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Setting The number of patients with non-tuberculous mycobacterial lung disease (NTM-LD) worldwide has been increasing. Mycobacterium avium complex lung disease (MAC-LD) accounts for 90% of NTM-LD. MAC-LD necessitates long-term treatment, but adverse reactions with long-term administration of drugs are poorly understood. Objective To evaluate adverse reactions with long-term administration of drugs for MAC-LD. Design We conducted a retrospective single-centre medical chart review of 364 patients administered two or more drugs between July 2010 and June 2015. Results The prevalence and median time to onset of adverse reactions were as follows: hepatotoxicity 19.5%, 55 days; leucocytopaenia 20.0%, 41 days; thrombocytopaenia 28.6%, 61.5 days; cutaneous reactions 9.3%, 30 days; ocular toxicity 7.7%, 278 days; and increase in serum creatinine 12.4%, 430.5 days. Multivariate analysis showed that rifampicin use was independently associated with thrombocytopaenia, and ethambutol use was independently associated with increases in serum creatinine. Conclusion The main adverse reactions appeared within 3 months after start of treatment. Most patients were able to continue treatment with liver-supporting therapy, antihistamine agents or desensitisation therapy; however, ocular toxicity must be monitored for up to 1 year after start of treatment.

The number of patients with non-tuberculous mycobacterial lung disease (NTM-LD) worldwide has been increasing.To evaluate adverse reactions with long-term administration of drugs for MAC-LD.We conducted a retrospective single-centre medical chart review of 364 patients administered two or more drugs between July 2010 and June 2015.The prevalence and median time to onset of adverse reactions were as follows: hepatotoxicity 19.5%, 55 days; leucocytopaenia 20.0%, 41 days; thrombocytopaenia 28.6%, 61.5 days; cutaneous reactions 9.3%, 30 days; ocular toxicity 7.7%, 278 days; and increase in serum creatinine 12.4%, 430.5 days. Multivariate analysis showed that rifampicin use was independently associated with thrombocytopaenia, and ethambutol use was independently associated with increases in serum creatinine.The main adverse reactions appeared within 3 months after start of treatment. Most patients were able to continue treatment with liver-supporting therapy, antihistamine agents or desensitisation therapy; however, ocular toxicity must be monitored for up to 1 year after start of treatment.

Oral administration of probiotics has been known to improve inflammatory responses against infectious diseases. Here, we describe the inhibitory effect of oral intake of heat-killed Lactobacillus pentosus strain b240 (b240) on pneumococcal pneumonia in a murine experimental model., Letters in Applied Microbiology, 53(1), pp.35-43; 2011

The phylogenetically-conserved vertebrate transcription factor, NFIB, is an orchestrator of glial differentiation in the developing mammalian central nervous system. We found NFIB expression to be reduced in glioblastoma (GBM), the commonest and most lethal primary adult brain cancer, so investigated what effect increased expression of NFIB had on GBM. Increased expression of NFIB in primary GBM cell lines induced expression of markers of glial differentiation, inhibited cell proliferation, reduced stem/progenitor cell growth, altered cell cycle progression and inhibited tumor growth in murine models of GBM. We thus identified NFIB to be a novel tumor suppressor gene in GBM.

For the purpose of a nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens in patients in Japan, the Japanese Society of Chemotherapy conducted their second year survey, during the period from January to August, 2007. A total of 1178 strains were collected from clinical specimens obtained from adult patients with well-diagnosed respiratory tract infections. Susceptibility testing was evaluable for 1108 strains (226 Staphylococcus aureus, 257 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 206 Haemophilus influenzae, 120 Moraxella catarrhalis, 122 Klebsiella pneumoniae, and 171 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 beta-lactams (four penicillins, three penicillins in combination with beta-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standards Institute (CLSI). The incidence of methicillinresistant Staphylococcus aureus (MRSA) was high, at 59.7%, and the incidences of penicillin-intermediateresistant and -resistant Streptococcus pneumoniae (PISP and PRSP) were 30.4% and 5.1%, respectively. Among Haemophilus influenzae strains, 19.9% of them were found to be beta-lactamase-non-producing ampicillin (ABPC)-intermediately-resistant (BLNAI), 29.1% to be beta-lactamasenon-producing ABPC-resistant (BLNAR), and 6.7% to be beta-lactamase-producing ABPC-resistant (BLPAR) strains. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae was not isolated. Two isolates (1.2%) of Pseudomonas aeruginosa were found to be metallo-beta-lactamase-producing strains, including one (0.6%) suspected multidrug-resistant strain showing resistance to imipenem, amikacin, and ciprofloxacin. These data will be a useful reference for future periodic surveillance studies and for investigations to control resistant infections as well. Continued surveillance is required to prevent the further spread of these antimicrobial resistances.

The Japanese Society of Chemotherapy (JSC) conducted the first nationwide surveillance of bacterial respiratory pathogens during the period from January to August 2006. With the cooperation of 32 medical institutions throughout Japan, a total of 924 strains belonging to seven clinically relevant bacterial species were collected from adult patients with well-diagnosed respiratory tract infections (RTIs). Antimicrobial susceptibility testing of the 887 evaluable strains (205 Staphylococcus aureus, 200 Streptococcus pneumoniae, 9 Streptococcus pyogenes, 165 Haemophilus influenzae, 91 Moraxella catarrhalis, 74 Klebsiella pneumoniae, and 143 Pseudomonas aeruginosa) to 42 antibacterial agents was conducted at the Central Laboratory of the Research Center for Anti-infective Drugs of the Kitasato Institute, according to recommendations issued by the Clinical and Laboratory Standards Institute (CLSI). The antibacterial agents employed were 25 beta-lactams, three aminoglycosides, four macrolides (including one azalide and one ketolide), one lincosamide, one tetracycline, two glycopeptides, five fluoroquinolones, and one oxazolidinone. The incidence of methicillin-resistant S. aureus (MRSA) was 63.4%, and the incidences of penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were 35.0% and 4.0%, respectively. Among H. influenzae, 21.2% of the strains were found to be beta-lactamase-nonproducing ampicillin (ABPC)-intermediately resistant (BLNAI), 29.1% to be beta-lactamase-nonproducing ABPC-resistant (BLNAR), and 4.8% to be beta-lactamaseproducing ABPC-resistant (BLPAR) strains. The incidence of extended-spectrum beta-lactamase-producing K. pneumoniae was 2.7% (2 of 74 strains). Three (2.1%) of the 143 P. aeruginosa strains were found to be metallo-beta-lactamaseproducing, including 1 (0.7%) multidrug-resistant strain. Through the nationwide surveillance, we obtained fundamental antimicrobial susceptibility data of clinically relevant bacterial pathogens in adult RTI to various antibacterial agents. These data will be a useful reference for future periodic surveillance studies, as well as for investigations to control antimicrobial-resistant pathogens.

This paper proposes a novel control strategy of a permanent-magnet motor drive without a rotor position sensor. The strategy is based on use of relative phase information of harmonic currents caused by frequency-modulated three-phase pulsewidth-modulation (PWM) carriers. In this system, the PWM carrier source is placed on an estimated rotor reference frame, and coordinate transformation is applied to the carrier source to generate the frequency-modulated three-phase PWM carriers on a stator reference frame. By modulating voltage references with the transformed carriers, a locus of the corresponding harmonic currents on the estimated rotor reference frame is observed as a stationary ellipse because of a rotor saliency. Since a long-diameter direction of the harmonic-current ellipse indicates a true d-axis direction, orienting the estimated d axis to the long-diameter direction makes the sensorless operation possible. The paper describes a theoretical aspect of the proposed method and, then, presents experimental results as well as computer simulation results. Consequently, not only excellent controllability over a wide speed range including zero speed has been verified, but also robustness to the motor parameter variations has been confirmed.

Summary form only given, as follows. A coaxial plasma opening switch is used with the inductive-voltage-adder generator to realize pulse sharpening by an inductive energy storage scheme. The POS has the conduction time over 1 /spl mu/s and provides 200 kA with less than 50 ns of rise time of the load current into Z-pinch load. In the present experiment, two cable guns mounted symmetrically on the outer electrode were used as a plasma source. The diameter of the inner cathode, outer anode, and the distance between the electrodes were 80 mm, 140 mm and 30 mm, respectively. Electron density was measured by a He-Ne laser interferometer with chordal lines-of-sight. In order to observe the motion of the POS plasma, the electron density was measured at many measurement locations in all over the POS region. From the result, the contours of the electron density at conduction, opening and post-opening phase were drawn. In the early time of the conduction phase, the plasma density became higher with time and stayed in the initial position. As conduction phase progressed, the high-density plasma spread downstream near the cathode and anode. The distance of plasma motion was larger near the cathode and smaller near the anode. At 800 ns, low-density region is seen at 10 mm from the cathode. After opening completed, the low-density gap disappeared and the shape of the corn-shape-like plasma was distorted. The plasma density after opening became higher with time. Through the experiment, the motion of POS plasma was understood and the low-density region was observed at the time of opening.

The current in a wire array during its exploding phase has been studied. The wire array consisting of many thin wires is used as a plasma source in a z-pinch X-ray radiation system. The current distribution in the exploding wire array plays an important role in producing an initial symmetrical plasma. In the present experiment, four tungsten wires of 0.1 mm in diameter were exploded in a vacuum. The experiment was carried out with an inductive voltage adder pulsed power generator providing a current of 160 kA at quarter period of 1.8 /spl mu/s The currents through and the voltage across the wires were measured simultaneously. It was found that the currents in the wires were inhomogeneous, especially after the wires became plasma. Once the currents became inhomogeneous, the inhomogeneity remained throughout the discharge. It was also studied how the dimensions of the wires affected the homogeneity of the currents. Wires of different lengths or different cross sectional areas resulted in strong inhomogeneities of the currents. The wires with shorter length or smaller cross-sectional area became plasmas earlier than other wires. Thus, the resistances of the wires were not equal. These differences in the resistance caused the inhomogeneity of the currents.

Penicillin-resistant Streptococcus pneumoniae (PRSP) is widespread all over the world, including countries previously free of PRSP. This study was undertaken to determine the prevalence, the common serotypes and the clonality of PRSP isolated over a period of 1 year, from various clinical samples from three major hospitals in Kuwait. Strains were identified by standard methods and their antibiotic susceptibility was determined by the agar dilution method. The clonality of the isolates was determined by repetitive extragenic palindromic sequence–polymerase chain reaction (REP–PCR) genomic profiling and pulsed field gel electrophoresis (PFGE). Serotyping was done by Quellung reaction using specific antisera. We found that 55% of the S. pneumoniae were resistant to penicillin (46% and 9% exhibited intermediate and full resistance, respectively). Nearly 41% were resistant to sulfamethoxazole-trimethoprim, 9% to cefotaxime and ceftriaxone, 15% to amoxycillin-clavulanate, 17% to cefuroxime, 77% to cefaclor, and 14% to clindamycin. The commonest serotypes among the PRSPs were 6A, 6B, 14, 19F, 23F and nontypable. PFGE and REP–PCR patterns showed a large diversity of genetic clones of the PRSP. Serotypes 6B, 14, 19F and 23F were more clonally related than the others. Our data showed that the prevalence of PRSP was high, the serotypes were diversified and different genetic clones make up the population of circulating PRSP in Kuwait.

Initial analysis of Pseudohynobius flavomaculatus chromosomes determined the chromosome number of this species to be 2n = 52. A re-examination of Ranodon shihi chromosomes detected 2n = 66 chromosomes, in contrast with a previous finding of 2n = 64. The C-banding patterns of these two species and that ofBatrachuperus pinchonii were compared with each other. Regions of homoeology in the C-banding pattern among these three species represented 33.51–48.30% of the total length of their chromosomes. We also detected two types of chromosome rearrangement in hynobiid species based on the results of the present and previous cytogenetic studies.

We investigated the drug efflux mechanism in azole-resistant strains of Candida albicans using rhodamine 6G (R6G). No significant differences in R6G uptake were observed between azole-sensitive B2630 (9.02 +/- 0.02 nmol/10(8) cells) and azole-resistant B67081 (8.86 +/- 0.03 nmol/10(8) cells) strains incubated in glucose-free phosphate buffered saline. A significantly higher R6G efflux (2.0 +/- 0.21 nmol/10(8) cells) was noted in the azole-resistant strain (B67081) when glucose was added, compared with that in the sensitive strain B2630 (0.23 < or = 0.14 nmol/10(8) cells). A fluconazole-resistant strain C40 that expressed the benomyl resistance gene (CaMDR) also showed a low R6G efflux (0.16 +/- 0.06 nmol/10(8) cells) as did the sensitive strains. Accumulation of R6G in growing C. albicans cells was inversely correlated with the level of CDR1 mRNA expression. Our data also suggest that measurement of intracellular accumulation of R6G is a useful method for identification of azole-resistant strains due to CDR1-expressed drug efflux pump.

The characteristics of a plasma generated by cable plasma guns have been studied by a laser interferometer. Cable plasma guns are frequently used as a plasma source in plasma opening switches. In our experiments, the plasma source consists of eight coaxial cable guns mounted on the outer electrode of concentric coaxial electrodes. The reproducibility of the gun in subsequent shots is found to be better than 10%, and the gun-to-gun difference is less than 15%. Assuming a symmetry of eight guns, the contour maps of the electron plasma density are plotted as functions of time. The plasma density becomes maximum near the gun nozzle and near the inner coaxial electrode. The plasma density is low in the area between the coaxial electrodes during the early time of the discharge. At a later time, the plasma fills the space between the two guns more uniformly. Still photographs of the plasma luminosity show a good correspondence with the plasma density plots which were taken 10 /spl mu/s after the discharge initiation. The plasma gun system is designed for use in a 400-kA inductive voltage adder with the inductive energy storage system.

The plasma opening switch operation (POS) was studied by optical diagnostics, such as laser interferometry and spectroscopy. The characterization of the plasma source (cable plasma gun) allowed us to determine initial plasma conditions for the switch. The process of the vacuum gap formation in a microsecond plasma opening switch was also investigated. Time- and spatially-resolved density measurements are performed in the POS, showing the density drop during switch-opening almost in the whole interelectrode gap. The density diagrams are compared to major switch characteristics, such as conduction time and load current dI/dt. The study of spectral line intensities from the cable gun plasma showed that CII line intensity corresponds in time with plasma density measured by an interferometer. The intensities of carbon spectral lines tend to drop during switch-opening that substantiates interferometry measurements.

The chromosome number of a Chinese salamander, Batrachuperus pinchonii, was re-examined. Adults and embryonic specimens had a diploid number of 66, with 33 bivalents during meiosis, in contrast to previous reported results. Furthermore, when C-banding analysis was performed with embryos, chromosomes with banding patterns homoeologous to those of Salamandrella keyserlingii and Hynobius species were found. It appears, therefore, that Batrachuperus, Salamandrella and Hynobius might be derived from a common ancestral species in eastern Asia.

To develop a model of chronic experimental asthma in guinea pigs, the animal was forced to inhale the mist of a low dose of ovalbumin (OA) adsorbed on fine Al(OH)3 for sensitization once every 4 weeks. The animal was challenged by inhalation with the mist of OA on day 14 after the respective sensitizations. Either the first or the second antigen challenge markedly induced an early asthmatic response (EAR), whereas there was hardly any late asthmatic response (LAR). At the 3rd challenge, LAR also emerged with some severity. These dual responses were consistently observed until the 10th challenge. On the other hand, repeated inhalation/challenge, once every 2 weeks, with OA alone at the same dose tended to lead to the desensitization of the EAR. In addition, LAR was hardly observed throughout the experiments. In both groups, gamma 1 and IgE levels in the serum were elevated by the repetitive antigen inhalations, yet no obvious relationship between these antibody levels and the intensity of either EAR or LAR was recognized. The present results indicate that the asthmatic model with reproducible EAR and LAR developed in this study appears to be very beneficial for the investigation of bronchial asthma and for the assessment of anti-asthma drugs.

Variations in repetitive DNA were examined in nine salamander species of the genera Hynobius and Onychodactylus. The data from Southern blot hybridization were processed by Manhattan distance analysis, and unrooted trees were drawn. The resulting trees suggest that the genus Hynobius can be divided into three groups: group 1 contains only H. retardatus with 40 chromosomes; group 2 contains H. kimurae, which has 58 chromosomes and is a mountain-brook type of Hynobius (this group probably contains all mountain-brook types of Hynobius with 58 chromosomes); and group 3 contains the other six pond-type species examined here, each with 56 chromosomes. Group 3 probably contains all species of Hynobius with 56 chromosomes. Furthermore, group 3 can be further separated into two groups: the first group includes H. leechii, H. tsuensis, H. nebulosus, H. nigrescens, and H. tokyoensis from Chita; and the second group includes H. tokyoensis (except the population from Chita) and H. lichenatus. According to this analysis and other information, it seems that the population from Aichi Prefecture, which belongs to H. tokyoensis, should be identified as H. nebulosus. Furthermore, it appears that the genus Onychodactylus is phylogenetically distant from Hynobius and Salamandrella.Key words: Hynobius, repetitive DNA, Southern blot hybridization, phylogenetics, neighbor-joining method.

A temperature-sensitive mutant (ts3) of Newcastle disease virus was physiologically characterized. All major viral structural proteins were synthesized at the permissive (37 degrees C) and nonpermissive (42 degrees C) temperatures, but the fusion (F) glycoprotein was not cleaved at 42 degrees C. In immunocytochemical electron microscopy, the F protein was abundant in the rough endoplasmic reticulum but not in cytoplasmic membrane at 42 degrees C. Noninfectious hemagglutinating virus particles containing all major structural proteins except the F protein were released at 42 degrees C from infected cells. We concluded that the defect in ts3 resides in the intracellular processing of the F protein.

Burst RF fields (BRFFs) were applied to Chinese Hamster Ovary (CHO) cells, and the cell response to the BRFF of two different frequencies, 20 kHz and 50 MHz, was investigated by means of the fluorescent microscopy. The field strength and duration of the BRFF were fixed at 1 kV/cm, and 100 mus, respectively. Cells were placed in a 100 mum-gap electrode plated on the slide glass for a microscopy. Acridine orange (AO), which mainly reacts to DNA, was used as the fluorescent dye. From the experiment, the BRFF of 20 kHz initiates the increase in the permeability of cell membrane. In contrast, the BRFF of 50 MHz does not act on cell membrane but causes degeneration of DNA or RNA. We have experimentally demonstrated that the burst RF fields with only a small electric field of 1 kV/cm cause not only membrane reaction but also intracellular effects.

There is currently no optimal second-line treatment after failure of Helicobacter pylori triple therapy.To determine effective salvage therapy after failure of lansoprazole-amoxicillin-clarithromycin.After failure of lansoprazole-amoxicillin-clarithromycin 123 out-patients were randomized to receive either 2-week rabeprazole (20 mg b.d.) + amoxicillin (1000 mg b.d.) (RA group) or 1-week rabeprazole (10 mg b.d.) + amoxicillin (750 mg twice b.d.) + metronidazole (250 mg b.d.) (RAM group). Eradication was assessed by the 13C-urea breath test. We also evaluated cytochrome p450 (CYP) 2C19 genotype status, determined by polymerase chain reaction - restriction fragment length polymorphism, and susceptibility to clarithromycin and metronidazole.On an intention-to-treat basis, H. pylori infection cure was achieved in 37 of 63 (59%) patients in the RA group and in 49 of 60 (82%) patients in the RAM group. Per protocol-based eradication rates in the RA and RAM groups were 66% (37/56) and 88% (49/56), respectively. In both analytic sets there were significant differences between the treatment groups (P0.01 in each). Mild adverse events were observed in eight and five patients from the RA and RAM groups, respectively. Genetic predisposition of CYP2C19 and antibiotic resistance did not influence the treatment outcome either regimen.The rabeprazole + amoxicillin + metronidazole therapy yielded satisfactory results. In contrast, the cure rate in high-dose rabeprazole + amoxicillin was below an acceptable level.

It is known that in eight hagfishes chromosome elimination occurs during early embryogenesis. The eliminated chromosomes are mostly C-band positive, so that none of the somatic cells have any C-band-positive chromatin. Recently, some highly repetitive DNA sequences have been reported as eliminated elements in these hagfishes based on molecular biological methods. However, no germline-restricted repetitive DNA have been directly isolated from the Japanese hagfish Eptatretus burgeri, from which approximately 21% of the total DNA is eliminated from presumptive somatic cells. Through electrophoretic investigation after digestion with restriction endonucleases, two DNA families that are restricted to germline DNA were isolated. Molecular cloning and sequence analysis revealed that these families are composed of closely related sequences of 64 and 57bp in length, respectively. Southern blot hybridization revealed that the two DNA families are restricted to germline DNA and were thus named EEEb1 and EEEb2, respectively. Moreover, these eliminated elements were highly and tandemly repeated, and it is predicted that they might amplify by saltatory replication and have evolved in a concerted manner. By densitometric scanning, EEEb1 and EEEb2 were found to amount to make up approximately 18.5 and 0.024% of the total germline genomic DNA, accounting for 88.6% of the total eliminated DNA. A fluorescence in situ hybridization experiment demonstrated that EEEb1 is located on all C-band-positive chromosomes that are limited to germ cells, suggesting that EEEb1 is the primary component of eliminated DNA of E. burgeri.

It is clinically important to evaluate the severity of right ventricular (RV) overload in patients with chronic pulmonary diseases (CPD). For such evaluation, echocardiography has been widely used because the procedure is noninvasive and can be performed repeatedly. We evaluated the severity of RV overload in CPD patients to assess the usefulness of pulsed Doppler echocardiography. The A/E ratio and deceleration time of early RV inflow velocity correlated significantly with the mean pulmonary artery pressure (MPAP) both in patients with and without CPD. The acceleration time/RV ejection time (AcT/RVET) was significantly lower in CPD patients than control subjects and correlated significantly with MPAP. Furthermore, AcT/RVET improved in patients with mild respiratory failure after oxygen therapy, along with a decrease in MPAP. We also compared the new index of myocardial performance (NI) in control subjects and patients with pulmonary tuberculosis sequelae (TB) undergoing home oxygen therapy. The NI was significantly higher in the TB group. Although these results were satisfactory, the pulsed Doppler echocardiography has certain disadvantages because monitoring is influenced by anatomical factors and it is difficult to perform in patients with atrial fibrillation or tachycardia. We conclude that echocardiography using a Doppler method is a useful noninvasive technique for assessment of the right heart system. The precision of this procedure can be improved by combination with other echocardiographic indices of RV overload.

BACKGROUND—Human β-defensin 2 (hBD-2) plays a role in the innate defence system at mucosal surfaces. Colonisation of Helicobacter pylori in the stomach is an important pathological factor in gastrointestinal illnesses, including gastritis, peptic ulcer, and gastric adenocarcinoma. AIMS—To evaluate the antibacterial role of hBD-2 against H pylori infection in the gastric mucosa. SUBJECTS—Biopsied gastric mucosa specimens from H pylori positive (n=6) and H pylori negative (n=6) individuals were used. H pylori was determined by the presence of urease activity and microscopic examination. METHODS—The specimens were examined for hBD-2 expression by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridisation. The antibacterial effect of hBD-2 against H pylori was evaluated by the number of colony forming units of H pylori after incubation with 0, 10−9, 10−8, 10−7, 10−6, or 10−5 M of hBD-2 peptide. RESULTS—All six H pylori positive specimens expressed a high level of hBD-2 mRNA while hBD-2 mRNA was not detected in the H pylori negative specimens by RT-PCR. Immunohistochemistry using anti-hBD-2 antiserum revealed that hBD-2 was expressed in the surface epithelium of H pylori infected specimens. In gastric specimens obtained after H pylori eradication, hBD-2 immunoreactivity had dramatically decreased. In situ hybridisation confirmed that hBD-2 transcripts were localised in the epithelium of H pylori infected gastric specimens. Incubation with hBD-2 reduced the growth rate of cultured H pylori in a dose dependent manner, and incubation with 10−5 M hBD-2 completely inhibited the proliferation of H pylori. CONCLUSIONS—H pylori infection induces hBD-2 expression in the human gastric epithelium. hBD-2 inhibited the growth of H pylori in vitro, suggesting that hBD-2 plays an antibacterial role in H pylori induced gastritis. Keywords: human β-defensin 2; Helicobacter pylori; gastritis; antimicrobial peptide

Acaeruloplasminaemia is characterized by excessive neurovisceral iron accumulation due to mutation of the caeruloplasmin gene. Excess iron functions as a potent catalyst of biological oxidation, and increased iron concentration is associated with the products of lipid peroxidation in the serum and cerebrospinal fluid. We investigated whether the amount of iron accumulated paralleled lipid peroxidation levels in acaeruloplasminaemia tissues, examining brains and visceral organs of two affected patients at autopsy for iron and copper content, and oxysterols, including 7-hydroxycholesterol and 7-ketocholesterol, which are directly produced from cholesterol by active oxygen species. The amount of iron accumulated in various tissues was correlated with the levels of the oxysterols. These findings suggest that lipid peroxidation produced by the intracellular accumulation of iron is involved in the pathogenesis of acaeruloplasminaemia.

A 51-year-old woman with acute myocardial infarction underwent emergency coronary angiography. The patient had an episode of idiopathic thrombocytopenic purpura, and underwent splenectomy at the age of 36. On admission, platelet count in the peripheral blood was 43.2x10(4)/microl. During the initial emergency left coronary angiography, a thrombus was detected in the left main trunk. The thrombus was drawn back to the orifice of the left coronary artery, and finally disappeared into the aorta by injecting contrast media. After the thrombus disappeared, no stenotic lesion was detected in the left coronary artery. One month later, when acetylcholine-provocation coronary angiography was performed, marked vasospasm was detected in the left coronary arteries. Coronary thrombosis in the patient might have been induced by a coronary spasm, and the presence of thrombocytosis might also have affected the development of a coronary thrombus. However, it was spontaneously drawn back to the aorta by back flow of contrast media, which was injected via the entrance of the left coronary artery. A case of acute myocardial infarction whose thrombus occluded the left main coronary artery and was removed at first injection of contrast media is presented.

To determine whether a 5-day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7-day regimen.A total of 139 H. pylori-infected patients were randomized to receive either a 5-day or 7-day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C-urea breath test.On the intention-to-treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5- and 7-day regimens, respectively (P0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5- and 7-day regimens, respectively (P0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance.Our 5-day regimen of RCA yielded inferior results, whereas the 7-day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor-clarithromycin-amoxicillin therapies cannot be recommended.

5S ribosomal DNAs (rDNAs) from two cyprinid species, Acheilognathus tabira subsp. 1 and Cyprinus carpio, were isolated and sequenced. Tandemly arranged rDNAs were 179 bp in A. tabira and 204 bp in C. carpio. The non-transcribed spacer region elucidates the size difference of 5S rDNA between the two species. Fluorescence in-situ hybridization (FISH) localized 5S rDNAs to the short arms of two pairs of chromosomes in A. tabira and two to four pairs in C. carpio. Subsequent analysis demonstrated NORs in one pair of chromosomes in both species. Both the NOR and 5S rDNA are carried by a chromosome pair in A. tabira, but they are located on different chromosomes separately in C. carpio. Karyotype evolution by tetraploidy seems complex in cyprinid species.

Irinotecan (CPT-11) and carboplatin have broad anti-tumor activities. We conducted a Phase I study of CPT-11 combined with carboplatin in previously untreated solid cancers, especially advanced lung cancer. The aim of the study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities in this regimen. In addition, we prospectively evaluated the Chatelut formula for predicting carboplatin clearance. Patients with advanced cancer were treated with CPT-11 (days 1, 8, and 15) and carboplatin (day 1) of a fixed-target area under the concentration-time curve (AUC) of 5 mg x min/ml. Carboplatin dose was determined by multiplying the AUC by the clearance predicted using the Chatelut formula. The CPT-11 dose was escalated from 40 mg/m2 to the MTD by 10 mg/m2. A total of 27 patients, 26 lung cancer patients and 1 colon cancer patient, were enrolled in this study. Dose-limiting leukoneutropenia, thrombocytopenia, and diarrhea, including one treatment-related death, were observed at 60 mg/m2 CPT-11, indicating that this level was the MTD. In 11 patients, the actual AUCs of carboplatin almost achieved the target AUC of 5. Fifteen (60%) of 25 evaluable patients showed an objective response, with an 85% response rate [11 of 13 patients (complete response, 31%; partial response, 54%)] in small cell lung cancers and a 36% response rate (4 of 11 patients) in non-small cell lung cancers. Neutropenia, thrombocytopenia, and diarrhea were the dose-limiting toxicities in this regimen. CPT-11 (50 mg/m2) under the carboplatin target AUC of 5 using the Chatelut formula was the recommended dose for further Phase II study, and this regimen seems to be active for small cell lung cancer.

Recently, we reported a reproducible model of asthma in guinea-pigs in vivo, which developed a late asthmatic response (LAR) as well as an early response. In this study, time-related changes in the occurrence of the LAR and leucocyte kinesis were assessed. Furthermore, the state of the activation of eosinophils that migrated into the lower airways was characterized in vitro. Guinea-pigs were alternately sensitized/challenged by inhalation with aerosolized ovalbumin adsorbed on aluminium hydroxide and ovalbumin alone, once every 2 weeks. At defined times before and after the fifth challenge, airway resistance was measured, blood was drawn and bronchoalveolar lavage (BAL) and nasal cavity lavage (NCL) were performed. Superoxide anion (.O2-) production of eosinophils was measured with cytochrome c. Occurrence of LAR and considerable increases in circulating eosinophils coincided with each other 5-7 h after the challenge. After 7 h, eosinophil infiltrations into bronchoalveolar spaces were observed. The capacity of eosinophils from the sensitized animals to produce .O2- was higher than those from the non-sensitized ones, when eosinophils were stimulated by platelet-activating factor. Although an increased number of eosinophils in the NCL fluid was observed, it was much less than that in the BAL fluid. Thus, it has been concluded that eosinophilia in the blood and the lung may participate in the occurrence of the late asthmatic response, which is thought to be preferentially evoked in the lower airways in guinea-pigs in vivo.

Because of the rapidly increasing incidence of serious candidal infections, a consensus conference of 22 investigators from the United States, Europe, and Japan was held to discuss strategies for the prevention and treatment of deep-organ infections caused by Candida species. Commonly asked questions concerning the management of candidal infections were selected for discussion by the participating investigators. Possible answers to the questions were developed by the investigators, who then voted anonymously for their preferences. In certain instances, unanimity or a strong consensus was the result. In all cases, the full spectrum of responses was recorded and is presented in this report. The forms of candidal infection addressed included candidemia, candiduria, hepatosplenic candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and candidal peritonitis. Prevention and treatment strategies were considered for patients who have undergone surgery, for neutropenic and nonneutropenic patients, and for patients who have undergone bone marrow and solid organ transplantation. The therapeutic roles of amphotericin B (standard and lipid formulations) and the azoles were considered.

Splenectomy increases the postoperative morbidity of total gastrectomy for carcinoma of the stomach. The reasons for this increased risk of postoperative infection are unknown. The aim of this study was to evaluate the impact of splenectomy on circulating immunoglobulin levels and to determine whether splenectomy was an independent risk factor for the development of postoperative infection in 154 patients undergoing total gastrectomy for carcinoma of the stomach. Splenectomy reduced circulating immunoglobulin M levels in the early postoperative period following total gastrectomy. However, it was not identified as an independent risk factor for the development of postoperative infection by multivariate analysis.

We describe the first known case of pneumonia caused by a mucoid Stenotrophomonas maltophilia (Xanthomonas maltophilia) strain in a patient with bronchiectasis. The patient was admitted because of mild hemoptysis and productive cough with infiltrative shadow in the right lower lung field on chest X ray. The clinical symptoms were mild, and treatment with minocycline was effective.

Double-stranded RNA viruses were detected in a strain of Blastomyces dermatitidis isolated from a patient in Uganda. The viral particles are spherical (mostly 44 to 50 nm in diameter) and consist of about 25% double-stranded RNA (5 kb) and 75% protein (90 kDa). The virus contains transcriptional RNA polymerase activity; it synthesized single-stranded RNA in vitro in a conservative manner. The newly synthesized single-stranded RNA was a full-length strand, and the rate of chain elongation was approximately 170 nucleotides per min. The virus-containing strain shows no morphological difference from virus-free strains in the mycelial phase. Although the association with the presence of the virus is unclear, the virus-infected strain converts to the yeast form at 37 degrees C, but the yeast cells fail to multiply at that temperature.