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.

High-energy molecular-frame photoelectron angular distributions: a molecular bond-length ruler.

We present a study on molecular-frame photoelectron angular distributions (MFPADs) of small molecules using circularly polarized synchrotron light. We find that the main forward-scattering peaks of the MFPADs are slightly tilted with respect to the molecular axis. This tilt angle is directly connected to the molecular bond length by a simple, universal formula. We apply the derived formula to several examples of MFPADs of C 1s and O 1s photoelectrons of CO, which have been measured experimentally or obtained by means of ab initio modeling. In addition, we discuss the influence of the back-scattering contribution that is superimposed over the analyzed forward-scattering peak in the case of homo-nuclear diatomic molecules such as N2.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

[Histoculture drug response assay guided concurrent chemoradiotherapy for non-small cell lung cancer].

Retrospective analysis was done to evaluate concurrent chemoradiotherapy (CCRT) using chemotherapeutic agents judged to be sensitive by histoculture drug response assay (HDRA) for non-small cell lung cancer (NSCLC). We treated 21 NSCLC patients with CCRT using senstivie agents judged by HDRA from 1999 to 2004. Objective response was evaluated in 20 patients. They were consisted of 1 complete response (CR) case, 18 partial response (PR) cases, and 1 stable disease (SD) case. The response rate was 95%. Ten cancer related deaths were observed during 816 +/- 861 (60-2,780) days follow-up. Median survival time was 604 days. One- and 5-year survival rates were 73.9% and 40.3%, respectively. In conclusion, HDRA may improve efficacy of CCRT for NSCLC.

APRIL polymorphism and systemic lupus erythematosus (SLE) susceptibility.

OBJECTIVE: Two novel non-synonymous polymorphisms of the APRIL gene, codon 67 (rs11552708) and 96 (rs3803800), were recently identified and tested for disease association. The 67G allele was reported to be associated with systemic lupus erythematosus (SLE) in a Japanese population. The aim of the study is to investigate whether the APRIL polymorphism associated with susceptibility to SLE in a Japanese population is associated with the susceptibility to SLE in other ethnic groups. METHODS: Three hundred and forty-eight SLE patients (204 European-American, 103 African-American and 41 Hispanic) and 345 ethnicity-matched controls (201 European-American, 104 African-American and 40 Hispanic) were included from the Lupus Multiplex Registry and Repository (LMRR) and evaluated for genetic association. The APRIL codon 67 and codon 96 were genotyped by a 3-base extension method. Statistical evaluations were performed using both chi-square and logistic regression analysis. RESULTS: Both the single-nucleotide polymorphisms (SNPs) were in Hardy-Weinberg equilibrium in cases and controls within each ethnic group. The APRIL codon 67 was significantly associated with SLE risk under the dominant model adjusted by ethnicity (odds ratio, 95% confidence interval and P-values were 1.45 and 1.02-2.06 and 0.036, respectively). Race-specific analysis also showed a trend for association in African-American and Hispanic SLE subjects. CONCLUSION The APRIL codon G67R polymorphism associated with SLE in a Japanese population may also be associated with SLE in other populations.

Serological diversity demonstrable by a set of monoclonal antibodies to eight serotypes of the mutans streptococci.

A set of monoclonal antibodies were prepared by the conventional cell fusion of myeloma cells (SP2/0-Ag14) with spleen cells from BALB/c mice immunised with whole cells of a strain of mutans streptococci. Their specificities were examined against 35 reference strains of mutans streptococci, 34 reference strains of other oral streptococci and 8 reference strains of other microorganisms often inhabiting the oral cavity. Specificity was examined by enzyme immunoassay using whole cells. A total of 52 strains, consisting of 19 strains isolated in Japan, 19 strains isolated in Italy and 14 strains isolated in England, were characterised by conventional physiological and biochemical tests and then serotyped by the use of 8 monoclonal antibodies with different specificities. They were also confirmed by guanine-plus-cytosine contents of their nucleic acid and DNA-DNA hybridisation test. The results indicated that all monoclonal antibodies are useful for identification of 8 serotypes of the mutans streptococci responsible for dental caries. They also suggest the existence of more serological varieties among mutans species.

Alterations in serum levels of trace elements in tuberculosis and HIV infections.

OBJECTIVE: To evaluate serum concentrations of trace elements in tuberculosis (TB) patients with or with out human immunodeficiency virus (HIV) coinfection before and after anti-TB chemotherapy. SUBJECTS: A total of 155 TB patients, 74 of which were coinfected with HIV, and 31 healthy controls from Gondar, Ethiopia. METHODS: Serum levels of copper, zinc, selenium and iron were determined using an inductively coupled plasma mass spectrometer from all subjects at baseline and from 44 TB patients (22 with HIV coinfection) at the end of an intensive phase of anti-TB chemotherapy. RESULTS: Compared with the control group, the concentrations of iron, zinc and selenium were significantly lower (P<0.05) while that of copper and copper/zinc ratio was significantly higher (P<0.05) in the serum of TB patients. TB patients with HIV coinfection had significantly lower serum zinc and selenium concentrations and significantly higher copper/zinc ratio compared to that in TB patients without HIV coinfection (P<0.05). The serum concentration of zinc had significantly increased at the end of intensive phase of anti-TB chemotherapy in patients without HIV coinfection (P<0.05). An increase in serum selenium level was observed in TB patients with or without HIV coinfection after therapy. On the contrary, serum copper concentration and copper/zinc ratio declined significantly after anti-TB chemotherapy irrespective of HIV serostatus (P<0.05). CONCLUSIONS: The results indicate that TB patients have altered profile of trace elements in their sera. This warrants the need for further investigations so that strategies for trace elements supplementation can be planned in addition to their potential as diagnostic parameters in monitoring responses to anti-TB chemotherapy.

Serum IgE levels of tuberculosis patients in a tropical setup with high prevalence of HIV and intestinal parasitoses.

Tuberculosis remains a major health problem worldwide in the era of HIV/AIDS. Co-infection with intestinal parasites has been suggested to worsen the outcome of infection by polarizing the immune response towards Th2. This study investigated serum IgE levels of 241 tuberculosis patients and compared the IgE profiles in the tuberculosis patients either with or without intestinal helminthic infection and/or HIV infection. The serum levels of IgE in tuberculosis patients before initiation of antimycobacterial chemotherapy were found to be 1722 +/- 1290 IU/ml (Mean +/- SD) in HIV seronegatives and 2366 +/- 1849 IU/ml in HIV seropositives. Further, the IgE level was significantly higher in patients coinfected with intestinal helminthes and HIV compared to those infected with helminthes or without coinfection (P < 0.05). Anti-tuberculosis chemotherapy significantly reduced serum IgE levels in HIV seronegative tuberculosis patients (P < 0.05). These findings might indicate an active role of therapy in shifting the immune response towards Th1 which is crucial for prognosis in tuberculosis patients.

Extremely high levels of C-reactive protein in patients with acute lupus serositis.

Abstract We present the cases of two patients (19- and 40-year-old women) with systemic lupus erythematosus (SLE) who showed marked elevation of C-reactive protein (CRP). In both patients, pleural and/or peritoneal effusions were caused by lupus serositis. Methylprednisolone pulse therapy was effective in improving the serositis and normalizing CRP. Although it is generally considered that the CRP response is relatively weak in lupus patients, these cases suggest that a strong CRP response can occur in a subset of SLE.

Successful treatment of patients with rheumatic disorders and acquired factor VIII inhibitors with cyclophosphamide and prednisolone combination therapy: two case reports.

Acquired haemophilia associated with autoimmune disorders can be fatal and has been reported to be refractory to steroid therapy alone. We report two cases of female patients, aged 24 years and 54 years, with acquired haemophilia caused by factor VIII inhibitors. Underlying diseases were systemic lupus erythematosus in the 24-year-old patient and rheumatoid arthritis in the 54-year-old patient. Both conditions were nearly quiescent when the patients manifested haemorrhagic diathesis. In response to combination therapy with prednisolone and cyclophosphamide, coagulation abnormalities were resolved together with complete elimination of factor VIII inhibitors in both patients. Thus, combination therapy with alkylating agents may be recommended as initial therapy for the management of autoimmune patients with factor VIII inhibitors.

GPS computer navigators to shorten EMS response and transport times.

GPS (global positioning satellite system to determine one's position on earth) units have become inexpensive and compact. The purpose of this study is to assess the effectiveness of a GPS enhanced computer street map navigator to improve the ability of EMS drivers in an urban setting to locate their destination and shorten response times. For part I, residential addresses in the city were randomly selected from a telephone directory. Two driver/navigator teams were assigned to drive to the address adhering to speed limits. One team used a standard street map, whereas the other team used a GPS computer navigator. The travel time and distance of the runs were compared. For part II, the computer GPS navigator was placed on an ambulance to supplement their normal methods of navigation to find the address requesting EMS. After the run was completed, EMS providers were interviewed to determine their opinion of whether the GPS navigator was helpful. For part I the results showed that in the 29 initial test runs, comparing the GPS team versus the standard map team, the mean distances traveled were 8.7 versus 9.0 kilometers (not significant) and the mean travel times were 13.5 versus 14.6 minutes (P=.02), respectively. The GPS team arrived faster in 72% runs. For part II the results showed that most EMS providers surveyed noted that the GPS computer navigator enhanced their ability to find the destination and all EMS providers acknowledged that it would enhance their ability to find a destination in an area in which they were unfamiliar. These results suggest that a portable GPS computer navigator system is helpful and can enhance the ability of prehospital care providers to locate their destination. Because these units are accurate and inexpensive, GPS computer navigators may be a valuable tool in reducing pre-hospital transport times.

Effect of removable orthodontic appliances on oral colonisation by mutans streptococci in children.

Little is known about the effect of removable orthodontic appliances on oral colonisation by mutans streptococci (MS). In the present study, the frequency of isolation and serotype distribution of MS were evaluated in two groups of children, one undergoing therapy with removable appliances and the other not subjected to any kind of orthodontic treatment, respectively. Streptococci isolated from dental plaque samples from both groups of children were identified as mutans streptococci on the basis of their morphological and biochemical properties and were then serotyped in an enzyme immuno-assay using monoclonal antibodies. The number of subjects harbouring MS in their dental plaque was statistically higher in the group of orthodontic children without caries experience (CF) in comparison with CF children of the control group (10/12, 83.3% vs. 15/44, 34%). No clear difference was observed in the distribution of the different MS serotypes between the experimental and control group: S. mutans c,f serotype was the most frequently isolated in both groups of children followed by S. mutans serotype e and S. sobrinus serotype g. Such results suggest that the use of removable appliances may lead to the creation of new retentive areas and surfaces, which favour the local adherence and growth of MS. The data obtained stress the importance of a careful monitoring of patients treated orthodontically for risk of caries development.

Comparison of ovarian follicular activity during treatment with a monthly injectable contraceptive and a low-dose oral contraceptive.

Ovarian follicular development occurs during treatment with combined and progestin-only oral contraceptive (OC) pills and progestin-containing subdermal implants, and can be associated with the development of persistent functional cysts that may require surgical removal. Lunelle is a once-a-month injectable contraceptive containing estradiol cypionate 5 mg and medroxyprogesterone acetate 25 mg. A randomized, comparative study was undertaken to compare the effect on ovarian follicular activity associated with use of Lunelle and a low-dose OC. A total of 30 ovulatory subjects were randomly assigned to receive two cycles of treatment with either an OC containing ethinyl estradiol 20 microg and 0.1 mg levonorgestrel or Lunelle. During the second cycle of treatment, pelvic sonography was performed every 4 days, at which time the maximum follicle diameter was measured. Study end points were the presence of follicles >/=10, 20, and 30 mm. In all, 13 of 15 subjects in the OC group and 14 of 15 in the Lunelle group completed the study. Follicles measuring >/=10 mm were present in 11 of 13 (84.6%) in the OC users and in four of 14 (28.6%) in the Lunelle users (p <0.05). In the OC group, six of 13 subjects (46.1%) developed follicles >/=20 mm, and one of 13 (7.7%) developed follicles >/=30 mm. No subjects in the Lunelle group developed a follicle >/=20 mm in diameter. This study indicates that Lunelle is associated with a significantly lower incidence of ovarian follicular development compared to that of an OC containing 20 microg ethinyl estradiol and 0.1 mg levonorgestrel.

Effects of pH variation and NaCl on in vitro digestibility of cow's milk proteins in commercially available infant formulas.

Allergenicity and antigenicity of food proteins are generally dependent on their heat-stability and resistance to digestive enzymes. Using the methods of SDS-PAGE and immunoblots, we assessed peptic-digestibility of major milk proteins (casein, beta-lactoglobulin and alpha-lactalbumin) in commercially available infant formulas in acidic pH range (pH 1.5 to 4.0), and we also investigated the effect of NaCl on peptic-digestibility of cow's milk proteins at pH 2.0. The profile of peptic-digestion of casein was similar at pH range from 1.5 to 3.5 where the intact protein of casein rapidly disappeared, whereas slow digestibility of the protein was found at pH 4.0. Beta-lactoglobulin and alpha-lactalbumin were digested at pH range from 1.5 to 2.5 and were almost entirely resistant to peptic digestion at over pH 3.0. In the presence of NaCl at pH 2.0, casein showed a good digestibility by pepsin similar to that in the absence of NaCl, in contrast to beta-lactoglobulin and alpha-lactalbumin both having their peptic-digestibility decreased in the presence of 0.2 M NaCl. As the state of the stomach in new born infants shows low amounts of secretary pepsin and out of optimum pH of peptic activity, low digestibility of beta-lactoglobulin and alpha-lactalbumin in cow's milk based infant formulas at over pH 3.0 is supposed to be responsible for their allergenicity.

Characterization of serotype II polysaccharide antigen of group E streptococci using a monoclonal antibody.

A Monoclonal antibody (MAb II-T) specific for serotypes II and V Group E streptococci (GES) was prepared by fusing myeloma cells with spleen cells of mice immunized with whole cells of a serotype II strain. MAb II-T reacted in an enzyme immunoassay (EIA) with whole cells of both serotypes and reacted in gel diffusion test with autoclaved-saline extraction of serotypes II and V. The extract was purified by DEAE-Sephadex A-25, followed by treatment with proteinase K, and further by chromatography with a Sephadex G-200 column. The purified polysaccharide (PS) antigen contained 98.6% carbohydrate and 1.4% protein, but no detectable phosphorus. In hapten inhibition tests using various sugars, D-mannosamine markedly inhibited the precipitin reaction. These results indicated that the antigenic determinant might have a structure similar to D-mannosamine.

Quantitation by enzyme immunoassay of spirosin from Lactobacillus reuteri and Escherichia coli.

Three EIA methods (Direct, Indirect and Sandwich EIA) were studied to quantify spirosin in Lactobacillus reuteri and Escherichia coli cultured under various conditions in an attempt to get some insight into the function of spirosome. Both Direct and Indirect EIA were suited well for the quantitation of L. reuteri spirosin while Direct EIA was appropriate for spirosin of E. coli. Sandwich EIA could not be applied successfully in either case. By use of these methods, the amounts of spirosin produced by E. coli were determined to be 1.4, 36.2 and 46.5 micrograms per mg protein of the cell lysate under aerobic, standing and anaerobic culture conditions, respectively. Since the production profile of spirosin coincided entirely with that of alcohol dehydrogenase, these findings supported the identity of spirosin to alcohol dehydrogenase in E. coli. In the same way, L. reuteri spirosin was quantified to be 73.5 and 65.4 micrograms/ mg protein of the lysate in standing and anaerobic culture, respectively. The production pattern of spirosin did not parallel that of alcohol dehydrogenase among three strains of L. reuteri, suggesting that spirosin might not be identical to alcohol dehydrogenase.

Possible role for a polysaccharide antigen shared between Streptococcus pyogenes and S. mutans in the pathogenesis of poststreptococcal glomerulonephritis.

Streptococcus mutans has been shown to share a polysaccharide (PS) antigen with S. pyogenes strains isolated from patients with acute poststreptococcal glomerulonephritis (PSGN), using a monoclonal antibody f-77 reactive with the PS. To investigate the pathogenetic role of the shared PS in PSNG, experimental nephritis was induced in animals. Rats were immunized thrice with heat-killed cells of S. mutans or S. pyogenes, followed by an intravenous injection of live cells of S. pyogenes. Histologic examination showed that both animal groups had comparable degrees of diffuse proliferative nephritis characterized by immune deposits. The shared PS antigen was detected in glomeruli of all nephritic rats by immunofluorescence using monoclonal antibody f-77. Furthermore, all nephritic rats had an elevated antibody titer to the shared PS antigen. These results suggest that prior sensitization (infections such as dental caries) to S. mutans modulates immune responses to subsequent S. pyogenes infections and induces immune-complex disease (PSGN) through the shared PS antigen.

Immunochemical analysis and localisation of a cell wall antigen of Streptococcus rattus with a specific monoclonal antibody.

A monoclonal antibody specific to a cell wall antigen of Streptococcus rattus (S. rattus) was prepared after cell fusion of mouse myeloma cells to the spleen cells of mice immunized with whole cells of strain FA1. The monoclonal antibody reacted with a crude and purified polysaccharide antigen of S. rattus in precipitin reactions as well as in a solid phase enzyme assay (EIA). It also reacted in the EIA with whole cells of S. rattus strains, but did not react with any other species of the mutans group or of other oral and streptococcal species. Moreover, among many haptenic sugars and their derivatives tested, D-galactosamine and D-glucosamine strongly inhibited the reaction in a competitive enzyme immunoassay using the purified antigen and whole cells, indicating that the type-specific antigenic determinant of the organism has a structure similar to the amino group of the sugar molecules. Furthermore, immunoelectron microscopy revealed that the antigen epitopes formed an irregular fibrous structure over the entire surface of individual cells.