KIS induces proliferation and the cell cycle progression through the phosphorylation of p27Kip1 in leukemia cells

CEM, MOLT4 and SUP-B15 cells were transduced with lentivirus-mediated siRNA KIS gene. The mRNA expressions of KIS were successfully reduced in all cell lines. On the other hand, the mRNA expressions of p27(Kip1) in CEM, MOLT4 and SUP-B15 cells were not affected by the transduction with siRNA KIS gene. We showed that KIS protein directly interacted with p27(Kip1) protein, and reduction of KIS inhibited the S10 phosphorylation of p27(Kip1) in leukemia cells. On these cells transfected with siRNA KIS, the inhibition of S10 phosphorylation of p27(Kip1) was strongly suppressed cell proliferation in a time-dependent manner. Moreover, the inhibition of S10 phosphorylation of p27(Kip1) increased a significant population in G0/G1 fraction. These data demonstrated that the KIS activity was induced during G0/G1, and it promotes cell cycle progression by phosphorylation of S10 on p27(Kip1). We showed that KIS mRNA expression was increased in primary leukemia specimens (acute myelogenous leukemia (AML); 37, myelodysplastic syndrome (MDS); 72, acute lymphoblastic leukemia (ALL); 23), and the mean ratios of KIS to G3PDH in AML, MDS and ALL specimens were 3.62+/-0.68, 3.27+/-0.73 and 3.17+/-0.58, respectively. Moreover, we found that KIS protein was overexpressed in all 132 adults cases of various leukemias, including 37 AML (8 M1, 12 M2, 2 M3, 7 M4, 8 M5), 72 MDS (42 RAEB-I, 30 REAB-II) and 23 ALL (23 L2). This study demonstrates that the elevated levels of KIS protein in leukemia cells promote the cell cycle progression in leukemia cells.     

Peripheral Pseudoaneurysm in Active Behçet’s Disease: Surgical and Perioperative Therapeutic Strategies

Since aneurysms in patients with Behçet’s disease are often pseudoaneurysmal and adjacent arteries are highly inflammatory, there is not only a risk of rupture but also a high incidence of late surgical complications at anastomotic sites. Furthermore, there is no consensus on perioperative medical therapeutic strategy in patients with active vasculo-Behçet’s disease who require surgery. Herein, we present two cases of active Behçet’s disease, a 51-year-old male with rupture of the left internal iliac artery who required emergent operation and a 31-year-old male with a rapidly developed pseudoaneurysm in the right superficial femoral artery. Surgical and perioperative therapeutic strategies are also discussed.     

Tetanic stimulation of the peripheral nerve before transcranial electrical stimulation can enlarge amplitudes of myogenic motor evoked potentials during general anesthesia with neuromuscular blockade

BACKGROUND: Neuromuscular blockade can suppress myogenic motor evoked potentials (MEPs). The authors hypothesized that tetanic stimulation (TS) of the peripheral nerve before transcranial stimulation may enhance myogenic MEPs during neuromuscular blockade. In the current study, the authors evaluated MEP augmentations by TS at different levels of duration, posttetanic interval, neuromuscular blockade, and stimulus intensity. METHODS: Thirty-two patients undergoing propofol-fentanyl-nitrous oxide anesthesia were examined. Train-of-five stimulation was delivered to C3-C4, and MEPs were recorded from the abductor hallucis muscle. In study 1, TS with a duration of 1, 3, or 5 s was delivered at 50 Hz to the tibial nerve 1, 3, or 5 s (interval) before transcranial stimulation, and the effects of TS on MEP amplitude were evaluated. In study 2, TS-induced MEP augmentations were evaluated at the neuromuscular blockade level (%T1) of 50% or 5%. In study 3, MEP augmentations by TS at stimulus intensities of 0, 5, 25, and 50 mA were evaluated. RESULTS: The application of TS significantly enlarged the amplitudes of MEPs at the combinations of duration (3, 5 s) and interval (1, 3, 5 s) compared with those without TS. TS-induced MEP augmentations were similarly observed at %T1 of both 50% and 5%. TS-induced MEP augmentations were observed at stimulus intensities of 25 and 50 mA. CONCLUSIONS: The results indicate that TS of the peripheral nerve before transcranial stimulation can enlarge the amplitude of MEPs during general anesthesia with neuromuscular blockade. TS of the peripheral nerve can be intraoperatively applied as a method to augment myogenic MEP responses.     

Mucous-flap method for cleft-lip revision using transverse everted full-length lower-lip flap

In patients who had undergone the first surgery for cleft lip and in whom the volume of tissue was smaller for the upper lip than for the lower lip, transfer of tissue from the lower lip using a full-length mucous flap allowed the tissue volume of the upper lip to be increased and external appearance of the lips to be improved. The subjects of this study were 6 patients who underwent this surgery between February and September 2001 and were followed for up to 3 years postoperatively. This surgery can be performed under topical anesthesia, without necessitating restriction on mouth opening and oral ingestion. Furthermore, it allows easy adjustment of the tissue volume in both upper and lower lips. This operative procedure is recommended for cases of cleft lip where surgical treatment has been performed before and the tissue volume is smaller in the upper prolabium than in the vermilion.     

Ramatroban (BAY u 3405): a novel dual antagonist of TXA2 receptor and CRTh2, a newly identified prostaglandin D2 receptor

It is known that thromboxane A2 (TXA2) contributes to various diseases such as bronchial asthma, ischemic heart disease, cerebrovascular disorders and allergic rhinitis. A number of TXA2 synthase inhibitors and TXA2 receptor (TP receptor) antagonists have been developed to treat these diseases. Ramatroban (BAY u 3405) was developed as a potent TP receptor antagonist with excellent efficacy against allergic rhinitis in many animal models and patients. Recent studies also revealed that ramatroban can block the newly identified PGD2 receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2). PGD2 induces migration and degranulation of eosinophils through CRTh2 and contributes to late-phase inflammation and cell damage. Accordingly, it was considered that ramatroban suppresses the late-phase inflammation via TP receptor and CRTh2 blockade. In terms of the efficacy on vascular systems, it was revealed that ramatroban can suppress the expression of monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in endothelial cells and prevent exacerbation of inflammation by blocking these responses. According to our recent studies in hypercholesterolemic rabbits ramatroban prevents macrophage infiltration through MCP-1 downregulation and neointimal formation after balloon injury and attenuates vascular response to acetylcholine. Therefore, ramatroban may be beneficial in the treatment of atherosclerosis.     

Effect of salazosulfapyridine and its metabolites on immunocompetent cells

Long-term administration of SASP does offer clinical benefit and has a demonstrable disease modifying effect in rheumatoid arthritis, though its mode of action remains obscure. We have studied the in vitro effects of SASP and its metabolites, that is SP, ASA, AcSP and AcASA, on the blast-formation of lymphocytes, the cytotoxic activity of NK cell, the phagocytosis and H2O2 production of monocyte and the fMLP-induced chemotaxis and superoxide anions production of PMNs. We have obtained the following results: (1) the blast-formation of lymphocytes by PHA and Protein A was significantly inhibited by SASP, but not by the metabolites; (2) the cytotoxic activity of the NK cell was inhibited by SP and AcSP, but not by SASP, ASA and AcASA; (3) on monocyte, SP, AcSP and AcASA inhibited phagocytosis, and all of drugs had no effect on the production of H2O2; (4) on PMNs, SASP, SP and ASA significantly inhibited fMLP-induced chemotaxis, and SASP and all of its metabolites significantly inhibited a release of superoxide anions by stimulation of fMLP and PMA; (5) SASP and ASA scavenged superoxide radical at the concentration comparable to clinical doses. In vivo, the above effects may be exhibited in proportion to each blood concentrations of drugs. In particular, it appears that SASP, SP and AcSP play an important role in the therapeutic efficacy in rheumatoid arthritis.     

Surgical treatment for hypertensive cerebellar hemorrhage--indication and characteristics of stereotaxic aspiration surgery

From May 1976, through May 1985, eighty-nine patients with hypertensive cerebellar hemorrhage were admitted to our university hospital and affiliated hospitals. The age at onset ranged from 42 to 86 years, with a mean of 65.1 years. Thirty-one of these patients underwent conservative treatment, 20 were given ventricular drainage, 23 underwent suboccipital craniectomy and 15 underwent stereotaxic aspiration surgery. The patients were classified into four categories according to the grading of hypertensive cerebellar hemorrhage proposed by Matsumoto in 1982. Twenty-two cases were of benign type, 20 were moderate type, 30 were severe type, and 17 were fulminant type. The 22 benign type cases showed good recovery (ADL 1 or ADL 2), whereas the mortality rate of severe type cases was 26.7%, and that of fulminant type cases was 70.6%. The site and extension of hematoma were identified by CT. Fourty cases (45.0%) were confined to the left hemisphere, and 19 (21.3%) were localized in the vermis. When the hematoma volume was more than 15 ml, surgical evacuation of the hematoma was considered. Since 1981, stereotaxic aspiration surgery has been performed in cases of hypertensive cerebellar hemorrhage with a mean patient age of 66.9 years, ranging from 51 to 82 years. Patients treated have consisted of 2 with moderate type hemorrhage, 10 with severe type, and 3 with fulminant type, with an overall surgical mortality rate of 33.3%. However, the outcome of fulminant type hemorrhage has remained ADL 2 or ADL 3. The benefits of this type of surgery are that it is not only indicated as an emergency treatment for patients who are aged or at high risk, but that it can be also performed for fulminant type hemorrhage.