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81.
Edward D. Huntley Leslie M. Swanson Giselle E. Kolenic Holli Bertram Ann Mooney Richard Dopp 《Behavioral sleep medicine》2021,19(1):1-11
ABSTRACT Background: In the context of a randomized controlled trial evaluating the efficacy of augmenting fluoxetine treatment in young adults with major depressive disorder (MDD) using a modified repeated partial sleep deprivation protocol contrasting 2 weeks of restricted time in bed (i.e., 6 h TIB) to no time in bed restriction (i.e., 8 h TIB) the study examines whether sleep duration and the timing of repeated partial sleep deprivation predicts patient-reported affect ratings. Participants: Participants included 58 young adults with DSM-IV-diagnosed MDD. Methods: Daily ratings of affect and sleep were collected during the first 2 weeks of initiating fluoxetine treatment, yielding 630 person-days. Actigraphy monitoring was employed to assess compliance with time in bed condition. Results: Negative affect ratings and positivity ratios in the morning were more improved among participants assigned to the 6 h TIB condition compared to the 8 h TIB group. Participants whose bedtime was delayed by 2-h nightly demonstrated the most significant improvement in negative affect and positivity ratio during the first 2 weeks of fluoxetine therapy. Moreover, the trajectory of morning negative affect ratings in the first 2 weeks was predictive of remission after 4 weeks of fluoxetine therapy. Conclusions: These findings suggest that monitoring changes in daily affect may be a valuable marker of early treatment response in young adults with MDD. 相似文献
82.
Longitudinal reliability of focus glycoprotein G-based type-specific enzyme immunoassays for detection of herpes simplex virus types 1 and 2 in women 下载免费PDF全文
Serologic assays that utilize herpes simplex virus (HSV) type-specific glycoproteins G-1 (HSV-1) and G-2 (HSV-2) to discriminate between antibodies against HSV-1 and HSV-2 are sensitive and specific. However, the high rates of seroreversion, defined as the change in an individual's antibody status from positive to negative over time, previously reported in longitudinal evaluations of glycoprotein G type-specific tests suggests that their use in HSV acquisitional studies would be problematic. To further explore the reliability of the glycoprotein G-based serologic tests, we evaluated HSV-1 and HSV-2 enzyme immunoassays from Focus Technologies in a longitudinal cohort of 1207 young women from Pittsburgh, Pa. On enrollment of the women in the study, HSV-1 and HSV-2 antibodies were detected in 46.6 and 24.9% of the women, respectively. Among the women with at least three visits, 3.4% (15 of 447) of those who were HSV-1 antibody positive had a subsequent negative result while fewer than 1% (2 of 227) of those who were HSV-2 antibody positive seroreverted. The median of mean positive index values for women who seroreverted to HSV-1 antibody was lower than that for women who remained seropositive (1.25 versus 7.06; P < 0.001). Similarly, the median of mean positive index values for women whose HSV-2 antibody status reverted from positive to negative was lower than that for those women who did not serorevert (1.83 versus 7.46; P = 0.02). Comparative Western blot analysis demonstrated that the lower positive index values, seen more often among the HSV seroreverters, often signified false-positive immunoassay results. Overall, the seroreversion rates were low; the use of glycoprotein G-based serologic tests for the measurement of HSV-1 and HSV-2 antibodies in incidence studies therefore appears warranted. 相似文献
83.
It has been hypothesized that two mutations in one gene are not sufficient and that three mutations between two genes are required for penetrance in some cases of Bardet-Biedl syndrome (the so-called "triallelic inheritance" model). McKusick-Kaufman syndrome (MKS) is allelic to one form of Bardet-Biedl syndrome (BBS). We describe an Amish family with MKS, where three children were affected with homozygous MKKS (BBS6) mutations (H84Y and A242S on both alleles), their father was a carrier, and their mother was homozygous for the same MKKS mutations, but she was non-penetrant. Genotyping and/or sequencing of BBS1, BBS2, BBS3, BBS4, BBS5, BBS7, and BBS8 excluded "triallelic inheritance" for each gene either by an incompatible inheritance pattern or an absence of mutations in the coding region and the intronic splice junctions of these genes. We conclude that the "triallelic" model does not explain the incomplete penetrance of MKS. 相似文献
84.
Andrea M. Gross Megan Frone Karen W. Gripp Bruce D. Gelb Lisa Schoyer Lisa Schill Beth Stronach Leslie G. Biesecker Dominic Esposito Edjay Ralph Hernandez Eric Legius Mignon L. Loh Staci Martin Deborah K. Morrison Katherine A. Rauen Pamela L. Wolters Dina Zand Frank McCormick Sharon A. Savage Douglas R. Stewart Brigitte C. Widemann Marielle E. Yohe 《American journal of medical genetics. Part A》2020,182(4):866-876
RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1‐related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, selumetinib was granted breakthrough therapy designation by the FDA for the treatment of PN. Other RASopathy manifestations may also benefit from RAS targeted therapies. The overall goal of Advancing RAS/RASopathy Therapies (ART), a new NCI initiative, is to develop effective therapies and prevention strategies for the clinical manifestations of the non‐NF1 RASopathies and for tumors characterized by somatic RAS mutations. This report reflects discussions from a February 2019 initiation meeting for this project, which had broad international collaboration from basic and clinical researchers and patient advocates. 相似文献
85.
Primitive Neuroectodermal Tumors of the Central Nervous System 总被引:2,自引:0,他引:2
Lucy Balian Rorke M.D. John Q. Trojanowski M.D. Ph.D. Virginia MY Lee Ph.D. Robert A. Zimmerman M.D. Leslie N. Sutton M.D. Jaclyn A. Biegel Ph.D. Joel W. Goldwein M.D. Roger J. Packer M.D. 《Brain pathology (Zurich, Switzerland)》1997,7(2):765-784
Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid-1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien-tists and pathologists.
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers. 相似文献
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers. 相似文献
86.
Ikeda S Cunningham LA Boggess D Hawes N Hobson CD Sundberg JP Naggert JK Smith RS Nishina PM 《Human molecular genetics》2003,12(9):1029-1037
Corneal disease is the most common cause of bilateral blindness in the world. Visual loss in this condition is often due to changes in morphology and function of the corneal epithelial surface. Corneal disease-1 (corn1) and corn1(2J) are spontaneous mouse mutants that develop irregular thickening of the corneal epithelium, similar to that observed in human corneal surface disease. These autosomal-recessive mutations cause an increase in the rate of proliferation of the corneal epithelial cells. Here, we report that the phenotypes in both mutants are caused by mutations within the destrin gene (also known as actin-depolymerizing factor). By positional cloning, we identified a deletion encompassing the entire coding sequence of the destrin gene in corn1 mice, and a point mutation (Pro106Ser) in the coding sequence of destrin in corn1(2J) mice. In situ analysis showed that destrin is highly expressed in the corneal epithelium. Consistent with the cellular roles for destrin, an essential regulator of actin filament turnover that acts by severing and enhancing depolymerization of actin filament, we observed that the corn1 mutations increased the content of filamentous actin in corneal epithelial cells. Our results suggest an in vivo connection between remodeling of the actin cytoskeleton and the control of cell proliferation, and a new pathway through which an aberrant actin cytoskeleton can cause epithelial hyperproliferation. 相似文献
87.
Low serum haemolytic function of the fourth complement component (C4) in insulin dependent diabetes. 下载免费PDF全文
G Senaldi B A Millward M J Hussain D A Pyke R D Leslie D Vergani 《Journal of clinical pathology》1988,41(10):1114-1116
Low serum concentrations of the fourth component of complement (C4) are found in insulin dependent diabetes, and may be important in the aetiology of the disease. To ascertain whether function of C4 is also impaired both its haemolytic activity and its concentration were measured in 34 insulin dependent diabetics, 15 non-insulin dependent diabetics, 20 healthy subjects, and 12 pairs of monozygotic twins discordant for insulin dependent diabetes. C4 function was measured by a radial immune haemolytic assay, and C4 concentration by laser nephelometry. Both measurements were significantly lower in insulin dependent diabetics (C4 function: median 47%, range 4-100%; C4 concentration: 0.22 g/l, 0.10-0.38 g/l) than in non-insulin dependent diabetics (67%, 33-138%, p less than 0.01; 0.27 g/l, 0.16-0.50 g/l, p less than 0.02) and controls (74%, 33-138%, p less than 0.01; 0.27 g/l, 0.18-0.40 g/l, p less than 0.03). C4 function and concentration were lower in both diabetic (48%, 12-100%; 0.17 g/l, 0.08-0.31 g/l) and non-diabetic twins (47%, 12-100%; 0.17 g/l, 0.07-0.36 g/l) than controls (p less than 0.01; p less than 0.01). Thirteen (38%) of the insulin dependent diabetics had a reduction in either C4 function or concentration, but in only five were both features reduced. Values of function and concentration were strongly correlated in both diabetic and non-diabetic twins (r = 0.95, p less than 0.001; r = 0.92, p less than 0.001). These results show defects in C4 function and concentration in insulin dependent diabetes, which--being present in the non-diabetic co-twin of diabetics--may represent a genetic predisposition to the disease. 相似文献
88.
Hemagglutination by polyoma virus has been shown to require sialic acid residues on cell surface oligosaccharides. This report presents evidence which suggests that adsorbtion of polyoma virus to erythrocytes is not due simply to a nonspecific electrostatic interaction with negatively charged sialic acids but rather requires the presence of specific sialyloligosaccharide structures. Newcastle disease virus (NDV) neuraminidase hydrolyzes sialic acids in the sequences NeuAcα2,3Gal and NeuAcα2,8NeuAc. Erythrocytes treated with NDV lost 40% of their surface sialic acid, retained full hemagglutination by certain influenza viruses which also bind sialyloligosaccharides, and yet were not agglutinated by polyoma virus. Erythrocytes treated with Vibrio cholerae neuraminidase, which removes virtually all sialic acid, were no longer agglutinated by influenza virus or polyoma virus. Selective replacement of sialic acid on V. cholerae neuraminidase-treated cells with purified β-galactoside α-2,3-sialytransferase in the sequence NeuAcα2, 3Gal completely restored hemagglutination by polyoma virus. In contrast, replacement of sialic acid by other sialyitransferases in the sequences NeuAcα2,6Gal or NeuAcα2,6GalNAc does not restore hemagglutination by polyoma virus. 相似文献
89.
Bolton Virginia N.; Braude Peter R.; Ockenden Kim; Marsh Simon K.; Robertson Gregory; Ross Leslie D. 《Human reproduction (Oxford, England)》1989,4(6):674-679
Twenty-nine couples with an average of 5 years of infertilitywere selected for treatment by intrauterine insemination ofwashed semen (AIH). The criteria for selection were (i) thefemale partner showed no detectable fertility disorders by routinescreening; (ii) the male partner showed subnormal semen qualityon conventional semen analysis. Ovulation was stimulated uniformlywith clomiphene citrate and precipitated with human chorionicgonadotrophin (HCG). Inseminations were performed 3132h post-HCG, with the day of HCG determined by ultrasound monitoringof follicular development. The fertilizing capacity of the malepartners spermatozoa was tested in vitro using donatedhuman oocytes and/or the zona-free hamster oocyte penetrationassay. Up to eight cycles of AIH were alternated with cyclesof natural intercourse. While no pregnancies occurred in thegroup during normal coital cycles, the AIH pregnancy rate was17% per couple, but only 3% per insemination cycle. Four furtherpregnancies were achieved spontaneously in couples from thestudy group within 3 years of completion of the AIH therapyand four patients became pregnant following subsequent GIFTor IVF treatments. Neither of the in-vitro tests was helpfulin predicting the outcome of AIH, spontaneous pregnancy norof subsequent assisted conception procedures. 相似文献
90.
Schüpbach J Böni J Bisset LR Tomasik Z Fischer M Günthard HF Ledergerber B Opravil M;Swiss HIV Cohort Study 《Journal of acquired immune deficiency syndromes (1999)》2003,33(3):292-299
An HIV-1 p24 antigen test involving signal amplification-boosted ELISA of heat-denatured plasma was evaluated prospectively in 55 patients whose viral RNA in plasma had previously been suppressed for at least 6 months under antiretroviral combination therapy. During a median follow-up of 504 days, CD4 counts increased by a median of 62 cells per year. By univariate and multivariate linear regression analysis, the level of p24 antigen as expressed by the absorbance/cutoff ratio was a significant inverse correlate of both the CD4 count in a sample (p =.013) and its annual change in a patient (p <.0001). The p24 antigen retained significance even among 48 individuals whose HIV-1 RNA, apart from occasional blips, remained below 400 copies/mL. Batch-wise retesting of 70 samples from 5 such patients with a further improved procedure showed measurable p24 antigen in all but 1 sample and an inverse correlation with both the CD4 count (p =.0331) and percentage (p <.0001), thus confirming the prospectively generated data. Comparison of p24 antigen and HIV-1 RNA concentrations indicate that the p24 antigen detected in these samples is not associated with viral RNA-containing particles and may originate from other compartments of virus expression. 相似文献