Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan.

The purpose of this trial was to evaluate the efficacy of 2-year consolidation therapy with nilotinib, at a dose of 300 mg twice daily, for achieving treatment-free remission in chronic myeloid leukemia patients with a deep molecular response ( ≤0.0032%). Successful treatment-free remission was defined as no confirmed loss of deep molecular response.

Multicenter phase II clinical trial of nilotinib for patients with imatinib-resistant or -intolerant chronic myeloid leukemia from the East Japan CML study group evaluation of molecular response and the efficacy and safety of nilotinib.

Background: Nilotinib is a second-generation tyrosine kinase inhibitor that exhibits significant efficacy as first- or second-line treatment in patients with chronic myeloid leukemia (CML). We conducted a multicenter Phase II Clinical Trial to evaluate the safety and efficacy of nilotinib among Japanese patients with imatinib-resistant or -intolerant CML-chronic phase (CP) or accelerated phase (AP).

Results: We analyzed 49 patients (33 imatinib-resistant and 16 imatinib-intolerant) treated with nilotinib 400 mg twice daily.

A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.

Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined.

[Mycotic aneurysm of the descending thoracic aorta].

A 55-year-old man was admitted with severe back pain and saccular aneurysm of the descending aorta on computed tomography. Laboratory examinations showed elevated serum C-reactive protein of 16.98 mg/dl.

Streptococcus pneumoniae-associated hemolytic uremic syndrome in a splenectomized adult patient.

A 62-year-old splenectomized woman was admitted because of upper respiratory tract symptoms, general fatigue, and purpura. Laboratory data demonstrated microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure, and a positive Streptococcus pneumoniae (SP) urinary antigen test. A renal biopsy showed thrombotic microangiopathic changes.

Usefulness of linezolid in the treatment of hospital-acquired pneumonia caused by MRSA: a prospective observational study.

Clinical results for linezolid (LZD) treatment of hospital-acquired pneumonia (HAP) caused by methicillin-resistant Staphylococcus aureus (MRSA), particularly microbiologically evaluable or severe cases, are limited in Japan. A prospective observational study was conducted in order to assess the usefulness of LZD in Japanese patients with MRSA pneumonia. The study tracked fifteen participants treated with LZD for pneumonia who met the criteria of the HAP guidelines and were confirmed to have pneumonia caused by MRSA.

Immunohistochemical study of the lymphatic vessels in major salivary glands of the rat.

This study was designed to examine whether lymphatic vessels are present in the lobules of major salivary glands in the rat. Immunostaining with an antibody against podoplanin, a lymphatic endothelial cell marker, was performed on sections of the submandibular, sublingual and parotid glands. Light microscopy demonstrated podoplanin-positive lymphatic vessels around the interlobular ducts and the interlobular arteries and veins in the interlobular connective tissue in all of the major salivary glands.

Successful treatment of post-MRSA infection glomerulonephritis with steroid therapy.

A 48-year-old man without underlying disease developed mediastinitis and was treated by mediastinal drainage. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in a culture of the abscess material. He was treated with anti-MRSA antibiotics and the MRSA infection improved.

Establishment and characterization of a human uterine endometrial undifferentiated carcinoma cell line, TMG-L.

A new cell line of human uterine endometrial undifferentiated carcinoma, designated as TMG-L, was established from the metastatic lymph node of 56-year-old patient TMG-L cells have been cultured with Ham's F-12 medium supplemented with 10% FCS and grew as a loosely adherent monolayer with polygonal or spindle-shaped cells exhibiting poor cell-cell contact and piled up against each other, showing a tendency to grow as floating cells. The doubling time of this cell line was about 48 hours, and chromosomal analysis revealed aneuploidy at passage 25. The cells formed tumors in SCID mouse, the histology of which was similar to that of undifferentiated carcinoma component of primary tumor.

[Ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade; report of a case].

The ruptured aortic arch aneurysm with cardiac tamponade is rare and has severely high mortality. We report a case of ruptured aortic arch aneurysm with cardiac tamponade. A 66-year-old man who had syncope attack was transferred to city hospital.

Relationship between the classification of vascular invasion severity and the prognosis of uterine endometrial cancer.

The objective of this research is whether the classification of vascular invasion severity can be used as a prognostic factor in cases of uterine endometrial cancer. Sixty-five patients with stage I to III uterine endometrial cancer were included in the study. All patients were seen between 1987 and 1997, and the types of their cancers were histologically confirmed.

Induction of tissue factor production but not the upregulation of adhesion molecule expression by ceramide in human vascular endothelial cells.

Binding of tumor necrosis factor-alpha (TNF-alpha) to p60 TNF-alpha receptor induces the activation of sphingomyelinase to generate ceramide, which in turn activates certain protein kinases and phosphatases, resulting in various TNF-alpha-mediated biological effects. We have investigated the role for the sphingomyelin/ceramide pathway in the TNF-alpha-induced upregulation of adhesion molecule expression and tissue factor production of human endothelial cells. TNF-alpha stimulated human umbilical vascular endothelial cells (HUVECs) to upregulate the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and HLA class I molecules in addition to the induction of procoagulant tissue factor production.

Defective apoptotic signal transduction pathway downstream of caspase-3 in human B-lymphoma cells: A novel mechanism of nuclear apoptosis resistance.

Mitochondria play a central role in controlling apoptosis, and activation of the caspase cascade appears to be crucial event during the apoptotic process. Human B lymphoma Raji cells are resistant to nuclear apoptosis induced by various stimuli. Using this cell line, we have asked whether reduction of the mitochondrial transmembrane potential and activation of caspase-3 are sufficient to induce DNA fragmentation during the apoptotic process.

Quantitative reverse transcription-PCR-HPLC for nerve growth factor mRNA using a deletion RNA as an internal standard.

We have developed a convenient method for the routine measurement of the absolute amount of nerve growth factor (NGF) mRNA in tissue samples. The method consists of RNA extraction, amplification by reverse transcription-PCR and detection by high-performance liquid chromatography. The addition of a deletion mutant RNA to tissue samples as an internal standard enabled correction for RNA recovery during extraction, and the target mRNA and the internal standard were both amplified with the same PCR primers.

"Crushed glass" appearance of particles observed in roentgenograms after hysterosalpingography as an indicator of pelvic abnormalities.

Objective: To evaluate the diagnostic value of the crushed glass appearance of particles observed on roentgenogram after hysterosalpingography in patients with pelvic abnormalities.

Design: Retrospective study of 32 patients whose roentgenogram had particles with a crushed glass appearance and 16 patients without crushed glass appearance, with laparoscopy conducted to determine the location and severity of the pelvic disease.

Setting: Fujita Health University Hospital, Aichi, Japan.

Cell-permeable ceramide inhibits the growth of B lymphoma Raji cells lacking TNF-alpha-receptors by inducing G0/G1 arrest but not apoptosis: a new model for dissecting cell-cycle arrest and apoptosis.

We examined the effects of a cell-permeable ceramide analog, C2-ceramide, on the growth of TNF-alpha-resistant B lymphoma Raji cells lacking TNF-alpha-receptors (TNF-R). C2-ceramide inhibited the clonal growth of not only TNF-alpha-sensitive myeloid leukemia cells (HL60 and U937) but also Raji cells. Following stimulation with C2-ceramide, HL60 and U937 cells showed apoptotic cell death, whereas Raji cells did not show a detectable level of apoptosis.

Dopamine D3 agonists disrupt social behavior in rats.

Behavioral studies were conducted in rats administered a selective D3 agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) or 4aR, 10bR-(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1] benzopyrano[4,3-b]-1,4-oxazin-9-ol (PD 128907). Both drugs induced disruption of huddling behavior in rats at doses that did not produce hyperlocomotion. The effects of the D3 agonists were dependent upon dosage and time after administration.

Transmembrane signaling through CD80 (B7-1) induces growth arrest and cell spreading of human B lymphocytes accompanied by protein tyrosine phosphorylation.

We addressed the issue of the role for CD80 (B7-1) expressed on human B cells in transmembrane signaling. Cross-linking of CD80 on B lymphoma Raji cells induced tyrosine phosphorylation in 160-, 120-, 55-, 46- and 44-kDa proteins, which was inhibited by genistein. CD80-mediated signaling resulted in the inhibition of DNA replication of B cells and induced the changes in morphology like macrophages or fibroblasts.

Autoantibodies against 70-kDa heat shock proteins (HSP70) in allogeneic bone marrow transplant recipients.

We report that autoantibodies against the 70-kDa heat shock protein family (HSP70) were detected in allogeneic bone marrow transplant recipients. Antibodies to HSP70 family proteins were detected in three out of 14 recipients of an allogeneic marrow graft but in none of the seven patients receiving autologous peripheral blood stem cell transplant (PBSCT). Immunoblotting analysis combined with two-dimensional SDS-PAGE revealed that these patients had antibodies to a constitutive 73-kDa/pI 5.

Signal transduction by B7/BB1 expressed on activated T lymphocytes: cross-linking of B7/BB1 induces protein tyrosine phosphorylation and synergizes with signalling through T-cell receptor/CD3.

We report here that B7/BB1 molecules expressed on activated T lymphocytes are involved in signal transduction. Anti-B7/BB1 monoclonal antibody (mAb) enhanced allogeneic proliferative responses against three different B lymphoma lines in a dose-dependent manner, while the same mAb inhibited T-cell response against allogeneic T cells expressing B7/BB1. Induction of B7/BB1 expression on T cells with allogeneic stimulation was confirmed by flow cytometric analysis.

Cloning, characterization, and tissue distribution of porcine SPAI, a protein with a transglutaminase substrate domain and the WAP motif.

The primary and gene structures and tissue distribution of porcine SPAI-2, a protein that belongs to the WAP protein superfamily and has a sodium-potassium ATPase inhibitory activity, were determined by molecular cloning and Northern analysis. A full-length cDNA clone was isolated from a porcine duodenum cDNA library. The cDNA insert encoded a polypeptide of 187 amino acids, which is composed of three domains: a hydrophobic presequence of 21 amino acids, a prosegment of 105 amino acids ending with Asp126, and the mature SPAI-2 sequence of 61 amino acids beginning with Pro127.