573

suggest that the viruses isolated from northern Zaire and southern Sudan are related serologically to the Marburg virus strain isolated in 1967. 18 convalescent sera collected in the Sudan did have fluorescent antibody titres ranging from 1/4 to 1/128 against one of the Zaire virus isolates. Although this evidence is slight it suggests that both outbreaks have been caused by viruses which are related if not identical. Studies are in progress to determine the relationship between the new isolates from Zaire and the Sudan with the Marburg strain isolated in 1967. to

REFERENCES 1. Wld Hlth Org. wkly epidem. Rec. 1976, 51, (42), pp. 325-332. 2. ibid. p. 325. 3. Zlotnik, I., Simpson, D. I. H., Howard, S. M. R. Lancet, 1968, ii, 26. 4. Zlotnik, I., Simpson, D. I. H., Bnght, W. F., Bowen, E. T. W., Batter-Hatton, D. Br. J. exp. Path. 1968, 49, 311. 5. Smith, C. E. G., Simpson, D. I. H., Bowen, E. T. W., Zlotnik, I. Lancet, 1967, ii, 1119. 6. Zlotnik, I. Trans. R. Soc. trop. Med. Hyg. 1969, 63, 310.

ISOLATION OF MARBURG-LIKE VIRUS FROM A CASE OF HÆMORRHAGIC FEVER IN ZAIRE

G.

S. PATTYN W. JACOB P. PIOT GROEN G. COURTEILLE

Fig. 2-Virus particles originating (reduced from x 112 000).

at

intracellular membranes

of newborn mice intracerebrally, and into 10 tubes of Vero-cell cultures (grown in medium 199 containing 7.5% calf serum). The serum was tested by complement fixation for Lassavirus antibodies (the result was negative) and by neutralisation on Vero cells for antibodies against yellow-fever virus (antibodies were present at 1/30 dilution). RESULTS OF INOCULATIONS

VAN DER

Mice

University of Antwerp and Institute of Tropical Medicine, Antwerp, Belgium, and Clinique Ngaliema, Kinshasa, Zaire WE record here our findings in the investigation of the outbreak of severe haemorrhagic fever in Zaire. SOURCE AND EXAMINATION OF SPECIMEN

A 42-year-old woman (patient M.E.) fell ill on Sept. 23, 1976, in Yambuku, Equateur Province, Zaire. She was transported by air on Sept. 25 to Kinshasa, where a haemorrhagic

syndrome gradually developed. Clotted blood taken on the Sth day of illness was sent on ice to the Institute of Tropical Medicine, Antwerp. The sample arrived in the evening of Sept. 29 and was kept in the refrigerator. The next morning serum was inoculated into 6 young adult mice by intracerebral and intraperitoneal routes, into 2 litters

One animal was found dead on the 4th day and a second on the 5th day. Brains were taken from these animals and the survivors on the 5th day.

Newborn Mice On the fifth day of observation one animal was found dead and partially eaten in each litter. In one litter several mice had disappeared on days 6 and 7, leaving only one animal. In the second litter, however, in which the animals had been very healthy during the whole observation period, only three young mice were left: one dead, one paralysed, and one very sick. The brains of these animals were removed and sent to the Microbiological Research Establishment, Porton, for further study.

Vero Cells

During the

days of observation

some cells in the botof most tubes became detached from the glass surface. Though this was first interpreted as a partial cytopathic effect, it did not increase during the following days and it was then judged to be non-specific. On day 5 the tissue-culture medium was changed to the succinate/succinic-acid buffered medium (as described by Plaisner et al.1) without serum. In our experience this medium permits the observation of Vero cells for several weeks, while many arboviruses produce a cytopathic effect in these conditions. On day 11 a very striking cytopathic effect was observed in these cultures, with most cells still attached to the glass. The cytopathic effect was almost complete on day 12.

first 4

tom

ELECTRON-MICROSCOPY FINDINGSS

. ’5’

’-eXtracellular

112 000).

straight

and cross-sectioned virus

particles (reduced from

x

The supernatant fluid of three tubes was decanted and they were filled with 3% glutaraldehyde for 30 min. The cells were then scraped off in a small amount of glutaraldehyde, rinsed with cacodylate-buffered sucrose (7.5%), postfixed in 1% phosphate-buffered osmium tetroxide, and prepared by the albumin coagulation method. Blocking staining

574

performed with 0.5% uranyl acetate, followed by dehydembedding in Spurr’s low-viscosity medium. Electron-microscopic examination of ultrathin sections of this material revealed extracellular straight and cross-sectioned virus particles morphologically similar to Marburg virus (fig. 1). Intracellular nucleocapsids were also seen, some of them apparently originating in vesicles (figs. 2 and 3). At the same time sections of the liver of the patient from was

ration and

whom this virus had been isolated and who had died on Oct. 1 became available. Although the ultra-structure of this tissue was very poorly preserved, similar virus particles were observed. CONCLUSION

It was concluded that the agent responsible for the epidemic of hsemorrhagic fever in Central Africa was either Marburg virus or a virus serologically different from it but belonging to the same virus group, either

rhabdovirus2

or

torovirus.3 REFERENCES

Plaisner, V., Hronovsky, V., Benda, R., Ćin&a cute;tl, J. Acta virol. 1974, 18, 445. Siegert, R., Shu, H. L., Slenczka, W., Peters, D., Muller, G. Dt. med. Wschr. 1967, 92, 2341. 3. Almeida, J. D., Waterson, A. P., Simpson, D. I. H. in Marburg Virus Disease (edited by G. A. Martini and R. Siegert). Berlin, 1971.

1. 2.

Fig. 3-Intracellular cross-sectioned virus particles (reduced from x 112 000).

Hypothesis

EVIDENCE

PRIMARY LESION IN OSTEOARTHROSIS L. E. GLYNN Mathilda and Terence Kennedy Institute of London W6 7DW

Rheumatology,

The primary disturbance in osteoarthrosis is generally regarded as occurring in the articular cartilage and as resulting from a combination of ageing and mechanical factors. An alternative hypothesis is that the primary disturbance is located in the synovial lining cells. It is suggested that proteolytic enzymes which normally leak from the phagocytic (A type) lining cells are in the healthy joint neutralised by inhibitors synthesised by the B-type lining cells. Osteoarthrosis is the result of an imbalance between leakage of enzymes and provision of inhibitors.

Summary

INTRODUCTION

OSTEOARTHRITIS is

now

widely

known

as

osteoarth-

rosis, and this change of name emphasises the currently held view that this is a degenerative rather than an inflammatory disease. Degeneration in the articular cartilage culminates in a progressive loss of the proteoglycans, shortly followed by that of the constituent collagen.’ The cause of the degenerative process has been variously ascribed to ageing, to fatigue fractures of collagen,2or as secondary to micro-fractures in the underlying cancellous bone.3 The view that osteoarthrosis is primarily the result of degeneration of the articular cartilage has remarkably little to support it and has been singularly unrewarding in suggesting methods of either prophylaxis or treatment. Can it be that the hypothesis is fundamentally wrong and that the primary site of the disease is elsewhere ? An alternative approach suggests that the synovial membrane is the site.

Electron microscopy of normal synovial tnembrane4 shows two distinct types of cell with some intermediate forms: type-A cells have the organelles of a macrophage with many large vacuoles, pinocytotic vesicles, lysosomes, and filopodia; type-B cells have the organelles of a protein-synthesising and secreting cell, namely much rough endoplasmic reticulum and a readily recognisable Golgi system. The A cells are actively phagocytic, as can be readily shown by injecting a joint with iron dextran’ or thorium dioxide.6 Since the A cells constitute about half the total number of lining cells, and since function determines structure, then one must accept that in the normal di-arthrodial joint, material is being constantly produced that requires removal by phagocytic cells. The A cells may therefore be regarded as functioning in the same way and for the same purpose as the oil filter in an internal combustion engine, namely to keep the bearings clean. When a phagocytic cell (polymorphonuclear cell or macrophage) engulfs foreign material it does so by invaginating its surface membrane to form a vesicle into which the foreign material is taken. This vesicle then merges at its internal border with an adjacent lysosome. "Since the vacuole is still open to the outside at the periphery, regurgitation of lysosomal hydrolases occurs".’ In the case of the synovial membrane these hydrolases are presumably released into the joint space where they would be free to attack the exposed surface of articular cartilage." This is a normal sequence of events, and since digestion of the cartilage is not evident in the normal healthy joint there is presumably some provision made to inhibit the undesirable effects of these leaking enzymes. The mammalian body is capable of producing powerful inhibitors of proteolytic enzymes-e.g., plasma «1 trypsin inhibitor and BX2-macroglobulin. Now although serum proteins are present in normal synovial fluid the BX2-macroglobulin, which is by far the most potent of the known inhibitors, is present at most in traces, which is not surprising because of its large mole-

Isolation of Marburg-like virus from a case of haemorrhagic fever in Zaire.

573 suggest that the viruses isolated from northern Zaire and southern Sudan are related serologically to the Marburg virus strain isolated in 1967...
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