Multiple system atrophy (MSA) is a sporadic neurodegenerative disease. The major pathological hallmark of MSA is the accumulation of alpha-synuclein in oligodendrocytes. In contrast to Parkinson's disease no definitive familial etiology for MSA has been determined. Yet, there is a growing body of evidence that perturbation of transcriptional processes leads to MSA pathology. Here we present the results of the first ribosomal-depleted strand-specific RNA-sequencing profile of the MSA brain frontal cortex tissue. Among the 123 differentially expressed genes over 50% were categorized as putative long intervening non-coding RNAs (lincRNAs). Along with the dysregulation of the non-coding portion of the transcriptome, the expression of protein coding genes was also affected, including serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SERPINA3), interleukin 1 receptor-like 1 (IL1RL1) and hemoglobin, beta (HBB). Also of interest was the alternative splicing of SNCA, along with the presence of an antisense transcript overlapping the 30 exon of SNCA. Moreover, we demonstrate widespread antisense transcription throughout the frontal cortex that is largely not affected by MSA-specific neurodegenerative process. MSA causes a large disruption of lincRNAs in the human brain along with protein coding genes related to iron metabolism and immune response regulation. Most of the lincRNAs specific for MSA were novel. Hence our study uncovers another level of complexity in transcriptional pathology of MSA. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Firearm wounds to the head are often fatal and are routinely encountered in the practice of forensic pathology in the United States. Often, the anatomic site of the entrance wound is used to support or refute the manner of death indicated by the scene investigation and/or circumstances of the case. The present retrospective study of 120 fatalities resulting from 140 firearm wounds to the head correlates the anatomic region of the entrance wound and range of fire with the manner of death. Other demographic data analyzed include age, race, and gender of the decedents, as well as evidence of drug and/or ethanol use. It is hoped that this study will provide concrete data to support the largely anecdotal associations between the specific site of entry of firearm injuries to the head and the manner of death.

CD4+ T cells have been found to play a critical role in immune protection against Chlamydia trachomatis infection. Since both humoral and cell-mediated antichlamydial immunity have been implicated in host protection, the crucial effector functions provided by the CD4+ T cells may rely on Th1 or Th2 functions or both. In the present study, we evaluated the development of natural immunity following vaginal infection with C. trachomatis serovar D in female gamma interferon receptor-deficient (IFN-gammaR-/-) mice with a disrupted Th1 effector system. We found that in comparison with wild-type mice, the IFN-gammaR-/- mice exhibited a severe ascending primary infection of prolonged duration which stimulated almost 10-fold-stronger specific local immunoglobulin A (IgA) and IgG responses in the genital tract. Following resolution of the primary infection and despite the augmented antibody responses to chlamydiae, the IFN-gammaR-/- mice were completely unprotected against reinfection, suggesting that local antibodies play a subordinate role in host protection against chlamydial infection. Immunohistochemical analysis of frozen sections of the genital tract revealed many CD4+ T cells in the IFN-gammaR-/- mice, with a dominance of interleukin 4-containing cells in mice following resolution of the secondary infection. However, in contrast to the findings with wild-type mice, the typical clusters of CD4+ T cells were not found in the IFN-gammaR-/- mice. Few and similarly distributed CD8+ T cells were observed in IFN-gammaR-/- and wild-type mice. Whereas chlamydia-infected macrophages from wild-type mice had no inclusion bodies (IB) and produced significant amounts of nitric oxide (NO) in the presence of IFN-gamma, macrophages from IFN-gammaR-/- mice contained many IB but no NO. These results indicate that CD4+ Th1 cells and IFN-gamma, rather than local antibodies, are critical elements in host immune protection stimulated by a natural ascending C. trachomatis infection in the female genital tract.

We evaluated the ability of mice made genetically deficient for B cells to resolve a primary infection and to develop protective immunity against vaginal challenge with a human isolate of Chlamydia trachomatis bacteria. The B‐cell‐deficient μmT mice cleared a primary ascending infection with similar or faster kinetics compared with wild‐type mice. The presence of chlamydial inclusion bodies and the degree of inflammation in the upper genital tract was comparable and showed similar kinetics in μmT as in wild‐type mice. Following resolution of the primary infection the mice were challenged by 100 ID50 of live bacteria and the level of protection and the extent of local inflammation was assessed. Strikingly, all μmT mice, as well as most of the wild‐type mice, demonstrated complete immune protection with no bacterial shedding. While high titres of chlamydia‐specific antibodies were stimulated locally and systemically in wild‐type mice, no antibodies were detected in μmT mice. However, in both strains, immunohistochemical analysis of the upper genital tract demonstrated the presence of large numbers of CD4+ T cells and increased levels of interferon‐γ (IFN‐γ)‐producing cells. The results unequivocally demonstrate that antibodies are not required for full protection to develop against ascending infection with a high dose of C. trachomatis in the female genital tract. Our study confirms the notion that cell‐mediated immunity, in particular that owing to CD4+ T helper 1 (Th1)‐type cells, is critical for host resistance against C. trachomatis in mice.

Chlamydia trachomatis is one of the major causes of infertility and preventable blindness in the world. The organism is of particular interest from an immunological point of view because it is one of the few obligate intracellular bacterial pathogens. There is some evidence that repeated infections in humans stimulate protective immunity. However, until recently, it was unclear which components of the adaptive immune system give rise to protection. Studies in gene knockout mice reported here and elsewhere now give a coherent and cogent picture of the importance of the Th1 response, in particular IFN‐γ, for the localization and eradication of C. trachomatis genital tract infection. The key questions still to be addressed are the identity of the IFN‐γ responsive cells and whether the mouse is truly representative of host protection against chlamydiae in humans.

The prevalence of Chlamydia trachomatis in the lower genital tract and amniotic fluid of women with preterm prelabour amniorrhexis was assessed by DNA amplification for C. trachomatis performed in cervical swabs and amniotic fluid obtained by amniocentesis. C. trachomatis was present in the cervix of 20 (23%) of the cases and in six (30%) of those the organism was also present in the amniotic fluid. There was no association with other pathogens in the lower genital tract or amniotic fluid. The presence of C. trachomatis was not associated with a significant decrease in the amniorrhexis to delivery interval or with an increase in perinatal mortality or morbidity.

Azithromycin has been recommended for the treatment of human chlamydial genital tract infections because of the sustained, chlamydicidal levels of the antibiotic which can be achieved after a single dose. The effect of single dose azithromycin on the prevention or reversal of chlamydial-induced damage to the oviduct or to fertility was assessed in a mouse model of chlamydial salpingitis which closely mimics the human disease. C3H mice were treated with progesterone and then inoculated under the ovarian bursa with a human genital tract isolate of Chlamydia trachomatis, serovar F. Azithromycin at doses from 135-250 mg/kg was administered by oral intubation. Morphological damage to the oviduct lumen was assessed by scanning electron microscopy, while fertility was assessed by breeding experiments. Treatment of mice two or seven days after infection with 135 mg/kg azithromycin completely reversed chlamydial-induced ultrastructural changes and infertility. Treatment 12 or more days after infection, at doses as high as 250 mg/kg, failed to prevent infertility. The onset of fertility correlated with the loss of ciliated epithelia from the oviduct. However, the regeneration of ciliated epithelia following azithromycin treatment did not necessarily restore tubal patency. These results, if true for women also, indicate the need for rapid, effective antibiotic therapy for chlamydial salpingitis to prevent infertility and other sequelae of tubal damage.

Intrauterine infection of mice with a human genital tract isolate of Chlamydia trachomatis (serovar F) resulted in salpingitis. In some cases, oviduct damage was sufficient to cause infertility due to lumenal blockage. Parenteral immunization with a purified, heterologous, recombinant major outer-membrane (rMOMP) preparation reduced the proportion of animals developing severe salpingitis by 77% compared with mock-immunized controls, but failed to reduce chlamydial colonization of the lower genital tract. In contrast, mice immunized with rMOMP directly into the Peyer's patches to stimulate mucosal immunity shed fewer chlamydiae from the vagina than controls, but showed little reduction in oviduct damage. No consistent correlation was observed between antibody levels to rMOMP in immunized mice and reduced lower genital tract colonization. Immunization with rMOMP via the presacral space, a route previously shown to stimulate mucosal immunity in the genital tract, produced high levels of circulating anti-rMOMP IgG but only traces of anti-rMOMP IgA in vaginal secretions. There was no difference in the severity of salpingitis in these animals compared with mock-immunized controls. Immunization with rMOMP conferred no protection against infertility resulting from direct inoculation of chlamydiae into the oviducts.

AnaesthesiaVolume 34, Issue 9 p. 913-913 Free Access Association of Dental Anaesthetists Michael E. Ward, Michael E. Ward Nuffield Department of Anaesthetics, The Radcliffe Infirmary, Oxford OX2 6HE.Search for more papers by this authorT.M. Young, T.M. Young Department of Anaesthesia, Manchester Royal Infirmary, Manchester M13 9WL.Search for more papers by this author Michael E. Ward, Michael E. Ward Nuffield Department of Anaesthetics, The Radcliffe Infirmary, Oxford OX2 6HE.Search for more papers by this authorT.M. Young, T.M. Young Department of Anaesthesia, Manchester Royal Infirmary, Manchester M13 9WL.Search for more papers by this author First published: September 1979 https://doi.org/10.1111/j.1365-2044.1979.tb08562.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume34, Issue9September 1979Pages 913-913 RelatedInformation

Class size reduction (CSR) is seen as a key reform strategy at both state and national levels. Federal funds for CSR are now available to states with a focus on grades K-3, based on research to date that shows positive outcomes at the early grades. California initiated a statewide CSR initiative in 1996-1997 to reduce class size to 20 in kindergarten through third grade. Other states have initiated class size reduction focusing on lower-income schools (e.g., Indiana's Prime Time and Wisconsin's Student Achievement Guarantee in Education (SAGE)). Perhaps the best- known and most well-designed large-scale CSR study was the Tennessee Student-Teacher Achievement Ratio (STAR) Study , running from 1985-89 for 79 schools in grades K-3.