Evaluation of the Interplanetary Magnetic Field Strength Using the Cosmic-Ray Shadow of the Sun.

We analyze the Sun's shadow observed with the Tibet-III air shower array and find that the shadow's center deviates northward (southward) from the optical solar disk center in the "away" ("toward") interplanetary magnetic field (IMF) sector. By comparing with numerical simulations based on the solar magnetic field model, we find that the average IMF strength in the away (toward) sector is 1.54±0.21_{stat}±0.20_{syst} (1.62±0.15_{stat}±0.22_{syst}) times larger than the model prediction. These demonstrate that the observed Sun's shadow is a useful tool for the quantitative evaluation of the average solar magnetic field.

Probe of the solar magnetic field using the "cosmic-ray shadow" of the sun.

We report on a clear solar-cycle variation of the Sun's shadow in the 10 TeV cosmic-ray flux observed by the Tibet air shower array during a full solar cycle from 1996 to 2009. In order to clarify the physical implications of the observed solar cycle variation, we develop numerical simulations of the Sun's shadow, using the potential field source surface model and the current sheet source surface (CSSS) model for the coronal magnetic field. We find that the intensity deficit in the simulated Sun's shadow is very sensitive to the coronal magnetic field structure, and the observed variation of the Sun's shadow is better reproduced by the CSSS model. This is the first successful attempt to evaluate the coronal magnetic field models by using the Sun's shadow observed in the TeV cosmic-ray flux.

Anisotropy and corotation of galactic cosmic rays.

The intensity of Galactic cosmic rays is nearly isotropic because of the influence of magnetic fields in the Milky Way. Here, we present two-dimensional high-precision anisotropy measurement for energies from a few to several hundred teraelectronvolts (TeV), using the large data sample of the Tibet Air Shower Arrays. Besides revealing finer details of the known anisotropies, a new component of Galactic cosmic ray anisotropy in sidereal time is uncovered around the Cygnus region direction. For cosmic-ray energies up to a few hundred TeV, all components of anisotropies fade away, showing a corotation of Galactic cosmic rays with the local Galactic magnetic environment. These results have broad implications for a comprehensive understanding of cosmic rays, supernovae, magnetic fields, and heliospheric and Galactic dynamic environments.

Observation by an air-shower array in Tibet of the multi-TeV cosmic-ray anisotropy due to terrestrial orbital motion around the Sun.

We report on the solar diurnal variation of the galactic cosmic-ray intensity observed by the Tibet III air shower array during the period from 1999 to 2003. In the higher-energy event samples (12 and 6.2 TeV), the variations are fairly consistent with the Compton-Getting anisotropy due to the terrestrial orbital motion around the Sun, while the variation in the lower-energy event sample (4.0 TeV) is inconsistent with this anisotropy. This suggests an additional anisotropy superposed at the multi-TeV energies, e.g., the solar modulation effect. This is the highest-precision measurement of the Compton-Getting anisotropy ever made.

Massive rhabdomyolysis and acute renal failure after acetonitrile exposure.

A case of systemic rhabomyolysis after acetonitrile exposure is reported. A 35-year-old previously healthy man suffered from vomiting, convulsion and consciousness loss 15 hours after exposure to acetonitrile. Since acetonitrile is known to be metabolized into cyanide, antidote therapy against cyanide poisoning was given. On admission, pain and all-over muscle swelling were marked. Although the initial therapy was effective, rhabdomyolysis and then acute renal failure developed. Renal function improved very slowly after six weeks of hemodialysis, but atrophy of the muscles remained. The rhabdomyolysis may have been caused by toxicity of the cyanide itself in combination with hypoxia and convulsion.

Relationship between triglyceride concentrations and LDL size evaluated by malondialdehyde-modified LDL.

BACKGROUND: Hypertriglyceridemia is associated with decreased HDL-cholesterol (HDL-C) and increased small dense LDL. In addition, small dense LDL is known to be susceptible to oxidation. METHODS: We measured LDL particle size, using gradient gel electrophoresis, and malondialdehyde-modified LDL (MDA-LDL), using an ELISA, and investigated the association between triglyceride (TG) concentrations, LDL size, and MDA-LDL. RESULTS: TG concentrations correlated negatively with the predominant LDL size (r = -0.650) and HDL-C concentration (r = -0.556). The relationship between TG concentration and LDL size, evaluated by measuring MDA-LDL, distinguished subgroups derived from four subfractions of TG concentrations and four distribution ranges of LDL size. These experiments indicated that there is a threshold for oxidation susceptibility at an LDL size of 25.5 nm and a TG concentration of 1500 mg/L. To investigate the relationship between LDL size, MDA-LDL concentration, and other lipids (TGs, HDL-C, apolipoprotein B, and total cholesterol), we evaluated them in control subjects and patients with diabetes mellitus or hypertriglyceridemia. When the size range for normal LDL was postulated to be 25.5 < or = phi (LDL diameter) < 26.5 nm, the MDA-LDL concentration was significantly higher in the subgroups of patients with LDL in the size range 24.5 < or = phi < 25.5 nm compared with patients with normal LDL. This result also suggests that the threshold is at a LDL size of 25.5 nm. CONCLUSION: The threshold for oxidation susceptibility coincided with the point of LDL size separation between the LDL subclass patterns A and B as an atherosclerotic risk.

Cyclophosphamide and 5-fluorouracil act synergistically in ovarian clear cell adenocarcinoma cells.

Chemosensitivity to the drugs plays a crucial role in the treatment of ovarian cancer. In this study, we evaluate the cytotoxicity of chemotherapeutic agents in six ovarian cancer cell lines; four clear cell adenocarcinoma and two serous papillary adenocarcinoma, using seven single drugs and seven sets of drug combinations with tetrazolium-based semiautomated colorimetric (MTT) assay. The drug concentration which produced 50% growth inhibition (IC50) of cisplatin was within clinically achievable range in five cell lines. The area under the curve (AUC) at IC50 of cyclophosphamide was below the clinically achievable AUC in two serous papillary cell lines. Paclitaxel was more effective in clear cells than serous papillary cells. The intensification of cytotoxicity was observed in the combinations of paclitaxel and cisplatin, and cyclophosphamide and cisplatin or 5-fluorouracil irrespective of histopathological characteristics of the original tumor. Our results indicate that ovarian cancer cell lines respond to chemotherapeutic agents heterogeneously depending upon histopathological features, indicating individualized regimens may improve survival in ovarian cancer patients.

Percutaneous transhepatic placement of metallic stents in the treatment of complicated intrahepatic biliary stricture with hepatolithiasis: a preliminary report.

OBJECTIVE: We aimed to study the effect of the metallic modified Gianturco-Rosch Z-stent in the management of refractory intrahepatic long-segment biliary strictures with hepatolithiasis. METHODS: Six symptomatic patients with hepatolithiasis and coexisting intrahepatic long-segment biliary strictures, who failed to respond to the silastic external-internal biliary stenting, were selected. The metallic modified Gianturco-Rosch Z-stent was placed via percutaneous transhepatic cholangiography at the strictured site. Patients were followed regularly to evaluate for recurrence of cholangitis, stones, or strictures. RESULTS: No complications were observed during the procedures. No recurrent strictures or formed calculi were found in these six patients during follow-up periods of 29 to 64 months. However, cholangitis and intrahepatic biliary muddy sludge occurred at 7 and 30 months in two patients after the placement of the metallic Z-stent. Percutaneous transhepatic cholangioscopy was used to clear sludge completely. CONCLUSIONS: Our experience suggests that the metallic stent is a well-tolerated and promising alternative in the management of refractory intrahepatic long-segment biliary strictures with hepatolithiasis. Though biliary sludge may develop, it can be detected and cleared early. Repeated surgery can thus be avoided.

Dynamic reaction in a homogeneous HDL-cholesterol assay visualized by electron microscopy.

BACKGROUND: Measurement of HDL-cholesterol (HDL-C) by homogeneous assays with automated analyzers is replacing precipitation methods. However, in this reaction-type assay, interactions between the reagents and lipoproteins remain unknown. METHODS: Electron microscopy was used to investigate the reactions in a homogeneous HDL-C assay. Negative staining with 10 g/L uranyl acetate was performed for lipoprotein visualization by electron microscopy. Observations of the interactions between lipoproteins and the reagents of a polyanion-polymer/detergent assay were achieved by cooling the reaction mixture in ice water. This treatment also allowed observation of the time course of the reaction. RESULTS: In the first-reagent reaction (polyanion-polymer), every lipoprotein aggregated almost completely. In the second-reagent reaction (enzymes and detergent), only HDL in the lipoprotein aggregates was selectively resolved and reacted enzymatically. Reagent 1 contains two important substances: polyanion and synthetic polymer. Using x-ray microanalysis, we confirmed that aggregation of lipoproteins in the first reaction occurred through interaction with the phosphotungstate of the polyanion. CONCLUSION: Electron microscopy morphologically revealed the dynamic reaction in a homogeneous HDL-C assay.

Observation of Multi-TeV Gamma Rays from the Crab Nebula using the Tibet Air Shower Array.

The Tibet experiment, operating at Yangbajing (4300 m above sea level), is the lowest energy air shower array, and the new high-density array constructed in 1996 is sensitive to gamma-ray air showers at energies as low as 3 TeV. With this new array, the Crab Nebula was observed in multi-TeV gamma-rays and a signal was detected at the 5.5 sigma level. We also obtained the energy spectrum of gamma-rays in the energy region above 3 TeV which partially overlaps those observed with imaging atmospheric Cerenkov telescopes. The Crab spectrum observed in this energy region can be represented by the power-law fit dJ&parl0;E&parr0;&solm0;dE=&parl0;4.61+/-0.90&parr0;x10-12&parl0;E&solm0;3 TeV&parr0;-2.62+/-0.17 cm-2 s-1 TeV-1. This is the first observation of gamma-ray signals from point sources with a conventional air shower array using scintillation detectors.

[Effective mechanisms of ATX-S10, a new photosensitizer, on HeLa tumors in nude mice].

Photodynamic therapy (PDT) is a treatment modality that utilizes a photosensitizing drug activated by laser generated light. PDT is effective for oncologic applications. Many cancer patients have undergone a hematoporphyrin derivative (HpD)-mediated PDT. The HpD showed a side effect causing prolonged cutaneous photosensitivity. But ATX-S10, a new photosensitizer, provides rapid plasma and tissue clearance, comparable photoactivation efficiency, and superior light absorption of visible red. In this study, the tumor rejection mechanisms of PDT using ATX-S10 on HeLa tumors in nude mice were investigated with morphological and fluorometric methods. The mice were intracutaneously inoculated with HeLa cells, 5 x 10(5) or 1 x 10(7) cells. When tumors grew to about 10-12 mm in diameter, mice were intraperitoneally administered ATX-S10, 30 mg/kg, and 2 hours later the ATX-S10 in tumors was indirectly measured by a fluorometric machine, PMA-10 (Hamamatsu Photonics K. K.) and the tumors were irradiated by Optical Parametric Oscillator (Hamamatsu Photonics K. K.) tuned to a wave length at 670 nm, 5 mJ/pulse, 100 J/tumor. Before and after the irradiation, the effective mechanisms of PDT with ATX-S10 were studied by histological and ultrastructural approaches. The results showed occlusive thrombi in the microvasculature of the tumors and tumor cell death. These occlusive thrombi were observed within one hour after PDT at both light and electron microscopy levels, and were more remarkable as time passed after PDT. Therefore, the morphological studies of PDT with ATX-S10 suggested that the rejection mechanisms occurred mainly as a result of the destructive changes of the microvasculature in the tumors first, and secondly or simultaneously, tumor cells were destroyed through necrosis, and finally the tumors were rejected.

Staining of the lens capsule for circular continuous capsulorrhexis in eyes with white cataract.

We have developed a technique of staining the anterior capsule with a solution of indocyanine green that facilitates performance of the circular continuous capsulorrhexis in eyes with a mature cataract. We compared the results of phacoemulsification and intraocular lens implantation in 10 eyes with the capsule stained with results of 10 eyes having the same procedure with standard circular continuous capsulorrhexis. The results of specular microscopy and laser flare-cell photometry showed no statistically significant differences between the 2 groups. Although the safety of intraocular indocyanine green dye has not yet been definitively established, the findings of this pilot study suggest that it is safe and useful in visualizing the anterior capsule of a mature cataract during cataract surgery.

Assay method for femtogram order of Ca2+, Mg(2+)-dependent endonuclease.

A sensitive method for the assay of Ca2+, Mg(2+)-dependent endonuclease was developed. The assay procedure is composed of two parts: (i) microscale endonuclease digestion of highly polymerized calf thymus DNA and (ii) the quantification of DNA breaks by measuring the activation of poly(ADP-ribose) polymerase, which is known to be activated proportionally to the number of nicks and ends of DNA added in the reaction mixture. This method was approximately 10(5)-fold more sensitive than a conventional DNase assay detecting acid-soluble DNA formation and, thus, the activity of 20 to 100 fg of purified bull seminal Ca2+, Mg(2+)-dependent endonuclease could be reliably measured. Ca2+ and Mg2+ requirements and the response to histone H2B of the endonuclease were also demonstrated by this method. Using this method, the assay of a very small amounts of Ca2+, Mg(2+)-dependent endonuclease in crude extracts of calf thymus chromatin was possible. This method may be applied to other types of endonucleases by modifying the mixture for endonuclease reaction.

Orthotopic vascularized osteochondral allografts in an immunosuppressed rat model.

This study examined the survival of orthotopic, vascularized, osteochondral allografts, following 12 weeks of immunosuppression and transfer into a naive, allograft host up to 14 weeks later, and compared the results with those previously reported for similar grafts in a heterotopic position. Knee-joint allografts between DA (donor) and Lewis (recipient) rat strains were assessed by quantitative histology up to 6 months after transplantation, and graft microcirculation was examined by India-ink infusion. Graft repopulation was assessed by re-transferring the graft to a naive, non-suppressed allograft host 12 to 26 weeks after the initial transplantation. Isografts survived for as long as grafts were examined (6 months) and showed good healing of the graft/host bone junction, although long-term isografts showed some deterioration of the growth plate. Non-suppressed allografts rejected within 2 weeks. Allografts in hosts immunosuppressed for 12 weeks remained healthy and healed in a similar manner to the isografts. Following cessation of immunosuppression, allografts progressively deteriorated, with mononuclear cell infiltration apparent in graft bone marrow and muscle in the later stages examined. Transfer to second non-suppressed hosts resulted in rapid rejection of the allografts, indicating that, as shown previously in heterotopic, osteochondral allografts, little or no graft repopulation by host-derived cells had occurred during the protected period in the first host.

Reappraisal of the systematic management of complicated hepatolithiasis with bilateral intrahepatic biliary strictures.

OBJECTIVE: To compare the results, limitations, and complications of the surgical treatment of bilateral hepatolithiasis and intrahepatic biliary strictures with left hepatectomy and without left hepatectomy. DESIGN: Case-controlled study. SETTING: Referral center. PATIENTS: During a 12-year period, 103 patients with bilateral hepatolithiasis and intrahepatic biliary strictures underwent surgical treatment. Group A (n = 73) received left hepatic resection (lateral segmentectomy or lobectomy) and postoperative biliary dilatation with residual stone extraction. Group B (n = 30) underwent the same procedures except for left hepatectomy. INTERVENTIONS: Left lateral segmentectomy or left lobectomy, choledocholithotomy, postoperative cholangioscopic treatments (electrohydraulic lithotripsy, other lithotripsy, lithotomy, balloon dilatation, etc. via T tube or precutaneous transhepatic route). MAIN OUTCOME MEASURES: Days of hospitalization, incidence of major and minor complications, mortality rates, and the rates of residual stones and stone recurrence were compared. RESULTS: Group A and B had similarly low postoperative 1-month mortality rates of 5.5% and 6.7%, respectively. The main cause of death in both groups was uncontrollable septicemia. The main major complications in group A were intra-abdominal abscess and upper gastrointestinal bleeding; the major complication in group B was massive hemobilia. Group B had a significantly higher overall rate of complications (53.3% vs 23.3%, P < .01) and a longer hospital stay than group A (median, 72 days vs 28 days, P < .03). When complications were classified as major or minor, only minor complications showed a significant difference (30% vs 13.7%, P = .05). After using biliary stricture dilatation and stone extraction, the rate of residual stones in the right lobe was similar in both groups, but patients in group B had a significantly higher rate of residual stones (12.5% vs 0%, P < .02) and stone recurrence in the left lobe (19% vs 0%, P < .003) than those in group A. CONCLUSIONS: Partial resection of the left lobe in cases of bilateral hepatolithiasis and biliary strictures can effectively simplify problems in the treatment of bilateral hepatolithiasis and intrahepatic biliary strictures. In addition, not only were surgical complications not increased, but a decrease in complications from postoperative manipulations for stone clearance was noted in our series.

Effects of the dopamine-related drug bromocriptine on event-related potentials and its relation to the law of initial value.

Effects of the dopamine-related drug bromocriptine (BCT) on event-related potentials (ERP) were investigated in 18 healthy volunteers. Bromocriptine 2.5 mg or an inactive placebo was administered according to a completely randomized double-blind, cross-over design. The ERP were recorded 3 h after medication was given. Although BCT prolonged the P300 latency, it had no effect on the amplitudes of the ERP components as a whole. Bromocriptine increased the latencies of N100, P200 and P300 in the respective short-latency subject group, and decreased the latency of N200 in the long-latency subject group. It increased the amplitude of N200 in the low-amplitude subject group. It was concluded that the prolongation of P300 latency as a whole and the different responses that take place are dependent on the initial values and were recognized in the effect of a single administration of BCT 2.5 mg. The results of this study are discussed in relation to the law of initial value.

Coexisting sharp ductal angulation with intrahepatic biliary strictures in right hepatolithiasis.

OBJECTIVE: To investigate the clinical characteristics of a coexisting sharp ductal angulation (< 90 degrees) with biliary stricture and to evaluate the difficulties it imposes in the management of retained or recurrent hepatolithiasis. DESIGN: Case-controlled study. SETTING: A referral center. PATIENTS: Eighteen consecutive patients having right-sided hepatolithiasis and a coexisting sharp ductal angulation associated with biliary stricture (group 1) were compared with 84 patients matched with sex, age, and conditions of hepatolithiasis and intrahepatic biliary stricture(s) but no sharp angulated duct (group 2). INTERVENTION: Postoperative cholangioscopic management (electrohydraulic lithotripsy or other lithotripsy, lithotomy, balloon dilation, biopsy, etc, via T-tube tract or percutaneous transhepatic route). MAIN OUTCOME MEASURES: Sessions of manipulations, incidence of complications associated with interventions or disease, and mortality were compared. RESULTS: Patients of group 1 needed more sessions of postoperative manipulation of stones and strictures (13.7 +/- 4.2 vs 8.0 +/- 2.3; P < .001). During management, there was a significantly increased vulnerability of severe and/or recurrent cholangitis (66.7% vs 9.5%; P < .001), septic shock (77.8% vs 11.9%; P < .001), liver abscess (55.6% vs 7.1%; P < .001), or massive hemobilia (33.3% vs 7.4%) in group 1 than in group 2. Their risks of coexisting secondary biliary cirrhosis (55.6% vs 9.5%; P < .001) and/or cholangiocarcinoma (16.6% vs 2.4%; P < .04) and mortality (27.8% vs 4.8%; P < .01) were also significantly higher in group 1. CONCLUSION: Our results suggest that the coexisting sharp ductal angulation with biliary strictures in right-sided hepatolithiasis is a distinct difficult clinical entity in the field of biliary tract calculi.

Vascularized heterotopic osteochondral allografts in a rat model following long-term immunosuppression.

The effect of 12 weeks of cyclosporin A (CyA) (7 mg/kg) on the survival of vascularized osteochondral allografts between rat strains--Dark Agouti (DA donor) and Lewis (recipient)--was examined up to 6 months after grafting. Grafts were assessed by India-ink infusion to examine their microcirculation, and by quantitative histology. Isografts (Lewis to Lewis) survived at least 25 weeks, but displayed progressive deterioration due to their non-weight bearing position. Rejection controls (allografts with no immunosuppression) showed rejection within 2 weeks. Allografts in immunosuppressed hosts remained healthy for the 12-week period of immunosuppression, but deteriorated progressively during the ensuing 14 weeks, particularly in the muscle, marrow, and growth plates. Graft repopulation by host cells was assessed by transferring grafts into fresh non-suppressed allograft hosts, following 12 to 26 weeks in the first, immunosuppressed host. All grafts were rejected rapidly following the second transfer, indicating that little or no cellular repopulation of the graft had occurred while in the first host.