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PubMed2006

Flow cytometric measurement of labile zinc in peripheral blood mononuclear cells.

Labile (i.e., free or loosely bound) zinc has the potential to modulate cellular function. Therefore, a flow cytometric assay for the measurement of labile zinc was developed to facilitate the investigation of the physiological roles of zinc. The zinc-sensitive fluorescent probe FluoZin-3 was used to quantify the amount of labile zinc in peripheral blood mononuclear cells isolated from human blood. Maximal fluorescence and autofluorescence of the probe were measured after the addition of zinc in the presence of the ionophore pyrithione, or the membrane-permeant chelator N,N,N',N'-tetrakis-(2-pyridyl-methyl)ethylenediamine, respectively. In this way, the intracellular concentrations of labile zinc in resting cells were estimated to be 0.17 nM in monocytes and 0.35 nM in lymphocytes. The method was successfully employed to monitor phorbol 12-myristate 13-acetate-induced zinc release, which occurred in monocytes but not lymphocytes, and the displacement of protein-bound zinc by the mercury-containing compounds HgCl(2) and thimerosal. Costaining with dyes that emit at higher wavelengths than FluoZin-3 allows multiparameter measurements. Two combinations with other dyes are shown: loading with propidium iodide to measure cellular viability and labeling with antibodies against the surface antigen CD4. This method allows measurement of the concentration of biologically active labile zinc in distinct cell populations.

Cell Line, Tumor↗
PubMed2005

Positive Montenegro skin test among patients with sporotrichosis in Rio De Janeiro.

We studied 52 patients with sporotrichosis confirmed by isolation of Sporothrix schenckii and reactivity to the Montenegro skin test (MST) during an ongoing outbreak of this mycosis in Rio de Janeiro. The objective was to emphasize the importance of parasitological confirmation and the possibility of incorrect diagnosis based on the lesion's appearance, epidemiological information, and immunological tests. The antigen used for the MST was conserved in either thimerosal 1:10,000 (group 1) or 0.4% phenol (group 2). Nineteen patients (39%) in group 1 and seven (12%) in group 2 presented an induration>or=10 mm (p<0.001). Sera from three patients (6.7%) reacted to indirect immunofluorescence (IIF) for leishmaniasis, while sera from 10 patients (22.2%) reacted to enzyme-linked immunosorbent assay (ELISA). Fifteen patients (28.8%) presented up to two lesions, with a predominance of ulcers. Forty-four patients (84.6%) were treated with itraconazole. In the differential diagnosis between sporotrichosis and cutaneous leishmaniasis, the possibility of co-infection, allergy to the reagent diluent, and cross-reactions should be further investigated, especially in regions with limited laboratory facilities.

Adolescent↗
PubMed2004

Angioedema related to the use of hyaluronidase in cataract surgery.

PURPOSE: To report a series of cases of angioedema related to the use of hyaluronidase in cataract surgery. DESIGN: Observational case series. METHODS: Three eyes of three patients who had periorbital angioedema after phacoemulsification at the Mayo Clinic, Rochester, Minnesota, between April 2001 and May 2002 were retrospectively skin tested for allergies using the prick technique. RESULTS: Skin testing was positive in all three patients for allergy to hyaluronidase (150 U/cc) and histamine control; and negative for prick control, 2% lidocaine, 1% cyclopentolate, 2.5% neosynephrine, 0.5% proparacaine, 0.3% ofloxacin, and thimerosal. CONCLUSIONS: The use of hyaluronidase in ophthalmic anesthesia injection may cause immediate type hypersensitivity reactions such as angioedema.

Angioedema↗
PubMed2005

Organic mercury compounds and autoimmunity.

Based on in vitro studies and short-term in vivo studies, all mercurials were for a long time considered as prototypic immunosuppressive substances. Recent studies have confirmed that organic mercurials such as methyl mercury (MeHg) and ethyl mercury (EtHg) are much more potent immunosuppressors than inorganic mercury (Hg). However, Hg interacts with the immune system in the presence of a susceptible genotype to cause immunostimulation, antinucleolar antibodies targeting fibrillarin, and systemic immune-complex (IC) deposits, a syndrome called Hg-induced autoimmunity (HgIA). Recent studies in mice with a susceptible genotype has revealed that the immunosuppressive effect of MeHg and EtHg will within 1-3 weeks be superseded by immunostimulation causing an HgIA-like syndrome. At equimolar doses of Hg, MeHg has the weakest immunostimulating, autoimmunogen, and IC-inducing effect, while the effect of thimerosal is similar to that of inorganic mercury. The immunosuppression is caused by the organic mercurials per se. Since they undergo rapid transformation to inorganic Hg, studies are being undertaken to delineate the importance of the organic substances per se and the newly formed inorganic Hg for induction of autoimmunity.

Animals↗
PubMed2006

Rapid method for detection of Salmonella in milk by surface plasmon resonance (SPR).

The Plasmonic surface plasmon resonance (SPR) device was used to develop a rapid, simple and specific immunoassay for detection of Salmonella in milk. Rapid detection of Salmonella contamination is a major challenge for the food industry. Salmonella contamination is well known in all foods including pasteurised milk. The SPR assay was developed as a sandwich model using a polyclonal antibody against Salmonella as capture and detection antibody. Milk spiked with Salmonella typhimurium cells, killed by thimerosal (1%, w/w) treatment was used. Using the Plasmonic SPR assay it was possible to detect S. typhimurium down to a concentration of 1.25 x 10(5) cells ml(-1) in both milk and buffer system. The results obtained are comparable with existing, approved rapid Salmonella detection techniques. No negative effects on the sensitivity of the assay are encountered due to the milk matrix. Hence, no sample preparation or clean-up steps are required. The sample volume requirement for the assay is only 10 microl. Using the assay S. typhimurium was detected in milk within 1h, whereas the cultural techniques require 3-4 days for presumptive positive isolates and further time for confirmation. The rapid tests require at least 24h for the results. The Plasmonic SPR device operates on the Kretschmann configuration and is a cuvette-based system with the advantage of having eight channels on one single SPR chip.

Animals↗
PubMed2006

Calcium signals and the in vitro migration of chick ciliary ganglion cells.

We have studied calcium signals and their role in the migration of neuronal and nonneuronal cells of embryonic chick ciliary ganglion (CG). In vitro, neurons migrate in association with nonneuronal cells to form cellular aggregates. Changes in the modulus of the velocity of the neuron-nonneuronal cell complex were observed in response to treatments that increased or decreased intracellular calcium concentration. In addition, both cell types generated spontaneous calcium activity that was abolished by removal of extracellular calcium. Calcium signals in neurons could be characterized as either spikes or waves. Neuronal spikes were found to be related to action potential generation whereas neuronal waves were due to voltage-independent calcium influx. Nonneuronal cells generated calcium oscillations that were dependent on calcium release from intracellular stores and on voltage-independent calcium influx. Application of thimerosal, a compound that stimulates calcium mobilization from internal stores, increased: (1) the amplitude of spontaneous nonneuronal oscillations; (2) the area of migrating nonneuronal cells; and (3) the velocity of the neuronal-nonneuronal cell complex. We conclude that CG cell migration is a calcium dependent process and that nonneuronal cell calcium oscillations play a key role in the modulation of velocity.

Animals↗
PubMed2004

The putative imidazoline receptor agonist, harmane, promotes intracellular calcium mobilisation in pancreatic beta-cells.

beta-Carbolines (including harmane and pinoline) stimulate insulin secretion by a mechanism that may involve interaction with imidazoline I(3)-receptors but which also appears to be mediated by actions that are additional to imidazoline receptor agonism. Using the MIN6 beta-cell line, we now show that both the imidazoline I(3)-receptor agonist, efaroxan, and the beta-carboline, harmane, directly elevate cytosolic Ca(2+) and increase insulin secretion but that these responses display different characteristics. In the case of efaroxan, the increase in cytosolic Ca(2+) was readily reversible, whereas, with harmane, the effect persisted beyond removal of the agonist and resulted in the development of a repetitive train of Ca(2+)-oscillations whose frequency, but not amplitude, was concentration-dependent. Initiation of the Ca(2+)-oscillations by harmane was independent of extracellular calcium but was sensitive to both dantrolene and high levels (20 mM) of caffeine, suggesting the involvement of ryanodine receptor-gated Ca(2+)-release. The expression of ryanodine receptor-1 and ryanodine receptor-2 mRNA in MIN6 cells was confirmed using reverse transcription-polymerase chain reaction (RT-PCR) and, since low concentrations of caffeine (1 mM) or thimerosal (10 microM) stimulated increases in [Ca(2+)](i), we conclude that ryanodine receptors are functional in these cells. Furthermore, the increase in insulin secretion induced by harmane was attenuated by dantrolene, consistent with the involvement of ryanodine receptors in mediating this response. By contrast, the smaller insulin secretory response to efaroxan was unaffected by dantrolene. Harmane-evoked changes in cytosolic Ca(2+) were maintained by nifedipine-sensitive Ca(2+)-influx, suggesting the involvement of L-type voltage-gated Ca(2+)-channels. Taken together, these data imply that harmane may interact with ryanodine receptors to generate sustained Ca(2+)-oscillations in pancreatic beta-cells and that this effect contributes to the insulin secretory response.

Animals↗
PubMed2005

A comparative study of the sensitivity of the 3-induction and 9-induction Buehler test procedures for assessing skin sensitisation potential.

Assessment of skin sensitization potential is a mandatory requirement for the registration or notification of most types of chemicals and products. Until recently, two methods using the guinea pig as test model were the most widely accepted; the guinea pig maximisation test and the Buehler test. In the case of agrochemical formulations, which constitute the final end use product in contact with operators, industry and also some regulatory authorities consider the Buehler method more appropriate as the methodology is more relevant to likely exposure in the field. However, certain European regulatory authorities have become concerned about the sensitivity of the Buehler test for this purpose and have requested that a modified method is used in which additional applications of test materials are used during the induction phase of the protocol (a total of 9 rather than the normal 3). This study was designed to assess whether this modification was justified. Six reference substances (formaldehyde, alpha-hexylcinnamaldehyde, fragrance mix, thimerosal, mercaptobenzothiazole and phthalic anhydride); all mild to moderate skin sensitizing chemicals, were assessed in a study, which compared the use of 3 and 9 induction applications. The results of this study demonstrated that, although most of these sensitisers were detected by both protocols, the modified method (9 induction applications) was no more sensitive than the standard method (3 induction applications). As the modified protocol is also potentially more stressful to the animals, it is concluded that the use of additional induction applications in the Buehler test cannot be justified from either a scientific or an animal welfare perspective.

Allergens↗
PubMed2005

Patch test results from the Mayo Clinic Contact Dermatitis Group, 1998-2000.

BACKGROUND: Patch testing is a diagnostic tool for the evaluation of patients with suspected allergic contact dermatitis. A standard series of allergens similar to that used by the North American Contact Dermatitis Group (NACDG) is used at Mayo Clinic. OBJECTIVE: Our aim was to report the results of patch testing with a standard series at Mayo Clinic from July 1, 1998, to Dec 31, 2000 and to compare our findings with those of the NACDG during the same period. METHODS: The results of patch testing with the standard series at Mayo Clinic were examined. Positive reaction rates were compared between Mayo Clinic and the NACDG. RESULTS: During the 30-month period, 1324 Mayo Clinic patients were patch tested with a standard series of allergens (mean, 60 allergens), whereas the NACDG standard series during this period included 50 allergens. Overall, 917 patients (69.3%) had at least one positive reaction and 606 patients (45.8%) had two or more positive reactions. The 10 allergens used both by Mayo Clinic and by the NACDG that most frequently caused positive reactions were nickel sulfate hexahydrate, balsam of Peru (Myroxylon pereirae), neomycin sulfate, cobalt chloride, fragrance mix, potassium dichromate (0.25%), thimerosal, bacitracin, formaldehyde, and glutaraldehyde. Statistically significant differences in positive reaction rates (P < .05) were observed for 12 of the 43 allergens common to both Mayo Clinic and the NACDG. CONCLUSION: With large standard patch test series, one can identify commonly encountered and potentially relevant contact allergens.

Adolescent↗
PubMed2006

Temporal association of entomopathogenic nematodes (Rhabditida: Steinernematidae and Heterorhabditidae) and bacteria.

Galleria mellonella L. larvae were infected with three species (seven strains) of Steinernema spp. or three species (three strains) of Heterorhabditis spp. Infected larvae were incubated at 22, 27, and 32 degrees C. Larvae were dorsally dissected every 6h over a 48-h period. Hemolymph was collected and streaked on tryptic soy agar plates. Several non-symbiotic bacterial species were identified from infected insect cadavers: Enterobacter gergoviae, Vibrio spp., Pseudomonas fluorescens type C, Serratia marcescens, Citrobacter freundii, and Serratia proteomaculans. At 18-24 h incubation, the nematode-associated symbiont occurred almost exclusively. Bacterial associates generally appeared outside the 18-24 h window. Infective juveniles of Steinernema feltiae (Filipjev) (27), Steinernema riobrave Cabanillas, Poinar, and Raulston (Oscar), or Steinernema carpocapsae (Weiser) (Kapow) were left untreated, or surface sterilized using thimerosal, then pipetted under sterile conditions onto tryptic soy agar plates. Several additional species of associated bacteria were identified using this method compared with the less extensive range of species isolated from infected G. mellonella. There was no difference in bacterial species identified from non-sterile or surface sterilized nematodes, suggesting that the bacteria identified originated from either inside the nematode or between second and third stage juvenile cuticles. Infective juveniles of S. feltiae (Cowles), S. carpocapsae (Cowles), and H. bacteriophora Poinar (Cowles) were isolated from field samples. Nematodes were surface-sterilized using sodium hypochlorite, mixed with G. mellonella hemolymph, and pipetted onto Biolog BUG (with blood) agar. Only the relevant symbionts were isolated from the limited number of samples available. The nematodes were then cultured in the laboratory for 14 months (sub-cultured in G. mellonella 7-times). Other Enterobacteriaceae could then be isolated from the steinernematid nematodes including S. marcescens, Salmonella sp., and E. gergoviae, indicating the ability of the nematodes to associate with other bacteria in laboratory culture.

Animals↗
PubMed2004

Mercury exposure in children: a review.

Exposure to toxic mercury (Hg) is a growing health hazard throughout the world today. Recent studies show that mercury exposure may occur in the environment, and increasingly in occupational and domestic settings. Children are particularly vulnerable to Hg intoxication, which may lead to impairment of the developing central nervous system, as well as pulmonary and nephrotic damage. Several sources of toxic Hg exposure in children have been reported in biomedical literature: (1) methylmercury, the most widespread source of Hg exposure, is most commonly the result of consumption of contaminated foods, primarily fish; (2) ethylmercury, which has been the subject of recent scientific inquiry in relation to the controversial pediatric vaccine preservative thimerosal; (3) elemental Hg vapor exposure through accidents and occupational and ritualistic practices; (4) inorganic Hg through the use of topical Hg-based skin creams and in infant teething powders; (5) metallic Hg in dental amalgams, which release Hg vapors, and Hg2+ in tissues. This review examines recent epidemiological studies of methylmercury exposure in children. Reports of elemental Hg vapor exposure in children through accidents and occupational practices, and the more recent observations of the increasing use of elemental Hg for magico-religious purposes in urban communities are also discussed. Studies of inorganic Hg exposure from the widespread use of topical beauty creams and teething powders, and fetal/neonatal Hg exposure from maternal dental amalgam fillings are reviewed. Considerable attention was given in this review to pediatric methylmercury exposure and neurodevelopment because it is the most thoroughly investigated Hg species. Each source of Hg exposure is reviewed in relation to specific pediatric health effects, particularly subtle neurodevelopmental disorders.

Child↗
PubMed1998

Sulfhydryl oxidation modifies the calcium dependence of ryanodine-sensitive calcium channels of excitable cells.

The calcium dependence of ryanodine-sensitive single calcium channels was studied after fusing with planar lipid bilayers sarcoendoplasmic reticulum vesicles isolated from excitable tissues. Native channels from mammalian or amphibian skeletal muscle displayed three different calcium dependencies, cardiac (C), mammalian skeletal (MS), and low fractional open times (low Po), as reported for channels from brain cortex. Native channels from cardiac muscle presented only the MS and C dependencies. Channels with the MS or low Po behaviors showed bell-shaped calcium dependencies, but the latter had fractional open times of <0.1 at all [Ca2+]. Channels with C calcium dependence were activated by [Ca2+] < 10 microM and were not inhibited by increasing cis [Ca2+] up to 0.5 mM. After oxidation with 2,2'-dithiodipyridine or thimerosal, channels with low Po or MS dependencies increased their activity. These channels modified their calcium dependencies sequentially, from low Po to MS and C, or from MS to C. Reduction with glutathione of channels with C dependence (native or oxidized) decreased their fractional open times in 0.5 mM cis [Ca2+], from near unity to 0.1-0.3. These results show that all native channels displayed at least two calcium dependencies regardless of their origin, and that these changed after treatment with redox reagents.

Animals↗
PubMed1996

Regulation of the functional activity of the human dopamine transporter by the arachidonic acid pathway.

The role of arachidonic acid was examined in the regulation of dopamine transport in C6 glioma cells stably expressing the human dopamine transporter. Exogenously added arachidonic acid (20-160 microM) stimulated [3H]dopamine uptake when pre-incubated for short times (15-30 min); 160 microM arachidonic acid inhibited following longer pre-exposures (45-60 min). Under the same conditions, only decreases were observed in the binding of the cocaine analog [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428). The reduction in dopamine transporter activity by arachidonic acid (at 160 microM for 60 min) was caused by a decrease in the Vmax (from 202 to 44 pmol/mg/min) opposed by a smaller reduction in K(m) (from 1.2 to 0.8 microM), whereas the effect of arachidonic acid (at 160 microM for 15 min) on [3H]WIN 35,428 binding was caused by a reduction in the Bmax (from 1.8 to 1.3 pmol/mg) without a change in Kd (7.2 nM). Upon 15-min exposure, melittin, an activator of phospholipase A2, and nordihydroguaiaretic acid, a lipooxygenase inhibitor, both expected to cause enhanced endogenous arachidonic acid, inhibited [3H]dopamine uptake and [3H]WIN 35,428 binding with an IC50 value close to 1 microM, whereas thimerosal, which raises arachidonic acid by inhibiting lipid reacylation, caused similar reductions at the sub-millimolar level. Co-presence of stauroporine (0.3-2 microM), an inhibitor of protein kinase C, had little or no effect on the melittin- or arachidonic acid-induced inhibition of [3H]dopamine uptake. Both the melittin- and arachidonic acid-, but not phorbol 12-myristate 13-acetate-induced inhibition of uptake were counteracted by bovine serum albumin (0.1 and 1 mg/ml) which binds arachidonic acid. The data taken together suggest that the inhibitory effects of arachidonic acid activators and those of protein kinase C activators on dopamine uptake are mediated by separate mechanisms.

Animals↗
PubMed1999

A comparative study of the calcium system in memory T cells and naive T cells.

The comparative analysis of responses of memory and naive T lymphocytes to Ca2+-mobilizing agents, namely Con A, thimerosal, thapsigargin and ionomycin, was carried out. The effect of these agents on both types of T cells differed qualitatively and quantitatively. The lack of intracellular Ca2+ stores in memory T cells was shown. Ca2+-mobilizing agents did not induce influx of Ca2+ in memory T cells from outside and this was the reason for their stability to Ca2+ ionophores. It was also shown that memory T cells were resistant to the 'Ca2+ paradox'.

Animals↗
PubMed1996

Pediatric tracheal homograft reconstruction: a novel approach to complex tracheal stenoses in children.

PURPOSE: Tracheal stenosis can be a life-threatening problem in children. Long-segment tracheal stenosis and recurrent tracheal stenosis are especially problematic. Tracheal homograft reconstruction represents a novel therapeutic modality for these patients. METHODS: Cadaveric trachea is harvested, fixed in formalin, washed in thimerosal (Methiolate), and stored in acetone. The stenosed tracheal segment is opened to widely patent segments proximally and distally. The anterior cartilage is excised and the posterior trachealis muscle or tracheal wall remains. A temporary silicone rubber intraluminal stent is placed and absorbable sutures secure the homograft. Regular postoperative bronchoscopic treatment clears granulation tissue. The stent is removed endoscopically after epithelialization over the homograft. Twenty-four children with severe tracheal stenosis (age 5 months to 18 years, mean +/- standard error of the mean = 8.18 +/- 1.21 years) underwent tracheal homograft reconstruction. All but one had had previous unsuccessful reconstructive attempts. Ten lesions were congenital, nine were posttraumatic, and five were due to prolonged intubation. RESULTS: Follow-up ranged from 5 months to 10 years (3.79 +/- 0.70 years). Twenty patients survive (20/24 = 83%), 16 without any airway problems. Four patients are still undergoing treatment. One patient requiring emergency extracorporeal membrane oxygenator support before the operation died 10 days after tracheal homograft reconstruction. Another patient with severe preoperative mediastinal sepsis died 3.5 months after tracheal homograft reconstruction. Two patients with functional airways died late of unrelated problems. CONCLUSIONS: Tracheal homograft reconstruction demonstrates encouraging short-term to medium-term results for children with severe recurrent tracheal stenosis. Postoperative bronchoscopic and histologic studies provide evidence of epithelialization and support the expectation of good long-term results.

Adolescent↗
PubMed1991

Microscopic hematuria: advances in identification of glomerular dysmorphic erythrocytes.

The high diagnostic sensitivity and specificity of microscopically visible, typically glomerular dysmorphic erythrocytes for identification of the cause of glomerular bleeding have been recognized worldwide. Although glomerular dysmorphic erythrocytes are simple to detect on phase contrast microscopy, immediate microscopic diagnosis still is indispensable, since a change in the morphology of the erythrocytes with restriction of the diagnostic relevance is anticipated because of the high autolytic potency of the urine. It may be postulated that this need for immediate diagnosis has led to the method being neglected owing to the high work load at hospitals and physician offices. Moreover, a physician who does not perform microscopic investigations or who lacks experience with the method will not be able to use this diagnostic technique, since it appeared to be impossible to transport urine samples by mail. In the context of a study comprising 30 patients, of whom 10 had histologically confirmed glomerulonephritis, we have shown that glomerular dysmorphic erythrocytes have a manifest form stability for at least 3 days. The preservative used was thimerosal. Also, the urine can be investigated independent of time even after alcoholic Papanicolaou staining without an alteration of erythrocyte morphology. The practicality of the form stability of glomerular erythrocytes can be exploited in everyday medical routine. There are well founded prospects that the rate of early diagnosis of glomerulonephritis will increase.

Erythrocytes, Abnormal↗
PubMed2005

Immunological findings in autism.

The immunopathogenesis of autism is presented schematically in Fig. 1. Two main immune dysfunctions in autism are immune regulation involving pro-inflammatory cytokines and autoimmunity. Mercury and an infectious agent like the measles virus are currently two main candidate environmental triggers for immune dysfunction in autism. Genetically immune dysfunction in autism involves the MHC region, as this is an immunologic gene cluster whose gene products are Class I, II, and III molecules. Class I and II molecules are associated with antigen presentation. The antigen in virus infection initiated by the virus particle itself while the cytokine production and inflammatory mediators are due to the response to the putative antigen in question. The cell-mediated immunity is impaired as evidenced by low numbers of CD4 cells and a concomitant T-cell polarity with an imbalance of Th1/Th2 subsets toward Th2. Impaired humoral immunity on the other hand is evidenced by decreased IgA causing poor gut protection. Studies showing elevated brain specific antibodies in autism support an autoimmune mechanism. Viruses may initiate the process but the subsequent activation of cytokines is the damaging factor associated with autism. Virus specific antibodies associated with measles virus have been demonstrated in autistic subjects. Environmental exposure to mercury is believed to harm human health possibly through modulation of immune homeostasis. A mercury link with the immune system has been postulated due to the involvement of postnatal exposure to thimerosal, a preservative added in the MMR vaccines. The occupational hazard exposure to mercury causes edema in astrocytes and, at the molecular level, the CD95/Fas apoptotic signaling pathway is disrupted by Hg2+. Inflammatory mediators in autism usually involve activation of astrocytes and microglial cells. Proinflammatory chemokines (MCP-1 and TARC), and an anti-inflammatory and modulatory cytokine, TGF-beta1, are consistently elevated in autistic brains. In measles virus infection, it has been postulated that there is immune suppression by inhibiting T-cell proliferation and maturation and downregulation MHC class II expression. Cytokine alteration of TNF-alpha is increased in autistic populations. Toll-like-receptors are also involved in autistic development. High NO levels are associated with autism. Maternal antibodies may trigger autism as a mechanism of autoimmunity. MMR vaccination may increase risk for autism via an autoimmune mechanism in autism. MMR antibodies are significantly higher in autistic children as compared to normal children, supporting a role of MMR in autism. Autoantibodies (IgG isotype) to neuron-axon filament protein (NAFP) and glial fibrillary acidic protein (GFAP) are significantly increased in autistic patients (Singh et al., 1997). Increase in Th2 may explain the increased autoimmunity, such as the findings of antibodies to MBP and neuronal axonal filaments in the brain. There is further evidence that there are other participants in the autoimmune phenomenon. (Kozlovskaia et al., 2000). The possibility of its involvement in autism cannot be ruled out. Further investigations at immunological, cellular, molecular, and genetic levels will allow researchers to continue to unravel the immunopathogenic mechanisms' associated with autistic processes in the developing brain. This may open up new avenues for prevention and/or cure of this devastating neurodevelopmental disorder.

Antibody Formation↗
PubMed1996

The effect of extracellular polyvalent cations on bovine anterior pituitary cells. Evidence for a Ca(2+)-sensing receptor coupled to release of intracellular calcium stores.

We have investigated the effects of extracellular cations ([ION]ex) on cytosolic free calcium levels ([Ca2+]i) in bovine anterior pituitary (bAP) cells, using single-cell microfluorimetry. Increasing the [Ca2+]ex from 1 mM to 20 mM caused [Ca2+]i to increase in 64 +/- 14% of bAP cells. The [Ca2+]ex-induced [Ca2+]i increase was observed when cells were maintained in the presence of the voltage-gated-calcium-channel antagonist nitrendipine, but not when cells were treated with thapsigargin. Addition of [La3+]ex (5-15 microM) decreased [Ca2+]i, whereas 30 microM-1 mM caused a [Ca2+]i rise in 60.9 +/- 8.8% of bAP cells. [La3+]ex-induced [Ca2+]i changes were abolished by treating bAP-cells with either thapsigargin or ionomycin, but not nitrendipine. [La3+]ex at 15 microM did not increase [Ca2+]i in any cells tested, but when cells were treated with thimerosal, [La3+]ex (15 microM) caused a [Ca2+]i increase in 62.5 +/- 12.2% of bAP cells. In the presence of 1 mM [Ca2+]ex, successive additions of La3+ caused successive [Ca2+]i rises, but in nominally [Ca2+]ex-free medium only the first addition of [La3+]ex caused a [Ca2+]i rise. Addition of thyroliberin (TRH) in the presence of 1 mM [Ca2+]ex, caused [Ca2+]i to increase in 70% of bAP cells; subsequent addition of [La3+]ex (1 mM) only caused [Ca2+]i increases in 75% of those cells which had already responded to TRH. However, all cells which responded to 1 mM [La3+]ex also responded subsequently to TRH. After treatment with TRH in medium that was nominally [Ca2+]ex free, addition of La3+ (0.5-1 mM) did not increase [Ca2+]i in any cells tested. The number of cells which showed [La3+]ex-induced [Ca2+]i increases decreased in culture: only 21.75 +/- 2.2% cells responded after 7-11 days. When cells were cultured for 7-11 days in the presence of tunicamycin, [La3+]ex failed to increase [Ca2+]i in any cells tested. [Mn2+]ex rapidly quenched the Fura-2 signal measured from all bAP cells, but at 10 mM it also triggered a [Ca2+]i rise in about 60% of bAP cells. The Mn(2+)-induced [Ca2+]i rise was specifically abolished in cells cultured in the presence of tunicamycin although quenching was still observed. From these data we suggest that bAP cells may express a polyvalent cation receptor coupled to the release of calcium from intracellular stores.

Animals↗