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PubMedDate not supplied

Michigan's fisheater cohorts: a prospective history of exposure.

Interest in environmental contaminants and their effect on human health emerged as a primary focus in the 1970s following the discovery of significant levels of mercury, dichloro diphenyl trichloroethane (DDT), and polychlorinated bihpenyls (PCBs) in recreationally caught Great Lakes fish. In response to these findings, the Michigan Department of Public Health, in 1971, initiated a series of "fisheater" cohort studies. These studies continue to be conducted today. The evolution of human exposure assessment by serum PCB determination parallels the evolution of more precise and sensitive analytical laboratory procedures over the past 25 years. Early work quantitated PCB with Aroclor 1254 standards. By 1980, the Webb and McCall packed-column method (Webb and McCall, 1972, 1973), which quantitates total PCB with Aroclor 1016 and 1260 standards, had gained the Association of Official Analytical Chemists (AOAC) approval and became the accepted method. This method was used in the 1978-1980 Michigan Great Lakes Fisheater Study, the first sizable study of this kind in the nation. The study confirmed that fisheaters had significantly more exposure (median 21.4 ppb vs 6.6 ppb) than controls. Toxicology studies have indicated the need to quantitate individual PCB congeners, in order to correlate exposure with possible toxicological and health outcomes. Today, capillary column gas chromatography and gas chromatography/mass spectrometry are used to search for trace components of the total PCB dose (Mullen et al., 1984). Because of the legacy of the earlier analytical data, Michigan also continues to conduct packed-column analysis for longitudinal comparisons. The Michigan fisheater study database and registry provide a significantly exposed and historic foundation for research testing health outcome hypotheses.

Cohort Studies↗
PubMed1994

Perspectives on interactions with QA--the regulatory perspective.

It has been my experience that the quality assurance unit (QAU) normally serves as the facility point-of-contact with the agency on matters relating to a Good Laboratory Practice (GLP) compliance inspection. The QAU usually receives the notification letter, does most of the coordinating for the GLP inspection, and often bears the criticism for deficiencies found during the inspection. In general, as inspectors, we have found it difficult to get management to show any interest in the inspection and, in many facilities, have been forced to communicate almost entirely with the QAU. The evolution of the relationship between regulators and the QA community, which parallels the evolution of the image of quality assurance personnel from inexperienced technicians to recognized professionals, is discussed. Also discussed are both typical and atypical examples of interaction between government inspectors and quality assurance units.

Facility Regulation and Control↗
PubMed1999

Evolution of the carabid ground beetles.

The phylogenetic relationships of the carabid ground beetles have been estimated by analysing a large part of the ND5 gene sequences of more than 1,000 specimens consisting of the representative species and geographic races covering most of the genera and subgenera known in the world. From the phylogenetic analyses in conjunction with the mtDNA-based dating, a scenario of the establishment of the present habitats of the respective Japanese carabids has been constructed. The carabid diversification took place ca. 40 MYA as an explosive radiation of the major genera. During evolution, occasional small or single bangs also took place, sometimes accompanied by parallel morphological evolution in phylogenetically remote as well as close lineages. The existence of silent periods, in which few morphological changes took place, has been recognized during evolution. Thus, the carabid evolution is discontinuous, alternatively having a phase of rapid morphological change and a silent phase.

Animals↗
PubMed2000

Progress in understanding hominoid dental development.

Teeth preserve a record of the way they grow in the form of incremental markings in enamel, dentine and cementum. These make it possible to reconstruct cellular activity and the timing of dental development in living and fossil primates, including hominids. They also provide a way of exploring the mechanisms that underlie morphological change during evolution and the nature of the relationship between ontogeny and phylogeny. All living great apes are dentally mature by about 11 y, irrespective of their body mass. While the early period of root formation in living great apes is shorter than in modern humans, enamel takes approximately the same time to form, irrespective of how thick it is. In general, differences in the total time taken to form enamel seem not to be due to differences in the rate at which enamel and dentine are secreted, but rather to faster or slower rates of differentiation of ameloblasts and odontoblasts and therefore to the number of secretory cells active at any one time during tooth formation. Tooth size, especially height, may influence the sequence of appearance of tooth mineralisation stages. The space available in the jaws may also have an influence on both the timing of tooth bud/crypt appearance and the sequence of gingival emergence. When each of these potential influences on dental development are carefully considered, and incremental markings used to calibrate key events, the developing dentition can provide an estimate of the period of dental maturation in fossil hominoids. However, the influence of body mass on the period of dental development among primates remains unclear. The earliest hominoids, dated at around 18 Mya, may still have had modern monkey-like maturational profiles, and the earliest hominids, dated between 1.8 and 3.7 Mya, modern great ape-like maturational profiles. Exactly when the extended or prolonged modern human-like maturational profile first appeared remains debatable, but the most secure suggestion might be at the time of the appearance of the earliest archaic Homo sapiens, when brain size and body mass were finally both within the ranges known for modern humans. But at present we should not reject the hypothesis that an extended, modern human-like, maturational profile arose more than once during human evolution in parallel with an increase in brain size.

Animals↗
PubMed2024

Repeated evolution on oceanic islands: comparative genomics reveals species-specific processes in birds.

Understanding the interplay between genetic drift, natural selection, gene flow, and demographic history in driving phenotypic and genomic differentiation of insular populations can help us gain insight into the speciation process. Comparing patterns across different insular taxa subjected to similar selective pressures upon colonizing oceanic islands provides the opportunity to study repeated evolution and identify shared patterns in their genomic landscapes of differentiation. We selected four species of passerine birds (Common Chaffinch Fringilla coelebs/canariensis, Red-billed Chough Pyrrhocorax pyrrhocorax, House Finch  Haemorhous mexicanus and Dark-eyed/island Junco Junco hyemalis/insularis) that have both mainland and insular populations. Changes in body size between island and mainland populations were consistent with the island rule. For each species, we sequenced whole genomes from mainland and insular individuals to infer their demographic history, characterize their genomic differentiation, and identify the factors shaping them. We estimated the relative (Fst) and absolute (dxy) differentiation, nucleotide diversity (π), Tajima's D, gene density and recombination rate. We also searched for selective sweeps and chromosomal inversions along the genome. All species shared a marked reduction in effective population size (Ne) upon island colonization. We found diverse patterns of differentiated genomic regions relative to the genome average in all four species, suggesting the role of selection in island-mainland differentiation, yet the lack of congruence in the location of these regions indicates that each species evolved differently in insular environments. Our results suggest that the genomic mechanisms involved in the divergence upon island colonization-such as chromosomal inversions, and historical factors like recurrent selection-differ in each species, despite the highly conserved structure of avian genomes and the similar selective factors involved. These differences are likely influenced by factors such as genetic drift, the polygenic nature of fitness traits and the action of case-specific selective pressures.

Animals↗
PubMed2000

The evolution of sex differences in language, sexuality, and visual-spatial skills.

The evolutionary neurological and physical foundations for human sex differences in language, sexuality, and visual spatial skills are detailed and primate and human studies are reviewed. Trends in the division of labor were established early in evolution and became amplified with the emergence of the "big brained" Homo erectus. A bigger brain necessitated a size increase in the birth canal and female pelvis. These and other physical changes, e.g., the swelling of the breasts and buttocks, may have paralleled the evolution of full-time sexual receptivity, the establishment of the home base, and exaggerated sex differences in the division of labor (hunting vs. gathering), which in turn promoted innate sex differences in visual spatial vs. language skills. For example, female primates produce more social and emotional vocalizations and engage in more tool use and gathering activities, whereas males tend to hunt and kill. Similar labor divisions are evident over the course of human evolution. "Woman's work" such as child rearing, gathering, and domestic tool construction and manipulation contributed to the functional evolution of Broca's speech area and the angular gyrus--which injects temporal sequences and complex concepts into the stream of language and thought. These activities gave rise, therefore, to a female superiority in grammatical (temporal sequential) vocabulary-rich language. Hunting as a way of life does not require speech but requires excellent visual-spatial skills and, thus, contributed to a male visual-spatial superiority and sex difference in the brain. Over the course of evolution males acquired modern human speech through genetic inheritance and because they had mothers who taught them language.

Affect↗
PubMed1994

Bioenergetics: the evolution of molecular mechanisms and the development of bioenergetic concepts.

Possible routes for the evolution of cell energetics are considered. It is assumed that u.v. light was the primary energy source for the precursors of the primordial living cell and that primitive energetics might have been based on the use of the adenine moiety of ADP as the u.v. chromophore. It is proposed that the excitation of the adenine residue facilitated phosphorylation of its amino group with subsequent transfer of a phosphoryl group to the terminal phosphate of ADP to form ATP. ATP-driven carbohydrate synthesis is considered as a mechanism for storing u.v.-derived energy, which was then used in the dark. Glycolysis presumably produced compounds like ethanol and CO2, which easily penetrate the membrane and therefore were lost by the cell. Later lactate-producing glycolysis appeared, the end product being non-penetrant and, hence, retained inside the cell to be utilized to regenerate carbohydrates when light energy became available. Production of lactate was accompanied by accumulation of equimolar H+. To avoid acidification of the cell interior, an F0-type H+ channel was employed. Later it was supplemented with F1. This allowed the ATP energy to be used for 'uphill' H+ pumping to the medium, which was acidified due to glycolytic activity of the cells. In the subsequent course of evolution, u.v. light was replaced by visible light, which has lower energy but is less dangerous for the cell. It is assumed that bacteriorhodopsin, a simple and very stable light-driven H+ pump which still exists in halophilic and thermophilic Archaea, was the primary system utilizing visible light. The delta mu-H+ formed was used to reverse the H(+)-ATPase, which began to function as H(+)-ATP-synthase. Later, bacteriorhodopsin photosynthesis was substituted by a more efficient chlorophyll photosynthesis, producing not only ATP, but also carbohydrates. O2, a side product of this process, was consumed by the H(+)-motive respiratory chain to form delta mu-H+ in the dark. At the next stage of evolution, a parallel energy-transducing mechanism appeared which employed Na+ instead of H+ as the coupling ion (the Na+ cycle).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine↗
PubMed1986

Evolution of cell and chromosome structure in eukaryote.

The analysis of the data so far available indicates that eukaryotic chromosome with splicing characteristics appeared quite early in evolution possibly parallel and not sequential to the prokaryotic system. The endosymbiotic origin of the eukaryotic cell involved a primitive undifferentiated unicellular eukaryote and a photosynthetic or non-photosynthetic microbe. Certain regulatory genes of extra-cellular organelles were transferred later through molecular hybridization to the nucleus. The evolution of multicellularity and sexual reproduction led to the origin of innumerable eukaryotic forms in the late precambrian period. This new concept of the author can account for the evolution of complex eukaryotic chromosome and harmonious functioning of extra-cellular organelles with the nucleus. The concept also explains the sudden spurt of innumerable eukaryotic fossils at the early palaeozoic era.

Animals↗
PubMed1979

[Symptomatic arterial hypertension in lupus nephropathy].

Sixty six patients with lupus nephropathy with hypertonic syndrome are examined. In patients with latent (inactive) lupus glomerulonephritis hypertonic syndrome developed 3--8 months after the initiation of the corticosteroid treatment, advancing with fluctuations, in some of the patients the arterial pressure being normalized after the discontinuation of that treatment. In patients with chronic active lupus glomerulonephritis without nephrotic syndrome, the hypertension develops before the initiation of the corticosteroid treatment, fluctuating at the beginning, and gradually assumes a stable character 3--5 months after the beginning of such treatment, sometimes with a malignant course and rapid development of renal insufficiency. The hypertonic syndrome advances most severely and malignantly in chronic lupus glomerulonephritis with nephrotic syndrome and is resistant to the active antihypertensive treatment. In 18, out of 25, such patients, the hypertonic syndrome is manifested in parallel with nephropathy before the inclusion of the cortocosteroid treatment. The grave and malignant course of the hypertonic syndrome is associated with the peculiarities of the clinical form and histomorphological type of that lupus nephropathy. In the patients with nephrosclerosis, the hypertonic syndrome is with a gradually progressing evolution, in parallel with the progress of the renal insufficiency.

Adolescent↗
PubMed1983

[Characteristics of testosterone binding to plasma proteins during the sexual cycle in a seasonally-reproductive animal, the male viviparous lizard].

Plasma testosterone binding activity was determined by an equilibrium dialysis method in the male of Lacerta vivipara during the annual cycle of activity (from March to September). Capacity showed significant variations during the sexual cycle although affinity remained constant. The variations of capacity were then compared with plasma testosterone levels measured by radioimmunoassay and plasma proteins content measured by the Lowry method. The three parameters showed parallel seasonal evolution except in May-June when binding activity increased although plasma testosterone and protein levels fell. The physiological meaning of this conspicuous phenomenon is discussed=an active mechanism of strengthening of the atrophy of accessory sexual organs is hypothesized. Furthermore, the increase of the binding activity which occurs in autumn and is parallel to the levels of testosterone must prevent these accessory organs from a full resumption of activity before the retreat since the lizard is a hibernating animal. These results emphasize the key role played by specific plasma binding proteins in the modulation of steroid hormone action.

Animals↗
PubMed1985

[Angiolymphoid hyperplasia with eosinophilia. Extensive form associated with thrombopenic purpura].

The authors report a case, on a 59-year-old female patient, of angiolymphoid hyperplasia with eosinophilia (AHE) associated to a thrombopenic purpura (TP) of which the evolution is parallel. The clinical aspect is made of sub-cutaneous nodules of various sizes (1 or 2 cm on an average) and of more superficial, erythematous, sometimes telangiectatic, pseudo-angiomatous nodules. There are (about) 25 nodules, located on the face, the neck, the arms and the thorax, sometimes pruriginous: the rest of the examination is negative excepting axillary and inguinal small size lymph nodes and of a dermographism. The anatomopathological examination in optical microscopy, shows a dermo-epidermal lymphocytic infiltrate with which mingle numerous eosinophilic leucocytes. The dermal vessels are very altered, with a swelling endothelium and a proliferation of endothelial and perithelial cells filling up in large part the vascular section. The biological investigation show essentially: a slight and altering hypereosinophilia (between 500 and 800/mm3); a low amount of blood-platelets (between 95,000 and 130,000/mm3); an increase of the seroconversion enzyme of angiotensin (75 UI; N less than 52 UI); are normal or negative: ESR, protein electrophoresis, immunological tests. The diagnosis of AHE is held back and the clinical evolution is done in several stages: under general corticotherapy (prednisone 1 mg/kg/j): progressive decrease of the nodules, but stopping of the therapy by the patient after 4 months; testing of treatment by thalidomide (100 mg/day) interrupted after 2 weeks because of the aggravation of the thrombopenia (25,000/mm3); occurrence of a thrombopenic purpura (TP) (amount of platelets 10,000/mm3) without a serious haemorrhagic syndrome, evolving in a parallel way to the outbreak of AHE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMedDate not supplied

Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging.

The appearance and evolution of brain infarcts over 3 days following proximal occlusion of the left middle cerebral artery (MCA) in SHR rats were measured non-invasively by magnetic resonance imaging (MRI). Infarcts were clearly visible in coronal, T2 weighted brain sections, 24, 48 and 72 h after MCA occlusion in the left hemisphere, as areas of increased NMR signals. The infarcts were quantified by pixel counting in each section, the sum of 4 sections representing an accurate estimate of the total infarct size. The location and extent of infarction, determined by MRI, were found to be highly reproducible and correlated well with post-mortem histological and biochemical data. A neurological score, made every 24 h, paralleled the evolution of the infarct size, which culminated after 48 h. Pre- or post-treatment of MCA occluded rats with the dihydropyridine calcium antagonist PN 200-110 resulted in a substantial reduction of infarct size, determined by MRI 24, 48 and 72 h after infarction, compared to vehicle treated controls. These findings were corroborated by corresponding improvements of the neurological scores as well as histological and biochemical data. Post-treatment with nimodipine showed qualitatively similar effects. These results support the notion that calcium antagonists, through vascular and/or metabolic mechanisms, are effective in treating acute stroke. Since they were obtained in a chronic, relevant model of stroke with a method directly applicable also to humans, they should encourage further clinical studies with calcium antagonists.

Animals↗
PubMed2026

Tracking the shifting landscape of SARS-CoV-2 variants in Lebanon among healthcare workers and hospitalized patients.

UNLABELLED: Genomic surveillance of SARS-CoV-2 is critical for tracking viral evolution and informing public health responses. This study characterized variants circulating among healthcare workers (HCWs) and hospitalized patients in Lebanon between January 2022 and September 2024. A total of 530 SARS-CoV-2-positive nasopharyngeal swabs were collected from five Lebanese governorates and subjected to whole-genome sequencing. Correlations between variant circulation and a number of demographic and clinical variables were assessed. Most HCWs were female (64%), young adults (20-30 years, 39%), and had no comorbidities (97%). In contrast, hospitalized patients were mostly older adults (>60 years, 55.6%) with underlying conditions (77%). Early 2022 was marked by BA.1- and BA.2-like Omicron variants, followed by the predominance of BA.5-like lineages. In 2023, recombinant XBB sublineages became widespread. By 2024, these were largely replaced by next-generation variants, including JN.1 and KP.3.1.1. Despite differences in demographics and exposure risk, both groups showed parallel variant evolution. These findings reflect global and regional patterns and highlight the dynamic nature of SARS-CoV-2 circulation in Lebanon. IMPORTANCE: This study provides a comprehensive snapshot of SARS-CoV-2 variant evolution in Lebanon between 2022 and 2024, focusing on healthcare workers and hospitalized patients. By combining genomic and clinical data, it reveals how successive Omicron subvariants emerged and spread within key population groups. The detection of diverse and evolving lineages, including XBB recombinants and next-generation variants such as JN.1, underscores the ongoing antigenic drift of SARS-CoV-2. These insights reinforce the value of continued genomic surveillance for pandemic preparedness, especially in regions where data remain limited. Understanding local variant dynamics can guide targeted vaccination strategies and health policy decisions.

Humans↗
PubMed1997

Effect of hypothermia on microglial reaction in ischemic brain.

Intra-ischemic hypothermia is known to protect neurons against ischemic injury. Microglial cells have been shown to become activated following ischemia and are speculated to play significant roles in the evolution of ischemic neuronal injury. In this study, we examined the effect of intra-ischemic hypothermia on the microglial reaction in the hippocampus following transient forebrain ischemia produced in gerbils by 10 min bilateral carotid occlusion at 30 degrees C or at 37 degrees C, followed by normothermic reperfusion for 1-7 days. Microglial cells were visualized by histochemical staining with isolectin-B4 from Griffonia simplicifolia. Brains subjected to normothermic ischemia showed activation of microglia at 1 day post-ischemia; this increased with further recirculation, becoming intense by 3 days and diminished by 7 days. Ischemia under hypothermic conditions was not associated with activation of microglia, and these brains showed no significant neuronal damage, whereas the brains subjected to normothermic ischemia showed extensive neuronal necrosis in the CA1 region after 1 and 7 days reperfusion. The presence of activated microglial cells in the CA1 region prior to and in parallel with evolution of ischemic neuronal damage, the lack of such activation in brains subjected to the neuroprotective action of intra-ischemic hypothermia, together with the known potential capability of microglial cells to release cytotoxic substances appear to indicate that these cells could contribute significantly to ischemic neuronal necrosis.

Animals↗
PubMed1983

Alterations of noradrenaline and serotonin uptake and metabolism in chronic cobalt-induced epilepsy in the rat.

The high affinity uptake of noradrenaline and serotonin, and the concentrations of these monoamines and their metabolites, have been measured in the perifocal cortical area at various stages of the evolution of cobalt-induced epilepsy in the rat. Noradrenaline uptake was maximally reduced at days 8-10 after cortical cobalt application, a time corresponding to the onset of epileptic discharges; it remained diminished during the spiking activity period of the focus (days 14-20) and was back to normal values at day 40, at which time the epileptic syndrome had disappeared. Serotonin uptake was also diminished at days 8-10 but to a lesser extent than was noradrenaline uptake. In the homotopic cerebral cortex contralateral to cobalt application, noradrenaline uptake was reduced at day 10 only and to a lesser extent than in the perifocal area, whereas serotonin uptake was unaffected. Kinetic analysis of the cobalt-induced monoamine uptake alterations at day 10 revealed a diminution of the maximal velocity with no change in the Km. Noradrenaline and dihydroxyphenylethyleneglycol concentrations in the perifocal area were also maximally reduced at days 8-10 but were unaffected at day 2 and day 40 post cobalt application. A reduction of serotonin levels in the perifocal area was observed only at days 8-10 while 5-hydroxyindoleacetic acid remained unaffected throughout the time period studied. The levels of these monoamines and their metabolites were unchanged in the homotopic contralateral cortex 2-40 days after cobalt application. These results indicate that cortical cobalt application induces alterations of the biochemical indices of the density of noradrenaline-containing terminals that closely parallel the evolution of the epileptic syndrome. These data further emphasize the important role of the cortical noradrenergic system in cobalt-induced epilepsy.

Animals↗
PubMed1999

Bi-penta-bi-decaradial symmetry: A review of evolutionary and developmental trends in holothuroidea (echinodermata)

Holothuroidea, comprising the sea cucumbers, is the least studied class of extant echinoderms, yet this group possesses a wealth of features of potential interest to developmental and evolutionary biologists. Holothuroids include the most morphologically derived echinoderms, including pelagic species and spheroid, plated taxa with mouth and anus adjacent at the end of a long, flexible stalk. To begin investigating this diversity of body form, we first estimated evolutionary relationships in the class Holothuroidea based on maximum parsimony analyses of 1,075 nt of the nuclear small subunit rDNA (for six species in four orders) and on 52 informative morphological characters (for the 25 extant families). Both the morphological and molecular evidence suggests almost an inversion of the prevailing higher level classification. Character-state optimizations indicated that pronounced adult bilateral symmetry evolved three times. In one group even a regain of secondary radial symmetry is found. Respiratory trees, structures unique to holothuroids, are a relatively late innovation, are ectodermally derived, and are bilaterally symmetric, supporting the possibility that the secondary gain of bilateral symmetry in holothuroids is ectodermally derived analogous to, say, the derivation of vertebrate limb dorso-ventral axis. The test of imbricating plates found in 10% of living holothuroids is apparently not homologous with that of other heavily armored echinoderms, evolving much later and at least twice. Indirectly developing larvae, auriculariae, occur in two evolutionarily disparate clades and unlike echinoids comprise a minority of clades. We suggest that this implies the parallel convergent evolution of this larval type or, more speculatively, some form of retention of developmental constraints. J. Exp. Zool. (Mol. Dev. Evol.) 285:93-103, 1999. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗
PubMed1986

Effects of silica on lung collagen.

A single intratracheal injection of 50 mg crystalline silica (quartz) into rats produces silicosis. This animal model may be used to study collagen metabolism during the early, middle, and late phases of lung injury, corresponding respectively to the stages of lung injury, development of discrete granulomas, and development of mature silicotic nodules. The early phase is characterized by a rapid increase in the rate of synthesis of lung collagen (within one week of instillation) and increased deposition of excess lung collagen (significant increases within two weeks of instillation). Later phases are characterized by a continuing increase in deposition of excess lung collagen for at least one year after instillation. Silica-induced fibrosis is unique among all the animal models (and in most human fibrotic diseases) thus far examined, in that the excess collagen deposited in the lung contains normal ratios of the two major collagen types of the lung: types I and III. This collagen is nonetheless biochemically different from normal lung collagen. There are reproducible and characteristic differences in the intermolecular cross-links of the collagen in lungs from rats injected with silica. Within one month of silica instillation (the earliest time point examined thus far), an increased hydroxylysine content of collagen can be appreciated. The reducible dysfunctional cross-links are also more likely to be derived from hydroxylysine (i.e. the ratio of dihydroxylated to monohydroxylated cross-links increases). Within four months of silica instillation (and increasingly thereafter), increased amounts of the mature trifunctional cross-link hydroxypyridinium (derived from three residues of hydroxylysine) can also be appreciated, seemingly paralleling the evolution of mature silicotic nodules in these lungs. These changes in cross-linking of lung collagen seem to be common to all the animal models of pulmonary fibrosis examined, and are also consistent with changes occurring in human fibrotic lungs. Preliminary observations suggest that the locus of cross-linking remains the same: hydroxylysine replaces lysine in the primary structure of a specific collagen alpha chain to form the altered cross-links. Thus, there may be molecular markers for the collagen of fibrosis in diseased lungs.

Animals↗
PubMed1983

Immunopathogenesis of experimental Chagas' disease in mice: damage to the autonomic nervous system.

Infection of mice with Trypanosoma cruzi produces pathological change which in many ways parallels the evolution of Chagas' disease in human patients. An essential element in this experimental pathology is the intense denervation observed during the resolution of acute-stage parasitaemia. Host cells, from a variety of tissues, have been shown to absorb parasite antigens and thus to become targets for the hosts' own anti-parasite immune response. The definition of common antigenic determinants, shared by T. cruzi and human neuronal cells, might explain why the electrical conduction systems and the autonomic nervous system are especially vulnerable to the postulated autoimmune process. We have the models, the tools and the hypotheses, and now we await the proof.

Animals↗