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Biomedical subjects

E Michael

Publications and source records attributed to E Michael.

At least 55 records · Page 3Linked to original sources

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Animals↗

Frequency distribution of Wuchereria bancrofti infection in the vector host in relation to human host: evidence for density dependence.

This paper uses detailed entomological data from Pondicherry to compare the microfilaria distribution in vector with that of human and also to examine the evidence for the operation of density dependence on parasite transmission. Analysis showed that the distribution in vector is similar to that in human. The expected distribution derived from the fit of a zero-truncated negative binomial to the human data, closely reflected the observed microfilaria distribution in the vector. This implies that a relatively large proportion of observed microfilaria negatives in the vector population may be true zeros, as observed in human, arising from the biting on true negatives (as yet uninfected, with unmated female worms or immune) in humans, rather than attributable to the blood sampling process. Further it was found that both the prevalence of infection and the degree of parasite aggregation in the vector population falls significantly with parasite stage, implying the operation of density dependence, perhaps via parasite-induced vector mortality.

Animals↗

Prevalence of antibodies to hepatitis C virus and other markers in Jamaica.

Three population groups, 1500 blood donors, 513 antenatal women representing a normal population group and 250 sicklers representing a multiply transfused group were studied to determine the prevalence of hepatitis C viral (HCV) infection in Jamaica. The relationship to liver enzyme levels, hepatitis B infection, syphilis and HIV infection was also investigated. Sera were screened by enzyme-linked immunoassay (EIA) for anti-HCV C100-3 and subsequently tested by a supplementary second generation recombinant immunoblot assay (RIBA). In the blood donors, the prevalence of anti-HCV was low, 0.3%-0.4%, the same level as that reported by several European countries. In the multiply transfused sicklers, the prevalence was more than seven times higher. No HCV infection was detected in the antenatal group. There was little correlation between HCV infection and surrogate markers alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) and no correlation with sexually transmitted diseases.

Adult↗

The association between microfilaraemia and disease in lymphatic filariasis.

A standard tenet in the epidemiology of lymphatic filariasis is that patent infection is negatively related to chronic disease. We examine the empirical evidence for this relation by using published data from field studies carried out in a variety of bancroftian filariasis endemic areas. Meta-analysis of the individual study results for each disease category of hydrocele in males only, lymphoedema only, and both conditions combined (total chronic disease) indicate, contrary to expectation, no evidence for a negative association between infection and disease. Indeed, the trend of the empirical evidence is towards the opposite direction, with the majority of studies showing equal propensity of disease in microfilaraemics (mf+ves) and amicrofilaraemics (mf-ves), and more studies indicating a positive rather than a negative relation. There was also a trend for more positive studies for hydrocele compared to lymphoedema. Theoretical analysis suggests that between-study differences in blood sample volumes are unlikely to confound this finding. Analysis of between-study heterogeneity suggests that variations in the local incidence or prevalence of infection rather than unique geographical, including vector, differences might underlie the observed between-study variability in the microfilaraemia-disease association. These results are discussed in terms of dynamic explanations for infection-disease relations in lymphatic filariasis.

Animals↗

Protein content of CBA/Ca mouse diet: relationship with host antibody responses and the population dynamics of Trichuris muris (Nematoda) in repeated infection.

The influence of host dietary protein on acquired immunity and intestinal helminth population dynamics during repeated infection was studied using the mouse-Trichuris muris experimental model. CBA/Ca mice fed a 2% (by mass) protein diet ad libitum maintained body weight during the experiment, but when fed diets containing either 4% or 16% (by mass) protein gained weight steadily. Infection with T. muris did not affect the growth of the latter mice but significantly reduced the growth of animals fed on the 2% protein diet. When repeatedly infected with either 5 or 50 eggs every 10 days, the mice fed the 2% or 4% protein diet accumulated adults in proportion to infection dose. The results show that this is due to both the establishment of larvae at each repeated infection and the survival of established adults. In contrast, very few worms were recovered from animals fed the 16% protein diet, principally as a result of the development of strong acquired immunity to reinfection. T. muris egg output/mouse increased with infection dose in animals fed the low protein diets, but no parasite eggs were detected in the faeces of hosts fed the 16% protein diet. Mouse antibody responses to adult worm excretory/secretory antigen were time- and infection dose-dependent in all 3 dietary groups. The major finding was that the specific antibody response was more intense, both quantitatively (serum OD levels) and qualitatively (antigen recognition by IgG1), in mice fed the low protein diets, even though they remained susceptible to infection. This study shows that host dietary protein deficiency, even at levels irrelevant to normal growth, can markedly potentiate the transmission of T. muris via alterations in host resistance. The high levels of antibody in susceptible animals suggest that this defect in resistance is unlikely to be due to nutrient deficiency-associated defects in humoral immunity.

Analysis of Variance↗

Nutrition, immunity and helminth infection: effect of dietary protein on the dynamics of the primary antibody response to Trichuris muris (Nematoda) in CBA/Ca mice.

The effect of dietary protein on the specific antibody responses (total immunoglobulins, IgG1 and IgA) to the intestinal nematode Trichuris muris was studied in CBA/Ca mice fed isocaloric diets containing 16% or 4% protein. Mice fed the 16% diet and given a high infection dose of 650 eggs expelled almost their entire primary infection by day 21 post infection. In similarly infected animals fed the 4% protein diet, there was prolonged survival of adult worms. At a low infection dose of 10 eggs, there was no evidence of an expulsion response in either dietary group. The primary antibody response to parasite excretory/secretory (E/S) antigen was time-dependent, regardless of dietary protein or infection dose, and was predominantly an IgG1 response. Within each dietary group, antibody production and antigen recognition occurred earlier and the antibody responses were more intense in mice given the higher infection dose. The principal finding was that the specific antibody response was more vigorous, both quantitatively (serum titres) and qualitatively (antigen recognition by IgG1), in mice on a low protein diet, even though worm expulsion did not occur in these hosts. This result suggests that serum antibody level or antigen recognition is not related simply to protective immunity against T. muris in CBA/Ca mice.

Animals↗

A model for the dynamics of human lymphatic filariasis.

In this paper, Bryan Gren fell, Edwin Michael and David Denham review the appropriateness of feline filariasis as a model of the population dynamics of human lymphatic filarial infection and disease. Because of the longevity of infection and our inability to measure the adult parasite population in humans, research in filariasis is particularly dependent on the use of laboratory animal models. We demonstrate that Brugia pahangi infection patterns in the cat closely parallel those of Brugia and Wuchereria in humans. Although primary infections in 'susceptible' cats are long-lived, repeatedly infected animals show evidence of concomitant immunity which prevents the establishment of later cohorts of infective larvae. Furthermore, there is some evidence from macro filarial length distributions of 'stunting' of adult worms during long-term repeat infections. Cats can also show an 'acute' response that spontaneously eliminates infections, and this appears to be due to a combination of intrinsic and dynamic mechanisms. As in humans, pathology in cat filariasis develops as a sequel to the asymptomatic microfilaremic state, largely as a result of re-expression of immunity. The relationship between macro filarial burdens and microfilariae in blood is positive but portrays a high degree of variability. The cat model provides an important tool for elucidating the relationships between infection, immunity and disease dynamics in lymphatic filariasis, and we conclude by suggesting directions for further work in this area.

Journal Article↗

The effect of the protein content of CBA/Ca mouse diet on the population dynamics of Trichuris muris (Nematoda) in primary infection.

The relationship between host dietary protein and intestinal helminth population biology during primary infection was studied using a mouse-T. muris experimental model. Uninfected CBA/Ca mice fed either a 4% (by mass) or 16% protein diet grew at a similar rate, but both suffered significant growth retardation when infected with T. muris. T. muris initial establishment and fecundity were unaffected by dietary protein content, but were significantly influenced by infection dose, declining at the higher level of infection. Dietary protein deficiency increased parasite survival at high infection levels. Heavily infected hosts fed the 16% protein diet were found to expel almost the whole of their infections around day 21 p.i. By contrast, this response appeared defective in hosts fed the lower 4% protein diet, resulting in the establishment and survival of large, chronic and patent infections. Mean faecal egg output per mouse increased with infection dose in animals fed a low protein diet, but was low and unrelated to infection exposure in hosts fed the 16% protein diet. It is concluded that low protein levels in diet, via alterations in host resistance, may have an important influence on the transmission of T. muris.

Analysis of Variance↗

Surgery of the parotid region: a new approach.

Many disorders of the parotid gland require treatment by subtotal or total parotidectomy. In such situations functional and esthetic complications may arise due to the location of the incisions or from permanent or temporary injuries to the facial nerve. This report describes a modified revision that gives good esthetic and functional results. A review of a similar series of cases treated surgically by the same surgeons using Yoel and Bilesio's technique showed no differences in morbility associated with parotidectomy performed using the proposed incision.

Adolescent↗

Density dependence in establishment, growth and worm fecundity in intestinal helminthiasis: the population biology of Trichuris muris (Nematoda) infection in CBA/Ca mice.

The results are presented of an experimental study of the population biology of chronic Trichuris muris (Nematoda) infection in cortisone-treated CBA/Ca mice. Attention is focused upon both the validity of the common use of faecal egg counts to demonstrate density dependence in helminth fecundity, and the identification of other possible density-dependent mechanisms that may regulate worm numbers in chronic trichuriasis. The results show that faecal egg counts, although demonstrating high daily variation, are not an artefact of host faecal output but a significant density-dependent function of worm burden. This finding contrasts with the observations on Heligmosomoides polygyrus infection in outbred MFI mice, but accords with similar studies in a wide variety of host - helminth systems. Worm establishment in the murine host is found to be a density related function of infection dose. This is attributed to the probable existence of a physical gut-carrying capacity in the murine host for T. muris. Worm distribution in the gut is also shown to the density dependent, with worms being displaced from the caecum to the colon at increasing intensities of infection. The sex ratio of the adult parasites, however, is found to be both unitary and independent of worm burden. Evidence for a significant density-dependent decline in female T. muris growth or size is presented. The results also show a significant positive association between female T. muris weight and per capita fecundity. These findings indicate that the stunted growth of individual worms at high parasite densities may be a potential mechanism underlying density dependence in helminth fecundity.

Animals↗

An investigation of hookworm infection and reinfection following mass anthelmintic treatment in the south Indian fishing community of Vairavankuppam.

Hookworm infections, as assessed by counting worms expelled following anthelmintic treatment and by egg output, were found to be of low prevalence and intensity in a South Indian fishing community. The initial overall prevalence of infection in the community was 43%, and the average burden was estimated at 2.2 hookworms per person. The age profiles of prevalence and intensity differed between males and females, with the latter harbouring significantly higher levels of infection. Children of both sexes under 10 years of age rarely harboured hookworms. Treatment with pyrantel pamoate was estimated to be 91% effective in clearing hookworm infections. Egg counts made on stools collected during an 11-month period of reinfection indicated that female patients became reinfected soon after treatment, while little hookworm egg excretion was observed in males during the observation period following treatment. Females acquired a significantly higher number of worms during the reinfection period compared with males, although the average burden in females reached only 28% of the initial, pre-treatment level. The hookworm population consisted of predominantly Necator americanus, and less than 10% of Ancylostoma duodenale. The parasites were highly aggregated within the host population with 10% of the community harbouring over 65% of the total hookworms. Low values of the negative binomial aggregation parameter, k, (indicating extreme over-dispersion) were recorded in groups stratified by age and sex. Highly significant positive correlations were observed between the initial (pre-treatment) and reinfection worm burdens of female (but not of male) patients. It is suggested that occupational practices related to walking through areas contaminated with hookworm larvae play an important role in generating the observed patterns of infection within this community.

Adult↗

Detection of early pregnancy factor (EPF) using the rabbit ovary and oviduct perfused in vitro.

Two peaks of rabbit serum EPF activity were seen over the course of pregnancy. Rabbit ovaries with or without attached oviducts were perfused in vitro for 5 h beginning 12, 16, 24, 48, 72 and 120 h after mating. Perfused isolated ovaries did not produce EPF in vitro, but significant EPF activity was detected in the perfusate of the ovary together with oviduct. Pseudopregnant animals and those rabbits that did not ovulate exhibited no perfusate EPF activity. Perfusate EPF activity was highest at the time embryos were at the pronuclear stage and continued through the morula stage. Although the location of embryos at 72 h after mating varied between oviduct and uterus, EPF activity was maintained over the perfusion period. The results suggest that EPF release occurs within 3 h of fertilization and that the presence of the preblastocyst embryo is crucial for EPF release.

Animals↗

The distribution and abundance of Enterobius vermicularis in a South Indian fishing community.

The distribution and abundance of Enterobius vermicularis in a fishing community in South India, as determined by counting worms expelled following mass anthelmintic chemotherapy, was examined in samples of patients stratified by age, sex and family grouping. The results of a worm expulsion study in January 1984 are compared with those of a second expulsion programme in November 1984, following an 11-month period of reinfection. The prevalence of Enterobius infection was consistently high in all age groups of both males and females. A comparison of the overall prevalence and intensity of infection in the January and November surveys revealed significant increases in both the percent infected and the mean number of worms harboured in November relative to the initial level. No significant trends in the intensity of Enterobius according to host age or sex were detected in either survey. The frequency distribution of Enterobius was found to be highly aggregated in the population as a whole and within age groups. At both sampling dates, the most heavily infected 25% of the community harboured over 90% of the total pinworms recovered. There was a significant pattern within most age groups for individuals to re-acquire worm burdens of a similar magnitude to their initial pre-treatment burdens. Heavy infections were found to be associated with household. A selective or targetted approach to treatment of heavily infected individuals or households is likely to be an efficient means of reducing parasite abundance on a community-wide basis. It must be stressed, however, that treatment must be applied at frequent intervals in order to achieve a long-term reduction in pinworm abundance and to avoid the possibility of increasing the intensity of infection, as was observed in this community.

Adolescent↗

The formation and final structure of the oocyst wall of Eimeria acervulina: a transmission and scanning electron microscope study.

The formation and final structure of the oocyst wall of Eimeria acervulina is described, based on a detailed electron microscope study of the maturing oocysts. After fertilization of the macrogametocyte the wall-forming bodies of type I progressively undergo disaggregation into smaller bodies and eventually move into spaces left by the pellicular membranes of the zygote, which simultaneously separate and elevate away from the zygote cytoplasm to form the outer layer of the oocyst wall. A newly formed membrane separates this layer from the cytoplasm. Following the formation of the outer layer, another membrane separates and elevates away from the cytoplasm, and the wall-forming bodies of type II, which by now have migrated to the periphery, move into the spaces and fuse together to form the inner layer of the oocyst wall. A newly formed membrane separates this layer from the cytoplasm. The wall of the young oocyst thus consists of two membrane-bound layers of approximately similar thickness; the outer layer being osmiophilic whilst the inner one is paler. An overlaying membrane covers the oocyst. The surface of the oocyst wall was smooth in appearance when viewed with the scanning electron microscope.

Animals↗

Sporozoites of Eimeria acervulina within intestinal macrophages in normal experimental infections: an ultrastructural study.

Sporozoites of Eimeria acervulina were observed in macrophages of the intestinal epithelium 5 and 6 days post-infection. These sporozoites lay within a well developed parasitophorous vacuole, were normal in structure and showed no signs of development. Macrophages harbouring sporozoites showed considerable structural changes, most pronounced being an absence of lysosomes, an enlarged nucleolus and extensive proliferation of the Golgi complex and endoplasmic reticulum. Possible mechanisms of survival and transport of sporozoites to preferred sites of development are discussed.

Animals↗

Structure and histochemistry of the normal intestine of the fowl. III. The fine structure of the duodenal crypt.

The fine structures of the development and maturation of intestinal chief cells from the duodenal crypts of the fowl has been described in detail. Three areas within the crypt can be recognised: 1) the crypt base where cell division is frequent but cell development is minimal; (2) the mid-crypt region where rapid growth and development of the cells takes place; and (3) the zone of differentiation where final developments and functional maturation occurs. The structure of the fowl's intestinal crypt is very similar to that described for the mammals. The results are discussed in relation to previous histochemical studies.

Animals↗