Effects of surface charge and palladium on hepatic and kidney injury induced by polystyrene nanoparticles co-administered to mice with paraquat and cisplatin.

Recently, with the advancement of nanotechnology, various nanoparticles have been developed and used in fields such as electronics, cosmetics, and foods. However, the toxicity of nanoparticles has yet to be fully investigated. In particular, the interactions between nanoparticles and therapeutic drugs require further study. We previously reported that unmodified polystyrene nanoparticles with a particle size of 50 nm (NPP50) co-administered with paraquat (PQ) or cisplatin (CDDP) induce hepatic and kidney injury. Here, we determined if NPP50 modified with the amino group (NPP50-NH2), carboxyl group (NPP50-COOH), or palladium (Pd-NPP50) caused liver or kidney injury when co-administered with PQ or CDDP. The results showed that when NPP50-NH2, NPP50-COOH, or Pd-NPP50 was administered alone via the mouse tail vein, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) did not increase or cause injury. When NPP50, NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with PQ, serum levels of ALT and AST increased in the NPP50 group but did not increase in the NPP50-NH2, NPP50-COOH, or Pd-NPP50 groups. When NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with CDDP, ALT, AST, and BUN values did not increase. These data suggest that injury due to the interaction of polystyrene nanoparticles with CDDP or PQ can be suppressed by changes in the surface charge of nanoparticles or by Pd modification.

Prevalent emm types and superantigen gene patterns of group A Streptococcus in Thailand.

Group A Streptococcus (GAS) are globally distributed bacterial pathogens. We examined the emm genotypes, which are important indicators of virulence, of 349 clinical GAS isolates collected using two surveillance systems, i.e. Invasive Bacterial Infection Surveillance (IBIS) from 2010 to 2011 (234 isolates) and routine surveillance of clinically isolated bacteria from various hospitals during 1996-2011 (115 isolates) in Thailand. The major emm genotypes in IBIS samples were emm44 (12·0%), emm104 (6·8%), emm22 (5·6%), and emm81 (5·6%), whereas only one isolate (0·4%) had the emm1 genotype, which is significantly more common in invasive cases in the Western world. In samples collected during routine surveillance, emm238 (10·4%), emm44 (8·7%), and emm165 (7·0%) were dominant. The major superantigen gene profiles were similar between the groups, and 30·1% of isolates did not possess the phage-encoded superantigens (speA, speC, speH, speI, speK, speL, speM, ssa). Although most isolates exhibited limited gene profiles, emm44 isolates had highly variable gene profiles (15 patterns). We conclude that emm44 is the predominant GAS genotype in Thailand, and isolates varied in superantigen gene profiles.

Toxicity of 50-nm polystyrene particles co-administered to mice with acetaminophen, 5-aminosalicylic acid or tetracycline.

We investigated whether nano-sized polystyrene particles affect drug-induced toxicity. The particles, which are widely used industrially, had diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals tested were acetaminophen (APAP), 5-aminosalicylic acid (5-ASA), tetracycline (TC), and sodium valproate (VPA). All treatments in the absence of the nanoparticles were non-lethal and did not result in severe toxicity. However, when mice were injected with APAP, 5-ASA or TC together with polystyrene particles, synergistic, enhanced toxicity was observed in mice injected with NPP50. These synergic effects were not observed in mice co-injected with NPP200 or NPP1000. On the other hand, co-administration of VPA and NPP50, NPP200 or NPP1000 did not elevate toxicity. The results show that NPP50 differs in hepatotoxicity depending on the drug co-administered. These findings suggest that further evaluation of the interactions between polystyrene nanoparticles and drugs is a critical prerequisite to the pharmaceutical application of nanotechnology.

Herschel detects a massive dust reservoir in supernova 1987A.

We report far-infrared and submillimeter observations of supernova 1987A, the star whose explosion was observed on 23 February 1987 in the Large Magellanic Cloud, a galaxy located 160,000 light years away. The observations reveal the presence of a population of cold dust grains radiating with a temperature of about 17 to 23 kelvin at a rate of about 220 times the luminosity of the Sun. The intensity and spectral energy distribution of the emission suggest a dust mass of about 0.4 to 0.7 times the mass of the Sun. The radiation must originate from the supernova ejecta and requires the efficient precipitation of all refractory material into dust. Our observations imply that supernovae can produce the large dust masses detected in young galaxies at very high redshifts.

Differential diagnosis of cerebral infarction using an algorithm combining atrial fibrillation and D-dimer level.

We created an algorithm for diagnosing subtypes of cerebral infarction (CI) during the acute stage by combining atrial fibrillation (AF) and D-dimer levels. One-hundred and eight patients hospitalized for acute CI were retrospectively analyzed. CI was classified into cardioembolic, atherothrombotic, lacunar infarction or others. Patients were classified in AF group if they had AF on admission or a prior history of AF. This group was diagnosed to suffer cardioembolic infarction. In non-AF group, cardioembolic infarction was diagnosed when D-dimer level exceeded the cutoff point determined using a receiver operating curve. Then, usefulness of the algorithm was validated prospectively in 259 consecutive patients with acute CI. For the retrospective group, cardioembolic infarction was found in 82% of the AF group. In non-AF group, cardioembolic infarction was found in only 2%, when D-dimer level was <1.6 microg/ml. However, 41% of non-AF group with atherothrombotic infarction had elevated D-dimer level (> or =1.6 microg/ml). Results for the validation group were similar to those for the retrospective group (sensitivity, 89%; specificity, 66%; positive predictive value, 50%; and negative predictive value, 94%). D-dimer level in combination with AF can be useful for distinguishing CI subtypes during the acute stage.

Identification of human-induced changes in atmospheric moisture content.

Data from the satellite-based Special Sensor Microwave Imager (SSM/I) show that the total atmospheric moisture content over oceans has increased by 0.41 kg/m(2) per decade since 1988. Results from current climate models indicate that water vapor increases of this magnitude cannot be explained by climate noise alone. In a formal detection and attribution analysis using the pooled results from 22 different climate models, the simulated "fingerprint" pattern of anthropogenically caused changes in water vapor is identifiable with high statistical confidence in the SSM/I data. Experiments in which forcing factors are varied individually suggest that this fingerprint "match" is primarily due to human-caused increases in greenhouse gases and not to solar forcing or recovery from the eruption of Mount Pinatubo. Our findings provide preliminary evidence of an emerging anthropogenic signal in the moisture content of earth's atmosphere.

[Lymphedema after radical prostatectomy: a case report].

We report a case of intractable lymphedema of the left leg following radical prostatectomy. The 69-year-old male patient complained of difficulty walking, caused by severe lymphedema. Intraarterial autologous lymphocyte transfusion therapy was performed because of failure of conventional conservative therapy, and the leg edema resolved almost completely. However, the treatment did not improve the penoscrotal edema necessitating excision of the edema and skin graft in a separate procedure. The post-operative course was excellent and the patient's performance status improved to 1 from 3.

Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C.

PURPOSE: To assess the functional characteristics of human organic anion transporter B (OATP-B) in comparison with those of the known, liver-specific OATP-C. METHODS: OATP-B or -C was expressed in HEK293 cells or Xenopus oocytes, and uptakes of estradiol-17beta-glucuronide and estrone-3-sulfate were measured using radiolabeled compounds. RESULTS: OATP-C transported both estrone-3-sulfate and estradiol-17beta-glucuronide, whereas OATP-B transported only the former. OATP-C-mediated uptake of estrone-3-sulfate exhibited biphasic saturation kinetics, whereas transports of estradiol-17beta-glucuronide by OATP-C and estrone-3-sulfate by OATP-B followed single-saturation kinetics. Inhibition kinetics showed that only the high-affinity site for estrone-3-sulfate on OATP-C was shared with glucuronide conjugates. Uptake of [3H]estrone-3-sulfate by OATP-B was inhibited by sulfate conjugates but not by glucuronide conjugates, whereas its uptake by OATP-C was inhibited by both types of conjugates. CONCLUSIONS: OATP-B accepted sulfate conjugates of steroids but not glucuronide conjugates, whereas OATP-C transported both types of steroid conjugates. Transport of estrone-3-sulfate by OATP-B and -C followed single- and biphasic-saturation kinetics, respectively, and the high-affinity site on OATP-C was the same as that for estradiol-17beta-glucuronide. Other OATPs, OATP-A and OATP-8, reportedly exhibit different preferences for steroid conjugates, and the specific recognition of sulfate conjugates seems to be unique to OATP-B.

[Prognostic factors of renal pelvic and ureteral cancer: a multivariate analysis].

We clinicopathologically reviewed 54 cases (40 males and 14 females) of renal pelvic and ureteral cancer examined between 1983 and 1998, in order to determine the impact of prognostic factors. Follow-up ranged from 2 to 173 months (mean, 45.6 months). The age of the patients ranged from 39 to 88 years (mean, 68.9 years). The 1, 3 and 5-year cause-specific survival rates (Kaplan-Meier's method) for all of the patients were 74.6%, 58.4% and 54.5%, respectively. According to univariate analysis, a high grade and high stage of tumor, the presence of lymphatic invasion and positive regional lymph nodes indicated a significantly poor prognosis. On the other hand, multivariate analysis using Cox proportional hazards regression revealed the presence of lymphatic invasion as the most significant predictor of survival. Therefore, patients with lymphatic invasion have a poor prognosis, and the development of effective adjuvant therapy is needed to improve the outcome in these patients.

[Bowel perforation after extracorporeal shock wave lithotripsy: a case report].

A case of intestinal perforation caused by ESWL for left ureteral calculus is reported. A 69-year-old male underwent the graft replacement for bilateral iliac aneurysm in March, 1996. In February, 1999, there appeared left flank pain, and a diagnosis of left ureterolithiasis was made by radiological examination. On March 29 he was admitted to our department for ESWL. On March 30, ESWL for calculus in the pelvic region was performed with the patient in the prone position. The patient complained of the left lower abdominal pain immediately after ESWL, but no muscular defense was observed. Since the pain was not relieved, CT was performed on March 31, but no evident abnormal finding was found. Thereafter the pain continued and on April 2 muscular defense was also noted. On CT performed a second time, free air and evidence of ileus were found, so emergency operation was performed. Two perforations about 2 mm in size were found in the jejunum 130 cm from the Treitz' ligament, which led to diagnosis of intestinal perforation due to ESWL. The patient followed a satisfactory postoperative course and was discharged on April 23. There has been only one reported case of intestinal perforation due to ESWL. It is a very rare complication. However, this complication should be taken into consideration where the patient has the history of abdominal surgery and where ESWL was performed with the patient in the prone position.

Respiratory modulation of muscle sympathetic nerve activity in patients with chronic heart failure.

BACKGROUND: Sympathoexcitation and respiratory instability are closely related to worsening of chronic heart failure. To elucidate the dynamic nature of respiratory modulation of sympathetic activity in patients with heart failure, we studied within-breath variation of muscle sympathetic nerve activity (MSNA) under various ventilatory volumes. METHODS AND RESULTS: MSNA, blood pressure, and respiratory flow were recorded in 23 patients with left ventricular ejection fraction

Methionine oxidation and its effect on the stability of a reconstituted subunit of the light-harvesting complex from Rhodospirillum rubrum.

An additional component in the purified core light-harvesting complex (LH1) from wild-type purple photosynthetic bacterium Rhodospirillum rubrum has been identified as an oxidized species of alpha-polypeptide by MALDI-TOF mass spectrometry. This component appears as a slightly earlier-eluting peak in the RP-HPLC chromatogram compared with the authentic alpha-polypeptide. The oxidation site has been determined to be the N-terminal methionine residue by high-resolution NMR spectroscopy, where the methionine is oxidized to methionine sulfoxide in a diastereoisomeric form. Interconversion between the oxidized and authentic alpha-polypeptides has been confirmed by selective oxidation and reduction. The oxidative modification of methionine is shown to have discernible effects on the ability to form B820 subunit with beta-polypeptide and bacteriochlorophyll a, and on the stability of the reconstituted B820 subunit. Both the ability and the stability for the samples using the oxidized alpha-polypeptide are moderately reduced, indicating that the oxidation-induced conformational change in the N-terminal domain of alpha-polypeptide may affect the pigment-binding environment through a long-range interaction. The MALDI-TOF mass results also reveal that the N-terminus of alpha-polypeptide is formylated and no phosphorylation has occurred in this polypeptide.

Instability of anticoagulation intensity contributes to occurrence of ischemic stroke in patients with non-rheumatic atrial fibrillation.

The efficacy of anticoagulation in reducing the risk of cardiogenic embolism has been demonstrated in patients with atrial fibrillation (AF), but there are few prospective studies assessing the influence of anticoagulation stability on ischemic stroke in such patients. Accordingly, the present study investigated prospectively whether an instability of the anticoagulation intensity would affect the efficacy of the therapy in a total of 156 patients with non-rheumatic AF (NRAF) who received oral anticoagulation with warfarin. During a 2-year follow-up period, the annual event rate of ischemic stroke was 2.1%. In patients without a history of prior stroke, no ischemic stroke occurred at a higher international normalized ratio (INR> or =2.0). In contrast, patients who had had a prior stroke had no INR-dependent reduction of incidence. The coefficient of variation (CV) of measured INRs was significantly greater in patients with ischemic stroke than in those without. By multivariate analysis, only greater CV (> or =0.3) of INRs was an independent risk for ischemic stroke, although New York Heart Association functional class > or =II and treatment with diuretics were of borderline significance by univariate analysis. The present results suggest that stability of anticoagulation intensity is important to protect thromboembolic events in patients with NRAF.

Structure of the H subunit of the photosynthetic reaction center from the thermophilic purple sulfur bacterium, Thermochromatium tepidum Implications for the specific binding of the lipid molecule to the membrane protein complex.

The photosynthetic reaction center (RC) is a transmembrane protein complex that catalyzes light-driven electron transport across the photosynthetic membrane. The complete amino-acid sequence of the H subunit of the RC from a thermophilic purple sulfur bacterium, Thermochromatium tepidum, has been determined for the first time among purple sulfur bacteria. The H subunit consists of 259 amino acids and has a molecular mass of 28 187. The deduced amino-acid sequences of this H subunit showed a significant (40%) degree of identity with those from mesophilic purple nonsulfur bacteria. The determined primary structure of the H subunit was compared with the structures of mesophilic B. viridis and R. sphaeroides based on the three-dimensional structure of the H subunit from T. tepidum, which has been recently determined by X-ray crystallography. One lipid molecule was found in the crystal structure of the T. tepidum RC, and the head group of the lipid appears to be stabilized by the electrostatic interactions with the conserved basic residues in the H subunit. The above comparison has suggested the existence of a lipid-binding site on the molecular surface at which a lipid molecule can interact with the RC in a specific manner.

Modulation of ventricular repolarization and R-R interval is altered in patients with globally impaired cardiac 123I-MIBG uptake.

BACKGROUND: Cardiac (123)I-metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. METHODS: Twenty-nine patients with prior myocardial infarction were divided into two groups by a heart-to-mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M >or= 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holter recording and a standard 12-lead electrocardiography were used for evaluation of HRV, QT-RR relation, and QT dispersion. RESULTS: Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT-RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 +/- 25 msec) than in group II (43 +/- 19 msec) and group III (28 +/- 9 msec). CONCLUSION: These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.

The dimerization of folded monomers of ribulose 1,5-bisphosphate carboxylase/oxygenase.

Spontaneous refolding and reconstitution processes of dimeric ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum have been investigated using size-exclusion high performance liquid chromatography (HPLC), spectroscopic, and activity measurements. When the unfolded Rubisco in guanidine hydrochloride is diluted at 4 degrees C, a folding intermediate (Rubisco-I) is rapidly formed, which remains in an unstable monomeric state and gradually develops into folded monomer (Rubisco-M) at 4 degrees C but undergoes irreversible aggregation at 25 degrees C. Refolding of Rubisco-I to Rubisco-M is a very slow process, taking about 20 h for 70% conversion at 4 degrees C. Rubisco-M is stable at 4 degrees C and is capable of forming an active dimer spontaneously when incubated at a temperature higher than 10 degrees C. The dynamic dimerization process has been measured in a temperature range of 4-35 degrees C by HPLC, and the results demonstrate that the dimerization is strongly facilitated by the temperature. It is found that dithiothreitol is essential for the spontaneous reconstitution of Rubisco.

Application of chemical selective cleavage methods to analyze post-translational modification in proteins.

Three chemical specific cleavage reactions, one for the carboxyl side of aspartyl peptide bonds, one for the carboxyl side of asparaginyl peptide bonds and another for the amino side of seryl/threonyl peptide bonds have been recently established. Additionally, these reactions simultaneously react on several post-translationally modified groups in peptides or proteins. The modified groups cover the external modifications N-formyl, N-acetyl, N-pyroglutamyi residues and C-terminal-alpha amide, as well as the internal modifications such as O-acetyl serine, phosphorylated serine/tyrosine, sulfonylated tyrosine, glycosylated serine/threonine and glycosylated asparagine. These three cleavage reactions relate to key amino acids for modifications, deamidation for asparagine, phosphorylation and acetylation for serine, and glycosylation for asparagine, serine and threonine. The chemical reactions on these modifications change the peptide mapping pattern, and information from these reactions may contribute characterization and location of post-translational modified groups in the protein.

Crystal structures of photosynthetic reaction center and high-potential iron-sulfur protein from Thermochromatium tepidum: thermostability and electron transfer.

The reaction center (RC) of photosynthetic bacteria is a membrane protein complex that promotes a light-induced charge separation during the primary process of photosynthesis. In the photosynthetic electron transfer chain, the soluble electron carrier proteins transport electrons to the RC and reduce the photo-oxidized special-pair of bacteriochlorophyll. The high-potential iron-sulfur protein (HiPIP) is known to serve as an electron donor to the RC in some species, where the c-type cytochrome subunit, the peripheral subunit of the RC, directly accepts electrons from the HiPIP. Here we report the crystal structures of the RC and the HiPIP from Thermochromatium (Tch.) tepidum, at 2.2-A and 1.5-A resolution, respectively. Tch. tepidum can grow at the highest temperature of all known purple bacteria, and the Tch. tepidum RC shows some degree of stability to high temperature. Comparison with the RCs of mesophiles, such as Blastochloris viridis, has shown that the Tch. tepidum RC possesses more Arg residues at the membrane surface, which might contribute to the stability of this membrane protein. The RC and the HiPIP both possess hydrophobic patches on their respective surfaces, and the HiPIP is expected to interact with the cytochrome subunit by hydrophobic interactions near the heme-1, the most distal heme to the special-pair.

Different laterality between the thumb and index finger in human SII activities.

We compared the ipsilateral and contralateral evoked activities in the secondary somatosensory cortex (SII) of four human subjects. Magnetic cortical fields, evoked by electrical stimulation of the distal interphalangeal joint of either the thumb or the index finger, were recorded by an 80-channel whole head type magnetoencephalography system (MEG). We calculated the ratio of the equivalent current dipole (ECD) moment of the ipsilateral area to that of the contralateral area. The mean ratio for the thumb across the subjects was 0.43 +/- 0.13, while that for the index finger was 0.77 +/- 0.20 (mean +/- s.d). The ratio for the index finger was significantly higher than that for the thumb (p = 0.039, two tailed t-test). These results show that the cortical index finger area is activated more bilaterally than the thumb area.