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61.
Joyce PR Porter RJ Mulder RT Luty SE McKenzie JM Miller AL Kennedy MA 《Psychological medicine》2005,35(4):511-517
BACKGROUND: Although diurnal variation of mood is a widely recognized symptom of depression, the clinical, neurobiological and psychopharmacological significance of this symptom has not previously been reported. METHOD: A total of 195 depressed out-patients underwent a detailed clinical and neurobiological assessment, and were then randomized to treatment with either fluoxetine or nortriptyline. RESULTS: Of the 195 depressed patients, 62 had a pattern of reversed diurnal variation (i.e. worse in the evening). Those with reversed diurnal variation had a poorer response to a serotonergic anti-depressant, were less likely to have bipolar II disorder, had a higher tryptophan: large neutral amino acid ratio and had different allele frequencies of the polymorphisms in the promoter region of the serotonin transporter. CONCLUSIONS: These findings raise the possibility of serotonergic influence on diurnal variation, and that the symptom of reversed diurnal variation is of relevance to antidepressant prescribing. 相似文献
62.
Hip fracture is a serious and common injury that can lead to permanent disability, pneumonia, pulmonary embolism, and death. Research to help prevent these fractures is essential. Computed tomographic (CT) scan-based finite element (FE) modeling is a tool that can predict proximal femoral fracture loads in vitro. Because this tool might be used in vivo, this study examined whether FE models generated from CT scans in situ and in vitro yield comparable predictions of proximal femoral fracture load. CT scans of the left proximal femur of two human cadavers were obtained in situ and in vitro, and three-dimensional FE models employing nonlinear mechanical properties were generated from each CT scan. The models were evaluated under single-limb stance-type loading by applying displacements incrementally to the femoral head. The FE-predicted fracture load (F(FE)) was the maximum femoral head reaction force. F(FE) for the in situ-derived models for the two subjects were 5.2 and 13.3% greater than for the in vitro-derived models. These results demonstrate that using CT scan data obtained in situ instead of in vitro to generate FE models can lead to substantially different predicted fracture loads. This effect must be considered when using this technology in vivo. 相似文献
63.
Detailed investigation of factors influencing amplification efficiency and allele drop-out in single cell PCR: implications for preimplantation genetic diagnosis 总被引:16,自引:0,他引:16
Preimplantation genetic diagnosis (PGD) of single gene disorders relies on PCR-based tests performed on single cells (polar bodies or blastomeres). Despite the use of increasingly robust protocols, allele drop-out (ADO; the failure to amplify one of the two alleles in a heterozygous cell) remains a significant problem for diagnosis using single cell PCR. In extreme cases ADO can affect >40% of amplifications and has already caused several PGD misdiagnoses. We suggest that an improved understanding of the origins of ADO will allow development of more reliable PCR assays. In this study we carefully varied reaction conditions in >3000 single cell amplifications, allowing factors influencing ADO rates to be identified. ADO was found to be affected by amplicon size, amount of DNA degradation, freezing and thawing, the PCR programme, and the number of cells simultaneously amplified. Factors found to have little or no affect on ADO were local DNA sequence, denaturing temperature (94 or 96 degrees C) and cell type. Consideration of the causal factors identified during this study should permit the design of PGD protocols that experience little ADO, thus improving the accuracy of PGD for single gene disorders. 相似文献
64.
Regulated CPEB phosphorylation during meiotic progression suggests a mechanism for temporal control of maternal mRNA translation
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CPEB is an mRNA-binding protein that stimulates polyadenylation-induced translation of maternal mRNA once it is phosphorylated on Ser 174 or Thr 171 (species-dependent). Disruption of the CPEB gene in mice causes an arrest of oogenesis at embryonic day 16.5 (E16.5), when most oocytes are in pachytene of prophase I. Here, we show that CPEB undergoes Thr 171 phosphorylation at E16.5, but dephosphorylation at the E18.5, when most oocytes are entering diplotene. Although phosphorylation is mediated by the kinase aurora, the dephosphorylation is due to the phosphatase PP1. The temporal control of CPEB phosphorylation suggests a mechanism in which CPE-containing mRNA translation is stimulated at pachytene and metaphase I. 相似文献
65.
Laura Cau Michael R. Williams Anna M. Butcher Teruaki Nakatsuji Jeffrey S. Kavanaugh Joyce Y. Cheng Faiza Shafiq Kyle Higbee Tissa R. Hata Alexander R. Horswill Richard L. Gallo 《The Journal of allergy and clinical immunology》2021,147(3):955-966.e16
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66.
Marianna Farnè Giovanna M. Tedesco Chiara Bedetti Amedea Mencarelli Daniela Rogaia Davide Colavito Giuseppe Di Cara Gabriela Stangoni Stefania Troiani Alessandra Ferlini Paolo Prontera 《American journal of medical genetics. Part A》2020,182(10):2377-2383
Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5‐year‐old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole‐exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen‐magnetic resonance spectroscopy (H‐MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7‐related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth. 相似文献
67.
Turnquist HR Vargas SE Schenk EL McIlhaney MM Reber AJ Solheim JC 《Immunologic research》2002,25(3):261-269
Prior to the binding of antigenic peptide, a complex of chaperone proteins associates with the Major Histocompatibility Complex
(MHC) class I heavy chain/β2m heterodimer. Although each dornain of the MHC class I heavy chain contains amino acid resid uses that influence chaperone
binding, there are several pieces of evidence that point to an interaction between the MHC clas 1α2/α3 domains and tapasin.
In egard to the site on tapasin involved in the tapasin/MHC interface, we have found that a particular region of tapasin (containing
amino acid residues 334–342) is necessary for the binding of tapasin to the MHC class I heavy chain. Our results also indicate
that amino acids in this region of tapasin also affect the proportion of MHC class I open forms expressed at the cell surface
and MHC class I egress from the endoplasmic reticulurn. Based on these results and those obtained by other laboratories, a
model for MHC class I/tapasin interaction is proposed. 相似文献
68.
We present 3 adults with cardiac rhabdomyomas, 2 in the atria and 1 in the right ventricle. One atrial tumor was discovered incidentally, and 1 resulted in supraventricular tachycardia. The ventricular lesion caused ventricular tachycardia. Compared with congenital rhabdomyomas, the tumors are relatively cellular, the cells are smaller, there are few spider cells, and there is evidence of cell proliferation. Two of the 3 tumors demonstrated spindling in contrast to adult rhabdomyomas of the head and neck. Although surgical excision was possible in all patients, long-term follow-up will be required to determine the true biologic behavior of these neoplasms. 相似文献
69.
70.
You Mie Lee John J Cope Gabriele E Ackermann Katsutoshi Goishi Ehrin J Armstrong Barry H Paw Joyce Bischoff 《Developmental dynamics》2006,235(1):29-37
Vascular endothelial growth factor-receptors (VEGF-Rs) are pivotal regulators of vascular development, but a specific role for these receptors in the formation of heart valves has not been identified. We took advantage of small molecule inhibitors of VEGF-R signaling and showed that blocking VEGF-R signaling with receptor selective tyrosine kinase inhibitors, PTK 787 and AAC 787, from 17-21 hr post-fertilization (hpf) in zebrafish embryos resulted in a functional and structural defect in cardiac valve development. Regurgitation of blood between the two chambers of the heart, as well as a loss of cell-restricted expression of the valve differentiation markers notch 1b and bone morphogenetic protein-4 (bmp-4), was readily apparent in treated embryos. In addition, microangiography revealed a loss of a definitive atrioventricular constriction in treated embryos. Taken together, these data demonstrate a novel function for VEGF-Rs in the endocardial endothelium of the developing cardiac valve. 相似文献