Hydrogeochemistry and arsenic contamination of groundwater in the Ganges Delta Plain, Bangladesh.

Geochemical composition and the level of Arsenic (As) contamination of groundwater in the Ganges Delta Plain, southwestern Bangladesh were elucidated. Hydrogeochemical data of tube well samples suggested that the groundwater is mostly Ca-Mg-HCO(3) type with bicarbonate (HCO(3)(-)) as the dominant anion, though other type waters are also observed. In contrast, the elevated EC, Cl(-) and high content of Na(+) relative to Ca(2+), Mg(2+) and K(+) in six groundwater samples suggest their saline origin. Low concentrations of NO(3)(-) and SO(4)(2-), and high concentrations of dissolved organic carbon (DOC), HCO(3)(-) and PO(4)(3-) indicate the reducing conditions of subsurface aquifer where sediments are deposited with abundant organic matter. The total As concentration in the analyzed samples is very high (0.0431-1.352 mg/L) along with high Fe (2.791-17.058 mg/L) and relatively low Mn (0.134-1.972 mg/L) at different depths. Distinct relationship of As with Fe and Mn, and strong correlation with DOC suggests that the biodegradation of organic matter and reductive dissolution of Fe-oxyhydroxide is considered to be the dominant processes to release As in aquifers. Moreover, negative correlation between As and SO(4)(2-) demonstrates the As may not be directly mobilized from sulfide minerals like arsenopyrite.

A novel backscatter focus diagnostic for the TRIDENT 200 TW laser.

Here we present the first direct focal spot images and analysis of an ultrahigh intensity short-pulse laser focus (>5x10(19) W/cm(2)) on target. Such a focal spot characterization is typically done previous to the shot with a low-power alignment beam using equivalent plane imaging techniques. The resulting intensity of the shot is then inferred from these results. We report on the development of a backscatter focus diagnostic, which enables imaging of the on-target full-power focal spot.

Percutaneous needle biopsy of lung nodules under CT fluoroscopic guidance with use of the "I-I device".

The aim of this study is to evaluate the feasibility and safety of CT fluoroscopic-guided needle biopsy with the use of the "I-I device", which was developed to assist in precisely advancing the needle while avoiding irradiation to the operator's hand. Using the "I-I device" under CT fluoroscopic guidance, 131 percutaneous needle lung biopsies were performed followed by histopathological evaluation. The final diagnosis was confirmed by independent surgical pathological findings or clinical follow-up. The rate of success in obtaining specimens adequate for histopathological analysis was 100% (131/131). For the 104 lesions that we were able to follow up, sensitivity, specificity and accuracy in diagnosing malignancy were 93.8%, 100% and 95.2%, respectively. In 51 lesions for which surgery was performed, the specific cell type was characterized in 98.0% (50/51; malignant, n = 38; benign, n = 12). The specific cell type was precisely diagnosed and confirmed after surgery in 36 malignant lesions and 8 benign lesions. Biopsy-induced complications were pneumothorax in 34.0% (44/131) and haemoptysis in 9.9% (13/131). None of the patients had serious complications. In conclusion, CT fluoroscopic-guided lung biopsy with use of the "I-I device" provides a high degree of diagnostic accuracy, allows specific characterization of lung nodules and can be performed safely.

[Cardiac angiosarcoma with diagnostic difficulty].

We report a case of cardiac angiosarcoma of the right atrium. A 20-year-old woman was admitted to the Kyoto Prefectural University of Medicine with severe chest pain and dyspnea. A cardiac tumor was diagnosed by computed tomography (CT), echocardiography, and cinecardiography. The tumor marker CA125 was 293 U/ml (normal : <35 U/ml). Therefore a CT-guided transthoracic needle biopsy under CT fluoroscopic guidance for definitive diagnosis was performed after obtaining the patient's informed consent. Pathohistologically, the tumor was diagnosed as a cardiac angiosarcoma. The use of an intravenous infusion of contrast material contributed greatly to clear visualization of the tumor margin and cardiac lumen and assisted in easily and correctly advancing the needle toward the tumor. Moreover, tumor marker CA125 was a good indicator of therapeutic efficacy.

Improving the thermal stability of lactate oxidase by directed evolution.

Lactate oxidase is used in biosensors to measure the concentration of lactate in the blood and other body fluids. Increasing the thermostability of lactate oxidase can significantly prolong the lifetime of these biosensors. We have previously obtained a variant of lactate oxidase from Aerococcus viridans with two mutations (E160G/V198I) that is significantly more thermostable than the wild-type enzyme. Here we have attempted to further improve the thermostability of E160G/V198I lactate oxidase using directed evolution. We made a mutant lactate oxidase gene library by applying error-prone PCR and DNA shuffling, and screened for thermostable mutant lactate oxidase using a plate-based assay. After three rounds of screening we obtained a thermostable mutant lactate oxidase, which has six mutations (E160G/V198I/G36S/T103S/A232S/F277Y). The half-life of this lactate oxidase at 70 degrees C was about 2 times that of E160G/V198I and about 36 times that of the wild-type enzyme. The amino acid mutation process suggests that the combined neutral mutations are important in protein evolution.

[Treatment for pinch-off syndrome using a video-assisted thoracoscopic surgery; report of a case].

Use of a central venous catheter (CVC) may be complicated by a catheter fracture, causing an embolism. Pinch-off syndrome is a recognized complication that develops from the use of implantable subclavian venous access devices. Although rare, as it occurs in only 0.8% of the reported cases, the condition can appear as a complication secondary to the insertion of a CVC. We experienced a case of CVC division in a 26-year-old male who had a CVC implanted through the subclavian vein. We failed in our attempt to remove the catheter fragment using video-assisted thoracoscopic surgery (VATS). If no complication occur over a long-term, it is highly possible that the catheter fragment will become adhered to the vessel wall. Therefore, it may not be necessary to remove the fragment in those cases.

Progress in pursuit of therapeutic A2A antagonists: the adenosine A2A receptor selective antagonist KW6002: research and development toward a novel nondopaminergic therapy for Parkinson's disease.

Research and development of the adenosine A2A receptor selective antagonist KW6002 have focused on developing a novel nondopaminergic therapy for Parkinson's disease (PD). Salient pharmacologic features of KW6002 were investigated in several animal models of PD. In rodent and primate models, KW6002 provides symptomatic relief from parkinsonian motor deficits without provoking dyskinesia or exacerbating existing dyskinesias. The major target neurons of the A2A receptor antagonist were identified as GABAergic striatopallidal medium spiny neurons. A possible mechanism of A2A receptor antagonist action in PD has been proposed based on the involvement of striatal and pallidal presynaptic A2A receptors in the "dual" modulation of GABAergic synaptic transmission. Experiments with dopamine D2 receptor knockout mice showed that A2A receptors can function and anti-PD activities of A2A antagonists can occur independent of the dopaminergic system. Clinical studies of KW6002 in patients with advanced PD with L-dopa-related motor complications yielded promising results with regard to motor symptom relief without motor side effects. The development of KW6002 represents the first time that a concept gleaned from A2A biologic research has been applied successfully to "proof of concept" clinical studies. The selective A2A antagonist should provide a novel nondopaminergic approach to PD therapy.

PET neuroreceptor imaging as predictor of severe cerebral ischemic insult.

Measurement of the adenosine A1 receptor (A1-R) with positron emission tomography (PET) using a newly developed positron ligand, [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX). were performed in a cat middle cerebral artery (MCA) occlusion and reperfusion. Eighteen adult cats underwent PET measurement of; 1) cerebral blood flow (CBF). 2) A1-R, 3) central benzodiazepine receptor (BDZ-R) and 4) glucose metabolism with 15O labeled water, MPDX, 11C-flumazenil (FMZ) and 18F-fluorodeoxyglucose (FDG), respectively. The CBF, A1-R, BDZ-R and FDG uptake were serially measured after 60 min occlusion of MCA in this order. MPDX binding and FMZ binding, but not CBF and FDG uptake, were significantly reduced in the groups with severer ischemic insult than in the groups with no or milder insults. Of the two receptor ligands, the reduction rate of the MPDX binding to A1-Rs was larger in a group that caused fatal ischemic insult. The newly developed PET in vivo imaging technique using MPDX was suitable in evaluating the function of adenosine and A1-Rs in relation to cerebral ischemia.

Occurrence of conjunctivitis, sinusitis and upper region tracheitis in Japanese quail (Coturnix coturnix japonica), possibly caused by Mycoplasma gallisepticum accompanied by Cryptosporidium sp. infection.

On a farm raising approximately 75,000 Japanese quail (Coturnix coturnix japonica) for egg production, the diseased quail showed clinical signs of swelling of the head, nasal discharge, increased lacrimation, and decreased egg production. The flock experienced a mortality rate of 5.7% per day. Macroscopic observation revealed large, gelatinous masses of caseous exudate in the sinuses, egg peritonitis, and airsacculitis. Microscopically, non-purulent or purulent inflammation accompanied by lymphoid hyperplastic tissue with germinal centers was observed in the oculofacial respiratory mucosa. The developing stage of the lesions was abscess formation. In the investigation of pathogens, antigens to Mycoplasma gallisepticum and Pasteurella multocida serotype D were immunolabeled on and demonstrated in the mucosal membranes. In addition, P. multocida, Escherichia coli, Staphylococcus sp., and Streptococcus sp. were isolated from the infraorbital sinuses, and Mycoplasma isolated from a diseased bird was confirmed as M. gallisepticum by polymerase chain reaction (PCR). Furthermore, Cryptosporidium sp. was frequently found in the brush border. Serological, bacteriological and PCR examinations, some with negative outcomes, were carried out concerning microbes that are known to cause swollen heads in birds (Haemophilus paragallinarum, Newcastle disease virus and turkey rhinotracheitis virus). The average concentration of ammonia fumes in the cages was 30.6 parts/106, which suggests that the high levels of ammonia fumes promoted infection and multiplication of M. gallisepticum in the quail, and that the clinical disease then worsened due to mixed infection with M. gallisepticum and Cryptosporidium sp. or other bacteria.

Evaluation of [4-O-methyl-(11)C]KW-6002 as a potential PET ligand for mapping central adenosine A(2A) receptors in rats.

KW-6002, a xanthine-based adenosine A(2A) antagonist, was labelled with the positron emitter carbon-11 by O-methylation of its precursor, KF23325, using [(11)C]iodomethane and was evaluated in rats as a putative in vivo radioligand for positron emission tomography (PET). Following intravenous injection of [(11)C]KW-6002, radioactivity was measured in blood, plasma, peripheral tissues, and in discrete brain tissues over a 2-h time period commensurate with PET scanning. In brain, [(11)C]KW-6002 showed highest retention in striata, with evidence of saturable binding, and lowest retention in frontal cortex (a tissue low in adenosine A(2A) receptors). PET scanning with [(11)C]KW-6002 demonstrated a specific signal in the striata which could be described using compartmental modelling. Specific binding was, however, also detected in extrastriatal regions, including brain areas reported to have low adenosine A(2A) receptor density. Blocking studies with the A(1) selective antagonist KF15372 and the non xanthine-type A(2A) antagonist ZM 241385 failed to elucidate the nature of this binding. Thus, although [(11)C]KW-6002 shows some potential for development as a PET ligand for quantifying striatal adenosine A(2A) receptor function, its in vivo selectivity requires further investigation.

Effects of gastrointestinal stimulant and suppressant pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic.

The effects of pretreatment with the gastrointestinal stimulant domperidone and the suppressant scopolamine butylbromide on the absorption of AS-924, a novel prodrug-type cephem antibiotic, were investigated in six healthy adult male volunteers by a cross-over method. The T(max) of ceftizoxime (CTIZ), the active moiety of AS-924, was slightly prolonged by scopolamine butylbromide (T(max)=1.8 vs. 1.5 h for the group without pretreatment). However, there were no significant differences in pharmacokinetic parameters including T(max), cumulative urinary excretion rates of CTIZ and cumulative urinary excretion rates of pivaloylcarnitine for 12 h after the dosing between the pretreated and control groups. Domperidone did not affect the absorption of AS-924.

Transactivation via RAR/RXR-Sp1 interaction: characterization of binding between Sp1 and GC box motif.

Modulation of Sp1 activity by nuclear receptors is a novel mechanism by which fat-soluble hormones regulate gene expression. We previously established that upon autoinduction of RARs by RA, RARs/RXRs physically interact with Sp1, potentiate Sp1 binding to the GC box motifs, and thus enhance transactivation of the urokinase promoter, which lacks a canonical RAR-responsive element/RXR-responsive element. Here, we examined whether a similar mechanism might participate in transcriptional regulation of other key RA-inducible genes in endothelial cells and characterized binding between Sp1 and GC box motifs. Northern blot analyses showed that in addition to urokinase, after induction of RARs, RA up-regulates GC-rich region-dependent mRNA expression of transglutaminase, TGF beta 1, and types I and II TGF beta receptors. RA failed to alter the expression of Sp1 at both mRNA and protein levels. Reporter and gel shift assays and Western blot analyses suggested that either RA-treatment or RAR/RXR-overexpression enhances transactivation of these genes through a GC-rich region and strengthens the affinity of Sp1 to GC box motifs, accompanying a potential conformational change of Sp1 as reflected in its increased immunogenicity. Detailed analyses of the GC box motifs within the urokinase and other promoters indicate that interaction between RAR/RXR and Sp1 does not occur in the presence of nonfunctional GC box motifs containing five tandem purine or pyrimidine bases at the 3'-flanking region of hexanucleotide core sequence. These findings provide insight into the molecular mechanisms underlying RARE/RXRE-independent transactivation of RA-inducible gene promoters.

Peripheral ameloblastoma with potentially malignant features: report of a case with special regard to its keratin profile.

A peripheral ameloblastoma with atypical features occurring on the left maxillary alveolar ridge of 40-year-old man is described, along with an immunohistochemical profile of its cytokeratin (CK). The lesion apparently originated from the surface gingival epithelium. The tumor nests or strands were highly cellular with a variable degree of squamous differentiation and microcyst formation. Occasional mitotic figures and dystrophic calcification, both of which are not seen in conventional ameloblastomas, were also observed. The tumor infiltrated deep into the alveolar mucosa, including the periodontal ligament, and showed histological and topographical evidence of atypism, resulting in resorption of the underlying alveolar bone. On the CK immunohistochemistry, CK19 was demonstrated in all the types of neoplastic epithelia, including microcyst-forming cells, densely packed round or spindle cells within the tumor nests, cells with squamous metaplasia, and peripheral tall columnar cells. The CK immunohistochemical findings suggest the lesion's cell of odontogenic origin; they may reflect an immature phenotypic expression of cell differentiation in the odontogenic epithelia during the tumor growth in the gingival mucosa.

Comparison of in-vitro activities of SCH27899 and other antibiotics against Mycoplasma pneumoniae.

We examined the in-vitro activities of various antibiotics against 25 strains of Mycoplasma pneumoniae (22 clinical isolates and 3 standard strains). In the 22 clinical isolates, the 90% minimum inhibitory concentrations (MIC 90) of SCH27899, ofloxacin, levofloxacin, ciprofloxacin, erythromycin, clarithromycin, roxithromycin, clindamycin, and minocycline were 16, 2, 2, 4, 0.0039, 0.0039, 0.016, 2, and 4 microg/ml, respectively. The minimum bactericidal concentrations (MBC 90) of SCH27899, ofloxacin, levofloxacin, ciprofloxacin, erythromycin, clarithromycin, roxithromycin, clindamycin, and minocycline were 64, 4, 2, 8, 0.0625, 0.0625, 0.125, 8, and 64 microg/ml, respectively. The low sensitivity of M. pneumoniae to SCH27899 may be a result of the impermeability of the bacteria to this molecule. The results of this study suggest that SCH27899 would not be a suitable antimicrobial agent to use in the alternative chemotherapy of M. pneumoniae infection.

Excluded volume in protein side-chain packing.

The excluded volume occupied by protein side-chains and the requirement of high packing density in the protein interior should severely limit the number of side-chain conformations compatible with a given native backbone. To examine the relationship between side-chain geometry and side-chain packing, we use an all-atom Monte Carlo simulation to sample the large space of side-chain conformations. We study three models of excluded volume and use umbrella sampling to effectively explore the entire space. We find that while excluded volume constraints reduce the size of conformational space by many orders of magnitude, the number of allowed conformations is still large. An average repacked conformation has 20 % of its chi angles in a non-native state, a marked reduction from the expected 67 % in the absence of excluded volume. Interestingly, well-packed conformations with up to 50 % non-native chi angles exist. The repacked conformations have native packing density as measured by a standard Voronoi procedure. Entropy is distributed non-uniformly over positions, and we partially explain the observed distribution using rotamer probabilities derived from the Protein Data Bank database. In several cases, native rotamers that occur infrequently in the database are seen with high probability in our simulation, indicating that sequence-specific excluded volume interactions can stabilize rotamers that are rare for a given backbone. In spite of our finding that 65 % of the native rotamers and 85 % of chi(1) angles can be predicted correctly on the basis of excluded volume only, 95 % of positions can accommodate more than one rotamer in simulation. We estimate that, in order to quench the side-chain entropy observed in the presence of excluded volume interactions, other interactions (hydrophobic, polar, electrostatic) must provide an additional stabilization of at least 0.6 kT per residue in order to single out the native state.

Characterization of MRSA transmission in an emergency medical center by sequence analysis of the 3'-end region of the coagulase gene.

The distribution of methicillin-resistant Staphylococcus aureus (MRSA) isolates at the St. Marianna University affiliated emergency medical center (EMC) was studied by sequence analysis of the 3'-end region of the coagulase gene. We collected a total of 42 MRSA isolates, consisting of 20 strains from the hospital environment, 13 strains from the nostrils or fingers of medical staff, and 9 strains from inpatients in the EMC. We compared our results with those from 27 stock strains of known coagulase serotype and 2 strains reported in the literature. All 69 strains tested have four to six tandem repeats in the 3'-end region of the coagulase gene. Among the 42 MRSA isolates collected, the base sequence of the 3'-end region of the coagulase gene was identical in 28 of them (67%). The number of isolates originating from the hospital environment, medical staff, and patients, respectively, that were identical to this representative strain were 18 (90%), 6 (46%), and 4 (44%). Phylogenetic analysis using the DNA sequences of the tandem repeat region demonstrated that almost all strains from the patients formed a concordant cluster with the representative strain from the hospital ward. We also assessed the value of sequence analysis of the 3'-end region of the coagulase gene as an epidemiological marker. Our results indicate that sequence analysis of the 3'-end region of the coagulase gene of MRSA may be a potent epidemiologic typing system.

[Middle fossa arachnoid cyst presenting an interesting clinical course: a case report].

The mechanism of the disappearance of arachnoid cysts is not fully understood. We report a case of arachnoid cyst which disappeared after head injury. A 28-year-old male was found to have an arachnoid cyst in the left middle fossa following head injury. We followed him up, because he had no symptoms. Two weeks later, he suffered from severe headache. CT image showed a dilatation of the subdural space, and his symptom deteriorated. We performed subdural-perifocal shunt, but one month after, he developed a subdural hematoma. The subdural hematoma was irrigated through a burr hole. His symptom disappeared post operatively. Two months later, CT image showed the disappearance of subdural hematoma and the arachnoid cyst. This case suggested one of the mechanisms involved in the disappearance of arachnoid cyst after head injury.