Hoek's formula, a cystatin C-based prediction formula for determining the glomerular filtration rate, is the most effective method for original adjusting the dosage of vancomycin.

OBJECTIVE: Some formulas using the serum cystatin C level to estimate the GFR have recently been reported. However, there has been no report of a serum cystatin C-based formula for adjusting the dosage of the drugs cleared by the kidney. In this study, we compared the predictive performance of the serum vancomycin trough concentration predicted using serum cystatin C-based formulas. METHOD: The data were collected from 158 hospitalized patients. Five formulas have been published to predict the GFR using serum cystatin C. The cystatin C-based formulas were divided into two groups, formulas with or without anthropometric data. We predicted the serum vancomycin trough concentrations using VCM-TDM S_edition ver. 1.00 software. RESULTS: In formulas with anthropometric data, the mean absolute error (MAE) using Hoek's formula was 2.38, the MAE using Grubb's 1 formula was 4.13, the MAE using Sjöström's formula was 2.90, and the MAE using Cockcroft and Gault formula based on creatinine was 4.42. On the other hand, in formulas without an anthropometric data group, the MAE using Larsson's formula was 3.07, and the MAE using Grubb's 2 formula was 3.63. CONCLUSION: These results suggested that Hoek's formula is the most useful formula for determining the initial dosage settings for vancomycin.

Achievement of ultralow emittance beam in the accelerator test facility damping ring.

For high luminosity in electron-positron linear colliders, it is essential to generate low vertical emittance beams. We report on the smallest vertical emittance achieved in single-bunch-mode operation of the Accelerator Test Facility, which satisfies the requirement of the x-band linear collider. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured at low intensity is 4 pm at a beam energy of 1.3 GeV, which corresponds to the normalized emittance of 1.0x1.0(-8) m. It increases by a factor of 1.5 for a bunch intensity of 10(10) electrons. The measured data agreed to the calculation of intrabeam scattering within much better than a factor of 2.

FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).

A t(4;11)(q21;q23) has been described in 50-70% of cases of infant acute lymphoblastic leukemia and, less frequently, in cases of pediatric and adult acute lymphoblastic leukemia and acute myeloid leukemia (AML). In t(4;11)(q21;q23) leukemias, the AF4 gene has been cloned as a fusion partner of the MLL gene. A human myeloid leukemia cell line, chronic neutrophilic leukemia (CNL)BC1, was established from a peripheral blood specimen of a patient with CNL in leukemic transformation. As with the original leukemia cells, the established line had a t(4;11)(q21;q23). We showed that the MLL gene on 11q23 was fused to the FLJ10849 gene on 4q21. The protein encoded by FLJ10849 belongs to the septin family, sharing highest homology with human SEPT6, which is one of the fusion partners of MLL in t(X;11)(q13;q23) AML. Our results suggest that FLJ10849 might define a new septin family particularly involved in the pathogenesis of 11q23-associated leukemia. The established cell line, CNLBC1, could provide a useful model for analyzing the pathogenesis of MLL-septin leukemias and chronic neutrophilic leukemia.

T-cell large granular lymphocytic leukemia occurring after autologous peripheral blood stem cell transplantation.

A 61-year-old man with angioimmunoblastic lymphoma in first complete remission underwent autologous peripheral blood stem cell transplantation. At 1 month post transplant, asymptomatic large granular lymphocytosis developed. The surface marker profile of the cells was CD3+CD8+CD56-CD57+. The disease course was chronic and indolent. The patient remains in complete remission from angioimmunoblastic lymphoma more than 6 months post transplant with persistent large granular lymphocytosis (lymphocyte count, 5-15 x 10(9)/l). Although post transplantation T-cell lymphoproliferative disorders have mostly occurred in allogeneic transplantation recipients and presented as aggressive lymphomas/leukemias, we suggest that chronic indolent T-cell large granular lymphocytic leukemia can occur after autologous stem cell transplantation.

Significance of cancer detection in the anterior lateral horn on systematic prostate biopsy: the effect on pathological findings of radical prostatectomy specimens.

OBJECTIVE: To clarify the significance of cancer detection in the anterior lateral horn (ALH) on systematic prostate biopsy in relation to its effect on the pathological findings from retropubic radical prostatectomy (RRP) specimens. PATIENTS AND METHODS: The study included 84 consecutive patients who underwent RRP at our institution between January 1999 and December 2002, after being diagnosed as having prostate cancer, based on systematic prostate biopsies that included the areas taken by standard sextant biopsies and the bilateral ALHs. Several clinicopathological factors of these patients were analysed in relation to the presence or absence of cancer in the ALH on systematic biopsy. RESULTS: Of the 84 patients, cancer was detected in the ALH in 44 (group A), but not in the remaining 40 (group B). There were no significant differences in age, preoperative serum prostate-specific antigen level, or prostate volume between the groups. However, the incidence of bilateral positive cores and the percentage of positive biopsy cores in group A were significantly higher than those in group B. Pathological examinations of RRP specimens showed no significant differences in the incidence of lymphatic invasion, vascular invasion and perineural invasion, or Gleason score between the groups, but group A had a significantly larger tumour volume and higher incidence of extraprostatic disease than group B. CONCLUSIONS: Despite similar biological tumour characteristics and irrespective of the cancer location in the ALH, advanced and extensive disease frequently involves the ALH. Therefore, more aggressive treatment should be considered if cancer is detected in the ALH by systematic prostate biopsy.

Polarimetry of short-pulse gamma rays produced through inverse Compton scattering of circularly polarized laser beams.

We have developed a polarimetry of ultrashort pulse gamma rays based on the fact that gamma rays penetrating in the forward direction through a magnetized iron carry information on the helicity of the original gamma rays. Polarized, short-pulse gamma rays of (1.1+/-0.2)x10(6)/bunch with a time duration of 31 ps and a maximum energy of 55.9 MeV were produced via Compton scattering of a circularly polarized laser beam of 532 nm off an electron beam of 1.28 GeV. The first demonstration of asymmetry measurements of short-pulse gamma rays was conducted using longitudinally magnetized iron of 15 cm length. It is found that the gamma-ray intensity is in good agreement with the simulated value of 1.0x10(6). Varying the degree of laser polarization, the asymmetry for 100% laser polarization was derived to be (1.29+/-0.12)%, which is also consistent with the expected value of 1.3%.

Lung image changes during bronchopulmonary lavage estimated using transoesophageal echocardiography.

Pulmonary alveolar proteinosis is often treated with bronchopulmonary lavage. Transoesophageal echocardiography has been used to detect lung atelectasis in critical situations. A 68-yr-old male with pulmonary alveolar proteinosis underwent bronchopulmonary lavage and was examined using transoesophageal echocardiography. His dependent left-lung area was observed through the descending aorta. Following saline infusion, no bright areas containing air were observed. The average area of the air-free region following instillation was 37.4 +/- 1.8 cm2, which decreased to 22.8 +/- 2.6 cm2 after drainage (P < 0.001). There was a significant relationship between the percentage venous admixture and air-free area during lavage (P < 0.05, r = -0.76). The image of the right lung was unclear. Transoesophageal echocardiography can yield useful information about the lung during bronchopulmonary lavage.

[A case of polyarteritis nodosa limited to both calves with a low titer of MPO-ANCA].

A-57-year-old woman had suffered from high fever, general malaise, and loss of weight (6 kg) since January, 2000. She was admitted to our hospital in May, 2000, because of gait disturbance following to swelling of bilateral calves with severe pain beside the above symptoms. Laboratory data showed leukocytosis (WBC 10,000/microliter), high ESR (98 mm/hr), positive CRP (3.43 mg/dl), positive ANA (x160), high titer of RA (266 IU/l), and a low titer of MPO-ANCA (18 EU). T 2-weighted magnetic resonance image (MRI) showed intensity area of the M. gastrocnemius. Skin biopsy specimens of the right leg demonstrated necrotizing arteritis of small-sized arteries. These findings supported the diagnosis of limited type of polyarteritis nodosa (PN). In this report, we demonstrate a rare case of PN limited to both calves with characteristic MRI findings and a low titer of MPO-ANCA.

Type-specific regulation of adenylyl cyclase. Selective pharmacological stimulation and inhibition of adenylyl cyclase isoforms.

Crystallographic studies have elucidated the binding mechanism of forskolin and P-site inhibitors to adenylyl cyclase. Accordingly, computer-assisted drug design has enabled us to identify isoform-selective regulators of adenylyl cyclase. After examining more than 200 newly synthesized derivatives of forskolin, we found that the modification at the positions of C6 and C7, in general, enhances isoform selectivity. The 6-(3-dimethylaminopropionyl) modification led to an enhanced selectivity for type V, whereas 6-[N-(2-isothiocyanatoethyl) aminocarbonyl] and 6-(4-acrylbutyryl) modification led to an enhanced selectivity for type II. In contrast, 2'-deoxyadenosine 3'-monophosphate, a classical and 3'-phosphate-substituted P-site inhibitor, demonstrated a 27-fold selectivity for inhibiting type V relative to type II, whereas 9-(tetrahydro-2-furyl) adenine, a ribose-substituted P-site ligand, showed a markedly increased, 130-fold selectivity for inhibiting type V. Consequently, on the basis of the pharmacophore analysis of 9-(tetrahydro-2-furyl) adenine and adenylyl cyclase, a novel non-nucleoside inhibitor, 2-amino-7-(2-furanyl)-7,8-dihydro-5(6H)-quinazolinone (NKY80), was identified after virtual screening of more than 850,000 compounds. NKY80 demonstrated a 210-fold selectivity for inhibiting type V relative to type II. More importantly, the combination of a type III-selective forskolin derivative and 9-(tetrahydro-2-furyl) adenine or NKY80 demonstrated a further enhanced selectivity for type III stimulation over other isoforms. Our data suggest the feasibility of adenylyl cyclase isoform-targeted regulation of cyclic AMP signaling by pharmacological reagents, either alone or in combination.

Phospholipase Cbeta4 and protein kinase Calpha and/or protein kinase CbetaI are involved in the induction of long term depression in cerebellar Purkinje cells.

Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKCgamma-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCbeta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCbeta1 was expressed weakly and uniformly, PLCbeta2 was not detected, PLCbeta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCbeta4 was expressed uniformly throughout. In PLCbeta4-deficient mice, expression of total PLCbeta, the mGluR1-mediated Ca(2+) response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCalpha, -betaI, -betaII, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKCalpha and PKCbetaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCbeta4 in rostral cerebellar Purkinje cells induced LTD via PKCalpha and/or PKCbetaI.

X-ray induced reduction of rare earth ion doped in Na2O-Al2O3-B2O3 glasses.

5Na2O-10Al2O3-85B2O3 glasses doped with 0.05 mol% Sm2O3 or 0.05 mol% Eu2O3 turn to orange after irradiation by focussed femtosecond pulsed laser or x-ray irradiation. To know the mechanism of photo-induced coloring, the glasses were studied by Sm or Eu L(III) XANES before and after x-ray or UV irradiation. XANES in both edges showed that a part of trivalent ion converted to divalent ion upon the irradiation of x-ray. These facts reveal that photoreduction of rare earth ion is the mechanism of photo-induced coloring. However no photoreduction upon UV irradiation occurred in both glasses.

Expression of the Gfi-1 gene in HTLV-1-transformed T cells.

Human T-cell leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and immortalizes human T cells interleukin-2 (IL-2)-dependently in vitro. Protracted culture of HTLV-I-infected T cells enables them to grow IL-2-independently. Although acquisition of IL-2-independent growth has been correlated with activation of signal transducers and activators of transcription (STATs), the precise mechanism of IL-2-independent growth is unknown. We found that expression of the Gfi-1 (growth factor independence-1) gene was elevated in most HTLV-I-transformed IL-2-independent cell lines but in few HTLV-I-infected IL-2-dependent cell lines. We also found elevated expression of Gfi-1 in fresh leukemic cells of ATLL patients. Although expression of Gfi-1 is correlated with activation of STAT3, induction of the dominant negative form of STAT3 in the HUT102 cell line does not alter the level of Gfi-1 expression. Furthermore, MT2 cells treated with Gfi-1 antisense oligonucleotide had reduced [3H]thymidine uptake compared with MT2 cells treated with Gfi-1 sense oligonucleotide. These findings indicate that Gfi-1 activation is involved in the IL-2-independent growth of HTLV-I-transformed T cells in vitro and in the development of ATLL in vivo, but is not induced by STAT activation.

Development of interferon-alpha resistant subline from human chronic myelogenous leukemia cell line KT-1.

OBJECTIVE: Interferon-alpha (IFN-alpha) is one of the most effective therapeutic agents for a number of hematological malignancies, including chronic myelogenous leukemia (CML). Nevertheless, its efficacy is limited because of the development of resistance to IFN-alpha therapy. Previously, we established the novel human CML cell line KT-1, which is sensitive to the antiproliferative effects of IFN-alpha. Here, we report the establishment of an IFN-alpha-resistant subline, KT-1/A3R alpha 1000, by culturing KT-1/A3 cells (IFN-alpha-sensitive subline of KT-1) with increasing concentrations of IFN-alpha, in order to analyze the mechanism of acquisition of IFN-alpha resistance in CML cells after IFN-alpha therapy. SUBJECTS AND METHODS: We developed an IFN-alpha-resistant tumor cell variant, KT-1/A3R alpha 1000, from the KT-1/A3 cell line by culturing cells with increasing concentrations of IFN-alpha. This subline was examined for its ability to proliferate and its resistance to apoptosis in high concentrations of IFN-alpha. The induction of the ISGF3 complex in response to IFN-alpha alpha in KT-1/A3R alpha 1000 was compared with that in the parental cell. RESULTS: The levels of interferon-stimulated gene factor 3 components (STAT1, STAT2, and p48) proteins and STAT2 tyrosine phosphorylation induced after IFN-alpha treatment were unchanged, but formation of the ISGF3 complex was remarkably reduced in KT-1/A3R alpha 1000 cells compared to parental cells. CONCLUSION: The KT-1/A3R alpha 1000 subline is a useful model for studying the mechanism of IFN-alpha resistance after IFN-alpha therapy.

Ketamine and midazolam kinetics during continuous hemodiafiltration in patients with multiple organ dysfunction syndrome.

OBJECTIVE: To assess the effect of continuous hemodiafiltration (CHDF) on ketamine and midazolam kinetics in multiple organ dysfunction syndrome (MODS). DESIGN AND SETTING: Consecutive clinical study in a general intensive care unit of a university hospital. PATIENTS: Twelve adult patients with MODS requiring CHDF. MEASUREMENTS AND RESULTS: A total of 68 samples were collected during CHDF for ketamine, norketamine, and midazolam assays. The clearance values for ketamine and norketamine were 10.8 +/- 6.6 and 10.9 +/- 11.5 ml/min and their daily extractions were 21.4 +/- 7.1 and 10.2 +/- 11.5 mg/day, respectively. Midazolam was not eliminated through the filter during CHDF. There were no changes in Ramsay Sedation Score or Glasgow Coma Scale during CHDF. CONCLUSIONS: Small fractions of ketamine and norketamine were eliminated during CHDF in MODS. Midazolam was not eliminated during CHDF. CHDF did not affect the sedation using ketamine and midazolam even in MODS patients.

CD20-positive adult T-cell leukemia.

A 67-year-old woman was admitted to our hospital because of lymphadenopathy and lymphocytosis. Monoclonal integration of HTLV-I provirus DNA was detected, and a diagnosis of adult T-cell leukemia (ATL) was made. Flow cytometry revealed that the ATL cells expressed CD20 as well as T-cell-associated antigens, and expression of CD20 mRNA was also demonstrated. A novel T-cell subpopulation expressing CD20 molecules has recently been identified. This is the first report of CD20-positive ATL, suggesting that HTLV-I can infect and transform CD20-positive T cells.

Density detection in dependent left lung region using transesophageal echocardiography.

BACKGROUND: Densities in dependent lung regions worsen oxygenation in patients with acute respiratory distress syndrome. Identification of these densities requires examination using computed tomography (CT). In this study, the authors evaluated the use of transesophageal echocardiography (TEE) to estimate densities in the dependent lung. METHODS: Forty consecutive patients with acute lung injury or acute respiratory distress syndrome who underwent CT and TEE examination were included in this study. Densities in the lower left lung area were detected through the descending aorta by TEE. Density areas observed by TEE were compared with those obtained by CT. The effect of positive end-expiratory pressure (PEEP) application on density area was also evaluated. RESULTS: Density areas in the dependent lung region measured by TEE were 12.0+/-6.1 cm2 (mean +/- SD) at mid esophageal position. Density areas evaluated using TEE in the left lung correlated significantly with those estimated with CT in the left and right lungs (P < 0.01 in both lungs). In addition, the authors observed a significant correlation between PaO2/FIO2 and density areas estimated using TEE (P < 0.05). During positive end-expiratory pressure application, the area of density estimated with TEE decreased and PaO2 improved. CONCLUSIONS: The authors clearly demonstrated that it is possible to estimate the density area of the dependent left lung regions in patients with acute lung injury or acute respiratory distress syndrome using TEE. It is also possible to observe the changes of density areas during application of positive end-expiratory pressure.

[Early detection of hypoxia with BIS monitoring during percutaneous cardiopulmonary support].

We report a patient in whom hypoxia developed during percutaneous cardiopulmonary bypass (PCPS) and was detected with the lowering of the bispectral index (BIS) values. A 7-yr-old boy was managed with PCPS for the treatment of cardiogenic shock after cardiac surgery. His circulation was dependent on PCPS and pulse pressure was nearly zero. Signals by pulse oxymetry were undetectable and periodical blood gas analysis was performed to confirm proper oxygenation. BIS was monitored, and a gradual decrease in the value was observed. Careful observation also revealed darkening of the blood in the PCPS circuit and blood gas analysis showed severe hypoxia. Oxygen concentration of the gas to a PCPS oxygenator was increased immediately and new PCPS circuit was prepared. It took almost two minutes to exchange the circuit. Near circulatory arrest might have occurred during the procedure and BIS and suppression ratio (SR) became below 10 and above 90, respectively. Both returned to the previous values 30 min after the replacement of the circuit. Severe hypoxia, otherwise overlooked, was detected with BIS monitoring and BIS reflected the circulatory status of the patient, especially of the brain. This monitoring is useful to confirm proper oxygenation during PCPS.

Presence of aldose reductase inhibitors in tea leaves.

Water extract from commercial English tea has a potent inhibitory activity against human placenta aldose reductase (NADPH oxidoreductase, E.C.1.1.1.21.). Inhibitory activity was separated into five major fractions by one-step chromatography with a C-18 reverse phase column. The most active fraction was further subjected to reverse phase column chromatography. As a result, a well-known flavone-glycoside, isoquercitrin, was isolated as the most potent chemical. The inhibitory character of isoquercitrin for aldose reductase was a mix of uncompetitive and noncompetitive inhibitions, and its IC50 was 1 x 10(-6) M. In rat sciatic nerve tissue preparations, sorbitol accumulation in the presence of high concentrations of glucose (30 mM) was inhibited by 38% at 5 x 10(-4) M of isoquercitrin. The flavone-glycoside isoquercitrin is the active inhibitor of aldose reductase inhibitor present in English tea. Given the ability of aldose reductase inhibitors to prevent diabetic complications, an epidemiological study of the effect of tea consumption on the pathogenesis and progression of diabetic complications would be interesting.