristics, plus youth on presentation, create the problem of an expanding population of chronically disabled patients.
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Pluripotential embryonal carcinoma (EC) cells do not produce interferon after treatment with a wide variety of inducers, nor are they sensitive to its action. Several differentiated lines derived from the EC cells, however, both produce and are sensitive to mouse interferon. Differentiation of EC cells in vitro is accompanied by development of interferon inducibility and sensitivity.
Three different inhibitors of RNA synthesis, actinomycin, alpha-amanitin and camptothecin, and five different inhibitors of protein synthesis were able to superinduce interferon production in human diploid fibroblasts treated with poly(rI).poly(rC). Camptothecin was shown to be a reversible inhibitor of virus induced interferon formation. It also substantially reduced the interferon yield from human diploid fibroblasts which had been superinduced with actinomycin D and cycloheximide. This suggests that the previously reported failure of camptothecin to inhibit interferon production in human diploid cells after induction with poly(rI).poly(rC) is the result of two mutually opposing effects: a marked inhibition of interferon messenger RNA synthesis, but a stimulation of the activity of the interferon messenger RNA that is formed.
Enucleation of L cells leads to loss of the capacity to produce interferon, showing that the cell nucleus is essential for interferon formation. However, when the cells were enucleated while interferon formation. However, when the cells were enucleated while interferon formation was proceeding, the cytoplasts were capable of continuing to synthesize interferon by a process shown to be protein synthesis, showing that the interferon messenger RNA leaves the nucleus after synthesis. Reconstructed cells were obtained by Sendai virus fusion of karyoplasts and cytoplasts. Such reconstructed cells were capable of producing at least as much interferon (43 interferon units/10(4) nucleated cells) as control cells (31 interferon units/10(4) nucleated cells).
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Both mouse and human cells elaborate more than one molecular species of interferon. Mouse interferon consists of a number of polypeptides which all probably have antiviral activity. Human fibroblast interferon is a single polypeptide, but other human cells produce special species of interferons, which show different physical and biological properties. The human interferons certainly differ in their extent of glycosylation and hydrophobicity, and may have different amino-acid sequences, since it has recently been reported that when the messenger RNAs extracted from fibroblast and lymphoblastoid cells are translated in Xenopus oocytes, the products are antigenically distinguishable (26,29,40). If the polypeptide sequences are different, then there may be at least two structural genes for human interferon. Both the antiviral and anticellular activities of mouse and human interferon probably reside in the same molecule.
Human embryonic fibroblasts produce interferon when incubated at 37 degrees C after being treated at 4 degrees C with poly(rI) - poly(rC), either by addition of the double-stranded duplex or by sequential addition of the constitutent single-stranded polynucleotides. Cells which have been incubated with double-stranded poly(rI) - poly(rC) can be prevented from forming interferon by washing the cells with high concentrations of salt, immediately after adsorption of polynucleotides, or by incubation of the cells with single-stranded polynucleotides. The inhibition is probably due to displacement of the inducing molecule from the cell surface. Interferon production by cells treated sequentially with poly(rI) and poly(rC) is not inhibited by either of these treatments and the polynucleotides are not easily displaced from the cell surface.
The results of treatment of injuries of the thoracic and thoraco-lumbar spine with neurological involvement have been reviewed in a retrospective study of 115 patients, of whom eighty-nine received conservative and twenty-six surgical treatment. Operation was reserved, in general, for patients with irreducible dislocations and incomplete neurological lesions, open reduction and internal fixation being the commonest procedure. Only three patients required a delayed spinal fusion for suspected instability after a period of conservative treatment. On the other hand, ten patients, eight of whom had been treated surgically, were left with severe chronic spinal pain. Of the patients treated conservatively, 35% showed significant neurological improvement compared to 38% of those treated surgically, but the latter group contained a much higher proportion of incomplete lesions with a far better prognosis. It is concluded that the place for early operation might be still further restricted.