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Biomedical subjects

A C White

Publications and source records attributed to A C White.

At least 109 records · Page 6Linked to original sources

Species and stage specificity of Leishmania donovani antigens.

Monoclonal antibodies D2 and D13 were produced in mice using Leishmania donovani promastigote membrane fractions. To study the species and stage specificity of the antigens recognized by these antibodies, we examined amastigotes prepared in vitro and cultured promastigotes by indirect immunofluorescence with monoclonal antibodies D2 and D13. Monoclonal antibody D2 showed weak reactivity for 9 of 9 strains of L. donovani complex promastigotes and 8 of 9 amastigotes. In contrast, only 2 of 22 strains from other complexes yielded equivocal reactions. Monoclonal antibody D13, however, had much broader reactivity. D13 reacted with all the promastigotes and amastigotes of L. donovani complex isolates as well as with 10 of 22 promastigotes and 8 of 13 amastigotes from other complexes. The high degree of species specificity seen with monoclonal antibody D2 provides a rationale for further study of this antibody and its purified antigen for parasite identification and serodiagnosis of visceral leishmaniasis. The strong fluorescent signal noted with D13 and the presence of the D13 epitope on all L. donovani complex parasites supports studies on its role as an antigen in immunoprophylaxis of visceral leishmaniasis.

Animals↗

Purification and characterization of an 80-kilodalton membrane protein from Leishmania donovani.

Visceral leishmaniasis is caused by the protozoan parasite Leishmania donovani. We previously described the development of 16 monoclonal antibodies specific for L. donovani. The epitope recognized by one of these monoclonal antibodies, D13, is present at high density on nearly all isolates of L. donovani and, along with two other monoclonal antibodies, has been used to develop a sensitive and specific competitive assay for serodiagnosis of visceral leishmaniasis. In this report, we characterize the antigens recognized by D13 by immunoprecipitation of [35S]methionine-labeled promastigotes as two proteins (apparent molecular mass, 72 and 80 kilodaltons). Pulse-chase studies showed no evidence of a precursor-product relationship for the two proteins. We purified the 80-kilodalton protein (p80) to homogeneity by detergent solubilization of promastigote membranes, immunoaffinity chromatography, and ion-exchange chromatography. The epitope on p80 recognized by D13 was completely destroyed by proteolysis but was not affected by periodic acid treatment. P80 did not bind to the radioiodinated lectins concanavalin A, wheat germ agglutinin, and Ricinus communis agglutinin. Its apparent molecular mass was not affected by tunicamycin. Thus, it does not appear to be glycosylated. This protein is highly immunogenic and may prove useful for immunoprophylaxis and serodiagnosis of visceral leishmaniasis.

Amino Acids↗

Development and evaluation of diagnostic radiometric assays for serogroup 4 L. pneumophila urinary antigens.

We previously reported that 80% of patients with serogroup 1 Legionella pneumophila pneumonia excrete detectable quantities of specific antigens in their urine. The purpose of this study was to determine whether specific antigens can be detected in urine from patients with serogroup 4 L. pneumophila pneumonia. Antisera were prepared in 15 rabbits and used to set up 25 solid-phase radioimmunoassays. The best of these assays detected specific antigens in urine from 4 of 5 patients with culture-proven serogroup 4 infections and from 1 of 2 patients with culture-proven serogroup 10 infections. None of 100 control specimens was positive in the assays. The antigens from serogroup 4 and 10 infections behaved differently in the assays, suggesting that they are not identical molecules. This study demonstrates that it is possible to detect specific antigens in the urine of patients with serogroup 4 L. pneumophila pneumonia. This may be a useful method for diagnosing these infections rapidly.

Animals↗

Steroid modulation of liver regeneration and hepatic microsomal enzymes in rats of either sex.

Rats of either sex as intact or partially hepatectomized (two-thirds liver removal) were injected s.c. daily for 7 days post-operatively with natural and synthetic estrogens, androgens or anabolic steroids, progesterone and adrenal cortical hormones and killed on day 10 at which time the livers were processed for microsomal analyses (protein, cytochrome P-450 and enzymes, aminopyrine demethylase and aromatic hydrocarbon or benzo[a]pyrene hydroxylase). Groups were also induced with phenobarbital injected i.p. on the last 3 days at 80 mg/kg each. With the intact males, hexestrol was the only estrogen which caused liver enlargement and at a daily dosage of 1.0 micrograms per rat as well as a decrease in the hydroxylase level. Estradiol benzoate (15 micrograms/rat daily) depressed cytochrome P-450 and the other steroids screened had little effect on the microsomal parameters except for a rise in demethylase with deoxycorticosterone acetate (1.0 mg). A greater sensitivity to estrogens and the other steroid types was noted with the partially hepatectomized males and in the direction of depressions in the microsomal elements, the respective data being expressed as percentages of the controls. Estrogens were better tolerated by the intact female and in general, liver enlargement was remarkable. Microsomal activity was elevated with estradiol benzoate or little affected by estrogens except for depressions in hydroxylase levels with equilin (15 micrograms) and the high dosages of hexestrol and diethylstilbestrol, the last agent also eliciting an increase in cytochrome P-450. No statistically significant effect on the microsomal parameters was observed with the intact female treated with 17-methyltestosterone and the anabolic steroids but decreases occurred on injection with testosterone propionate and the cortical hormones. As with the operated male, partially hepatectomized females exhibited no hepatotrophic response to estrogens and the microsomal changes were moderate with such agents as with the other steroid types and resembling the findings for intact males. Competitive inhibition was followed by Lineweaver-Burke analyses of aminopyrine demethylase in operated females treated with several of the steroids.

Animals↗

Lithium augmentation in the treatment of delusional depression.

Five patients suffering with delusional depression, and who were resistant to tricyclic antidepressants, were successfully treated with lithium carbonate. Delusional depression does not usually respond to tricyclic antidepressants, and ECT has been considered the treatment of choice. Such patients often refuse to acknowledge that they are ill. They, therefore, understandably often refuse to accept ECT. In order to treat, the Mental Health Act 1983 must be invoked. Treatment with lithium carbonate is more acceptable to most patients, and in the cases described, patients agreed to take this drug whereas they had refused to accept ECT.

Adult↗

Serological diagnosis of Staphylococcus aureus osteomyelitis.

We have evaluated serological tests for the diagnosis of Staphylococcus aureus osteomyelitis. Antiteichoic acid antibodies were elevated in 17 of 23 patients with acute and 16 of 46 with chronic S. aureus osteomyelitis but in none of 33 patients infected with other gram-positive or gram-negative bacteria. Immunoglobulin G antibodies to S. aureus were elevated in 12 of 23 patients with acute and 22 of 47 with chronic S. aureus osteomyelitis, in 2 of 12 infected with other gram-positive bacteria, and in 4 of 21 with other gram-negative bacteria. Assays for S. aureus antibodies may be useful for identifying patients with S. aureus bacteremia complicated by metastatic sites of infection in bone and for identifying the etiological agents in patients with negative or mixed cultures or from whom cultures are not readily available. Prospective studies are needed to test these hypotheses.

Antibodies, Bacterial↗

Liver regeneration and hepatic microsomal enzyme induction by acetaminophen and derivatives.

Liver regeneration was stimulated in male rats with two-thirds of the liver removed by feeding a basal diet supplemented with acetaminophen (0.35-1.5%; weight basis), 2-acetamidophenol (1.0%) and acetophenetidin (1.0%) over a period of 10 days po, but was in the control range with the m-isomer, 3-acetamidophenol (1.0%), N-butyryl-p-aminophenol (1.0%), o-, m- and p-aminophenols (0.50%) and 4-acetamidothiophenol. In fact, the latter inhibited at a level of 0.60%. The operated young or mature female underwent no significant increase in control response with acetaminophen (1-1.5%). However, as with the male, the wet and dry liver weight percentages were markedly increased in the intact female fed acetaminophen (1.0-1.5%) as also with 2-acetamidophenol (1.0%). Liver enlargement occurred in the intact male with acetophenetidin (1.0%) but not with the N-butyryl- and thiophenol derivatives fed at 1.0 and 0.50%, respectively. Hepatic microsomal preparations from the intact and operated series showed no remarkable changes in cytochrome P-450 nor in the enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase, with the more polar acetaminophen and the N-butyryl compound but the enzymes were elevated in the group fed acetophenetidin. Inductive effects on microsomal enzymes were further amplified by injection of several animals per group with phenobarbital ip daily at 80 mg/kg for the last 3 days prior to sacrifice. Increases in increments or liver weight percentages ensued over the basal values and as investigated in an intact male series, the enzymes ranged higher than the uninjected controls and with the thiophenol-fed group, exceeded those of the phenobarbital-injected controls.

Acetaminophen↗

Antibody response to peptidoglycan during staphylococcal infections.

Levels of antibodies to peptidoglycan were measured by solid-phase radioimmunoassay in 76 patients with Staphylococcus aureus infections and 44 patients with infections caused by other bacteria. Levels of IgM antibodies to peptidoglycan were elevated in 24% of the patients with endocarditis or complicated bacteremia caused by S. aureus, 21% of those with serious infections caused by other gram-positive cocci, none of those with less serious infections caused by S. aureus or gram-negative bacilli, and 5% of the normal controls. Levels of IgG antibodies to peptidoglycan were elevated in 50% of the patients with endocarditis or complicated bacteremia caused by S. aureus, 3% of those with less severe infections caused by S. aureus, 17% of those with infections caused by other gram-positive cocci, 20% of those infections caused by gram-negative bacilli, and 5% of the normal controls.

Antibodies, Bacterial↗

Pre-accident medication and alcohol in burn and other accident victims.

The level of pre-accident drinking was found, to be high in a consecutive series of severely injured burn victims and also a group of other accident victims matched for age and sex. More males than females had drunk prior to their accident. Similarly, the number of victims who had taken medication in the 25 h prior to the accident was high. More females than males had taken medication: predominantly drugs with effect on the central nervous system.

Accidents↗

Psychiatric study of patients with severe burn injuries.

About two-thirds of a consecutive series of patients severely injured with burns followed up one year after discharge were found to have psychological sequelae. Duration of hospital stay and the presence of certain mental illnesses were related to the incidence and severity of psychological symptoms. This relation did not apply to the site of the burn and the existence of a claim for compensation. The incidence of post-traumatic neurosis in patients with burn injuries could be reduced by identifying and treating, soon after the accident, those who need psychiatric help.

Adult↗

Growth and histology of a human mammary-carcinoma cell line at different sites in the athymic mouse.

Experiments were conducted to determine whether the histological pattern of tumour growth of hormone-responsive MCF-7 human mammary adenocarcinoma varied in different tissues of athymic mice. Tumours in the uterus following intrauterine injection were rapidly proliferating and highly invasive. Tumours injected intracerebrally were also highly invasive. In contrast, s.c. tumours and those which arose in the lung following intrapleural injection, grew as small localized nodules without evidence of aggressive invasion of surrounding tissues. These findings indicate that selective implantation of human tumours in athymic mice can be used to develop different models of tumour growth and aggressiveness.

Adenocarcinoma↗