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.     

Effective peer responses to impaired nursing practice

Subplate neurons, the first neurons of the cerebral cortex to differentiate and mature, are thought to be essential for the formation of connections between thalamus and cortex, such as the system of ocular dominance columns within layer 4 of visual cortex. To learn more about the requirement for subplate neurons in the formation of thalamocortical connections, we have sought to identify the neurotransmitters and peptides expressed by the specific class of subplate neurons that sends axonal projections into the overlying visual cortex. To label retrogradely subplate neurons, fluorescent latex microspheres were injected into primary visual cortex of postnatal day 28 ferrets, just prior to the onset of ocular dominance column formation. Subsequently, neurons were immunostained with antibodies against glutamate, glutamic acid decarboxylase (GAD-67), parvalbumin, neuropeptide Y (NPY), somatostatin (SRIF), or nitric oxide synthase (NOS). Retrograde labeling results indicate that the majority of subplate neurons projecting into the cortical plate reside in the upper half of the subplate. Combined immunostaining and microsphere labeling reveal that about half of cortically projecting subplate neurons are glutamatergic; most microsphere-labeled subplate neurons do not stain for GAD-67, parvalbumin, NPY, SRIF, or NOS. These observations suggest that subplate neurons can provide a significant glutamatergic synaptic input to the cortical plate, including the neurons of layer 4. If so, excitation from the axons of subplate neurons may be required in addition to that from lateral geniculate nucleus neurons for the activity-dependent synaptic interactions that lead to the formation of ocular dominance columns during development.     

Effectiveness of physicians-in-training counseling for smoking cessation in African Americans

This study examined the effectiveness of smoking cessation counseling by physicians-in-training (residents) with African-American patients. One hundred fifty-eight family and internal medicine residents at a large urban public general hospital participated in the study; two thirds of the residents underwent a 2-hour smoking cessation training program. Ninety-two of the trained physicians counseled from 1 to 18 patients. The majority of physicians were male, with 8% being current smokers. Over a 26-month period, 1086 patients were randomly assigned to intervention and control (usual care) groups. Mean patient age was 44 years, mean years smoking was 25, and mean number of cigarettes smoked per day was 14. There were no differences in biochemically validated smoking cessation rates between the intervention and control groups at 3 or 12 months postenrollment (2% versus 1.8% and 2.2% versus 2.8%, respectively). Losses to follow-up were high at both 3 and 12 months (38% and 40% respectively). Implications for future trials in minority populations are discussed. A brief physician-based smoking cessation message does not appear to be an effective strategy for use with African-American smokers in a large urban public general hospital.     

Chromosomal instability is correlated with telomere erosion and inactivation of G2 checkpoint function in human fibroblasts expressing human papillomavirus type 16 E6 oncoprotein

Cell cycle checkpoints and tumor suppressor gene functions appear to be required for the maintenance of a stable genome in proliferating cells. In this study chromosomal destabilization was monitored in relation to telomere structure, lifespan control and G2 checkpoint function. Replicative senescence was inactivated in secondary cultures of human skin fibroblasts by expressing the human papillomavirus type 16 (HPV-16) E6 oncoprotein to inactivate p53. Chromosome aberrations were enumerated during in vitro aging of isogenic control (F5neo) and HPV-16E6-expressing (F5E6) fibroblasts. We found that structural and numerical aberrations in chromosomes were significantly increased in F5E6 cells during aging in vitro and fluorescence in situ hybridization (FISH) analysis using chromosome-specific probes demonstrated the occurrence of rearrangements involving chromosome 4 and 6 in genetically unstable F5E6 cells. Flow cytometry and karyotypic analyses revealed increased polyploidy and aneuploidy in F5E6 cells only at passages > 16, although these cells displayed defective mitotic spindle checkpoint function associated with inactivation of p53 at passages 5 and 16. G2 checkpoint function was confirmed to be gradually but progressively inactivated during in vitro aging of E6-expressing cells. Aging of F5neo fibroblasts was documented during in vitro passaging by induction of a senescence-associated marker, pH 6.0 lysosomal beta-galactosidase. F5E6 cells displayed extension of in vitro lifespan and did not induce beta-galactosidase at high passage. Erosion of telomeres during in vitro aging of telomerase-negative F5neo cells was demonstrated by Southern hybridization and by quantitative FISH analysis on an individual cell level. Telomeric signals diminished continuously as F5neo cells aged in vitro being reduced by 80% near the time of replicative senescence. Telomeric signals detected by FISH also decreased continuously during aging of telomerase-negative F5E6 cells, but telomeres appeared to be stabilized at passage 34 when telomerase was expressed. Chromosomal instability in E6-expressing cells was correlated (P < 0.05) with both loss of telomeric signals and inactivation of G2 checkpoint function. The results suggest that chromosomal stability depends upon a complex interaction among the systems of telomere length maintenance and cell cycle checkpoints.     

Determination of DNA damage in F344 rats induced by geometric isomers of tamoxifen and analogues

The transformation of Trypanosoma cruzi epimastigotes to mammal-infective metacyclic trypomastigotes (metacyclogenesis) can be performed in vitro under chemically defined conditions (TAU 3AAG medium). During this process, changes in the nature of cell surface sugar composition and sugar distribution was evaluated using FITC and gold-labeled lectins and observed by flow cytometry and transmission electron microscopy. The pattern of labeling with the lectins from Triticum vulgaris (WGA), Arachis hypogaea (PNA), Limax flavus (LFA), Canavalia ensiformis (Con-A), and Ricinus communis (RCA-I) significantly changed during the metacyclogenic process. The results obtained are discussed in relation to the role played by T. cruzi cell surface carbohydrate residues on the process of parasite-host cell interaction.     

Support for school-based sexuality education among South Carolina voters

A random-digit dialed telephone survey was conducted in a traditionally conservative southern state to determine the level of support for sexuality education in the public schools including support for specific sexuality education topics, the earliest grade level at which each topic should be taught, and the amount of instruction time required for sexuality education in the high schools. Survey data were obtained from 534 South Carolina registered voters in late January/early February 1997. Results demonstrated that most South Carolina registered voters: 1) supported sexuality education in the public schools; 2) supported instruction on a variety of sexuality education topics; 3) supported instruction at all grade levels, especially beginning in middle school; and 4) believed instruction time for sexuality education in the high schools should either remain the same or be increased. In addition, a significant increase in support for sexuality education occurred from the beginning of the survey to the end, suggesting that the instrument itself may have served as an educational tool for respondents. The characteristics of registered voters who supported sexuality education at the beginning of the survey and at the end were examined and compared. These results may assist in the development of educational and marketing strategies designed to build support for school-based sexuality education programs in South Carolina and elsewhere.     

Cognitive performance in conversion hysteria

In order to test some neurobiologically based assumptions pertaining to attention and memory dysfunction in conversion hysteria, a series of tasks was given to 17 hospitalized patients with hysterical conversion reaction and to a control group of nonpsychotic patients under conditions of nonstress and stress. The results indicated significant differences in performance between hysteria and control subjects. The former group, in comparison to controls, had heightened suggestibility, greater field dependency, and greater impairment of recent memory and vigilance-attention. A discriminant analysis indicated the feasibility of using such tests as objective diagnostic criteria for hysteria.     

Functioning oxyphil adenoma of parathyroid gland. An ultrastructural and biochemical study

Oxyphil cells and oxyphil cell adenomas of parathyroid glands are, in most instances, regarded to be nonfunctioning. Although 21 cases of hyperparathyroidism associated with parathyroid oxyphil cell adenoma have been reported, secretion of hormone by these tumors has not been conclusively demonstrated. A parathyroid adenoma, diagnosed by light microscopy as oxyphil type, together with the results from ultrastructural and biochemical studies of the patient's adenomatous tissue, are reported here. The patient, a 64-year-old male, was found to have elevated serum calcium, low serum phosphorus, and elevated serum immunoreactive parathormone: findings consistent with hyperparathyroidism. After excision of two small normal-appearing glands and one greatly enlarged (1.9 g) parathyroid gland, those laboratory values returned to normal. Light microscopy of the enlarged parathyroid indicated that it consisted almost entirely of an oxyphil adenoma. Electron microscopy revealed that the adenoma was composed mainly of mitochondria-rich oxyphil cells but also of interspersed transitional oxyphil cells and rare scattered chief cells. Golgi zones, rough endoplasmic reticulum, and prosecretory and secretory-like granules were observed in some oxyphil cells, in most transitional oxyphil cells, and in the infrequent chief cells. Thus, many of these cells appear to contribute to the production and secretion of parathormone. Biochemical studies performed directly on the adenomatous tissue demonstrated that it was able to synthesize proparathormone and parathormone, although the proportion of hormonal peptide synthesis relative to that of the total protein synthesis in this tissue was much smaller (0.9%) than that found in normal parathyroid tissue (5.7%). There was a small increase in immunoreactive parathormone when the adenoma tissue was incubated in a low-calcium medium. These findings indicate that this oxyphil adenoma of the parathyroid gland synthesized and secreted parathormone, apparently to some extent autonomously, but suggest that its capacity to do so was largely dependent on its component of cells other than fully developed oxyphil cells, such as transitional oxyphil cells.     

Gender gaps within management

Traditional roles need not become self-fulfilling prophecies if managers can bridge the gender gap. Feminine, as well as masculine, characteristics can be incorporated into managerial styles to enhance effective leadership. Autonomy, decision-making and assertiveness are as important as nurturing and caring. What are little girls made of? Little girls are made of sugar and spice and everything nice. What are little boys made of? Little boys are made of rats and snails and puppy dog tails.     

Retrograde blood circulation and ischemic heart disease

The author performed experiments on 350 dogs and X-ray postmortem studies of 1520 corpses of subjects who had died of various diseases and injuries. It was found that in occlusive great vessels in the ischemic organs and tissues, retrograde circulation developed, which completely maintained their viability under definite conditions. Retrograde venous blood flow to diseased organs and tissues drastically increased in insufficient retrograde arterial blood circulation. Under certain conditions, surplus venous blood influx caused edema and their dysfunctions. The mechanisms of retrograde circulation account for asymptomatic occlusion of the great vessels.