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Biomedical subjects

C D Mackenzie

Publications and source records attributed to C D Mackenzie.

At least 73 records · Page 4Linked to original sources
PubMed1982

Morphological characteristics and isoenzyme patterns of an Onchocerca sp. found in cattle in Southern Mexico.

An Onchocerca sp. was isolated from the nuchal ligaments of 78 out of 79 naturally infected cattle in Southern Mexico. Infections were moderate to heavy, averaging 20-30 parasites per nuchal ligament. Microfilariae were concentrated in the skin of the head and neck, although small numbers were found in the skin of the withers, brisket and medial abdomen. High numbers of microfilariae were found in the skin around the eye, but not in the ocular tissues themselves a situation dissimilar to that found in human onchocerciasis. Morphologically, adult females, males and microfilariae were identified as being O. gutturosa. Analysis of the isoenzyme patterns of LDH, MDH, PGM, GPI, PGD and ES of adult female worms, showed the Mexican parasite to be the same as O. gutturosa from England and Australia.

Animals↗
PubMed1982

Circulating antigen-antibody complexes in onchocerciasis.

The presence of circulating antigen-antibody complexes in the sera of patients with onchocerciasis was investigated using the Clq and conglutinin solid-phase binding assays. Only 50% of patients' sera had demonstrable complexes, levels of complexes were unrelated to microfilarial load and specific anti-onchocercal antibody titres and results with the two tests for complexes were not correlated. Both IgM- and IgG-containing complexes were commonly involved but there was no correlation between the levels of complexes containing these isotypes. Evidence for the presence of IgE in complexes of sera from a minority of individuals was also obtained.

Antibodies↗
PubMed1981

Chemotherapy of onchocerciasis: a controlled comparison of mebendazole, levamisole, and diethylcarbamazine.

Four drug regimens for treating onchocerciasis were compared in a double-blind study in persons from an endemic area in southern Mexico. 40 men were randomly assigned to receive either diethylcarbamazine (DEC) (200 mg/day), mebendazole (2 g/day), levamisole (150 mg per week), or mebendazole plus levamisole. DEC produced the most rapid fall in skin microfilaria counts, but by 6 months the two groups receiving mebendazole showed similar or slightly greater reductions. Despite the administration of corticosteroids to persons receiving DEC, more systemic side-effects were seen in this group. Ocular complications were also commoner and more severe in those receiving DEC. The reduction in the number of intraocular microfilariae at 6 months was similar to those receiving DEC and mebendazole, alone or in combination with levamisole. Levamisole alone had no significant effect on microfilaria counts. Examination of adult worms in nodules excised at 2 months showed changes suggestive of an interruption of embryogenesis in those persons receiving the mebendazole-containing regimens only. The findings suggest that mebendazole may be a useful alternative to DEC in the treatment of onchocerciasis.

Adolescent↗
PubMed1981

The in-vitro interaction of eosinophils, neutrophils, macrophages and mast cells with nematode surfaces in the presence of complement or antibodies.

The adherence in vitro of leucocytes to the surface of various stages in the life cycle of T. spiralis and N. brasiliensis in the presence of serum was examined. Considerable differences were observed in the behaviour of mast cells, eosinophils, neutrophils and macrophages in this interaction. Mast cells adhered for a short time, did not flatten onto the surface and did not degranulate. Adherence ceased after 4-6 hr. Eosinophils adhered within minutes to the surface or worms, flattened and degranulated; only their cytoplasmic remnants could be seen on the worms' surface after 24 hr in culture. In contrast, only a small area of the cytoplasmic membrane of neutrophils flattened on the surface of the worms and adherence ceased after 2-24 hr. The NBT conversion reaction showed a positive deposit at the interface between neutrophils and parasites during neutrophil adherence. This deposit remained as "foot prints" on the surface of the nematodes following neutrophil detachment. This positive NBT reaction occurred only with neutrophils and not with eosinophils, mast cells or macrophages. Macrophages adhered permanently to the surface of these worms, they did not flatten and retained their integrity. Under the light microscope the cytoplasmic inclusions appeared to decrease in size during culture. Electron microscopy revealed the presence of fewer granules and an increased number of vacuoles in later cultures of macrophages. These findings are discussed in relationship to the immunopathology of nematode infection in vivo.

Animals↗
PubMed1981

Serum-mediated adherence of feline granulocytes to microfilariae of Brugia pahangi in vitro: variations with parasite maturation.

Feline eosinophils and neutrophils readily adhered in vitro to the sheaths of microfilariae of Brugia pahangi in the presence of suitable serum. Both cell types flattened along the surface of the parasite undergoing cytoplasmic changes which included degranulation. Adherence was dependent on properties of both the serum and the history of the microfilaria used. Two types of serum factor were found to mediate adherence. Heat labile factors were present in sera from infected and uninfected cats as well as in sera from other species. They were removed by preincubation of sera with zymosan suggesting that complement components were involved. This suggestion was supported by the demonstration of C3 on the surface of microfilariae participating in adherence reactions. A heat stable factor, present in the serum of less than 10% of infected cats, also mediated adherence. This factor was demonstrated to be IgG by immunoadsorption and immunofluorescence. The ability of the microfilariae to participate in the adherence reaction mediated by complement factor varied with maturation of the parasite. Microfilariae obtained directly from the uteri of adult worms, or produced in vitro, did not possess the ability to participate in adherence. Young blood microfilariae (i.e. taken from the blood of cats recently patent) were similar to the in vitro produced parasites; however, the majority of blood microfilariae from infections of greater than three weeks patency participated in this form of adherence. No difference between blood and uterine/in vitro microfilariae was seen in adherence reactions mediated by heat stable antibody.

Animals↗
PubMed1979

Inflammatory reactions in onchocerciasis: a report on current knowledge and recommendations for further study.

This report concerns the host's reactions to the presence of the parasite both in the course of the natural disease and during drug treatment. The various stages of Onchocerca volvulus are discussed in terms of the type of tissue reaction seen. The discussion then turns to basic hypotheses concerning the etiology of these reactions, emphasis being placed on the fact that while pathological changes are considerable in some locations there is a remarkable lack of reaction in others. Some of the mechanisms possibly involved in this apparent absence of host response are discussed, including anti-complement factors, poor antigenicity, acquisition of host antigen, immune tolerance, and blocking antibodies. In any study of the inflammatory response it is recommended that critical evaluations be made of histological material, haematological studies, the definition of the antigenic nature of O. volvulus, characterization of immunological reactivity of patients, and the definition of the migratory pathways of the parasite.The marked host reactions seen following chemotherapy, especially those related to the interaction of the drug diethylcarbamazine with microfilariae, are discussed at some length. The etiology of these reactions is considered and recommendations are made for the experimental elucidation of the mechanisms involved. Emphasis is placed on the necessity for detailed sequential histopathological and immunopathological studies in the definition of the tissue lesions found in onchocerciasis. Characterization of these lesions will assist greatly the approach to control of the adverse reactions seen during treatment.The use of anti-inflammatory agents in clinical trials is discussed and comments are made concerning the most suitable clinical situations for testing drugs and the types of drug that should be tested.

Anti-Inflammatory Agents↗
PubMed1978

Variation in delayed hypersensitivity in onchocerciasis.

Soluble antigen preparations were made from Onchocerca volvulus adults recovered from subcutaneous nodules, and from Necator americanus third-stage larvae. Intradermal skin tests were carried out on a total of 100 individuals clinically classified as having either the generalized form of onchocerciasis (86 cases, or the localized sowda form (14 cases). 91 of the people studied produced immediate reactions to the onchocercal antigen, but only those with sowda showed delayed reactions, though one person with generalized disease showed a doubtful delayed reaction. Reactions to N. americanus antigen, both immediate and delayed, were seen in both forms of the disease. The lack of delayed skin reaction in the generalized form of onchocerciasis is discussed, and a comparison is made with other diseases. Preliminary evidence for the existence of a true spectrum of clinical and immunological forms of onchocerciasis is suggested by one case in this study.

Adolescent↗
PubMed1977

Ultrastructural observations on the in vitro interaction between rat eosinophils and some parasitic helminths (Schistosoma mansoni, Trichinella spiralis and Nippostrongylus brasiliensis).

Rat eosinophils form an intimate association with the surfaces of parasitic helminths, in vitro, in the presence of immune serum. The parasite presents a non-phagocytosable surface to the cell. The initial response of the eosinophil is degranulation which leads to the formation of large cytoplasmic vacuoles. Peroxidase, an enzyme localized in the matrix of the crystalloid secretion granules, is discharged into these vacuoles as a consequence of degranulation. The vacuoles eventually become connected to the adherent basal plasma membrane of the eosinophil, and peroxidase is secreted directly onto the surface of the parasite. There is no morphological evidence to suggest that this particular secretion affects the integrity of the parasite surface.

Ancylostomatoidea↗
PubMed1977

Antibody-mediated adherence of rat eosinophils to schistosomula of Schistoma mansoni in vitro.

Eosinophils from the peritoneal washings of normal rats adhered to live or formalin-fixed schistosomula of Schistosoma mansoni in vitro, in the presence of heat-inactivated serum from infected rats. Eosinophil adherence caused permeability changes in the schistosomula as revealed by 51Cr release and methylene blue uptake. The serum factor which mediated adherence resided in the 7S fraction after Sephadex G-200 gel filtration. Protein A from Staphylococcus aureus which binds specifically to the Fc piece of IgG inhibited adherence, thereby demonstrating that IgG was the antibody responsible for this reaction and that the Fc portion was the site of interaction between eosinophil and antibody; rat eosinophils were shown to possess Fc receptors. The antibody mediating adherence reached high titres in the sera of rats 5-8 weeks after exposure to 500 cercariae, but thereafter there was a gradual decline in titre. Surface membrane from adult S. mansoni inhibited adherence, indicating the presence of cross-reacting antigens in adult worms and schistosomula.

Animals↗
PubMed1975

Histological development of the thymic and intestinal lymphoid tissue of the horse.

The basic components of the immune system, and the defence mechanisms in the gastrointestinal tract, are briefly reviewed. Histological studies in 84 equine foetuses showed that lymphoid cells begin populating the thymic primordium at 11-12 weeks, the mesenteric lymph nodes at 13 weeks, the spleen at 25 weeks and the intestinal lamina propria at 13-14 weeks' gestation. Lymphocytes were seen in the intestinal epithelium very early in gestation. Histological signs of response to antigenic stimulation were seen in five foetuses, indicating that the horse is likely to be capable of mounting an immune response in utero. The changing status of the foal as it becomes fully immunocompetent is discussed.

Animals↗
PubMedDate not supplied

The effect of antimalarial chloroquine therapy and prophylaxis on concurrent infection with Onchocerca volvulus in Ecuador.

The effect of chloroquine phosphate on Onchocerca volvulus in vivo was studied in Ecuadorians undergoing treatment for malaria. All persons with a diagnosis of acute malaria and treated with 2500 mg of chloroquine over 3 d showed a 100% reduction of dermal O. volvulus microfilariae 7 d after treatment. However, 28 d after treatment the microfilarial densities returned to their pre-treatment levels and at 35 d they had increased to 121.6% of their pre-treatment values. Treatment did not appear to have any effect on the adult O. volvulus examined histologically in extirpated nodules. Patients treated for acute malaria and subsequently kept on a prophylactic regimen of 500 mg chloroquine weekly showed a reduction of 56.7% from pre-treatment microfilarial density after 27 weeks. Patients who underwent nodulectomy as well as treatment for acute malaria and were given 500 mg of chloroquine prophylactically for 27 weeks showed a reduction in dermal microfilarial density of 93.6%. Symptoms of onchocerciasis were reduced in the latter group of patients, with the elimination of all acute dermatological changes within 6 weeks. Ocular examination of these surgically and chemotherapeutically treated individuals revealed reductions of 94.9% of microfilariae in the anterior chamber, 95.9% of live microfilariae in the cornea, and 95.1% of dead microfilariae in the cornea. There was a reduction of 69.8% in corneal fluffy opacities. No alteration in the visual acuity or in visible lesions in the posterior segment was recorded. The results suggest that a complex interaction between chloroquine and O. volvulus takes place in vivo, which can be beneficial to the patient over a long period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMedDate not supplied

Ivermectin treatment in severe asymmetric reactive onchodermatitis (sowda) in Sudan.

Ivermectin efficacy and post-treatment reactions in asymmetric severe reactive ochodermatitis (sowda) were studied in 8 patients with sowda syndrome and 6 with mild generalized onchodermatitis in Sudan. Initial skin snips from 12 patients contained microfilariae (1-9 per mg skin). Patients were treated in hospital with a single oral dose of c. 150 micrograms/kg ivermectin (103-200 micrograms/kg) and monitored for frequency and severity of post-treatment reactions for 4 weeks. Serial samples of heparinized blood were collected over the first 24 h after treatment for determination of ivermectin pharmacokinetics. Skin snips from all patients on days 3 and 28 revealed no microfilariae. Post-treatment reactions were more common and severe in individuals with sowda; they consisted mainly of musculoskeletal pain, local swellings with pitting oedema, and lymph gland tenderness and enlargement. No relation was established between these reactions, the microfilarial infection intensity, or the plasma pharmacokinetic profiles. A single oral dose of ivermectin cleared the skin of microfilariae and led to improvement of symptoms and dermatological signs of sowda, but resulted in more marked reactions than in cases of generalized onchodermatitis.

Adolescent↗
PubMedDate not supplied

Two FMRFamide-like peptides from the free-living nematode Panagrellus redivivus.

Peptides of the FXRFamide family, where X = M, I or L, are broadly distributed among invertebrates. Two such peptides were purified and sequenced from the free-living nematode, Panagrellus redivivus. Immunohistochemical techniques localized FMRFamide-like material in several regions of these organisms, including the nerve cords and, most prominently, in paired groups of cells located caudally to the base of the pharynx. RIA determinations gave an estimate of 2.8 nmol immunoreactive peptide/g of an acetone extract of P. redivivus. Four sequential HPLC purification steps, followed by sequencing by automated Edman degradation and FAB-MS, led to the identification of Ser-Asp-Pro-Asn-Phe-Leu-Arg-Phe-amide (SDPNFLRFamide) and Ser-Ala-Asp-Pro-Asn-Phe-Leu-Arg-Phe-amide (SADPNFLRFamide) as members of the FXRFamide family in this nematode.

Amino Acid Sequence↗