Synchronization of thermoacoustic quasiperiodic oscillation by periodic external force.

Quasiperiodic oscillations can occur in nonequilibrium systems where two or more frequency components are generated simultaneously. Many studies have explored the synchronization of periodic and chaotic oscillations; however, the synchronization of quasiperiodic oscillations has not received much attention. This study experimentally documents forced synchronization of the quasiperiodic state and the internally locked state of a thermoacoustic oscillator system. This system consists of a gas-filled resonance tube with a nonuniform cross-sectional area. The thermoacoustic oscillator was designed and built in such a way that nonlinear interactions between the fundamental acoustic oscillation mode and the third mode of the gas column are controlled by a temperature difference that is locally created in the resonance tube. Bifurcation diagrams were mapped out by changing the forcing strength and frequency. Separated Arnold tongues were found and both modes were entrained to the external force through complete synchronization. A saddle-node bifurcation was observed in the route from partial to complete synchronization when the forcing strength was relatively weak. However, a Hopf (torus-death) bifurcation was observed when the forcing was relatively strong. In the internally locked state, the bifurcation occurred after the internal locking was broken down by the external force.

Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study.

OBJECTIVE: To investigate pregnancy outcomes, especially the risk of pregnancy-related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR). DESIGN: Retrospective case series study. SETTING: Tertiary perinatal care centre at a university hospital. POPULATION: Pregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute. METHODS: The pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records. MAIN OUTCOME MEASURES: Obstetrical management and complication including the incidence of AD throughout the peripartum period. RESULTS: Among 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P < 0.05, Chi-square test). CONCLUSIONS: Our study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre-pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm. TWEETABLE ABSTRACT: MFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.

Clinical significance of intramedullary Gd-DTPA enhancement in cervical myelopathy.

STUDY DESIGN: Prospective multicenter study. OBJECTIVE: To clarify the significance of intramedullary Gd-DTPA enhancement in cervical myelopathy, the prevalence, morphologic features, clinical relevance and postoperative change were investigated. SETTING: Four hospitals in Japan. METHODS: A total of 683 patients with cervical myelopathy who underwent decompressive surgery were consecutively examined. T1, 2 and Gd-DTPA-enhanced MRI were taken before surgery. Fifty consecutive cases without intramedullary enhancement were allocated in the non-enhancement group. The following variables were investigated: prevalence of the enhancement, the morphologic feature, the relationship between the enhancement and T2 high-intensity areas, the change of the Japanese Orthopedic Association (JOA) score for cervical myelopathy and the change of the enhancement after surgery. RESULTS: Intramedullary enhancement was observed in 50 cases (7.3%). The enhancements were observed between the most severely compressed disc and the cranial half of the lower vertebral body. On axial images, they were observed at the posterior or posterolateral periphery of the spinal cord. Enhancement areas were observed within T2 high-intensity areas and smaller than them. The preoperative JOA score was 9.8+/-2.8 points in the enhancement group and 9.8+/-3.3 points in the non-enhancement group (NS). The postoperative JOA score was 12.7+/-2.9 points in the enhancement group and 14.2+/-2.4 in the non-enhancement group (P=0.006). Intramedullary enhancement disappeared in 60% of the patients 1 year after surgery. CONCLUSION: Intramedullary enhancement indicated not the severity of preoperative symptoms, but a sign of a worse prognosis.

Facet cyst haematoma in the lumbar spine: a report of four cases.

We present 4 cases of facet cyst haematoma in the ligamentum flavum of the lumbar spine. All patients presented with a one-to-3-month history of back pain or numbness in the legs, and sudden neurological deterioration. One also developed cauda equina syndrome and another developed radiculopathy. In all cases, magnetic resonance imaging showed a mass with high signal intensity on both T1- and T2-weighted images. Facet arthrography and computed tomography revealed communication between the mass and the neighbouring facet joint. The haematomas were removed en bloc with the ligamentum flavum. They were surrounded by the ligament and contained degenerated and lacerated elastic fibres but no synovial lining cells. Facet cyst haematoma is so-named because of bleeding from tissue adjacent to the facet joint into a pre-existing facet cyst.

Symptomatic epidural haematoma after cervical laminoplasty: a report of three cases.

Symptomatic epidural haematoma after cervical laminoplasty is rare. We report 3 patients who required emergency evacuation of an epidural haematoma. Timely diagnosis and removal of the haematoma is important to prevent neurological deficits. The causative factors in these patients were preoperative coagulopathy, hypertension, and the malfunction of a closed-suction drain.

Systematic isolation of genes expressed at low levels in inflorescence apices of Arabidopsis thaliana.

We constructed an equalized cDNA library from Arabidopsis inflorescence shoot apices including inflorescence meristem, floral meristem and flower tissue collected before stage 5 of flower development. The cDNA clones were arrayed on membranes and were differentially screened using cDNA pools from vegetative and inflorescence tissues as probes. Each clone was classified by expression specificity and expression level. By removing the clones that displayed hybridization signals, 384 out of 3264 clones in this library remained as candidates for inflorescence-specific mRNAs expressed at low levels. Sequence analysis of all selected clones indicated that 53 were identical and 120 were homologous to genes in public protein databases. The remaining 211 selected clones had no significant amino acid sequence similarities with those deduced from any reported genes, though 62 of them appeared in Arabidopsis expressed sequenced tags (ESTs). About 40% of the selected clones were novel, validating the present approach for gene discovery. Northern blot analysis of 22 randomly selected clones confirmed that most were expressed preferentially in inflorescence tissues. In addition, many clones were transcribed at relatively low levels. We demonstrate that the screening method of the present study is useful for systematic classification of cDNA species based on expression specificity.

Gene arrangement at the Rhesus blood group locus of chimpanzees detected by fiber-FISH.

The Rhesus (Rh) blood group system in humans is encoded by two genes with high sequence homology. These two genes, namely, RHCE and RHD, have been implied to be duplicated during evolution. However, the genomic organization of Rh genes in chimpanzees and other nonhuman primates has not been precisely studied. We analyzed the arrangement of the Rh genes of chimpanzees (Pan troglodytes) by two-color fluorescence in situ hybridization on chromatin DNA fibers (fiber-FISH) using two genomic DNA probes that respectively contain introns 3 and 7 of human RH genes. Among the five chimpanzees studied, three were found to be homozygous for the two-Rh-gene type, in an arrangement of Rh (5'-->3') - Rh (3'<--5'). Although a similar gene arrangement can be detected in the RH gene locus of typical Rh-positive humans, the distance between the two genes in chimpanzees was about 50 kb longer than that in humans. The remaining two chimpanzees were homozygous for a four-Rh-gene type, in an arrangement of Rh (5'-->3') - Rh (3'<--5') - Rh (3'<--5') - Rh (3'<--5') within a region spanning about 300 kb. This four-Rh-gene type has not been detected in humans. Further analysis of other great apes showed different gene arrangements: a bonobo was homozygous for the three-Rh-gene type; a gorilla was heterozygous for the one-Rh- and two-Rh-gene types; an orangutan was homozygous for the one-Rh-gene type. Our findings on the intra- and interspecific genomic variations in the Rh gene locus in Hominoids would shed further light on reconstructing the genomic pathways of Rh gene duplication during evolution.

A primary cell culture system for human cytotrophoblasts of proximal cytotrophoblast cell columns enabling in vitro acquisition of the extra-villous phenotype.

Cytotrophoblast (CT) differentiation into the extra-villous phenotype is a crucial process in initiating their invasion into the decidua and thereby developing the placenta. However, how CTs differentiate into extra-villous CTs (EVCTs) is not fully elucidated. To address this, a suitable culture model for CTs has been long-sought. But this has been hampered by annoying problems such as; cell aggregation, in vitro syncytialization, low plating efficiency, etc. The aim of this study is to develop a culture system in which CTs differentiate into EVCTs. CTs were isolated from the first trimester placenta using density gradient separation and immuno-depletion using anti-CD9 antibody to remove contaminating fibroblasts and EVCTs. The resultant isolated CTs were found to have the character similar to poorly differentiated CTs comprising proximal cytotrophoblastic cell columns as confirmed by immunocytochemical and flowcytometric analyses. When cultured on type 4 collagen-coated plates in culture media containing low calcium concentration, CTs neither aggregated nor syncytialized, remaining mononuclear and monolayer state. Interestingly, cultured CTs gradually upregulated integrin alpha1, CD9, and human leukocyte antigen (HLA)-G; the known markers specific for EVCTs invading into the decidua diffusely. Hence, the CT culture system provides a sophisticated experimental model in which highly purified CTs acquire the extra-villous phenotype without syncytialization.

Allogeneic peripheral blood stem cell transplantation for standard-risk leukemia. A multicenter pilot study: Japanese experience. Japan Blood Cell Transplantation Study Group.

A multicenter phase II study of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was conducted. Twenty-two patients (median age, 36 years) with standard-risk leukemia were transplanted with G-CSF-mobilized PBSC from an HLA-identical sibling donor, and received cyclosporine and methotrexate for GVHD prevention. Median days to ANC >500/microl and platelets >50,000/microl were 12 (9-20) and 16 (11-32), respectively. Grade II-IV acute GVHD developed in 6/21 (29%) and extensive chronic GVHD in 12/20 (60%). These observations indicate that allo-PBSCT is characterized by rapid hematologic engraftment, no increase of acute GVHD and an increased risk of chronic GVHD, and can be used as an alternative to allogeneic bone marrow transplantation.

Wound-induced phenylalanine ammonia-lyase in potato tuber tissue. Development of enzyme activity and effects of antibiotics.

Phenylalanine ammonia-lyase [EC 4.3.1.5.] activity increased rapidly after a 3-hr lag period in potato tuber (Solanum tuberosum L. cv. May Queen) disks incubated in a suitable medium in the dark at 25 degrees. The activity reached a maxinum after incubation for about 40 hr. The effects of actinomycin D, 6-methylpurine, cycloheximide, chloramphenicol, and mitomycin C on the induction of phenylalanine ammonia-lyase were investigated during incubation of the disks. Actinomycin D, 6-methylpurine, and cycloheximide all inhibited the formation of phenylalanine ammonia-lyase, though cycloheximide was the most effective at low concentrations. Application of actinomycin D for the initial lag period (3 hr) caused strong inhibition; however, if it was supplied later it did not inhibit but actually increased phenylalanine ammonialyase formation. In contrast, cycloheximide was effective over most of the incubation period. Chloramphenicol and mitomycin C did not inhibit phenylalanine phenylalanine ammonialyase induction, but markedly stimulated it. Light was not an essential factor for phenylalanine ammonia-lyase induction in the wounded tissue.

1 alpha-Hydroxyvitamin D3 in the treatment of primary myelofibrosis: in vitro effect of vitamin D3 metabolites on the bone marrow fibroblasts.

Thrombocytopenia and splenomegaly improved in one of the four patients receiving 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3) for treatment of primary myelofibrosis (PMF). We compared the clinical results with the in vitro effects of vitamin D3 metabolites on the growth and collagen synthesis of bone marrow fibroblasts. The effects of vitamin D3 metabolites on control human bone marrow fibroblasts were first studied in vitro. On the growth, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) inhibited the platelet derived growth factor (PDGF) or human serum-induced proliferation at the concentrations of more than 10(-10) M, while in the presence of transforming growth factor-beta (TGF-beta) the inhibitory effects were mild or non-inhibitory. Both vitamin D3 metabolites inhibited procollagen synthesis at a concentration of more than 10(-8) M. The effect of 1,25(OH)2D3 on the PMF patients was examined. In two of the four patients, the human serum-induced growth inhibitory effect was observed at the concentration of 10(-8) M, in one patient no inhibition was observed and in one patient inhibition was observed at 10(-10) M, as was observed in the control donors. During the treatment with 1 alpha(OH)D3 the serum level of 1,25(OH)2D3 was 1-2 x 10(-10) M. These findings suggest that a minority of PMF patients have marrow fibroblasts with growth sensitivity to a pharmacological level of vitamin D3 and could be treated with 1 alpha(OH)D3 with some clinical improvements.

Expression of c-Mpl and c-Mpl ligand gene in hematopoietic cells of individuals with and without myeloproliferative disorders and leukemia cell lines.

We examined the expression of c-Mpl (MPL) and c-Mpl ligand (ML) gene in hematopoietic cells in individuals with and without myeloproliferative disorders (MPD) and leukemic cell lines by RT-PCR. The MPL gene transcripts were detected in normal CD34+ cells, platelets, megakaryocytes and monocytes, while the ML gene was expressed in CD34+ cells, megakaryocytes, T cells, monocytes and bone marrow fibroblasts, as well as liver tissue. The ML gene product produced in the bone marrow microenvironment might, in part, be involved in hematopoiesis. The MPL gene expression was detected in platelets and peripheral blood mononuclear cells from the majority of patients with MPD including chronic myelocytic leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In contrast, the ML gene expression was found in the majority of ET and CML patients, but not in PV or PMF patients. These findings suggest that even in MPD the megakaryocytopoiesis depends on the MPL signal transduction system, and that in ET and CML, the ML production by mononuclear cells in the bone marrow microenvironment might play a part in the higher megakaryocytopoiesis observed in these diseases. Both the MPL and ML gene expression were detected in all the leukemic cell lines tested, suggesting that this cytokine/receptor system is involved in cell growth through autocrine and paracrine systems.

Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome.

We report a patient with aplastic anemia (AA)-paroxysmal nocturnal hemoglobinuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacked CD59 antigen on their surface and were positive for P-glycoprotein. Heteroduplex and single-strand conformation polymorphism analysis followed by sequencing of the leukemic cells in the bone marrow disclosed 1 frameshift-type mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) gene, which deductively produces truncated PIG-A protein. These findings provide direct evidence that the leukemic cells evolved from the affected PNH clone. Cytogenetic analysis in the bone marrow in each stage of AA-PNH, AML, and at relapse of AML showed normal, -7, and -7 plus -20, respectively, showing evidence of a clonal evolution. Because complete remission of AML was not achieved by intensive chemotherapies, allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient's HLA-matched sister was performed successfully with recovery of CD59 antigen on bone marrow hematopoietic cells; however, leukemia relapsed 4 months after PBSCT. Leukemia derived from PNH may be resistant to intensive chemotherapy, and a highly myeloablative regimen may be required for stem cell transplantation to eradicate the PNH-derived leukemia clone.

c-kit Point mutation in patients with myeloproliferative disorders.

Myeloproliferative disorders (MPD) constitute a group of hematopoietic neoplasms at the myeloid stem cell level. Myeloid stem cells and/or progenitor cells from MPD have been considered sensitive to hematopoietic growth factors, including erythropoietin, thrombopoietin and stem cell factor (SCF). SCF is a ligand for c-kit receptor with tyrosine kinase. We analysed the gene alteration of the c-kit extracellular domain in MPD patients by PCR-SSCP and subsequent nucleotide sequencing. The point mutation in the N-terminal part of the domain, codon 52 (Asp-->Asn), was found in two patients with primary myelofibrosis and one with chronic myelogenous leukemia. We review the literature regarding the role of SCF/c-kit system in the oncogenesis of leukemia and MPD, and then discuss the significance of our finding in the context of growth advantage of the mutated clones over the normal clones.

Platelet derived growth factor expression, myelofibrosis and chronic myelogenous leukemia.

CML is often associated with myelofibrosis, and fibrosis in the accelerated phase is one of the diagnostic criteria for this accelerated phase. In this review, the mechanism of myelofibrosis associated with CML is discussed with emphasis on the cell origin of the production and release of platelet derived growth factor (PDGF) and its interaction with marrow fibroblasts. In the initial stage of myelofibrosis in chronic phase CML, atypical small megakaryocytes might leak PDGF, possibly PDGF-AB, together with other growth factors. As the clinical phase of the disease progresses to accelerated or blastic phase, a larger quantity of PDGF-AB or PDGF-BB might be secreted from blastic cells with myeloid phenotype. In addition some fibroblasts may be attracted by the PDGF and proliferate, and deposit collagen as well as fibronectin in the bone marrow stroma.

L-selectin expression in CD34 positive cells in chronic myeloid leukemia.

L-selectin is a cell adhesion molecule, expressed on leukocytes and involved in the regulation of leukocyte traffic. This adhesion receptor is implicated in hematopoiesis by the interaction of hematopoietic stem cells and progenitors to stroma in the bone marrow microenvironment. We found that L-selectin expression on CD34++ cells from patients with chronic myelogenous leukemia (CML) is decreased or deficient, reflecting one of the features of malignant CML progenitors. In this review, we briefly describe the structure and function of L-selectin, and its role in hematopoiesis and its expression in leukemia and lymphoma. Finally, we discuss the abnormal adhesiveness of CML progenitor cells, and the role of L-selectin in this defect.

Leukemic transformation of primary myelofibrosis: immunophenotype, genotype and growth characteristics of blast cells.

Blast cells from six patients with leukemic transformation of primary myelofibrosis (PMF) were studied by morphology, immunophenotype and genotype as well as response to hematopoietic growth factors. The majority of the patients showed granulocytic or granulo-monocytic blasts, and only one had T lymphoid-monocytic blasts. None of the patients showed rearrangement of Ig or TCR genes, or the existence of the bcr-abl fused gene. A prominent growth response to GM-CSF and IL-3 was evident in all of the patients examined in liquid as well as semisolid cultures. The response to G-CSF was observed in four of the six patients in suspension culture, and in two of three patients in the clonogenic assay. Stem cell factor (SCF) was a weak growth stimulant, however the combination of this factor with GM-CSF or IL-3 was synergistically stimulatory. These results suggest that leukemic transformation of PMF occurs mainly at the level of myeloid stem cell, and that GM-CSF, IL-3, G-CSF and SCF are major growth factors for the blast cells in these cases.

Myocardial hypertrophy of the recipient twins in twin-to-twin transfusion syndrome and cerebral palsy.

OBJECTIVES: This study was performed to determine risk factors for cerebral palsy (CP) in monochorionic twins, especially with twin-to-twin transfusion syndrome (TTTS). METHODS: In 33 pathologically confirmed monochorionic pregnancies, we analyzed the incidence of cardiovascular and neurological complications. RESULTS: Seventeen cases were diagnosed as TTTS. Myocardial hypertrophy was detected in seven recipient twins of TTTS, but not found in the donor twins of TTTS or in non-TTTS. CP developed in six out of 29 in TTTS and one out of 32 in non-TTTS. In TTTS, all the cases with CP were seen in the recipient twins. The development of CP was significantly associated with cardiovascular complications such as myocardial hypertrophy and hydropic changes. CONCLUSIONS: Myocardial hypertrophy found in the recipient twins in TTTS seems to be a risk for developing CP later on, which may have implications in understanding the pathogenesis of CP.

Effects of sairei-to and tokishakuyaku-san on cytokine release from peripheral blood mononuclear cells upon recognition of HLA-G protein in the treatment of recurrent abortion.

Human leukocyte antigen (HLA)-G has been shown to play a role in establishing pregnancy through the mechanism of modulating cytokine secretion from maternal lymphocytes. To elucidate the mechanisms of actions of the herbal medicines, Sairei-to and Tokishakuyaku-san, in the treatment of recurrent abortion, we investigated whether these medicines modulate cytokine secretion from peripheral blood mononuclear cells (PBMCs) upon recognition of HLA-G protein on trophoblasts. Sairei-to and Tokishakuyaku-san increased the interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha secretion and decreased the IL-3 secretion from PBMCs regardless of whether these cells recognized HLA-G protein or not. Accordingly, Sairei-to nullified the effects of HLA-G to reduce the secretion of IL-1 beta and TNF-alpha and to enhance the secretion of IL-3. Tokishakuyaku-san also abolished the effect of HLA-G to reduce IL-1 beta and TNF-alpha secretion but did not affect the increase in IL-3 secretion. Thus, it is conceivable that Sairei-to may normalize Th1/Th2 balance by enhancing Th1 polarization in autoimmunity-related recurrent abortion in which Th1/Th2 balance might be shifted towards Th2 polarization. However, the mechanisms of action of Tokishakuyaku-san when used in treating unexplained recurrent abortion, cannot be explained only by the Th1/Th2.

[Nationwide survey of allogeneic peripheral blood stem cell transplantation from related donors in Japan: current trends and issues].

In December 1997, we conducted a nationwide survey of cases of primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) performed in Japan between December 1994 and November 1997 Data was collected on 103 patients with hematologic malignancies, aplastic anemia, or solid tumors. Eighty-seven patients received transplants from HLA-identical siblings, and 16 from HLA-mismatched related donors. Granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) were collected from donors by 1 to 3 aphereses. Apheresis products contained a median 5.4 (1.0-30.4) x 10(6) CD34 + cells/kg. Most patients were given cyclosporine and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Median days to ANC > 500/microliter and platelets > 50,000/microliter were 13 (7-49) and 16 (10-94), respectively. Grade II-IV acute GVHD developed in 37/99 (37.4%) and chronic GVHD in 59/86 (68.6%) patients. The incidence of treatment-related mortality within 100 days after transplant was 16.1%. Fifty-five patients (59.6%) were alive after a median follow-up of 794 days. More patients and longer follow-up periods will be required to assess the efficacy of allo-PBSCT and evaluate graft-versus-leukemia effect along with the incidence of acute and chronic GVHD.