ABSTRACT
Blood coagulation factors play an essential role in pregnancy. We describe a 30-year-old pregnant woman whose course was complicated by dysfibrinogenemia with polymorphism of fibrinogen AαThr312Ala (rs6050) GG genotype. She was admitted to our hospital for genital bleeding and a huge subchorionic hematoma at 6 gestational weeks. Her first pregnancy and delivery had been uneventful, whereas her second and third pregnancies had resulted in spontaneous abortions with massive subchorionic hematomas. Her fibrinogen activity level was 125 mg/dl and this was lower than her fibrinogen antigen level. We administered tranexamic acid early in the pregnancy, and the subchorionic hematoma diminished in size in accordance with the increase of her fibrinogen level. At 16 gestational weeks, her D-dimer levels were elevated, and heparin treatment was initiated as an alternative. A male infant was delivered at 36 gestational weeks. Intrapartum hemorrhage was 600 g. Patients with coagulation abnormalities are often asymptomatic in the absence of pregnancy. However, when they become pregnant, the spontaneous abortion rate is high. Careful observation and effective management of coagulation abnormalities are essential for such patients to carry their pregnancies to term.
Subject(s)
Afibrinogenemia/genetics , Fibrinogens, Abnormal/genetics , Polymorphism, Single Nucleotide , Pregnancy Complications, Hematologic/genetics , Adult , Female , Fibrinogens, Abnormal/analysis , Humans , Pregnancy , Protein S/analysisABSTRACT
The Japan Baptist Medical Foundation has established a "hospice triangle" system consisting of the hospice ward, general ward, and home hospice. Palliative care is provided for patients with various types of cancer, including hematological malignancies, in the place where they desire to receive care. From December 2010 to December 2013, 37 patients with hematological malignancies received palliative care and died at our foundation. Eleven (30%) patients died in the hospice ward, 24 (65%) in the general ward, and 2 (5%) at home. The median interval between the final dose of chemotherapy and death was 12 (1- 88) days. Twenty (54%) patients received transfusions during the last 2 weeks prior to death. Quick response to patient situations and early introduction of palliative care are essential to support end-of-life decision-making processes, because the clinical course of hematological malignancies generally differs from that of other cancers.
Subject(s)
Hematologic Neoplasms/therapy , Palliative Care , Aged , Aged, 80 and over , Female , Humans , Japan , Male , Middle AgedABSTRACT
BACKGROUND: The centromere is the chromosome domain on which the mitotic kinetochore forms for proper segregation. Deposition of the centromeric histone H3 (CenH3, CENP-A) is vital for the formation of centromere-specific chromatin. The Mis6-Mal2-Sim4 complex of the fission yeast S. pombe is required for the recruitment of CenH3 (Cnp1), but its function remains obscure. METHODOLOGY/PRINCIPAL FINDINGS: Mass spectrometry was performed on the proteins precipitated with Mis6- and Mis17-FLAG. The results together with the previously identified Sim4- and Mal2-TAP precipitated proteins indicated that the complex contains 12 subunits, Mis6, Sim4, Mal2, Mis15, Mis17, Cnl2, Fta1-4, Fta6-7, nine of which have human centromeric protein (CENP) counterparts. Domain dissection indicated that the carboxy-half of Mis17 is functional, while its amino-half is regulatory. Overproduction of the amino-half caused strong negative dominance, which led to massive chromosome missegregation and hypersensitivity to the histone deacetylase inhibitor TSA. Mis17 was hyperphosphorylated and overproduction-induced negative dominance was abolished in six kinase-deletion mutants, ssp2 (AMPK), ppk9 (AMPK), ppk15 (Yak1), ppk30 (Ark1), wis4 (Ssk2), and lsk1 (P-TEFb). CONCLUSIONS: Mis17 may be a regulatory module of the Mis6 complex. Negative dominance of the Mis17 fragment is exerted while the complex and CenH3 remain at the centromere, a result that differs from the mislocalization seen in the mis17-362 mutant. The known functions of the kinases suggest an unexpected link between Mis17 and control of the cortex actin, nutrition, and signal/transcription. Possible interpretations are discussed.
Subject(s)
Centromere , Schizosaccharomyces pombe Proteins/physiology , Schizosaccharomyces/metabolism , Blotting, Western , Cell Cycle , Phosphorylation , Promoter Regions, Genetic , Schizosaccharomyces/cytology , Schizosaccharomyces pombe Proteins/chemistry , Schizosaccharomyces pombe Proteins/metabolism , Tandem Mass SpectrometryABSTRACT
The centromere is the chromosomal site that joins to microtubules during mitosis for proper segregation. Determining the location of a centromere-specific histone H3 called CENP-A at the centromere is vital for understanding centromere structure and function. Here, we report the identification of three human proteins essential for centromere/kinetochore structure and function, hMis18alpha, hMis18beta, and M18BP1, the complex of which is accumulated specifically at the telophase-G1 centromere. We provide evidence that such centromeric localization of hMis18 is essential for the subsequent recruitment of de novo-synthesized CENP-A. If any of the three is knocked down by RNAi, centromere recruitment of newly synthesized CENP-A is rapidly abolished, followed by defects such as misaligned chromosomes, anaphase missegregation, and interphase micronuclei. Tricostatin A, an inhibitor to histone deacetylase, suppresses the loss of CENP-A recruitment to centromeres in hMis18alpha RNAi cells. Telophase centromere chromatin may be primed or licensed by the hMis18 complex and RbAp46/48 to recruit CENP-A through regulating the acetylation status in the centromere.
Subject(s)
Autoantigens/metabolism , Centromere/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Adaptor Proteins, Signal Transducing , Amino Acid Motifs , Amino Acid Sequence , Animals , Cell Cycle Proteins , Centromere/drug effects , Centromere Protein A , Chromosomal Proteins, Non-Histone/chemistry , Chromosome Segregation/drug effects , Consensus Sequence , Genome, Human/drug effects , HeLa Cells , Humans , Hydroxamic Acids/pharmacology , Metaphase/drug effects , Molecular Sequence Data , Mutation/genetics , Phylogeny , Protein Binding/drug effects , Protein Transport/drug effects , Proto-Oncogene Proteins c-myb/metabolism , RNA Interference , Recombinant Fusion Proteins/metabolism , Schizosaccharomyces pombe Proteins/metabolism , Telophase/drug effects , VertebratesABSTRACT
Centromeres contain specialized chromatin that includes the centromere-specific histone H3 variant, spCENP-A/Cnp1. Here we report identification of five fission yeast centromere proteins, Mis14-18. Mis14 is recruited to kinetochores independently of CENP-A, and, conversely, CENP-A does not require Mis14 to associate with centromeres. In contrast, Mis15, Mis16 (strong similarity with human RbAp48 and RbAp46), Mis17, and Mis18 are all part of the CENP-A recruitment pathway. Mis15 and Mis17 form an evolutionarily conserved complex that also includes Mis6. Mis16 and Mis18 form a complex and maintain the deacetylated state of histones specifically in the central core of centromeres. Mis16 and Mis18 are the most upstream factors in kinetochore assembly as they can associate with kinetochores in all kinetochore mutants except for mis18 and mis16, respectively. RNAi knockdown in human cells shows that Mis16 function is conserved as RbAp48 and RbAp46 are both required for localization of human CENP-A.
