Mercury-induced autoimmunity in Brown Norway rats: kinetics of changes in RT6+ T lymphocytes correlated with IgG isotypes of circulating autoantibodies to laminin 1

Repeated exposure to mercury causes various autoimmune effects in rats of the Brown Norway (BN) strain. Previous studies from our laboratory have shown that on day 15 of HgCl2 treatment BN rats exhibit a relative decrease in RT6.2+ T cells. At the same time, they produce high levels of autoantibodies to renal antigens and experience a membranous glomerulonephropathy. In contrast, Lewis (LEW) rats are resistant to autoimmunity caused by mercury and do not demonstrate a decrease in RT6+ cells after administration of HgCl2. In the present paper we provide novel information on the correlation between changes in RT6.2+ lymph node T cells and the production of autoantibodies to laminin 1, obtained by detailed kinetic studies of HgCl2-treated BN rats. We have confirmed a decrease in the percentage of RT6.2+ lymphocytes on day 15 of mercury treatment, despite a significant increase in the number of peripheral lymphocytes. No such changes were observed in LEW rats. We have determined that on day 15 the percentage decrease in RT6+ cells is evident in both RT6.2+CD4+ and RT6.2+CD8+ T cell subsets. Kinetic studies demonstrated that significant changes in the percentage of RT6.2+ cells are first observed by day 8 and continue through days 11 and 15. We have also observed a significant percent decrease in CD4+ T lymphocytes as well as an increase in CD4-CD8- cells. The dramatic increase in the percentage of these double negative cells at the level of peripheral lymphoid tissues does not appear to be due to higher thymic output, since there was a decrease in the percentage of TCR+Thy1+ cells, a phenotype that is associated with recent thymic emigrants. Finally, we have demonstrated that 100% of HgCl2-treated BN rats had circulating antibodies that reacted with both mouse and rat laminin 1, i.e. are autoantibodies to laminin 1. These autoantibodies were predominantly of the IgG1 and IgG2a isotype, possibly as the result of a polarized autoimmune response driven by Type 2 cytokines. A kinetic investigation showed that significant levels of IgG1 and IgG2a autoantibodies to laminin 1 were first presentin the circulation by day 11. The inverse correlation between levels of RT6.2+ T lymphocytes and autoantibodies to laminin 1 suggests that mercury may induce autoimmune responses in BN rats by its effects on these immunoregulatory cells.     

Effect of riblets on the streaky structures excited by free stream tip vortices in boundary layer

In this study, experimental investigations were made regarding the effect of riblets on the streak instability in boundary layer. The streak instability is now regarded as a major source of the self-regeneration mechanism for the hairpin type coherent structures in turbulent boundary layer flow. Thus, it is important to control the instability to suppress the drag-inducing vortical structure in terms of drag reduction. Toward enhancing the measurement accuracy and spatial resolution, an enlarged version of riblets was applied to a streak which was artificially induced by a microwing in a laminar boundary layer. It is found that the riblets have attenuation effect on the streak instability, i.e., to reduce the spanwise velocity gradient of the quasi-streamwise streak in boundary layer.     

Characterization by fluorescence and electron microscopy in situ hybridization of a double Y isochromosome

A patient with mixed gonadal dysgenesis and Y isochromosomes i(Y) is described. Lymphocyte cultures from peripheral blood contained a high proportion of 45,X cells and several other cell lines with two different marker chromosomes (mars). These markers had either a monocentric (mar1) or a dicentric appearance (mar2). Following high-resolution GTG, RBG, QFQ, and CBG bandings, five cell lines were identified; 45,X/46,X,+mar1/46,X,+mar2/47,X,+mar1x2/47,X,+mar2x 2. The percentages were 66/6/26/1/1%, respectively. Chromosome banding analyses were insufficient for characterization of the markers. In situ hybridization of specific probes for the Y centromere and its short arm showed, both in fluorescence and electron microscopy (EM), two different Y rearrangements. Mar1 is an isochromosome for the short arm i(Yp) and mar2 is a dicentric which was shown by EM to be a double isochromosome Yp, inv dup i(Yp). The breakpoint producing mar1 is within the centromere and the one producing mar2 is within one of the short arms of the Y isochromosome. The findings of different cell populations in peripheral blood lymphocytes indicate the postzygotic instability of this i(Yp).     

Variation in incidence of indinavir-associated nephrolithiasis among HIV-positive patients

BACKGROUND: Nephrolithiasis may be an important consequence of indinavir therapy; however little has been published on the variation in incidence between different populations of patients or the possible mechanisms of calculus formation. OBJECTIVE: To examine variation in the incidence of indinavir-associated nephrolithiasis (IAN) in HIV-positive patients in relation to hemophilia and hepatitis C virus (HCV) infection. METHODS: Clinical data were abstracted retrospectively from the medical records of all adult patients treated with indinavir from September 1995 to September 1997. Occurrence of first IAN, defined as flank pain and hematuria after initiation of therapy, was analyzed in relation to hemophilia status and HCV infection. RESULTS: There were 17 episodes of IAN (22%) among 79 patients treated with indinavir. Of 10 patients with hemophilia, 50% developed IAN as compared with 17% of patients without hemophilia (P = 0.03). Median days to first IAN was 22 (range 7-110 days) for hemophiliacs and 156 (range 5-611 days) for those without hemophilia. Data for HCV status were available for 74 out of 79 patients: 10 out of 27 (37%) patients with HCV developed IAN compared with six out of 42 (14%) without HCV (P = 0.02). CONCLUSION: Overall incidence of IAN was higher than that previously reported and was significantly greater in hemophiliacs than in non-hemophiliacs. HCV may be a contributing factor.     

Can idiopathic tinnitus be caused by hyperuricemia?

It is hypothesized that heretofore medically untreatable idiopathic tinnitus of intermittent intensity may be related to hyperuricemia. A number of pathogenic features common to both are given. Hyperuricemia is treatable.     

The first cesarean section in Norway

The first reported caesarean section in Norway was performed on 20 August 1843 by a general practitioner, Lars Thalian Backer (1812-84). The operation took place in Lardal, Vestfold County, on a 27 year old woman who had been in labour for six days. The outcome was disastrous; she was delivered of stillborn twins and died 2 1/2 days after the operation. In the 19th century, infection, bleeding and thromboembolic disease made caesarean section a dangerous operation, and only 26 such operations are known in Norway, most of them performed outside hospitals. The first caesarean section in Norway resulting in a living child was performed in 1849, but no mother survived the operation before 1890. We recapitulate the caesarean section of 1843; Dr Backer and his qualifications for operative obstetrics; and the state of instrumental and surgical obstetrics in Norway at that time.     

Medication side effects in anxious patients: negative placebo responses?

Heart sounds produce an incessant noise during lung sounds recordings. This noise severely contaminates the breath sounds signal and interferes in the analysis of lung sounds. In this paper, the use of a wavelet transform domain filtering technique as an adaptive de-noising tool, implemented in lung sounds analysis, is presented. The multiresolution representations of the signal, produced by wavelet transform, are used for signal structure extraction. In addition, the use of hard thresholding in the wavelet transform domain results in a separation of the nonstationary part of the input signal (heart sounds) from the stationary one (lung sounds). Thus, the location of the heart sound noise (1st and 2nd heart sound peaks) is automatically detected, without requiring any noise reference signal. Experimental results have shown that the implementation of this wavelet-based filter in lung sound analysis results in an efficient reduction of the superimposed heart sound noise, producing an almost noise-free output signal. Due to its simplicity and its fast implementation the method can easily be used in clinical medicine.     

Photoneural regulation of rat pineal nitric oxide synthase

We report here a photoneural regulation of nitric oxide synthase (NOS) activity in the rat pineal gland. In the absence of the adrenergic stimulation following constant light exposure (LL) or denervation, pineal NOS activity is markedly reduced. A maximal drop is measured after 8 days in LL. When rats are housed back in normal light:dark (LD) conditions (12:12), pineal NOS activity returns to normal after 4 days. A partial decrease in pineal NOS activity is also observed when rats are placed for 8 days in LD 18:6 or shorter dark phases, indicating that pineal NOS activity reflects the length of the dark phase. Because it is known that norepinephrine (NE) is released at night from the nerve endings in the pineal gland and this release is blocked by exposure to light, our data suggest that NOS is controlled by adrenergic mechanisms. Our observation may also explain the lack of cyclic GMP response to NE observed in animals housed in constant light.