Advances in the immunodiagnosis of parasitic infections

Summary In summary, with the availability of commercial reagents, the growth of parasitic serology is rapidly accelerating. I believe the diagnostic work being performed today represents an investigation of the tip of the iceberg. Unless some policy of evaluation and certification is initiated, we risk the appearance of poor reagents in the diagnostic laboratory and the publication of critical articles suggesting that our tests are nonspecific and useless.Technical developments have brought us to the full or partial automation of serologic tests. Research on the purification and isolation of parasitic antigens has not kept pace with the development and evaluation of serologic methodology. Evaluation of sophisticated methods, such as radioimmunoassay, for the diagnosis of parasitic infections is only beginning to appear in the literature. Greater emphasis must be placed on the use of such sensitive methods in the diagnostic laboratory.With the exception of the Asian workers, who have reported the recovery of antigen in the urine of patients with parasitic diseases, and recent reports of antigen in the serum of patients with schistosomiasis in the United States, the entire focus of parasitic serology has been on the detection of antibodies. Since parasitic antigens have been shown to circulate in the serum and body fluids of individuals with a number of parasitic infections, both specific and sensitive methods must be evaluated for their detection.In the serology of parasitic infections, the diagnosis of protozoan infections is most highly developed. For the helminth infections we require enhanced sensitivity and specificity, especially in areas where more than one species infects man. The serology of nematode infections requires the most work. Toward this end, we have to encourage further work on the separation and purification of parasitic antigens for use in the diagnostic laboratory.Presented at the 3rd International Congress of Parasitology, Munich, Germany, 25–31 August 1974.     

Nanomedicine and nanotoxicology: two sides of the same coin

Current advances in nanotechnology have led to the development of the new field of nanomedicine, which includes many applications of nanomaterials and nanodevices for diagnostic and therapeutic purposes. The same unique physical and chemical properties that make nanomaterials so attractive may be associated with their potentially calamitous effects on cells and tissues. Our recent study demonstrated that aspiration of single-walled carbon nanotubes elicited an unusual inflammatory response in the lungs of exposed mice with a very early switch from the acute inflammatory phase to fibrogenic events resulting in pulmonary deposition of collagen and elastin. This was accompanied by a characteristic change in the production and release of proinflammatory to anti-inflammatory profibrogenic cytokines, decline in pulmonary function, and enhanced susceptibility to infection. Chemically unmodified (nonfunctionalized) carbon nanotubes are not effectively recognized by macrophages. Functionalization of nanotubes results in their increased recognition by macrophages and is thus used for the delivery of nanoparticles to macrophages and other immune cells to improve the quality of diagnostic and imaging techniques as well as for enhancement of the therapeutic effectiveness of drugs. These observations on differences in recognition of nanoparticles by macrophages have important implications in the relationship between the potentially toxic health effects of nanomaterials and their applications in the field of nanomedicine.     

Orientation and direction selectivity of neurons in V1 of alert monkeys: functional relationships and laminar distributions

We studied orientation selectivity in V1 of alert monkeys and its relationship to other physiological parameters and to anatomical organization. Single neurons were stimulated with drifting bars or with sinusoidal gratings while compensating for eye position. Orientation selectivity based on spike counts was quantified by circular variance and by the bandwidth of the orientation tuning curve. The circular variance distribution was bimodal, suggesting groups with low and with high selectivity. Orientation selectivity was clearly correlated with spontaneous activity, classical receptive field (CRF) size and the strength of surround suppression. Laminar distributions of neuronal properties were distinct. Neurons in the output layers 2/3, 4B and 5 had low spontaneous activity, small CRFs and high orientation selectivity, while the input layers had greater diversity. Direction-selective cells were among the neurons most selective for orientation and most had small CRFs. A narrow band of direction- and orientation-selective cells with small CRFs was located in the middle of layer 4C, indicating appearance of very selective cells at an early stage of cortical processing. We suggest that these results reflect interactions between excitatory and inhibitory mechanisms specific to each sublamina. Regions with less inhibition have higher spontaneous activity, larger CRFs and broader orientation tuning. Where inhibition is stronger, spontaneous activity almost disappears, CRFs shrink, and orientation selectivity is high.     

Sexually inappropriate behaviour in demented elderly people

Aim: To determine the prevalence, aetiology, and treatment profile of abnormal sexual behaviour in subjects with dementia in psychogeriatric practices. Methods: A retrospective cross sectional study was conducted in a long term care psychiatry consultation service, community based geriatric psychiatry service, and an inpatient dementia behavioural unit in Edmonton, Canada. Results: Forty one subjects (1.8%) had sexually inappropriate behaviour. Of those cognitively impaired subjects with sexually inappropriate behaviour, 20 (48.8%) were living in nursing homes and the rest, 21 (51.2%) in the community. Of these subjects, 53.7% had vascular dementia, 22% had Alzheimer''s, and 9.8% had mild cognitive impairment. History of alcohol misuse and psychosis were reported in 14.6% and 9.8% of subjects respectively. Twenty seven (65.7%) had verbally inappropriate behaviour and 36 (87.8%) had physically inappropriate behaviour. In this study, verbally inappropriate behaviour was more commonly seen in the community sample (81%) than in the nursing home sample (50%) (p = 0.04). Behavioural treatment was also more commonly seen in the community sample (81%) than in the nursing home sample (45%) (p = 0.01). Conclusion: In this study sexually inappropriate behaviour was seen in all stages of dementia, more commonly associated with subjects of vascular aetiology, and is as commonly seen in community dwelling subjects with dementia as in nursing home subjects.     

Better late than never: a re-examination of ethical dilemmas in coping with severe acute respiratory syndrome

At the end of 2002 severe acute respiratory syndrome (SARS) emerged and spread worldwide. The pathogen was unknown, as was its mechanism of transfer, and there was no effective therapy for the disease. There was a large element of hysteria and anxiety in society's reaction to SARS. The initial steps taken to cope with SARS were clear-cut and even dramatic. Decision-making in a time of emergency is associated with a high potential for ethical dilemmas and conflicts. In the course of efforts to cope with a threatening disease, it is important to appraise our activities from an ethical point of view. A retrospective look at this period of time shows that we did not do this. This article examines the ethical aspects of the process undertaken to cope with SARS in our medical centre.     

Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in Alzheimer's disease brain

The study is based on the premise that the enzyme lysyl oxidase (LO), which catalyzes the crosslinking of extracellular matrix (ECM) proteins, participates in ECM modulation and senile plaque formation in Alzheimer's disease (AD). Experiments on hippocampal samples indicate that LO activity is increased (about 30%) in AD, but also in non-Alzheimer's dementia, as compared to controls with unrelated diseases. Immunohistochemistry with specific LO antibody indicates localization in blood vessel walls and in plaque-like structures. The number of LO-positive plaque-like structures in AD was over two-fold higher as compared to both non-Alzheimer's dementia and control groups. The findings lead us to suggest that active LO molecules in the ECM may be associated with plaque formation.     

Association of selected phenotypic markers of lymphocyte activation and differentiation with perinatal human immunodeficiency virus transmission and infant infection

This study of a subset of women and infants participating in National Institutes of Health Pediatric AIDS Clinical Trials Group protocol 185 evaluated lymphocyte phenotypic markers of immune activation and differentiation to determine their association with the likelihood of human immunodeficiency virus (HIV) transmission from the women to their infants and the potential for early identification and/or prognosis of infection in the infants. Lymphocytes from 215 human immunodeficiency virus type 1 (HIV)-infected women and 192 of their infants were analyzed by flow cytometry with an extended three-color panel of monoclonal antibodies. Women who did not transmit to their infants tended to have higher CD4+ T cells. Most notably, levels of total CD8+ T cells and CD8+ CD38+ cells made significant independent contributions to predicting the risk of mother-to-child transmission. Adjusting for HIV-1 RNA level at entry, a one percentage-point increase in these marker combinations was associated with a nine percent increase in the likelihood of maternal transmission. Total as well as naive CD4+ T cells were significantly higher in uninfected than infected infants. Total CD8+ cells, as well as CD8+ cells positive for HLA-DR+, CD45 RA+ HLA-DR+, and CD28+ HLA-DR+ were elevated in infected infants. Detailed immunophenotyping may be helpful in predicting which pregnant HIV-infected women are at increased risk of transmitting HIV to their infants. Increasing differences in lymphocyte subsets between infected and uninfected infants became apparent as early as six weeks of age. Detailed immunophenotyping may be useful in supporting the diagnosis of HIV infection in infants with perinatal HIV exposure.     

Clinicopathological study of the WHO classification in childhood lupus nephritis

Over the past 10 years, at our center, 25 children diagnosed with systemic lupus erythematosus (SLE) have undergone an early renal biopsy; 15 underwent a second biopsy. The objective of this study was to determine whether clinical and laboratory parameters used to evaluate lupus disease activity and nephritis correlated with the WHO class on biopsy. At diagnosis, the presence of proteinuria, hematuria, a lower serum albumin, and the need for blood pressure medication were all associated with a worse class of lupus nephritis (P<0.05). On follow-up biopsy, however, none of these parameters correlated with the WHO class. Thus, it appears that while the WHO classification is useful for categorizing disease at presentation, it may be less useful for the evaluation of disease progression. Other biopsy indices need to be evaluated in serial renal biopsies to better understand the progression of lupus nephritis once treatment has been initiated.