Ultra-long coherence times amongst room-temperature solid-state spins.

Solid-state single spins are promising resources for quantum sensing, quantum-information processing and quantum networks, because they are compatible with scalable quantum-device engineering. However, the extension of their coherence times proves challenging. Although enrichment of the spin-zero 12C and 28Si isotopes drastically reduces spin-bath decoherence in diamond and silicon, the solid-state environment provides deleterious interactions between the electron spin and the remaining spins of its surrounding. Here we demonstrate, contrary to widespread belief, that an impurity-doped (phosphorus) n-type single-crystal diamond realises remarkably long spin-coherence times. Single electron spins show the longest inhomogeneous spin-dephasing time ([Formula: see text] ms) and Hahn-echo spin-coherence time (T2 ≈ 2.4 ms) ever observed in room-temperature solid-state systems, leading to the best sensitivities. The extension of coherence times in diamond semiconductor may allow for new applications in quantum technology.

Anticoagulation with a selective thrombin inhibitor in a woman with heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia is an immunologic complication of heparin therapy with potentially serious venous and arterial thrombotic sequelae. Progression to overt thrombosis is the most serious complication, occurring in approximately 0.5% of heparin-treated patients. Previous strategies for treatment of the associated thrombosis with heparin-induced thrombocytopenia have frustrated clinicians with poor outcomes. CASE: A 45-year-old woman with stage IB endometrial cancer underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. She suffered a pulmonary embolism postoperatively. The pulmonary embolism was treated with heparin, and heparin-induced thrombocytopenia and central vein catheter-related thrombosis developed. She underwent thrombectomy and was successfully anticoagulated with a selective thrombin inhibitor instead of heparin. CONCLUSION: This treatment should be considered for patients with heparin-induced thrombocytopenia in either a prophylactic or a treatment regimen.

Results of degenerative spondylolisthesis treated with posterior decompression alone via a new surgical approach.

OBJECT: The purpose of this study was to assess radiologically demonstrated results and clinical outcomes in patients with degenerative spondylolisthesis who underwent posterior decompressive surgery via a new (unilateral) approach. This approach allows surgeons to perform central and bilateral decompression while only stripping the muscles unilaterally, thus preserving the posterior osteoligamentous complexes. METHODS: The authors evaluated 51 consecutive patients in whom surgery was performed between 1987 and 1996. The mean follow-up period was 4.7 years. There was no statistically significant difference between the pre- and postoperative measurements in percentage of vertebral slippage. Postoperative dynamic angulation statistically decreased compared with its preoperative value (p < 0.05). Improvement of an average of 67% was shown on the Japanese Orthopaedic Association scale, and in 78% of these patients, good to excellent results were demonstrated. Secondary fusion was required in only three patients (5.9%). CONCLUSIONS: This new surgical technique offers a potential alternative for the treatment of degenerative spondylolisthesis in a minimally invasive manner, avoiding the risk of causing or aggravating postoperative spinal instability.

Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA.

In vertebrates, the biological consequences of DNA methylation are often mediated by protein factors containing conserved methyl-CpG binding domains (MBDs). Mutations in the MBD protein MeCP2 cause the neurodevelopmental disease Rett syndrome. We report here the solution structure of the MBD of the human methylation-dependent transcriptional regulator MBD1 bound to methylated DNA. DNA binding causes a loop in MBD1 to fold into a major and novel DNA binding interface. Recognition of the methyl groups and CG sequence at the methylation site is due to five highly conserved residues that form a hydrophobic patch. The structure indicates how MBD may access nucleosomal DNA without encountering steric interference from core histones, and provides a basis to interpret mutations linked to Rett syndrome in MeCP2.

Solution structure and dynamic character of the histidine-containing phosphotransfer domain of anaerobic sensor kinase ArcB from Escherichia coli.

An Escherichia coli sensor kinase, ArcB, transfers a phosphoryl group to a partner response regulator in response to anaerobic conditions. Multidimensional NMR techniques were applied to determine the solution structure of the histidine-containing phosphotransfer signaling domain of ArcB (HPt(ArcB)), which has a phosphorylation site, His717. The backbone dynamics were also investigated by analyses of the (15)N relaxation data and amide hydrogen exchange rates. Furthermore, the protonation states of the histidine imidazole rings were characterized by means of (1)H and (15)N chemical shifts at various pHs. The determined solution structure of HPt(ArcB) contains five helices and forms a four-helix bundle motif like other HPt domains. The obtained order parameters, S (2), [(1)H]-(15)N heteronuclear NOE values, and chemical exchange parameters, R(ex), showed that the alpha-helical regions of HPt(ArcB) are rigid on both picosecond to nanosecond and microsecond to millisecond time scales. On the other hand, helix D, which contains His717, exhibited low protection factors of less than 4000, indicating the presence of fluctuations on a slower time scale in helix D. These results suggest that HPt(ArcB) may undergo a small conformational change in helix D upon phosphorylation. It was also shown that the imidazole ring of His717 has a pK(a) value of 6.76, which is similar to that of a solvent-exposed histidine imidazole ring, and that a pair of deprotonated neutral tautomers are rapidly exchanged with each other. This is consistent with the solution structure of HPt(ArcB), in which the imidazole ring of His717 is exposed to the solvent.

Effect of Helicobacter pylori eradication on malignant transformation of gastric adenoma.

BACKGROUND: A nonrandomized trial of Helicobacter pylori eradication was conducted in patients with endoscopically diagnosed gastric adenoma to determine the long-term effect of antimicrobial treatment on progression of the adenoma. METHODS: Of 64 patients with an endoscopically diagnosed gastric adenoma and H pylori infection, 32 were treated with omeprazole and antibiotics to eradicate the infection, and 32 were not. RESULTS: During 2 years of follow-up, 4 (12.5%) of the 32 patients in the untreated group developed an early stage, intestinal-type gastric cancer, whereas no gastric cancer was found in the 32 patients in the treated group. CONCLUSION: H Pylori eradication may inhibit progression of gastric adenoma to carcinoma.

Mechanism of transcriptional regulation by methyl-CpG binding protein MBD1.

MBD1 is a mammalian protein that binds symmetrically methylated CpG sequences and regulates gene expression in association with DNA methylation. This protein possesses a conserved sequence, named methyl-CpG binding domain (MBD), among a family of methyl-CpG binding proteins that mediate the biological consequences of the methylation. In addition, MBD1 has at least five isoforms due to alternative splicing events, resulting in the presence of CXXC1, CXXC2, and CXXC3 in MBD1 isoforms v1 (MBD1v1) and MBD1v2, and CXXC1 and CXXC2 in MBD1v3 and -v4. In the present study, we have investigated the significance of MBD, CXXC, and the C-terminal transcriptional repression domain (TRD) in MBD1. A bacterially expressed MBD binds efficiently to densely methylated rather than to sparsely methylated DNAs. In both methylation-deficient Drosophila melanogaster SL2 cells and mammalian CHO-K1 cells, MBD1v1 represses transcription preferentially from both unmethylated and sparsely methylated promoters, while MBD1v3 inhibits densely methylated but not unmethylated promoter activities. The CXXC3 sequence in MBD1v1 is responsible for the ability to bind unmethylated promoter. Furthermore, we have constructed mutant-type MBD1s in which the functionally important residues Arg22, Arg30, Asp32, Tyr34, Arg44, Ser45, and Tyr52 are changed to alanine to investigate the correlation between the structure and function of the MBD in MBD1. Excepting those for Ser45 and Tyr52, none of the recombinant MBD mutants bound to the densely methylated or unmethylated DNAs, and green fluorescent protein-fused MBD1 mutants did not localize properly in the nucleus. All the MBD1v1 and -v3 mutants lost the activity of methylation-dependent gene repression. Based on these findings we have concluded that MBD1 acts as a transcriptional regulator depending on the density of methyl-CpG pairs through the cooperation of MBD, CXXC, and TRD sequences.

Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1.

CpG methylation in vertebrates is important for gene silencing, alterations in chromatin structure and genomic stability, and differences in the DNA-methylation status are correlated with imprinting phenomena, carcinogenesis and embryonic development. Methylation signals are interpreted by protein factors that contain shared methyl-CpG-binding domains (MBDs). We have determined the solution structure of the MBD of the human methylation-dependent transcriptional repressor MBD1 by multi-dimensional heteronuclear NMR spectroscopy. It folds into an alpha/beta-sandwich structure with characteristic loops. Basic residues conserved in the MBD family are largely confined to one face of this fold and a flexible loop, which together form a large positively charged surface. Site-directed mutagenesis and chemical shift changes upon complexing with a methylated DNA facilitated identification of this surface as the DNA interaction site. In addition to three basic residues, conserved Tyr34 and Asp32 were shown to be important for the DNA binding.

[Clinical study on a concomitant therapy with fluconazole and human recombinant granulocyte colony stimulating factor in the treatment of systemic fungal infections with hematological disorders].

The clinical efficacy and the safety of concomitant therapy with fluconazole and recombinant human granulocyte colony stimulating factor (rhG-CSF) was compared with fluconazole monotherapy in neutropenic patients with hematological disorders. The clinical efficacy rate was 73.5% (25/34) in the combination therapy and 48.1% (37/77) in monotherapy. The difference between the two is statistically significant. Side effects were not observed in the combination group, but laboratory abnormalities were found in 6 patients with an incident rate of 11%. The combination therapy with fluconazole and rhG-CSF may be selected as empiric therapy for systemic fungal infection associated with hematological disorders, since this combination therapy showed high efficacy and low incident of side effects. Some patients, however, did not show increased neutrophil counts in spite of rhG-CSF administration.

Effects of interleukin-1 and tumor necrosis factor on megakaryocytopoiesis: mechanism of reactive thrombocytosis.

We studied the effects of interleukin-1 (IL-1) and tumor necrosis factor (TNF) on mouse megakaryocytopoiesis to evaluate the role of these cytokines in reactive thrombocytosis associated with inflammation. Injections of IL-1 or TNF to mice induced a significant increase in the megakaryocyte progenitor cell (CFU-Meg) count in the spleen. When IL-1 and TNF were injected simultaneously, the splenic CFU-Meg count was remarkably increased compared with mice injected with either IL-1 (p < 0.003) or TNF (p < 0.001) alone. On the other hand, neither IL-1 nor TNF showed any megakaryocyte-potentiating or -stimulating effects in vitro. In the sera obtained 4 h after administration of IL-1, TNF or both, high megakaryocyte potentiating activities were found. Furthermore, an extremely high level of IL-6 was detected in the serum after administration of both IL-1 and TNF. These results strongly suggest that IL-1 and TNF stimulate megakaryocytopoiesis indirectly via other cytokine(s) induced from accessory cells, and that increased levels of IL-1 and TNF play important roles in the development of reactive thrombocytosis caused by inflammation.

Chemotherapy for minimally differentiated acute myeloid leukemia (AML-M0). A report on five cases and review of the literature.

With the objective of establishing the optimal therapy for minimally differentiated acute myeloid leukemia (AML-M0), we examined the therapeutic results of five AML-M0 cases and reviewed the literature. In a series of 63 patients with newly diagnosed acute leukemia who were admitted to the Main Hospital of Nippon Medical School, five patients fit the criteria for AML-M0: negative myeloperoxidase (MPO) and Sudan black B reaction by light microscopy, negative for B- and T-lineage markers, and positive for myeloid markers. They were treated by means of AdVP [adriamycin, vincristine, and prednisolone (PSL)] therapy and/or BHAC-DMP [behenoylcytosine arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP), and PSL] therapy. The AdVP therapy was unsuccessful in the two patients who received it, while a complete remission (CR) was achieved with the BHAC-DMP therapy in three of four patients. Although one patient treated with BHAC-DMP did not achieve CR, his blasts were apparently sensitive to the therapy. In assessable cases in the literature where leukemic blasts were MPO-negative, myeloid marker-positive and B- and T-lineage marker-negative, CR was achieved in 54.5% and 44.4% with anti-acute myeloid leukemia therapy and anti-acute lymphocytic leukemia therapy, respectively. Five cases in the literature were treated with a chemotherapeutic regimen containing BHAC [or cytosine arabinoside (Ara-C)], DNR, and 6-MP, and all achieved CR. The regimen containing BHAC (or Ara-C), DNR, and 6-MP may be useful as induction chemotherapy for AML-M0.

Megakaryocyte, erythroid and granulocyte-macrophage colony formation in myelodysplastic syndromes.

Bone marrow progenitor cell assays of three cell lineages, i.e., colony-forming unit megakaryocytes (CFU-Meg), burst-forming unit erythrocytes (BFU-E) and colony-forming unit granulocyte-macrophages (CFU-GM), were performed for 21 patients with myelodysplastic syndromes (MDS). Markedly reduced or absent colony formation was found in 67% of the patients for CFU-Meg and all patients except 2 with refractory anemia (RA) for BFU-E. Abnormal CFU-GM colony formation was found in only 5 of 12 patients with RA and RA with ring sideroblasts, in contrast to all of the RA patients with excess of blasts and excess of blasts in transformation. Defective colony formation of all three cell lineages was seen in 63% of the MDS patients. The colony number of CFU-Meg correlated significantly with the numbers of both BFU-E and CFU-GM. These findings indicate that hematopoiesis in MDS patients is disturbed due to a qualitative or quantitative defect at the multipotent stem cell level.

Low-dose etoposide: a potential therapy for myelodysplastic syndromes.

Four patients with refractory anaemia with excess blasts in transformation (RAEB-t) and seven patients with acute leukaemia (AL) transformed from myelodysplastic syndromes (MDS) were treated with etoposide (50 mg, 2 h infusion, two to seven times per week) for at least 4 weeks. Of 10 assessable patients, three RAEB-t patients achieved partial response and one AL patient achieved complete remission. Three of the four responders were resistant to prior repeated low-dose cytarabine therapy. The responders did not require transfusions for 2-9 months while continuing on etoposide therapy. The side-effects were mild and well tolerated. Three possible mechanisms, i.e. a cytotoxic effect, differentiation-induction of malignant cells, and prolongation of blood cell survival by destroying the reticuloendothelial system, may explain the effects of etoposide. We conclude that low-dose etoposide is a potential therapy for MDS and atypical leukaemia.

A possible correlation between the type of bcr-abl hybrid messenger RNA and platelet count in Philadelphia-positive chronic myelogenous leukemia.

The Philadelphia (Ph1) chromosome, in which the hybrid bcr-abl gene is formed, is thought to be the initial event in chronic myelogenous leukemia (CML). The position of the breakpoint within the breakpoint cluster region (bcr) on Ph1 chromosome and the splicing pattern determine the species of the fused bcr-abl messenger RNA (mRNA). We tried to detect the two types of fused mRNAs in 57 chronic-phase cases of Ph1-positive CML using the polymerase chain reaction procedure (RT-PCR). The bcr exon 2/abl exon 2 fused mRNA (b2-a2) was detected in 17 patients, the bcr exon 3/abl exon 2 fused mRNA (b3-a2) was detected in 34 patients, and both types of mRNA were detected in six patients. The platelet counts of patients who expressed b3-a2 mRNA or both types were significantly higher than those of patients who expressed only b2-a2 (841.5 v 373.5 x 10(9)/L; P less than .015), although there was no significant difference in the white blood cell counts or hemoglobin. This finding suggests a possibility that the type of bcr-abl mRNA may affect the thrombopoietic activity in CML.

[Reconstruction of femoral vein using ePTFE grafts].

Rare cases of reconstruction of peripheral veins were reported. We experienced two patients with liposarcomas of the thigh in which the femoral vessels were resected with the tumor and reconstructed with ePTFE grafts. In a 51-year-old male, the left femoral vein was reconstructed with an ePTFE graft 6 mm in diameter and 11 cm in length; but the graft occluded early in the postoperative period. In another case, a 33-year-old male, the right femoral vein was reconstructed with a ringed ePTFE graft 8 mm in diameter and 9 cm in length, with an arterio-venous fistula. The graft maintained its patency for 7 months after surgery.

[Successful treatment of adult T-cell leukemia with interferon-alpha-2b by systemic and local administration].

A 59 years old woman, born in Fukuoka Prefecture, was admitted to our hospital in Aug, 1988 because of diarrhea, fever and skin eruption. Physical examination revealed systemic lymphadenopathy and hepatosplenomegaly. The white blood cell count was 11,200/microliters with 28% atypical lymphocytes with convoluted nuclei. Mild anemia, thrombocytopenia and hypercalcemia were also observed. Antibody against the adult T-cell leukemia (ATL) associated antigen in serum was positive. OKT 4/8 ratio was high. A diagnosis of ATL was made. Because of the complications of pneumonia and herpes simplex, systemic chemotherapy was not given, and interferon (IFN)-alpha-2b was intramuscularly injected daily from Oct, 1988, resulting in the disappearance of atypical lymphocytes and improvement of skin lesions. The effect of IFN therapy lasted for three months, followed by increase of atypical lymphocytes. Although the patient became refractory to systemic IFN therapy, local injection of IFN into a buccal tumor infiltrated with atypical lymphocytes resulted in its regression of size. In spite of continued administration of IFN, the patient died of pneumonia in Jan, 1989.

[Philadelphia-positive acute mixed leukemia with monosomy 7].

A 26-year-old male was admitted to our hospital because of fever and leukocytosis. On admission, a white blood cell count was 28,300/microliters with 46.5% blast cells and 16.0% atypical monocytoid cells, a hemoglobin level 13.7 g/dl, and a platelet count 15.0 X 10(4)/microliters. Bone marrow contained 58.8% of peroxidase-negative blast cells. He was diagnosed as acute lymphoblastic leukemia (ALL L2) according to the FAB classification. Chromosome analysis revealed the marrow cells to contain 45, XY, -7, t(9; 22) (q34; q11). On surface marker analysis, the leukemic cells were positive for both lymphoid (CD10) and myeloid markers (CD13). Two color flow-cytometric analysis showed two distinct populations with CD10 and CD1 3, respectively. Rearrangements of both immunoglobulin heavy chain and T cell receptor beta-chain were observed. The "breakpoint cluster region" on chromosome 22 was not rearranged. On the basis of these findings, we thought this case being acute mixed leukemia. He was refractory to AdVP therapy and BHAC-DMP therapy. He is now under treatment with A-Triple-V therapy.

[Successful treatment of secondary erythroleukemia with androgen].

A case of secondary erythroleukemia treated with apparent success with androgen is reported. The patient is 63-year-old Japanese female. She had a history of multiple myeloma and had been treated with melphalan, vincristine and prednisolone. She developed erythroleukemia 88 months after the initiation of chemotherapy, while her myeloma was a complete remission. She was treated first with vitamin D3 with no beneficial effect and subsequently with 0.5 mg/kg of mepitiostane. A hematologic improvement began two months from the initiation of androgen therapy, and a complete remission of erythroleukemia was attained thereafter. A chromosomal abnormality of bone marrow cells, which was observed at the time of developing erythroleukemia, also disappeared after the treatment. She remained in good condition and hematologic remission under the androgen therapy at the latest follow-up, 1-year after the development of erythroleukemia. Androgen therapy may be considered as a useful treatment for secondary erythroleukemia.

[Extensive bone marrow necrosis associated with carcinomatosis 7 years after operation for gastric cancer].

A case of extensive bone marrow necrosis due to cancer metastasis is reported. A 55-year-old female, who had a history of subtotal gastrectomy for signet ring cell carcinoma of the stomach 7 years ago, was admitted to our hospital with a complaint of lumbago on October 25, 1987. Red blood cell count was 92 X 10(4)/microliters, hemoglobin 2.7 g/dl, hematocrit 8.0%, platelet 6.4 X 10(4)/microliters, and white blood cell count 13,400/microliters with leukoerythroblastosis. Bone marrow aspiration of the sternum, left iliac crest, and bilateral posterior superior iliac supine showed extensive bone marrow necrosis. Serum ALP was increased to 7410IU/l, dominated isozyme of bone type. Hemostatic findings suggested a complication of consumption coagulopathy. Skull, vertebrae, iliac and pelvic bone X-ray showed multiple osteolytic lesions, and irregular isotope uptake was recognized on the bone scintigraphy using 99mTc. Sixth bone marrow examination at the right iliac crest revealed signet ring cell carcinoma metastasis. In spite of detailed examinations, there was no evidence of primary carcinoma, including the remnant of stomach. We speculated that the signet ring cells were originated from the respected gastric cancer. The patient has received anti-cancer chemotherapy with UFT and OK432, and is still alive 9 months after diagnosis.