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Biomedical subjects

R McLeod

Publications and source records attributed to R McLeod.

At least 109 records · Page 6Linked to original sources
PubMed1985

Influence of Toxoplasma on manifestations of Moloney virus infections.

Considerable evidence documents the importance of co-factors, including the immune response, in expression of oncogenicity of tumour viruses. To determine whether a common protozoal infection that can depress lymphocyte function alters manifestations of oncogenic virus infection, a mouse model of Toxoplasma infection with depressed T lymphocyte function was developed. In this model, Toxoplasma depressed blastogenic transformation to the T-cell mitogen Concanavalin A and primary antibody response to sheep red blood cells which requires T cell help. Uninfected and Toxoplasma-infected mice were then infected with Moloney leukaemia or Moloney sarcoma viruses and development of lymphoma and sarcoma were evaluated. Toxoplasma infection, which induced depression of T-cell function, decreased the incidence of Moloney sarcoma virus induced rhabdomyosarcomas but did not alter progression or regression of tumour in those mice that developed tumour. Conjoint infection with Toxoplasma and Moloney leukaemia virus did not increase incidence of lymphoma when compared with incidence of lymphoma in mice infected with Moloney leukaemia virus alone.

Animals↗
PubMed1985

Effects of adjuvants and Toxoplasma gondii antigens on immune response and outcome of peroral T. gondii challenge.

Toxoplasma gondii antigens and adjuvants administered parenterally and perorally were tested for their ability to produce serum antibody to T. gondii, to enhance peritoneal microbicidal capacity for T. gondii, and to prevent acquisition of infection by T. gondii ingested subsequently. N-acetylmuramyl-L-alanyl-D-isoglutamine-6-0-stearoyl (MDP) incorporated into liposomes administered intramuscularly to mice with 80 micrograms of T. gondii antigens and the synthetic adjuvant N,N-dioctadecyl-N',N'bis (2-hydroxyethyl) propanediamine (CP 20,961) administered intramuscularly to mice with 80 micrograms of T. gondii lysate antigens produced the highest titres of antibody to T. gondii in sera (i.e., the mean +/- S.D. of the log2 of the reciprocal of the antibody titre to T. gondii measured by Sabin Feldman Dye test was 9 +/- 2 in sera of mice that received T. gondii antigens plus MDP and was 8 +/- 1 in sera of mice that received T. gondii antigens plus CP 20,961). No orally administered preparation produced high titres of serum antibody to T. gondii. None of the preparations which were tested protected mice against infection with T. gondii when cysts containing the parasite were administered by mouth subsequently or enhanced macrophage microbicidal capacity between two and three weeks after the last immunizations. These experiments demonstrate that presence of Toxoplasma antibody (i.e., when log2 of the reciprocal of Toxoplasma antibody titres is 10 or less measured by Sabin Feldman dye test) does not protect mice against dissemination of ingested T. gondii from the gastrointestinal tract. The method of peroral challenge with T. gondii developed for this study is useful for examining effects of other potentially protective regimens in preventing acquisition of ingested T. gondii.

Adjuvants, Immunologic↗
PubMed1985

Urinary proteins in a patient with Tangier disease.

We have investigated the possibility that the mild proteinuria in a patient with Tangier disease is directly related to the plasma HDL-deficiency through excretion of apolipoprotein A-I (Mr 28,300). An increased urinary excretion of a 29,000 polypeptide was observed in this patient. However, western blot analysis of the urine showed that this protein was not apolipoprotein A-1 or its precursor form. Subsequent investigations identified the urinary protein as immunoglobulin light chains. The elevated excretion may be a consequence of the patient's plasma polyclonal gammopathy which had resulted from a chronic infection.

Adult↗
PubMed1985

Alveolar macrophage function and inflammatory stimuli in smokers with and without obstructive lung disease.

To explore possible cofactors in the development of chronic obstructive pulmonary disease (COPD) in smokers, we performed bronchoalveolar lavage in 6 smokers with normal pulmonary function, 6 smokers with COPD (FEV1/FVC less than or equal to 65%) matched for smoking history and age, and 9 age-matched nonsmoking control subjects. Elastase release by macrophages from smokers with COPD was significantly higher (p less than 0.016) than was elastase release by macrophages from normal smokers. There were no differences between chemoattractiveness of alveolar macrophage supernatants for one person's polymorphonuclear leukocytes among the groups of smokers and there was no detectable C5/C5a in these supernatants (limit of detection of C5a greater than 1 ng/ml). There were no significant differences in numbers or species of bacteria in aerobically and anaerobically cultured bronchial brushings. There was no difference in alveolar macrophage superoxide anion release with particulate or membrane-perturbing stimuli for the smokers. Alveolar macrophages from the 3 groups of subjects had similar limited microbicidal ability for the obligate intracellular protozoan, Toxoplasma gondii, and similar numbers of elastase receptors and affinity for elastase.

Adult↗
PubMed1985

Lymphocyte anergy specific to Toxoplasma gondii antigens in a baby with congenital toxoplasmosis.

A baby's clinical course during her first year of life documented her congenital infection with Toxoplasma gondii. Certain of her peripheral blood lymphocyte subtype numbers and functions were studied at intervals during this year: This patient's lymphocytes did not respond to Toxoplasma gondii antigens when she was 2 or 6 months old but did respond when she was 1 year old. Her lymphocyte anergy appeared to be a specific impairment or delay in lymphocyte blastogenic response to T. gondii antigens as her peripheral blood lymphocytes responded normally to the T-cell mitogen Concanavalin A and to allogeneic lymphocytes in mixed lymphocyte cultures. She had normal numbers of total peripheral blood lymphocytes and normal proportions of peripheral blood T cells with T4 and T8 surface antigens.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Role of lymphocyte blastogenesis to Toxoplasma gondii antigens in containment of chronic, latent T. gondii infection in humans.

Lymphocyte blastogenic transformation in response to Toxoplasma lysate antigen was markedly impaired in six of eight patients with chronic, latent Toxoplasma gondii infection and treated Hodgkin's disease. None of these patients with serum antibody to T. gondii measured by the Sabin Feldman Dye test and impaired lymphocyte transformation to T. gondii antigens had clinical or serologic evidence of disseminated, active infection with T. gondii. Partial depletion of adherent mononuclear leukocytes improved the impaired lymphocyte transformation of three of six patients; treatment of cultures from all patients with indomethacin improved their blastogenic transformation but culture with normal heterologous serum did not. These studies indicate that lymphocyte blastogenic response to T. gondii antigens is impaired in some patients with chronic, latent T. gondii infection and treated Hodgkin's disease but that this impairment of lymphocyte function is not sufficient to cause reactivation of chronic, latent T. gondii infection.

Adult↗
PubMed1984

Plasma lipoproteins and lecithin:cholesterol acyltransferase distribution in patients on dialysis.

Plasma lipoproteins and LCAT activity were studied using a single spin density gradient separation and an exogenous substrate enzyme assay in 41 patients on chronic hemodialysis and in 11 normal subjects. The plasma HDL cholesterol was markedly decreased (33 vs. 63 mg/dl, P less than 0.001) while total and LDL-cholesterol were unchanged in the patients. Plasma LCAT activity was significantly lower in the patient group (42 vs. 59 nmoles/4 hr/ml, P less than 0.001), but the distribution of activity (studied in 13 dialysis patients and 12 control subjects) was not different between the two groups: 90% being associated with HDL and VHDL lipoprotein fractions. To examine the possible genetic influence on the development of hypertriglyceridemia in the patient group, we examined the ratio of apolipoproteins E3/E2 and CII/CIII in ten of the patients and another group of 13 control subjects. The frequency of heterozygotes for E3 deficiency was not different between the patient (one of ten) and the control (two of 13) groups. While the patient group had lower CII/CIII ratio, the figures did not reach statistical significance. The low LCAT activity in the face of higher plasma triglycerides and low HDL may contribute to impaired lipolysis previously documented in uremic patients. A follow-up study performed 1 year after the initial study confirmed the decreased HDL (51 vs. 71 mg/dl, P less than 0.01) and LCAT activity (50 vs. 59 nmoles/hr/ml, P less than 0.02) in an exogenous substrate system (N = 20). LCAT measured using the endogenous substrate was not significantly different from the control group (49 vs. 55 nmoles/hr/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Immune response of mice to ingested Toxoplasma gondii: a model of toxoplasma infection acquired by ingestion.

SWR/J mice perorally infected with the Me49 strain of Toxoplasma gondii developed thymic cortical atrophy, clusters of epithelioid cells and plasma cells in lymphoid tissue, and hepatic inflammation during the first month after infection; the inflammation subsequently decreased. Antibody to T gondii was present in serum on day 14 after infection, reached a maximal titer by one month, and remained at this titer for five months. Splenic lymphocyte blastogenesis in response to concanavalin A was depressed for one month but returned to normal in most mice by two months. Splenic lymphocyte blastogenesis in response to toxoplasma antigens (stimulation index, greater than or equal to 1.6) developed in one-third of mice after two months of infection but did not develop in others even after five months of infection. Peritoneal macrophages had an enhanced microbicidal capacity against T gondii from 14 days until five months after infection. Peroral administration of the Me49 strain of T gondii was lethal for Beige-C57BL/6J and C57BL/6J mice; these strains of mice showed the most extensive changes, necrosis, thrombi, and many trophozoites in tissues.

Animals↗
PubMed1984

New micromethod to study the effect of antimicrobial agents on Toxoplasma gondii: comparison of sulfadoxine and sulfadiazine individually and in combination with pyrimethamine and study of clindamycin, metronidazole, and cyclosporin A.

An in vitro method by which reagents, cells, and Toxoplasma gondii trophozoites are conserved (micromethod) was developed to quantitate the effect of antimicrobial agents on T. gondii. Sulfadoxine alone had no effect on T. gondii in vitro when evaluated with a macromethod, the new micromethod, or visual inspection of Giemsa-stained preparations. Sulfadoxine combined with pyrimethamine inhibited T. gondii more than did pyrimethamine alone, but the combination of sulfadoxine plus pyrimethamine was slightly less active than was the combination of sulfadiazine plus pyrimethamine. Neither clindamycin nor metronidazole, alone or in combination with sulfadiazine or pyrimethamine and sulfadiazine, had any effect on intracellular T. gondii. Brief exposure (10 min before and during challenge) to clindamycin had no effect on extracellular T. gondii when clindamycin was studied alone or with sulfadiazine or pyrimethamine plus sulfadiazine. Cyclosporin A inhibited T. gondii replication at concentrations of ca. greater than or equal to 2 micrograms/ml.

Animals↗
PubMed1984

Action of a microbial glycerophospholipid:cholesterol acyltransferase on plasma from normal and LCAT-deficient subjects.

The action of a bacterial acyltransferase similar in overall reaction mechanism to the plasma enzyme lecithin:cholesterol acyltransferase (LCAT) has been studied using normal plasma and lipoproteins and plasma from LCAT-deficient patients. The microbial enzyme (GCAT) catalyzed acyl transfer using phosphatidylcholine and cholesterol in all of the lipoprotein fractions, presumably because it has no apolipoprotein cofactor. In addition, the enzyme was capable of hydrolyzing cholesteryl ester in lipoproteins but not in small unilamellar vesicles nor in micellar dispersions containing low amounts of Triton X-100. This suggests that cholesteryl ester is exposed on the surface of lipoprotein particles or that it may be transferred there quickly from the interior. Although considerable interconversion of radiolabeled cholesterol and cholesteryl ester could be demonstrated upon treatment of normal plasma or lipoproteins with the enzyme, there was little change in the actual amount of either steroid. This indicates that the rate of cholesteryl ester formation is very similar to the rate of hydrolysis. The relative proportions of cholesterol and cholesteryl ester in normal plasma are therefore near the equilibrium ratio for the reaction carried out by GCAT, or the ratio is controlled by the properties of the lipoproteins themselves. During reaction with the microbial acyltransferase, the ratio of cholesterol to cholesteryl ester in plasma from LCAT-deficient patients was reduced substantially, suggesting that the enzyme may have some practical applications.

Acyltransferases↗
PubMed1983

Pneumocystis pneumonia: importance of gallium scan for early diagnosis and description of a new immunoperoxidase technique to demonstrate Pneumocystis carinii.

Pneumocystis pneumonia presented in a homosexual with fever, a normal chest radiograph, and pulmonary gallium uptake. Bronchial washings yielded Mycobaterium tuberculosis, but despite antituberculosis therapy he remained febrile, and gallium uptake in the lung increased. Subsequently, silver stain of transbronchial lung biopsy obtained 2 months earlier at the time that tuberculosis was diagnosed showed many Pneumocystis cysts in alveolar spaces. In contrast to Pneumocystis cysts in infected lung tissue from other humans, our patient's Pneumocystis cysts reacted more avidly with antiserum to rat Pneumocystis than with antiserum to human pneumocystis, raising the possibility that organisms that infect humans may have varied surface antigenic properties.

Adult↗
PubMed1983

Primary perineal wound closure following excision of the rectum.

Management of the perineal wound following rectal excision was assessed in 57 patients at the Toronto General Hospital; 40 had ulcerative colitis, 4 had Crohn's disease, 10 had carcinoma of the rectum, 2 had carcinoma of the anus and 1 had anal incontinence. The preferred technique was careful anatomical dissection with meticulous hemostasis, and primary skin closure with a laterally placed closed Hemovac suction system. Alternatively, wounds were packed and allowed to heal secondarily. Overall, the perineal wound healed primarily in 41 patients (72%). Primary closure was possible in 50 patients (88%); in 41 (82%) the wound healed without complication but in 9 (18%) the wound had to be opened because of hematoma and abscess (8 patients) or bleeding (1 patient). In 41 (91%) of the 44 patients with inflammatory bowel disease the perineal wound was closed primarily; 34 wounds (83%) healed without complication. In seven patients the perineal wound was packed at surgery because of bleeding (four), fecal spillage (two) or sepsis (one). Healing time averaged 6 months. These results indicate that primary closure is the optimal management of perineal wounds. Primary healing is achieved in a high proportion of patients and postoperative morbidity is decreased. Results are excellent in patients with inflammatory bowel disease as well as in those with carcinoma.

Adult↗
PubMed1982

Lecithin: cholesterol acyl transferase (LCAT).

Esterification of cholesterol in plasma is mediated by LCAT. The mechanism of the three reactions catalysed by the enzyme is beginning to be understood. LCAT has been purified from human plasma and partially characterized. The enzyme is closely associated with HDL and exists most likely as a complex with its activator apo A-I and apo D. Antibodies were raised against LCAT and the enzyme concentration in plasma has been estimated to range between 4.5 and 8.0 mg/L. In patients with familial LCAT deficiency only trace amounts or no LCAT protein is found. Heterozygotes for this disorder have approximately half the normal amount of the enzyme. LCAT reactivity is essential for normal lipoprotein metabolism and for a proper equilibrium between tissue and plasma cholesterol.

Animals↗
PubMed1982

Detection of heterozygotes for familial lecithin: cholesterol acyltransferase (LCAT) deficiency.

"Rocket" immunoelectrophoresis using specific anti-lecithin: cholesterol acyltransferase (LCAT) antiserum showed no immunoreactive protein in two patients with familial LCAT deficiency. Subnormal quantity of plasma LCAT was found in the maternal grandmother, the parents, and in two of four siblings of the patients (3.3-3.4 mg/l vs. 5.4 +/- 0.5 mg/l in 12 controls). The immunochemical quantitation of the enzyme correlated well (r = .93) with LCAT activity in an artificial substrate assay. These two methods allow detection of heterozygotes for LCAT deficiency.

Female↗