Tracing Photoinduced Hydrogen Migration in Alcohol Dications from Time-Resolved Molecular-Frame Photoelectron Angular Distributions.

The recent implementation of attosecond and few-femtosecond X-ray pump/X-ray probe schemes in large-scale free-electron laser facilities has opened the way to visualize fast nuclear dynamics in molecules with unprecedented temporal and spatial resolution. Here, we present the results of theoretical calculations showing how polarization-averaged molecular-frame photoelectron angular distributions (PA-MFPADs) can be used to visualize the dynamics of hydrogen migration in methanol, ethanol, propanol, and isopropyl alcohol dications generated by X-ray irradiation of the corresponding neutral species. We show that changes in the PA-MFPADs with the pump-probe delay as a result of intramolecular photoelectron diffraction carry information on the dynamics of hydrogen migration in real space. Although visualization of this dynamics is more straightforward in the smaller systems, methanol and ethanol, one can still recognize the signature of that motion in propanol and isopropyl alcohol and assign a tentative path to it. A possible pathway for a corresponding experiment requires an angularly resolved detection of photoelectrons in coincidence with molecular fragment ions used to define a molecular frame of reference. Such studies have become, in principle, possible since the first XFELs with sufficiently high repetition rates have emerged. To further support our findings, we provide experimental evidence of H migration in ethanol-OD from ion-ion coincidence measurements performed with synchrotron radiation.

Femtosecond charge and molecular dynamics of I-containing organic molecules induced by intense X-ray free-electron laser pulses.

We studied the electronic and nuclear dynamics of I-containing organic molecules induced by intense hard X-ray pulses at the XFEL facility SACLA in Japan. The interaction with the intense XFEL pulse causes absorption of multiple X-ray photons by the iodine atom, which results in the creation of many electronic vacancies (positive charges) via the sequential electronic relaxation in the iodine, followed by intramolecular charge redistribution. In a previous study we investigated the subsequent fragmentation by Coulomb explosion of the simplest I-substituted hydrocarbon, iodomethane (CH3I). We carried out three-dimensional momentum correlation measurements of the atomic ions created via Coulomb explosion of the molecule and found that a classical Coulomb explosion model including charge evolution (CCE-CE model), which accounts for the concerted dynamics of nuclear motion and charge creation/charge redistribution, reproduces well the observed momentum correlation maps of fragment ions emitted after XFEL irradiation. Then we extended the study to 5-iodouracil (C4H3IN2O2, 5-IU), which is a more complex molecule of biological relevance, and confirmed that, in both CH3I and 5-IU, the charge build-up takes about 10 fs, while the charge is redistributed among atoms within only a few fs. We also adopted a self-consistent charge density-functional based tight-binding (SCC-DFTB) method to treat the fragmentations of highly charged 5-IU ions created by XFEL pulses. Our SCC-DFTB modeling reproduces well the experimental and CCE-CE results. We have also investigated the influence of the nuclear dynamics on the charge redistribution (charge transfer) using nonadiabatic quantum-mechanical molecular dynamics (NAQMD) simulation. The time scale of the charge transfer from the iodine atomic site to the uracil ring induced by nuclear motion turned out to be only ∼5 fs, indicating that, besides the molecular Auger decay in which molecular orbitals delocalized over the iodine site and the uracil ring are involved, the nuclear dynamics also play a role for ultrafast charge redistribution. The present study illustrates that the CCE-CE model as well as the SCC-DFTB method can be used for reconstructing the positions of atoms in motion, in combination with the momentum correlation measurement of the atomic ions created via XFEL-induced Coulomb explosion of molecules.

Ink4a and Arf are crucial factors in the determination of the cell of origin and the therapeutic sensitivity of Myc-induced mouse lymphoid tumor.

The cell of origin of tumors and the factors determining the cell of origin remain unclear. In this study, a mouse model of precursor B acute lymphoblastic leukemia/lymphoma (pre-B ALL/LBL) was established by retroviral transduction of Myc genes (N-Myc or c-Myc) into mouse bone marrow cells. Hematopoietic stem cells (HSCs) exhibited the highest susceptibility to N-Myc-induced pre-B ALL/LBL versus lymphoid progenitors, myeloid progenitors and committed progenitor B cells. N-Myc was able to induce pre-B ALL/LBL directly from progenitor B cells in the absence of Ink4a and Arf. Arf was expressed higher in progenitor B cells than Ink4a. In addition, N-Myc induced pre-B ALL/LBL from Arf(-/-) progenitor B cells suggesting that Arf has a predominant role in determining the cell of origin of pre-B ALL/LBL. Tumor cells derived from Ink4a/Arf(-/-) progenitor B cells exhibited a higher rate of proliferation and were more chemoresistant than those derived from wild-type HSCs. Furthermore, the Mdm2 inhibitor Nutlin-3 restored p53 and induced massive apoptosis in mouse pre-B ALL/LBL cells derived from Ink4a/Arf(-/-) cells and human B-ALL cell lines lacking Ink4a and Arf expression, suggesting that Mdm2 inhibition may be a novel therapeutic approach to the treatment of Ink4a/Arf(-/-) B-ALL/LBL, such as is frequently found in Ph(+) ALL and relapsed ALL. Collectively, these findings indicate that Ink4a and Arf are critical determining factors of the cell of origin and the therapeutic sensitivity of Myc-induced lymphoid tumors.

Influence of prednisolone-induced osteoporosis on bone mass and bone quality of the mandible in rats.

OBJECTIVES: The aim of this study was to clarify the effects of steroid treatment on the mandible. METHODS: We divided 24 male Fisher rats, aged 10 weeks, into 2 groups: a control group (n = 11) and a prednisolone (Pred) treatment group (n = 13). The dose for the Pred group was 40 mg kg(-1) and was administered orally three times per week for 8 weeks. At the end of the experiment, we measured bone mass, bone strength and trabecular structure of the mandible and femur. RESULTS: Pred treatment decreased cortical bone mineral content (BMC), cortical thickness, stress/strain index and tissue volume of the mandible. However, there were no marked changes in trabecular structure parameters. A strong correlation was seen between mandibular and femoral cortical BMC (r = 0.71). CONCLUSIONS: These findings suggest that steroid treatment decreases the cortical BMC, bone area and bone strength of the mandible.

[A prosthetic ring annuloplasty with edge-to-edge repair for a treatment of severe tricuspid regurgitation].

A 59-year-old woman admitted to our hospital with shortness of breath and edema of the lower extremities was diagnosed with right ventricular failure stemming from severe tricuspid valve regurgitation (TR). She had undergone mitral valve replacement (MVR) with a mechanical valve at the age of 42. The approach to the heart was established via a right thoracotomy at the 4th intercostals space. A beating heart cardiopulmonary bypass procedure was performed in which tricuspid valve repair was performed with the edge-to-edge repair and MC3 annuloplasty system. The operative course was uneventful. This technique may be feasible and clinically effective in the treatment of severe TR.

The prevalence of abnormal cervical cytology in a sexually transmitted diseases clinic.

Women seeking sexually transmitted disease (STD) services are at high risk of human papillomavirus infections. Cervical cytological screening with Papanicolau staining (Pap smear) is not consistently offered at public STD clinics. We reviewed Pap smear results on a series of 1000 female STD clinic attendees, abstracted demographics, risk behaviours and STD diagnosis from the clinical record and tested for associations with abnormal Pap smear. In all, 5.7% of the satisfactory specimens (56/993) were abnormal; increasing age category, genital warts, and chlamydia infections were independently associated with an abnormal Pap smear in multivariate analysis. Routine Pap smear screening provided satisfactory results in the STD clinic and, where population-based programmes are not available, should be fully integrated into public STD care, (particularly in settings serving younger women).

[Left ventricular reconstruction on the beating heart with retrograde coronary perfusion for repair of a left ventricular aneurysm associated with aortic regurgitation: report of a case].

A 67-year-old male was undergoing hemodialysis for renal failure. He had carotid stenosis, multiple liver cysts with impaired liver function, and mild aortic regurgitation in addition to a left ventricular aneurysm with reduced left ventricular function. We used intraaortic balloon pumping with a view to maintaining cerebral and hepatic blood flow during extracorporeal circulation. However, this procedure risked increased regurgitation at the aortic valve. Therefore, after aortic cross-clamping, we performed the left ventricular reconstruction while cardiac pulsation was maintained by retrograde coronary perfusion using normothermic oxygenated blood. Coronary artery bypass grafting followed after the cross-clamp was released. The patient's postoperative progress was smooth and he was discharged on 14th postoperative day.

Diffuse neurodeficits in intravascular lymphomatosis with ADAMTS13 inhibitor.

Inhibitory antibody to von Willebrand factor (vWF)-cleaving protease (ADAMTS13) was detected in a patient with intravascular lymphomatosis. The increased serum level of the antibody paralleled an increase in the expression of uncleaved vWF, which might cause microvascular thrombosis and platelet consumption. Malignant cell proliferations with superimposed thrombosis within the lumina throughout the entire vasculature account for diffuse neurodeficits observed in the patient.

Competitive plasma protein adsorption onto fluorinated polyimide surfaces.

A series of fluorinated polyimides cured at different temperatures was prepared, and plasma protein adsorption and platelet adhesion onto the polyimide films were evaluated in vitro using scanning electron microscopy, a micro-bicinchoninic acid protein assay, and a gold-colloid-labeled immunoassay. In particular, we focused on competitive plasma protein adsorption onto polyimide film because elucidation of the competitive adsorption mechanism is needed for a good understanding of in vivo biocompatibility of polyimide. Interestingly, the trend of IgG adsorption onto the polyimide surface measured in human plasma was completely contrary to that observed with IgG dissolved in PBS, and the adsorption increased with an increase in the curing temperature. We propose that the human plasma F(c) region in IgG might selectively adsorb onto polyimide film cured at high temperatures because of competitive plasma protein adsorption to the surface.

Late recurrence of resistant Trichomonas vaginalis vaginitis: relapse or re-infection?

Distinguishing between re-infection and relapse of trichomonas infections is often a difficult task in the clinical setting. The chronicity of trichomonas infections and the ongoing sexual activity are two confounding factors. We present a patient with recurrent resistant vaginal trichomoniasis shortly following a sexual contact with an untreated partner after a complete response to treatment with tinidazole for nine months. We hypothesise that re-infection occurred from the asymptomatic partner who was an untreated chronic carrier of resistant trichomonas in the urogenital tract.

[Recurrent pulmonary embolism with prolonged right heart failure and hypoxia after cerebral bleeding; report of a case].

A 56-year-old woman with right hemiplegia for recent cerebral bleeding suddenly complained of dyspnea and chest pain with hypoxia during rehabilitation. Eight days after this first attack, she suffered prolonged right heart failure and hypoxia due to recurrent pulmonary embolism. Arterial blood gas analysis of room air showed 34.5 mmHg of PaO2 and 29.2 mmHg of PaCO2. Echocardiography showed enlargement of the right atrium and ventricle with pulmonary hypertension. Enhanced chest computed tomography revealed pulmonary emboli from the main pulmonary artery to the periphery. Despite intensive treatment, heart failure and hypoxia did not improve. We conducted pulmonary embolectomy under cardiopulmonary bypass requiring percutaneous cardiopulmonary bypass support for 2 days due to right heart failure. She is currently doing well in the 9 months following surgery.

Biocompatibility of fluorinated polyimide.

Contact between blood and biomaterial triggers a complex series of events including protein adsorption, leukocyte adhesion and activation, and complement activation. In this article, a series of fluorinated polyimides cured at a different temperatures was prepared, and the biocompatibility of the membranes was evaluated using in vitro protein adsorption, neutrophil adhesion, and complement activation experiments under static conditions. We found that protein adsorption, neutrophil adhesion, and complement activation for the polyimides significantly depends on the curing temperature and decreases with an increase in the temperature and that the polyimide has a good biocompatibility compared with poly(styrene) and polydimethylsiloxane. We concluded that the rearrangement of molecules such as CF(3), sulfone, and ketone at the outermost surface occurs because of curing, which induces an increase in the hydrophobicity and that the cured polyimide suppresses protein adsorption, neutrophil adhesion, and complement activation because of its high hydrophobicity and low surface free energy.

Complete response of Sister Mary Joseph Nodule from gastric adenocarcinoma treated with combination chemotherapy of low-dose S-1 and cisplatin.

A case of an unresected, advanced gastric cancer with Sister Mary Joseph nodule was presented. It was treated with new combination chemotherapy of low-dose S-1 and cisplatin producing complete response of periumbilical metastasis. Few treatments are efficacious for umbilical invasion of peritoneal dissemination. A complete response for Sister Mary Joseph nodule from gastric adenocarcinoma has not been ever reported.

Early pregnancy does not reduce the C(50) of propofol for loss of consciousness.

UNLABELLED: Requirements for inhaled anesthetics decrease during pregnancy. There are no published data, however, regarding propofol requirements in these patients. Because propofol is often used for induction of general anesthesia when surgery is necessary in early pregnancy, we investigated whether early pregnancy reduces the requirement of propofol for loss of consciousness using a computer-assisted target-controlled infusion (TCI). Propofol was administered using TCI to provide stable concentrations and to allow equilibration between blood and effect-site (central compartment) concentrations. Randomly selected target concentrations of propofol (1.5-4.5 microg/mL) were administered to both pregnant women (n = 36) who were scheduled for pregnancy termination and nonpregnant women (n = 36) who were scheduled for elective orthopedic or otorhinolaryngologic surgery. The median gestation of the pregnant women was 8 wk (range, 6-12 wk). Venous blood samples for analysis of the serum propofol concentration were taken at 3 min and 8 min after equilibration of the propofol concentration. After a 10-min equilibration period of the predetermined propofol blood concentration, a verbal command to open their eyes was given to the patients twice, accompanied by rubbing of their shoulders. Serum propofol concentrations at which 50% of the patients did not respond to verbal commands (C(50) for loss of consciousness) were determined by logistic regression. There was no significant difference in C(50) +/- SE of propofol for loss of consciousness between the Nonpregnant (2.1 +/- 0.2 microg/mL) and Pregnant (2.0 +/- 0.2 microg/mL) groups. These results indicate that early pregnancy does not decrease the concentration of propofol required for loss of consciousness. IMPLICATIONS: The C(50) of propofol for loss of consciousness in early pregnancy did not differ from that in nonpregnant women, indicating that there is no need to decrease the propofol concentration for loss of consciousness when inducing general anesthesia for termination of pregnancy.

Comparison of plasma alpha glutathione S-transferase concentrations during and after low-flow sevoflurane or isoflurane anaesthesia.

BACKGROUND: We evaluated the effect of low-flow sevoflurane anaesthesia, in which compound A is generated, and isoflurane anaesthesia, in which compound A is not generated (n=13 in each group), on hepatocellular integrity using alpha glutathione S-transferase (GST). Alpha GST is a more sensitive and specific marker of hepatocellular damage than is aminotransferase activity and correlates better with hepatic histology. METHODS: Sevoflurane or isoflurane were delivered without nitrous oxide with a fresh gas flow of 1 l/min. Concentrations of compound A in the circuit were measured hourly, and plasma alpha GST concentrations were measured perioperatively. RESULTS: Mean duration of anaesthesia was 338+/-92 min in the sevoflurane group and 320+/-63 min in the isoflurane group. Mean compound A concentration in the sevoflurane group was 28.6+/-9.0 ppm. There was no significant difference in alpha GST concentrations between the sevoflurane and isoflurane groups during or after anaesthesia. CONCLUSION: These results indicate that low-flow sevoflurane and isoflurane anaesthesia have the same effect on hepatic function, as assessed by plasma alpha GST concentrations.

Effects of topical latanoprost on optic nerve head circulation in rabbits, monkeys, and humans.

PURPOSE: To evaluate the effect of topically administrated latanoprost on optic nerve head (ONH) circulation in Dutch rabbits, cynomolgus monkeys, and normal humans. METHODS: The ONH tissue blood velocity (NB(ONH)) was determined using the laser speckle method. Latanoprost (0.005%, 30 microl) was instilled into one eye, and vehicle into the other eye as a control. In rabbits, NB(ONH) was measured for 90 minutes after a single instillation and before and after a 7-day once-daily instillation regimen. In monkeys, NB(ONH) was measured before and after 1, 4, and 7 days of a once-daily instillation regimen. The effect of intravenous indomethacin on the latanoprost-induced NB(ONH) change was also studied in rabbits and monkeys. In humans, the time-course changes in NB(ONH) were measured for 4.5 hours before and after a 7-day once-daily instillation regimen. Intraocular pressure (IOP) and systemic parameters were simultaneously studied in each experiment. All measurements were performed by investigators masked to the experimental condition. RESULTS: Latanoprost significantly increased NB(ONH) 10% to 19% in treated eyes after a single instillation (P = 0.035) or 7-day instillation regimen (P = 0.035) in rabbits, after a 4-day (P = 0.035) or 7-day (P = 0.035) instillation regimen in monkeys, and after a 7-day (P = 0.013) instillation regimen in humans, whereas there were no significant changes in the vehicle-treated eyes in any of the experiments (P > 0.5). Pretreatment with indomethacin (5 mg/kg) abolished the NB(ONH) increase but not the IOP reduction in latanoprost-treated eyes in rabbits and monkeys. IOP remained unchanged in both eyes in rabbits (P > 0.4), whereas it significantly decreased only in latanoprost-treated eyes in monkeys (P < 0.05) and humans (P < 0.05). CONCLUSIONS: Topical latanoprost significantly increased ONH blood velocity only in treated eyes in rabbits, monkeys, and humans. This effect was independent of the IOP-reducing effect of latanoprost and probably was associated with local penetration of the drug and the production of endogenous prostaglandins.

[A pilot study of low-dose TS-1 and cisplatin combination chemotherapy for advanced gastric cancer].

TS-1, a novel oral formation of 5-fluorouracil, consists of tegafur (5-FU), CDHP and Oxo. Low-dose cisplatin (CDDP) and TS-1 was evaluated in 12 patients with advanced or recurrent gastric cancer. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 80 mg/body of TS-1 was orally administered as many times as possible. The response rate was 41.7%. Median survival time was 13.3 months. In one case, an adverse reaction of grade 3 leucopenia was observed. Thus, thought it is necessary to watch for leucopenia, this chemotherapy could well be effective for patients with advanced or recurrent gastric cancer.

[Gross spreading multiple extramedullary plasmacytomas to the skin in the terminal stage of multiple myeloma].

A 71-year-old woman with an 8-year history of IgG-kappa type multiple myeloma was admitted because of severe lumbago and bone destruction. Her serum IgG level was elevated to 5,565 mg/dl at admission. Despite treatment with doxorubicin, vincristine, dexamethasone, melphalan and interferon-alpha, the response was transient. Nine months later, multiple skin nodules appeared on her chest, abdominal wall and right thigh accompanied by elevation of the serum IgG level. Response to combination chemotherapy with cyclophosphamide, ranimustine, vincristine and prednisolone was also transient. The skin tumors on the bilateral thighs, especially on the left side, acquired chemotherapy resistance and gradually enlarged. Although the serum IgG level was maintained by chemotherapy within the range 1, 790-2,676 mg/dl, the skin tumors on the left thigh had spread very rapidly and appeared "rock-like". The enlarged tumors caused necrosis with erosions and oozing hemorrhage. A skin biopsy from the tumors on the left thigh showed plasmacytoma in which infiltration of large anaplastic plasma cells was observed. The patient died of sepsis 8 months after the skin tumors initially developed. This is a very rare case of multiple myeloma in which multiple large plasmacytomas of the skin developed and grew aggressively at the terminal stage after a long-term indolent course.