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Biomedical subjects

C D Mackenzie

Publications and source records attributed to C D Mackenzie.

At least 55 records · Page 3Linked to original sources
PubMed1986

Pathology in tropical medicine.

The pathology o f a parasitic disease is a major link between the investigating parasitologist and those concerned with its epidemiology, socioeconomic impact, clinical treatment and control. The epidemiologist requires information about the incidence and prevalence of major pathological lesions attributable to on infection, which in turn will determine the social and economic impact of the disease and thus its priority for control. For both diagnosis and treatment, the clinician requires an understanding of the pathological mechanisms, and the potential for new drugs or vaccine development largely depends on such understanding. Recent years have seen remarkable improvements in determining the nature of pathology associated with parasitic infections. and in understanding their causative mechanisms. With this issue, Parasitology Today begins a series of special reviews designed to bring together these insights into parasite pathology (see pages 271-282). In this introductory overview. Charles Mackenzie traces the origins and development of the science.

Editorial↗
PubMed1985

Mononuclear and multinuclear macrophages in filarial infections.

Filarial infections commonly involve chronic tissue responses to these complex and resiliant organisms. These responses, which occur with a number of the parasitic stages of filariae, involve macrophages, and these cells appear to be important in immunologically induced destruction and removal of these important parasites of man and animals. Details of their presence and experimental induction as well as their distinction into a number of morphological types, including multinuclear (giant cell) forms, is described in this communication. The ability of these various forms to function in phagocytic and immunologically mediated adherence assays is also described.

Animals↗
PubMed1985

The induction of functional mononuclear and multinuclear macrophages in murine brugian filariasis: morphological and immunological properties.

This present study describes the ontogeny and morphology of mononuclear and multinuclear macrophages in murine Brugia pahangi infections. Intraperitoneal infection with L 3 resulted in the development of adult worms and the production of microfilariae in many mice; however, all worms were usually removed by 100 days post infection (p.i.). The infection induced predominantly mononuclear and multinuclear macrophage responses in the peritoneal cavity, with maximum numbers of peritoneal cells being achieved by 8-12 weeks p.i. and at this time some 20% of the macrophages were multinucleated. Lymphocyte numbers were also increased during infection. The reactions around the filariae involved macrophages (both single and multinucleated), eosinophils, fibroblasts and the laying down of collagen. Most worms were involved in these cellular reactions by 5-6 weeks p.i., with the multinuclear macrophages generally seen lying close to the parasites. All stages of parasites developed vacuolar internal changes early in their degeneration with calcification being a later change. The destruction and removal of the sheath was not apparently a prerequisite for degeneration of the body of microfilariae. Rosetting techniques showed that 75% of peritoneal cells (macrophages) in infected animals possessed Fc receptors compared with 32% of those in uninfected mice, and for C3 receptors the respective results were 35% and 5%. The multinuclear cells possessed both types of receptors at levels similar to those of mononuclear macrophages. Likewise both cell types were found to readily phagocytose yeast and latex particles, as well as staining positively for non-specific esterases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Biochemical surface components of Brugia pahangi microfilariae.

The sheath and cuticle of microfilariae of Brugia pahangi were examined by electron microscopy and the presence of various proteins, carbohydrate and enzymes sought. The epicuticle of microfilariae consists of a pentalaminate structure (24.0 +/- 1.4 nm), a cortex (13.7 +/- 3.6 nm) and a basal zone (27.8 +/- 4.8 nm) which is often banded in appearance. The pentalaminate layers are not continuous at the base of the interannular grooves. The sheath and the epicuticle of B. pahangi stained positively with concanavalin A and saccharated iron oxide. The sheath of approximately 50% of microfilariae showed activity for acid phosphatase, 5' nucleotidase and peroxidase, but not for ATPases, alkaline phosphatase or esterase. No enzymes were detected in the epicuticle although the cortex and basal layers of the cuticle did show enzymic activity. Structures beneath the cuticle in the main body of the worms contained considerable enzymic activity. Microfilariae directly isolated from the blood of infected cats were found by immunochemical means to carry serum proteins on their sheaths but not on their cuticles. These studies extend the definition of the outer structures of microfilariae and confirm that they significantly differ in morphology and enzyme content from typical mammalian cell membranes.

Acid Phosphatase↗
PubMed1984

Increased activity of macrophages from mice infected with Brugia pahangi: in vitro adherence to microfilariae.

After the inoculation of infective larvae of Brugia pahangi into the peritoneal cavities of CBA/Ca mice adult worms developed, but by 12 weeks post-infection the parasites were usually dead and surrounded by granulomatous tissue. Macrophages were the most common cell type in these granulomas and were also found in increasing numbers free in the peritoneal cavity. We have investigated the ability of macrophages to damage microfilariae in vitro, in a system where microfilariae were cultured together with cells and serum taken from either uninfected female CBA/Ca mice or at various intervals after infection. Macrophages adhered to and killed microfilariae in this system and there was an increase in vitro adherence of these cells during the course of infection. The peak level of in vitro activity of these cells coincided with the phase of parasite killing in vivo. The presence of serum also affected the degree of macrophage adherence and subsequent death of the parasite. Analysis of serum components using EGTA, zymosan or heat inactivation suggested that complement and possibly heat labile antibody were involved. Immunoglobulins were shown by immunofluorescence to be present on the surface of microfilariae cultured in serum from infected mice. It is concluded from this study that macrophages are actively involved in the termination of murine filarisis.

Animals↗
PubMed1984

Protection against Trichinella spiralis induced by a monoclonal antibody that promotes killing of newborn larvae by granulocytes.

Mouse monoclonal antibodies directed against biochemically defined surface antigens of Trichinella spiralis were selected and tested for their ability to destroy parasites in vivo and in vitro. One of these (NIM-M5; IgG1), which recognised a surface component of approximately 64 K molecular weight in newborn larvae (NBL), bound to a surface component of this stage (as shown by fluorescence), and mediated the adherence of rodent eosinophil leucocytes to the surface of living NBL. Following cell adherence mediated by this monoclonal antibody, the worms were killed. This effect was enhanced by fresh normal serum suggesting a role for complement in this phenomenon. A monoclonal antibody directed against a surface component of infective larvae (NIM-M1; IgM) did not promote adherence of cells nor killing of NBL in vitro. The effect of NIM-M5 on the development of NBL to the intramuscular stage was examined. Treatment of NBL with the NIM-M5 monoclonal antibody prior to their injection into mice, together with passive transfer of NIM-M5 for 3 days, significantly reduced (36-51%) the proportion of larvae recovered by digestion 28 days later. Thus a single monoclonal antibody to NBL was able to mediate eosinophil-dependent destruction of worms in vitro and reduce infectivity in vivo. These observations suggest that antibodies capable of mediating eosinophil-induced destruction of nematodes in vitro may also be important in protection against infection.

Animals↗
PubMed1984

The effects of diethylcarbamazine, mebendazole and levamisole on Onchocerca volvulus in vivo and in vitro.

The effects of mebendazole, levamisole, diethylcarbamazine citrate (DEC-C), and the combination of mebendazole and levamisole, on adult Onchocerca volvulus and on the in utero development of microfilariae was studied in nodules excised from patients in Southern Mexico. Adult worms isolated from patients treated with mebendazole showed a reduction in mobility and contained 40 times fewer developing microfilarial forms than did worms from untreated patients. Most of the developmental forms found in adult worms from mebendazole-treated patients were either oocytes or early morulae, with more mature forms being scarce or morphologically abnormal. Treatment with levamisole had a similar effect on embryogenesis, however it was much less marked. The number and distribution of developing forms in worms from patients treated with DEC-C was similar to that found in the control groups. The effect of the same three drugs on microfilariae in vitro was also tested. DEC-C at concentrations of 0.5 microgram - 2000 micrograms/ml did not have any obvious effect on motility or morphology of the worms provided the pH was maintained at physiological levels; levamisole also had no effect in vitro. Mebendazole induced the death of microfilariae when used at concentrations greater than 100 micrograms/ml, however these levels are greater than those found in the blood of patients under treatment. The optimal conditions for short-term maintenance of O. volvulus microfilariae in culture, are discussed. It is apparent from these studies that mebendazole has an effect on the maturation of microfilariae in utero and may also, at high concentrations, have a direct effect on mature microfilariae.

Animals↗
PubMed1983

Some properties of the surface of nematode larvae.

The nature of complement binding to the surface to infective larvae of Trichinella spiralis and Nippostrongylus brasiliensis differs. When worms were incubated in serum from uninfected hosts, washed and incubated in fluorescent reagent the whole surface of T. spiralis fluoresced but in N. brasiliensis fluorescence was confined to the anterior end and some internal organs. The outer structure of the cuticle of the T. spiralis larvae was shown not to contain ATP-ase, thus differing from many cell membranes.

Adenosine Triphosphatases↗
PubMed1983

Selective localization of intravenously injected 111indium-labelled eosinophils in rat tissues infected with Nippostrongylus brasiliensis.

111Indium-oxine-labelled rat eosinophils were injected i.v. into rats infected with Nippostrongylus brasiliensis and controls. Radionuclide imaging was done to measure the rate and extent of radioactive uptake into different regions of the body in vivo. Radioactivity appeared first in the lungs then in the livers and spleens. The distribution of radioactivity and parasites was studied by gamma counting, histology and parasite counts. In infected rats, increased amounts of radioactivity localized in the skin, lungs and small intestines during the dermal, pulmonary and intestinal stages of the disease. It was concluded that localization of radioactivity was closely related to the tissue distribution of migratory larvae and adult worms. This technique may be of value in measuring alterations in eosinophil distribution and tissue localization in vivo, especially in helminthic infections and other disease where many eosinophils accumulate in tissues.

Animals↗
PubMed1983

Infection of inbred and nude (athymic) rats with Brugia spp.

Infective larvae of Brugia pahangi were injected subcutaneously into inbred PVG (-RTIc) rats, and 'nude' (PVG-rnu/rnu) (athymic) rats. Adult worms or circulating microfilariae were recovered from 20/34 (59%) of PVG-RTIc rats and from 30/30 (100%) of 'nude' rats. Fertile worms were regularly found in the lumbar lymphatics and hearts of both strains of rat. Blood eosinophilia first developed in PVG-RTIc rats about 17 days, and in all such animals by 6 weeks. High circulating eosinophil counts persisted only in patent animals, proving a useful hallmark for the presence of microfilariae. Nude rats despite patency, developed eosinophilia only latterly and then to a lesser extent. Specific anti-B. pahangi IgG antibody was first detected at 7 days in all infected PVG-RTIc rats, with levels rising until 8 weeks and remaining high only in microfilaraemic animals; total IgE showed a similar response. Specific IgE rose in all the eight patent rats inconsistently and only to low levels in eight non-patent infected rats. IgG and IgE were undetectable in nude rats. Other strains of inbred rats of different RTI haplotype were also successfully infected with B. pahangi and the human parasite B. malayi, a total of 10/23 (43%) and 5/15 (33%) becoming patent respectively. In the small numbers tested no major influence of RTI haplotype was detected. Infection by the intraperitoneal route did not result in the development of microfilariae. The difference in patency rates between 'nude' and normal PVG rats supports the contention that the development of filarial infections is T lymphocyte dependent. Inbred and 'nude' rats provide a valuable model of human filariasis, in which many features of filarial immunopathology can be studied.

Animals↗
PubMed1982

Survival of Loa loa following transplantation from drills (Mandrillus leucophaeus) into jirds (Meriones unguiculatus): parasitology and pathology.

Two drills infected with Loa loa maintained a microfilaraemia for four and a half years ranging from less than 1 mf/100 microliters to 1150 mf/100 microliters. No significant tissue reactions to the adult worms were seen at autopsy. Adult worms were transplanted into the peritoneal cavities of naive jirds when a persistent microfilaraemia first developed by 17 days. Retransplantation of adult worms into naive jirds produced a microfilaraemia and microfilariae in the peritoneal cavities of three out of five animals. These three animals were all negative for circulating parasites by eight and a half months. The tissue reactions to the worms in the jirds are described, including a granulomatous response surrounding adults and a myositis involving microfilariae.

Animals↗