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Biomedical subjects

E J Ross

Publications and source records attributed to E J Ross.

At least 19 recordsLinked to original sources

Severity of imported falciparum malaria: effect of taking antimalarial prophylaxis.

OBJECTIVE: To investigate the effects of antimalarial chemoprophylaxis and other variables on the severity of falciparum malaria. DESIGN: Review of consecutive malaria cases between 1987 and 1991. SETTING: The Hospital for Tropical Diseases, London. SUBJECTS: 250 consecutive cases of mild and 51 consecutive cases of severe falciparum malaria. RESULTS: Prophylaxis was taken in 52.4% (131/250) of the cases of mild malaria and 21.6% (11/51) of cases of severe malaria. Severe malaria was more common in white patients than in those of African origin and was also seen more commonly in people returning from central, southern, and east Africa than in those returning from west Africa. Patients with severe malaria presented sooner than patients with mild malaria. CONCLUSIONS: Prior chemoprophylaxis led to a reduction in the severity of falciparum malaria. Ethnic origin, time to presentation, and sex were also associated with the severity of malaria.

Adult

Comparative abilities of various metabolites of vitamin D to protect cultured human macrophages against tubercle bacilli.

Vitamin D metabolites have several biologic functions besides the best-known one of controlling mineral metabolism, one of which may be protection against tuberculosis. The chemical structures of the metabolites govern their functions. The most potent metabolite for regulating calcium metabolism is 1,25(OH)2-vitamin D3 (1,25-D3). This metabolite also is able to protect cultured human monocytes and macrophages (MP) against tubercle bacilli (TB). To determine whether these two functions are connected, 14 other analogs or metabolites of vitamin D were compared with 1,25-D3 for ability to protect cultured MP against TB. Blood-derived MP from 18 different donors were used in 70 experiments. The MP were infected with TB, then incubated for 7 days in medium containing 4 micrograms/ml of metabolite or synthesized analog. Growth of TB in the MP was measured by colony-forming unit counts from samples of lysed MP at 0, 4, and 7 days after infection. The metabolites, none of which inhibited TB in the absence of MP, varied from unprotective to bacteriostatic in the MP. Four of them were nearly as protective as 1,25-D3, and the metabolite 25S, 26(OH)2-vitamin D3 was consistently more protective. An analog synthetically designed for maximum ability to promote cell differentiation was unprotective. There was no correlation between metabolite ability to protect and known ability to stimulate calcium mobilization. These results suggest that antituberculosis protection of human MP by vitamin D metabolites or analogs can be separated from their functions of inducing cell differentiation and controlling mineral metabolism.

Adult

Inhibition by retinoic acid of multiplication of virulent tubercle bacilli in cultured human macrophages.

The immunologically active vitamin retinoic acid (RA) was tested for the ability to increase the resistance of cultured human macrophages (MP) to experimental infection with virulent Mycobacterium tuberculosis Erdman (tubercle bacilli [TB]). It was added to MP in various concentrations and addition regimens. Protection against TB was measured by counting live TB (CFU) in lysates of samples of MP taken at 0, 4, and 7 days after MP infection. RA was protective when added after infection at the pharmacologic concentration of 10(-5) M and when added before infection at the physiologic concentration of 10(-7) M. The protection lengthened intracellular generation times for TB, occasionally caused bacteriostasis, and regularly kept CFU counts at 7 days (end of the period of infection) 1 to 2 log10 CFU below control values. Significant protection was seen in a series of 16 experiments with MP from seven different donors, but the degree of protection varied considerably. The protection depended partly on and was inversely proportional to concentrations of a serum substitute or autologous serum used as a supplement in the RPMI 1640 MP culture medium. It was strongest at concentrations of serum below 1%. RA at concentrations used in the MP cultures did not inhibit TB in the absence of MP. These results suggest that RA (vitamin A), like vitamin D, may have some immunoprotective role against human tuberculosis, as historically intimated by the regular use of vitamin A- and D-rich cod liver oil for the treatment of tuberculosis before the introduction of modern chemotherapy.

Cells, Cultured

Inhibition by 1,25(OH)2-vitamin D3 of the multiplication of virulent tubercle bacilli in cultured human macrophages.

Historically, sunlight has seemed to fortify antituberculosis resistance. Evidence is presented here suggesting a role for vitamin D in this effect. The active metabolite of this photosynthesized vitamin, 1,25-dihydroxy-vitamin D3 (1,25D), promotes maturation and activation of human monocytes and macrophages (MPs). Therefore, it was tested for ability to protect MPs against virulent tubercle bacilli. MPs were derived by 7-day culture from blood monocytes, infected with the bacilli, and exposed to 1,25D in several regimens. Their inhibition of bacilli was measured by lysing samples of the cultures at 0, 4, and 7 days after infection and making bacillary CFU counts from serial dilutions of the lysates. 1,25D enabled MPs to slow or stop bacillary replication. Autologous serum supported the 1,25D-induced protection because the vitamin was not effective in medium supplemented with a serum substitute and was less effective in a heterologous AB serum than in autologous serum. The protection developed rapidly and could be induced even when 1,25D was added 3 days after infection. A concentration on the order of 4 micrograms/ml was needed for protection by the regimens used in these experiments. That is considerably higher than normal circulating concentrations of 1,25D but could be reached in infectious granulomas, because MPs can make 1,25D from precursor 25-hydroxyvitamin D3. The precursor circulates at levels 10(3) higher than those of 1,25D and is directly influenced by dietary intake or photosynthetic production of vitamin D. These results identify 1,25D as an immunomodulator which can reproducibly activate human MPs to express tuberculoimmunity. They connect vitamin D, sunlight, and tuberculoimmunity and suggest that vitamin D should be considered a vital factor in the practical control of tuberculosis.

Calcitriol

Immunological relationships among proteins making up the Bacillus thuringiensis subsp. israelensis crystalline toxin.

The immunological relationships among the proteins of the mosquito larvicidal toxin produced by Bacillus thuringiensis subsp. israelensis have been investigated by using polyclonal antisera specific for the 28-, 70-, and 135-kilodalton proteins. Each of these proteins was immunologically distinct. There was no cross-reaction among the three proteins and the two non-homologous antisera. Treatment of toxin proteins with larval gut enzymes for 20 h identified protease-resistant domains at approximately 65, 38, and 22 kilodaltons. Similar domains were generated by treatment with trypsin and chymotrypsin. Our immunological and kinetic data indicate that the 28-kilodalton protein is degraded successively to protein bands at 26, 25, 23, and 22 kilodaltons, the 70-kilodalton protein is degraded to a protein at 38 kilodaltons, and the 135-kilodalton protein is degraded successively to protein bands at 94, 72, and, probably, 65 kilodaltons. Solubilized toxin possesses two biological activities, larvicidal and general cytolytic (hemolytic). We used nondenaturing gel electrophoresis to show that the hemolytic activity resides in the 28-kilodalton protein. However, higher-molecular-weight proteins are required to achieve the level of toxicity observed in intact toxin.

Antibody Specificity

The clinical response to treatment in adult Cushing's syndrome following remission of hypercortisolaemia.

The clinical response of 57 adult patients with Cushing's syndrome due to bilateral adrenocortical hyperplasia or adrenocortical adenoma is documented following resolution of hypercortisolaemia by various forms of treatment. Despite satisfactory biochemical remission of the disease the clinical result was far less satisfactory when assessed by persistence of obesity (55%), menstrual irregularity (41%), hypertension (29%) and insulin-dependent diabetes (22%). Myopathy, hirsuitism and psychological abnormalities persisted to a lesser extent. The mortality rate of the series over a 30 year follow-up period was 4 times that of a general population matched for sex, age and year of entry into the series. Cardiovascular disease was the cause of death in 85%. Irreparable cardiovascular disease is produced early in the course of hypercortisolaemia, emphasizing the vital importance of the earliest possible recognition and treatment of this disease.

Adenoma

Cushing's syndrome: current status.

The evolution of ideas concerning the aetiology of Cushing's syndrome over the past 70 years is reviewed briefly. It is now agreed that about 70% of patients have a pituitary adenoma, not necessarily basophil, the removal of which results in remission but follow-up is currently too short for assessment of ultimate cure. Whether or not the pituitary lesion is primary or secondary to events in the cerebrum or brainstem is discussed, but a definite answer cannot be given at present.

Adenoma

Prolonged survival with adrenal cortical carcinoma.

Recurrence of adrenal cortical carcinoma 22 years after first presentation is reported in a 54-year-old woman with Cushing's syndrome. This tumour is normally associated with poor prognosis and prolonged survival is rare. Although the patient had remained well with apparent 'cure' in the intervening years, it is suggested that hormonal changes related to the menopause and the development of primary hypoadrenalism stimulated recurrence of malignant activity and return of Cushingoid features.

Adrenal Cortex Neoplasms

An isolation system for aldosterone and tetrahydroaldosterone prior to estimation by gas liquid chromatography or radioimmunoassay.

We report a method of isolation of aldosterone and tetrahydroaldosterone from urine and undiluted plasma which is based on extraction with Amberlite XAD-2 resin and purification by low pressure liquid chromatography using microbore LH-20 columns. Thin-layer chromatography on polyamide plates is introduced as the final step of a procedure designed to reduce destruction of steroids to a minimum, and to provide, in addition, a facility for multisample processing. Using a synthetic substrate, it has been shown that enzyme hydrolysis of steroid conjugates is possible whilst still adsorbed to the resin after extraction although the yield is lower than when hydrolysis is performed in solution.

Aldosterone