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Biomedical subjects

D S Ellis

Publications and source records attributed to D S Ellis.

At least 55 records · Page 3Linked to original sources

The chemotherapy of rodent malaria. XLII. Halofantrine and halofantrine resistance.

As a blood schizontocide, halofantrine is about three times as active against a drug-sensitive line of Plasmodium berghei (N strain) as chloroquine, but it lacks any causal prophylactic effect. This activity is retained against parasites highly resistant to primaquine, cycloguanil, pyrimethamine, sulphaphenazole and menoctone. A marked resistance to halofantrine is shown by parasites resistant to mefloquine, quinine, chloroquine and amodiaquine, although the moderately chloroquine-resistant 'NS line' is sensitive. The artemisinin-resistant line shows a moderately reduced response. A high level of resistance was rapidly developed in the 'NS line' to halofantrine (NS/HAL line) but not in the N strain (N/HAL). The NS/HAL line was cross-resistant to mefloquine, amodiaquine and, to a lesser degree, artemisinin, but remained sensitive to chloroquine and quinine. The implications to a lesser degree, artemisinin, but remained sensitive to chloroquine and quinine. The implications of these observations for the possible future clinical deployment of halofantrine are discussed, and emphasis is laid on the need to find means of impeding the resistance to it of Plasmodium falciparum.

Animals↗

Congenital neurocutaneous melanosis with metastatic orbital malignant melanoma.

Proptosis and ptosis, caused by a large orbital mass that was excised and determined to be malignant melanoma, developed in a 4-year-old girl with congenital neurocutaneous melanosis (multiple large or giant cutaneous nevi associated with abnormal leptomeningeal pigmentation). Shortly thereafter, the patient had evidence suggestive of systemic metastases and died. The orbital tumor was likely metastatic from a primary meningeal melanoma. Other possible sources of metastatic tumor are discussed. It is unlikely that this was a primary orbital melanoma because the patient had no clinical or pathologic manifestations of pre-existing oculocutaneous melanosis, orbital melanosis, or orbital blue nevus.

Biopsy↗

The chemotherapy of rodent malaria XLI. Causal prophylaxis. Part V. Effect of mefloquine on exoerythrocytic schizogony in Plasmodium yoelii yoelii.

Previous studies using mefloquine in rodents have suggested that this compound has no effect on pre-erythrocytic schizogony. In the present study, direct observations on 46-hour-old pre-erythrocytic schizonts of P. yoelii in the liver of rats have shown that mefloquine does induce recognizable changes in the peripheral, enzyme-containing vesicles but that these are insufficient to hinder the maturation of the parasites, thus confirming that this compound has no causal prophylactic value.

Animals↗

The behaviour of trypanosomes within the midguts of wild-caught tsetse from Zimbabwe.

Trypanosomes infecting the midgut of wild-caught tsetse from Zimbabwe were found on electron microscopic examination to be penetrating the peritrophic membranes and so entering the ecto-peritrophic space in the mycetome region of the midgut. Other trypanosomes entered midgut cells, behaviour similar to that previously reported in laboratory-infected tsetse colonies.

Animals↗

The chemotherapy of rodent malaria, XXXIX. Ultrastructural changes following treatment with artemisinine of Plasmodium berghei infection in mice, with observations of the localization of [3H]-dihydroartemisinine in P. falciparum in vitro.

Ultrastructural changes were followed in Plasmodium berghei after the treatment of the mouse host with a single 10 mg kg-1 dose of artemisinine (qinghaosu). After 30 minutes, changes in the limiting and other membranes of the parasite were seen, together with alterations in ribosomal organization and endoplasmic reticulum. No changes were noted in digestive vacuoles or pigment, but nuclear membrane blebbing developed after one hour and segregation of the nucleoplasm after three hours. Further degenerative changes with disorganization and death occurred from eight hours onwards. The morphological changes in ribosomes and endoplasmic reticulum correlate in time with the depression in protein synthesis observed in P. falciparum in vitro. Similarly, the onset of nucleoplasmic segregation correlates with the development of nucleic acid synthesis inhibition. Tritiated reduced drug was shown to be localized in parasite membranes, indicating that changes in membrane integrity might precede the early depression of protein synthesis. Membrane association of artemisinine may be related to its amphipathic characteristics and similarity in some respects to a sterol.

Animals↗

Persistent lymphadenopathy in homosexual men: a clinical and ultrastructural study.

Ultrastructural changes (tubuloreticular structures and tube and ring shaped forms) previously described in patients with acquired immunodeficiency syndrome (AIDS) are described for the first time in the lymph nodes and circulating lymphocytes of patients with persistent lymphadenopathy. These observations support the view that the persistent lymphadenopathy syndrome and AIDS are caused by the same transmissible agent(s).

Acquired Immunodeficiency Syndrome↗

Preliminary observations on unidentified particles in mouse "L" cells found by electron microscopy.

Long particles, 75 nm in diameter, some branching and some curled at their ends, were found within vacuoles in "L" cells. These could be easily transmitted to Vero cells, which like the "L" cells were killed. The particles were up to 20 microns in length with hollow cores 37 nm in diameter surrounded by a smooth unit membrane from which no spikes protruded. The particles could not be assigned to any known taxon.

Animals↗

A method for increasing the surface details of resin embedded viruses using Congo/Crimean haemorrhagic fever virus as a model.

The surface details of resin embedded viruses can be greatly enhanced by the use of uranyl acetate block staining. The virions are embedded in agar immediately after fixation and block stained with 3% uranyl acetate in methanol during dehydration. This technique allows those particles outside their host cells to show clearly the spikes normally seen only by the separate use of negative staining.

Bunyaviridae↗

Leber's congenital amaurosis associated with familial juvenile nephronophthisis and cone-shaped epiphyses of the hands (the Saldino-Mainzer syndrome).

Three affected children (a 13-year-old girl and her 7- and 8-year-old brothers) in a sibship of eight had findings consistent with the Saldino-Mainzer syndrome (skeletal dysplasia associated with Leber's congenital amaurosis, familial juvenile nephronophthisis, and cone-shaped epiphyses of the hands). Two also had pigmented midline nevi. Although tapetoretinal degeneration and familial juvenile nephronophthisis are associated in the inherited Senior-Loken syndrome, the rare association of these abnormalities with cone-shaped epiphyses of the hands suggested an autosomal recessive syndrome with variable expression remarkably similar to the Saldino-Mainzer syndrome, which may or may not be distinct from the Senior-Loken syndrome. The association of tapetoretinal degeneration with skeletal dysplasia may indicate asymptomatic renal or hepatic disease.

Adolescent↗

The chemotherapy of rodent malaria, XXXVIII. Studies on the activity of three new antimalarials (WR 194,965, WR 228,258 and WR 225,448) against rodent and human malaria parasites (Plasmodium berghei and P. falciparum).

In addition to their blood schizontocidal action on Plasmodium berghei in vivo, two Mannich bases WR 194,965 and 228,258 are also active against chloroquine-sensitive and chloroquine-resistant lines of P. falciparum in vitro. The response of the lines to each drug differs but shows no correlation in either case with response to chloroquine. The 8-aminoquinoline WR 225,448 is also active against P. falciparum in vitro but at much higher concentrations than the Mannich bases. Application of the 'chloroquine-induced pigment clumping (CIPC) test' and the study of ultrastructural changes induced in P. berghei in drug-treated mice indicate that WR 194,965 has a mode of action somewhat resembling that of quinine. WR 228,258 in vitro shows a chloroquine-like effect, but not in vivo, suggesting that its mode of action in vivo is different from that of chloroquine. WR 225,448 has no action in the CIPC in vitro and affects primarily mitochondria of the parasites in vivo. It probably acts through a metabolite. Both pre-erythrocytic and erythrocytic stages of rodent malaria parasites are affected by WR 225,448.

Aminoquinolines↗