Search

Optical properties of infrared-bright (IR-bright) dust-obscured galaxies (DOGs) are reported. DOGs are faint in optical but very bright in mid-IR, which are powered by active star formation (SF) or active galactic nucleus (AGN), or both. The DOGs is a candidate population that are evolving from a gas-rich merger to a quasar. By combining three catalogs of optical (Subaru Hyper Suprime-Cam), near-IR (VIKING), and mid-IR (ALLWISE), we have discovered 571 IR-bright DOGs. Using their spectral energy distributions, we classified the selected DOGs into the SF-dominated DOGs and the AGN-dominated DOGs. We found that the SF-dominated DOGs show a redder optical color than the AGN-dominated DOGs. Interestingly, some DOGs shows extremely blue color in optical (blue-excess DOGs: bluDOGs). A possible origin for this blue excess is either the leaked AGN light or stellar UV light from nuclear starbursts. The BluDOGs may be in the transition phase from obscured AGNs to unobscured AGNs. [ABSTRACT FROM AUTHOR]

Temporal context is a crucial factor in timing. Previous studies have revealed that the timing of regular stimuli, such as isochronous beats or rhythmic sequences (termed beat-based timing), activated the basal ganglia, whereas the timing of single intervals or irregular stimuli (termed duration-based timing) activated the cerebellum. We conducted a functional magnetic resonance imaging (fMRI) experiment to determine whether top-down processing of perceptual duration-based and beat-based timings affected brain activation patterns. Our participants listened to auditory sequences containing both single intervals and isochronous beats and judged either the duration of the intervals or the tempo of the beats. Whole-brain analysis revealed that both duration judgments and tempo judgments activated similar areas, including the basal ganglia and cerebellum, with no significant difference in the activated regions between the two conditions. In addition, an analysis of the regions of interest revealed no significant differences between the activation levels measured for the two tasks in the basal ganglia as well as the cerebellum. These results suggested that a set of common brain areas were involved in top-down processing of both duration judgments and tempo judgments. Our findings indicate that perceptual duration-based timing and beat-based timing are driven by stimulus regularity irrespective of top-down processing., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Estradiol-17β (E 2 ) promotes the transcription of vitellogenin (Vtg) via nuclear estrogen receptor (ER). Three Vtg (VtgAa, VtgAb, and VtgC) and ER subtypes (ERα, ERβ1, and ERβ2) have been reported in perciform fish; however, the relationship between the transcriptional regulation of Vtg and ER subtypes remains unclear. Molecular characterization was performed and the expression profiles of vtg and er subtypes were investigated to elucidate mechanisms of synthesis of vtg subtypes in yellowtail, Seriola quinqueradiata. Primary structures and promoter regions were revealed in three subtypes of vtg and er, and all the vtg subtypes and erα were presumed to be estrogen-responsive genes. When all vtg subtypes were expressed significantly in the liver, hepatic expression levels of all the er subtypes also increased. Conversely, although plasma E 2 concentrations did not change significantly, the concentrations were high at the same time. Hepatic expression levels of all the vtg subtypes were highly correlated with hepatic erα, rather than with hepatic erβ subtypes and plasma E 2 . A high positive correlation was also observed between erβ1 and β2, which seemed to be highly expressed at the pre- and late-vitellogenic stages. The results of the present study suggest that the transcription of the three vtg subtypes are regulated by three ER subtypes jointly, and ERα is the key transcription factor regulating the three vtg subtypes in yellowtail., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Signaling by the TGFβ super-family, consisting of TGFβ/activin- and bone morphogenetic protein (BMP) branch pathways, is involved in the central nervous system patterning, growth, and differentiation during embryogenesis. Neural progenitor cells are implicated in various pathological conditions, such as brain injury, infarction, Parkinson's disease and Alzheimer's disease. However, the roles of TGFβ/BMP signaling in the postnatal neural progenitor cells in the brain are still poorly understood. We examined the functional contribution of Smad4, a key integrator of TGFβ/BMP signaling pathways, to the regulation of neural progenitor cells in the subventricular zone (SVZ). Conditional loss of Smad4 in neural progenitor cells caused an increase in the number of neural stem like cells in the SVZ. Smad4 conditional mutants also exhibited attenuation in neuronal lineage differentiation in the adult brain that led to a deficit in olfactory bulb neurons as well as to a reduction of brain parenchymal volume. SVZ-derived neural stem/progenitor cells from the Smad4 mutant brains yielded increased growth of neurospheres, elevated self-renewal capacity and resistance to differentiation. These results indicate that loss of Smad4 in neural progenitor cells causes defects in progression of neural progenitor cell commitment within the SVZ and subsequent neuronal differentiation in the postnatal mouse brain., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In Japan, two treatment guidelines exist for pediatric patients with hypertension. The Guidelines for Drug Therapy in Pediatric Patients with Cardiovascular Diseases (JCS2012), by the Japanese Circulation Society, cite the stethoscopy-based American guidelines. The Guidelines for the Management of Hypertension (JSH2009), by the Japanese Society of Hypertension, focus on Japanese data obtained from automated sphygmomanometry. The frequent use of automated sphygmomanometers in clinical practice implies that the JSH2009 guidelines might be better; however with strict low reference values for the diastolic phase, overtreatment may result. Only the Japanese Circulation Society's guidelines include a therapeutic strategy, and the Chronic Kidney Disease (CKD) Guide, CKD Guidelines, and school urinary screening tests all cite these guidelines on stethoscopy-based blood pressure determination. Stethoscopy should be conducted during a medical examination; however, due to limited time in clinical practice, most physicians use automated sphygmomanometers while nevertheless relying on the Japanese Circulation Society reference values--which are stethoscopy-based. To find a compromise, we compared reference values in Japan with those from South Korea (automated sphygmomanometer-based) and those from the United States (stethoscopy-based). Moreover, we examined the results of recent accuracy tests for automated sphygmomanometers. Although the JSH2009 reference values for the systolic phase were consistent with those in the United States (stethoscopy-based), the reference values for the diastolic phase were lower. We observed the same tendency when comparing JSH2009 reference values with those in South Korea (automated sphygmomanometer-based). Conversely, there were only small differences between automated sphygmomanometry and mercury measurement, and we found it was possible to substitute the values from automated sphygmomanometry for stethoscopy. A large-scale study that takes into account patient height, measurement method, and treatment criteria is required to establish appropriate reference values. Even if automated sphygmomanometry is used until appropriate values are established, we consider the criteria provided in the American guidelines as appropriate.

Background: Emerging evidence suggests that innate immunity and increased oxidative stress contribute to pathomechanisms in amyotrophic lateral sclerosis (ALS). The aim of the present study was to verify the involvement of monocyte chemoattractant protein-1 (MCP-1) and its specific CC chemokine receptor 2 (CCR2) in the disease progression of ALS. We here demonstrate the expression state of MCP-1 and CCR2 in lumbar spinal cords of mice overexpressing a transgene for G93A mutant human superoxide dismutase 1 (SOD1) (ALS mice) as a mouse model of ALS as well as the involvement of MCP-1/CCR2-mediated signaling in behavior of cultured astrocytes derived from those mice., Results: Quantitative polymerase chain reaction analysis revealed that MCP-1 and CCR2 mRNA levels were significantly higher in ALS mice than those in nontransgenic littermates (control mice) at the presymptomatic stage. Immunoblot analysis disclosed a significantly higher CCR2/β-actin optical density ratio in the postsymptomatic ALS mouse group than those in the age-matched control mouse group. Immunohistochemically, MCP-1 determinants were mainly localized in motor neurons, while CCR2 determinants were exclusively localized in reactive astrocytes. Primary cultures of astrocytes derived from ALS mice showed a significant increase in proliferation activity under recombinant murine MCP-1 stimuli as compared to those from control mice., Conclusions: Our results provide in vivo and in vitro evidence that MCP-1 stimulates astrocytes via CCR2 to induce astrocytosis in ALS with SOD1 gene mutation. Thus, it is likely that MCP-1/CCR2-mediated sigaling is involved in the disease progression of ALS.

Purpose: The present study was aimed at defining developmental roles of Smad4, a key mediator of the TGF-β superfamily signaling system, in the embryonic mouse retina., Methods: Using a Cre/loxP-mediated conditional gene targeting approach, Smad4 gene function was deleted from the embryonic mouse retina. Mutant phenotypes were morphologically and molecularly examined., Results: Loss of Smad4 in the developing retina led to varying degrees of microphthalmia at birth, presumably because of elevated apoptosis observed transiently at embryonic day 12.5 in the developing retina. This was also associated with an apparent delay in accumulation of retinal ganglion cells. Smad4 conditional mutants also exhibited alterations of retinal spatial patterning along the dorsal-ventral axis, consistent with a known function of BMP signaling in the embryonic retina. However, despite a known role for BMP signaling in retinal cell survival, proliferation, and differentiation, Smad4 mutant retinal progenitor cells were capable of maintaining growth and neurogenesis throughout embryonic development. We also found that the loss of Smad4 led to abnormal targeting of retinal ganglion cell axons to the optic nerve head, a phenotype consistent with reduced BMP signaling in the developing retina., Conclusions: These results suggest that Smad4 is essential for a subset of, but not all, TGF-β/BMP-dependent developmental processes in the embryonic retina. In addition, genetic requirements for Smad4 in the embryonic retina are evident predominantly in the developmental events regulated by the BMP branch of the TGF-β signaling pathway.

Upon activation, NF-kappaB translocates into the nucleus and initiates many biological events. This NF-kappaB signaling is mainly induced by the protein kinase IKK beta. Early in this signaling pathway, IKK beta is phosphorylated for activation by several factors, such as pro-inflammatory cytokines and the Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1). In cells expressing Tax protein, IKK beta is persistently phosphorylated, which chronically activates NF-kappaB signaling. But the active IKK beta is conjugated with a monoubiquitin by the E3 ubiquitin ligase Ro52, and the IKK beta-induced NF-kappaB signaling is downregulated. However, the mechanism of the downregulation has been unknown. Here, we show that Ro52-mediated monoubiquitination is involved in the subcellular translocation of active IKK beta to autophagosomes. Furthermore, using reporter assays, we show that Ro52 suppresses IKK beta-induced NF-kappaB signaling and that this suppression is blocked by an autophagy inhibitor. These results suggest that Ro52-mediated monoubiquitination plays a critical role in the downregulation of active IKK beta through autophagy., ((c) 2010 Elsevier Ltd. All rights reserved.)

The RING-finger protein Ro52/TRIM21 is known as an autoantigen and is recognized by anti-Ro/SSA antibodies, which are commonly found in patients with Sjögren's syndrome and systemic lupus erythematosus. Recently, Ro52 has been shown to localize to distinct structures called cytoplasmic bodies and function as an E3 ubiquitin ligase. However, the Ro52 cytoplasmic bodies have not been well characterized. In this study, we investigated the Ro52 cytoplasmic bodies using fluorescence microscopy. This analysis revealed that the Ro52 cytoplasmic bodies are diffusely located in the cytoplasm and exist independently of TRIM5alpha cytoplasmic bodies. Our results further showed that the Ro52 cytoplasmic bodies are not stained with MitoTracker dye and are not colocalized with the proteasome subunit Rpt5, the caveolae component caveolin-1, the endosome markers (EEA1, Rab5, and Rab7), and the lysosome marker LAMP2. These results indicate that the Ro52 cytoplasmic bodies are not mitochondria, proteasome-enriched structures, caveolae, endosomes, or lysosomes. Importantly, the Ro52 cytoplasmic bodies are highly motile and are located along the microtubule network. These results suggest that the Ro52 cytoplasmic bodies are unidentified structures that are transported along the microtubule network.

Upon activation, NF-kappaB translocates into the nucleus and initiates biological events. This NF-kappaB signalling is mainly regulated by the protein kinase IKKbeta. Early in this signalling pathway, IKKbeta is phosphorylated for activation by several factors, such as pro-inflammatory cytokines and the Tax oncoprotein of HTLV-1. In cells infected by HTLV-1, IKKbeta is persistently phosphorylated and conjugated with monoubiquitin due to Tax expression. Although this Tax-induced monoubiquitination appears to be an important regulation system for IKKbeta, how the monoubiquitination occurs is unknown and its role in NF-kappaB signalling is still unclear. Here, we show that an E3-ubiquitin ligase Ro52 interacts weakly with wild-type IKKbeta but strongly with a phosphomimetic mutant IKKbeta to conjugate monoubiquitin in cooperation with an E2-ubiquitin-conjugating enzyme UbcH5B. These results suggest that the Tax-induced phosphorylation of IKKbeta causes an interaction with Ro52 for the subsequent monoubiquitination. NF-kappaB reporter assays have shown that the IKKbeta activity is suppressed by wild-type Ro52, but not by its inactive mutant. In addition, monoubiquitin fusion of IKKbeta reduced its activity for NF-kappaB signalling. We also found that Ro52 dramatically reduces the level of Tax. These results suggest that Ro52 down-regulates Tax-induced NF-kappaB signalling by monoubiquitinating IKKbeta and by reducing the level of Tax.

Emerging evidence suggests the involvement of programmed cell death and inflammation in amyotrophic lateral sclerosis (ALS). To assess molecular pathological effects of the anti-inflammatory peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist pioglitazone in ALS, we verified changes in the population of neurons, astrocytes, and microglia in the ventral horns of spinal cord lumbar segments from the pioglitazone-treated and non-treated groups of mice carrying a transgene for G93A mutant human superoxide dismutase-1 (SOD1) (ALS mice) and non-transgenic littermates (control mice), performed immunohistochemical and immunoblot analyses of PPARgamma, active form of phosphorylated p38 mitogen-activated protein kinase (p-p38) and inhibitor of nuclear factor-kappaB (NF-kappaB)-alpha (IkappaBalpha) in the spinal cords, and compared the results between the different groups. Image analysis revealed that optical density of NeuN-immunoreactive neurons was significantly lower in the non-treated groups of presymptomatic and advanced ALS mice than in the non-treated groups of age-matched control mice and was recovered with pioglitazone treatment, and that optical densities of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia were significantly higher in the non-treated group of advanced ALS mice than in the non-treated group of control mice and were recovered with pioglitazone treatment. Immunohistochemical analysis demonstrated that immunoreactivities for PPARgamma and p-p38 were mainly localized in neurons, and that IkappaBalpha immunoreactivity was mainly localized in astrocytes and microglia. Immunoblot analysis showed that pioglitazone treatment resulted in no significant change in nuclear PPARgamma-immunoreactive density, a significant decrease in cytosolic p-p38-immunoreactive density, and a significant increase in cytosolic IkappaBalpha-immunoreactive density. Our results suggest that pioglitazone protects motor neurons against p38-mediated neuronal death and NF-kappaB-mediated glial inflammation via a PPARgamma-independent mechanism.

Objectives: It is known that prophylaxis with imipenem reduces the risk of infection accompanying severe acute pancreatitis. In this study,we modified a rat experimental model of severe acute pancreatitis for antibiotic evaluation, and the effect of biapenem was compared with that of imipenem to determine the usefulness of biapenem., Methods: Severe acute pancreatitis was induced by 5% sodium taurocholate. Antibiotics were subcutaneously administered at 3 and 6 hours and evaluated at 12 hours after the pancreatitis induction. For pharmacokinetic evaluation, antibiotics were subcutaneously administered at 3 hours after the pancreatitis induction., Results: From 3 hours after the induction, bacteria were detected from the pancreas. The total bacterial count increased in a time-dependent manner for 12 hours. Biapenem administration reduced the total bacterial count in the pancreas, as observed in imipenem administration. The plasma concentration of biapenem was almost equivalent to that of imipenem; however, the pancreatic penetration of biapenem was approximately twice that of imipenem in this model., Conclusions: Biapenem was suggested to be effective in prophylactic treatment of infectious complications as much as imipenem because of its superior penetration to the pancreas in severe acute pancreatitis.

The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing beta-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillinsusceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.

Several studies have documented the involvement of oxidative stress represented by lipid peroxidation in the pathogenesis of Alzheimer's disease (AD). To test whether the highly reactive carbonyl crotonaldehyde (CRA), generated during lipid peroxidation, is involved in AD, we performed an immunohistochemical analysis in AD and age-matched control hippocampi using a specific antibody against protein-bound CRA (P-CRA). In the AD cases, P-CRA immunoreactivity was preferentially localized in reactive astrocytes and microglia around senile plaques (SPs) and those present in the neuropil, while it was weakly detectable in neurons and neurofibrillary tangles. P-CRA immunoreactivity was also localized in all portions of diffuse SPs and the dystrophic neurites of neuritic and classical SPs, but was undetectable in amyloid cores. Age-matched controls showed P-CRA immunoreactivity only very weakly in neurons. In contrast to P-CRA, immunoreactivities for protein-bound acrolein and 4-hydroxy-2-nonenal were mainly localized to neurons and rarely seen in glial cells. Our results suggest that increased oxidative stress and CRA formation in glial cells is implicated in the disease processes of AD.

This study determined the concentrations of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), organochlorine (OC) pesticides, and tris(4-chlorophenyl) methane (TCPMe) in human breast milk samples collected in 2003 from primipara mothers living in Penang, Malaysia. OCs were detected in all the samples analyzed with DDTs, hexachlorocyclohexane isomers (HCHs), and PCBs as the major contaminants followed by chlordane compounds (CHLs), hexachlorobenzene (HCB), and TCPMe. The residue levels of DDTs, HCHs, and CHLs were comparable to or higher than those in general populations of other countries, whereas PCBs and HCB were relatively low. In addition, dioxins and related compounds were also detected with a range of dioxin equivalent concentrations from 3.4 to 24 pg-TEQs/g lipid wt. Levels of toxic equivalents (TEQs) were slightly higher than those in other developing countries but still much lower than those of industrialized nations. One donor mother contained a high TEQs level, equal to the mean value in human breast milk from Japan, implying that some of the residents in Malaysia may be exposed to specific pollution sources of dioxins and related compounds. No association was observed between OCs concentrations and maternal characteristics, which might be related to a limited number of samples, narrow range of age of the donor mothers, and/or other external factors. The recently identified endocrine disrupter, TCPMe, was also detected in all human breast milk samples of this study. A significant positive correlation was observed between TCPMe and DDTs, suggesting that technical DDT might be a source of TCPMe in Malaysia. The present study provides a useful baseline for future studies on the accumulations of OCs in the general population of Malaysia.

Combined effects of arbekacin (ABK) with biapenem (BIPM) were examined on both in vitro and in vivo model of a mixture of MRSA and Pseudomonas aeruginosa. As a result, significant effect in vitro was observed in combined use of ABK (1/2 MIC) with BIPM (1/4 and 1/2 MIC) against MRSA as compared with ABK or BIPM alone. Against P. aeruginosa combined effect was also observed, showing reduction of viable cells to the limitation of detection within 2 hours. Moreover, with respect to the protective effect on mixed systemic infection of MRSA and P. aeruginosa, the combined treatment with ABK and BIPM showed more excellent efficacy as compared with the single use of each drug.

A 54 year-old male was admitted for highly advanced ascending colon cancer with multiple bone and liver metastases and pleuritis carcinomatosa. He was treated with pharmacokinetic modulating chemotherapy (PMC) and low-dose CPT-11. UFT (400 mg) was orally administered daily and a 2-hour infusion of l-leucovorin (250 mg/m2/day) with a continuous infusion of 5-FU (600 mg/m2/24 h) was given once a week on an outpatient basis. CPT-11 (80 mg/body/2 h) was administered every 2 weeks. Partial response was obtained in the liver for 6 months and in the primary lesion for 9 months. Significant decrease of pain from the multiple bone metastases was observed for 4 months without severe side effects, which led to an improvement in performance status and quality of life for the patient. He survived more than 11 months after initial treatment. The duration of his stay at home was 288 days, accounting for 83% of the treatment period. This case suggests the efficacy of home anticancer therapy with PMC and low-dose CPT-11 for highly advanced colon cancer in terms of QOL.

Study Design: The present study investigated the relationship of obesity and glucose metabolism in persons with ossification of the anterior longitudinal ligament, ossification of the nucal ligament, and ossification of the posterior longitudinal ligament of the cervical spine., Objective: To provide a insight into the etiology of ligamentous ossification of the cervical spine., Summary of Background Data: The high incidence of ligamentous ossification of the cervical spine with obese patients has been reported, but no definite association was reported between the incidence of ossification of the anterior longitudinal ligament, ossification of the nucal ligament, and ossification of the posterior longitudinal ligament and their bone mass index values., Methods: Lateral cervical radiographs and 75 g oral glucose tolerance tests of more than 4802 Japanese men aged 48-57 years at the Self Defense Force Hansin Hospital were evaluated., Results: The incidences of ossification of the anterior longitudinal ligament, ossification of the nucal ligament, and ossification of the posterior longitudinal ligament were 23.1% (1110 of 4802), 23.3% (1117 of 4802) and 4.1% (198 of 4802), respectively. In the groups whose body mass index was 25 or more, the incidences of ossification of the anterior longitudinal ligament, ossification of the nucal ligament, and ossification of the posterior longitudinal ligament were significantly high (P < 0.01). The higher incidence of diabetes or impaired glucose tolerance was statistically significant in ossification of the anterior longitudinal ligament and ossification of the posterior longitudinal ligament but not in ossification of the nucal ligament. The rates, which showed significantly high glucose response by 1-hour or 2-hour plasma glucose level after oral glucose tolerance tests with body mass index-matched control subjects, were ossification of the anterior longitudinal ligament, 93.5%; ossification of the posterior longitudinal ligament, 52.0%; and ossification of the nucal ligament, 14.0%, respectively., Conclusions: From this study, obesity was shown to be the major risk factor of ossification of the nucal ligament, and obesity and glucose intolerance were risk factors in ossification of the anterior longitudinal ligament and ossification of the posterior longitudinal ligament. The authors concluded the morbidity rates of ossification of the anterior longitudinal ligament. ossification of the nucal ligament, and ossification of the posterior longitudinal ligament were high in obesity, however, concerning the glucose intolerance, ossification of the nucal ligament is etiologically different from ossification of the anterior longitudinal ligament and ossification of the posteior longitudinal ligament.

The time-lag/sequential/step by step chemotherapy by fosfomycin plus sulbactam/cefoperazone including a short time small dose of steroid was done for 27 severely infected patients suffered from various cancer or other severe basal diseases. And the staggered "intensive" chemotherapy with added arbekacin or vancomycin to the previous staggered chemotherapy was done against 13 severely infected patients having MRSAs among their infecting pathogens. 1. Bacteriological effects Pseudomonas aeruginosa 6/8, Staphylococcus epidermidis 5/5, Enterococcus faecalis 3/6, Acinetobacter calcoaceticus 2/2, Klebsiella pneumoniae 2/2, MRSA 2/2, Xanthomonas maltophilia 2/3 and other 10/10 were eradicated (84.2%) by the staggered chemotherapy and MRSA 7/13, P. aeruginosa 3/4, E. faecalis 3/5, A. calcoaceticus 2/2, X. maltophilia 1/1 and others 2/2 were eradicated (53.8% in MRSA, 78.6% in others and 66.7% in total) and 3 of MRSAs were colonized. 2. Clinical effects 1) Staggered chemotherapy: Excellent 18/27, good 8/27, fair 1/27, poor 0/27 (96.3%). 2) Staggered "intensive" chemotherapy: Excellent 6/13, good 4/13, fair 2/13, poor 1/13 (76.9%) in total: excellent 60.0%, efficacy rate 90.0%.

We studied the combined effect of fosfomycin (FOM) with sulbactam/cefoperazone (SBT/CPZ) on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA, 246 strains) and Pseudomonas aeruginosa (190 strains) in vitro. In ratio of mixed serum concentration of antibiotics at three hours after intravenous administration, the combination of FOM with SBT/CPZ and alone of arbekacin showed over 90% in cumulative percentage of MIC against MRSA and P. aeruginosa. The effect of the combination of FOM and SBT/CPZ was observed in MRSA strains of > 16 micrograms/ml of SBT/CPZ MIC and > 256 micrograms/ml FOM MIC. As well as in P. aeruginosa strains, the effect of the combination of FOM and SBT/CPZ was observed in strains of > 16 micrograms/ml of SBT/CPZ MIC and < 256 micrograms/ml FOM MIC, but it was not remarkable in strains of > 256 micrograms/ml FOM MIC. These results suggests that the combination treatment of FOM and SBT/CPZ may be effective for mixed infection of MRSA and P. aeruginosa.

A total of 62 conjugative R plasmids detected in 48 Escherichia coli and 19 conjugative R plasmids in 16 Salmonella strains from domestic (carrier and emerald) and feral pigeons, crows (Japanese jungle crows and carrion crows) and black kite, were examined for genetic properties. Out of the 62 E. coli R plasmids examined for fertility inhibition (Fi), 29 (46.8%) were Fi+, and the remainder were Fi-. Among the 62 R plasmids, 16 (25.8%) were classified into incompatibility (Inc) group FII, 15 (24.2%) into I alpha, 7 (11.3%) into H1 and 2 (3.2%) into N. The remaining 23 R plasmids could not be classified in this study. Among the 19 Salmonella R plasmids, 4 showed thermosensitive (ts) transfer. Out of the 18 plasmids tested, 13 (72.2%) including 4 ts-R plasmids were Fi-, and the remaining 5 (27.8%) were Fi+. Five R plasmids containing 4 Fi- were IncI alpha, while 4 ts-R plasmids belonged to IncH1 (1 R plasmid) and H2 (3 R plasmids). The remainings were not tested. In E. coli strains, IncFII and I alpha were widely (4 of 6 lots of birds, respectively) distributed, followed by N (2 lots) and H1 (1 lot). IncN R plasmid was detected from domestic pigeons and crows, but not from feral pigeons. In Salmonella strains from 5 lots of birds, IncFII and N plasmids which were detected from E. coli were not found, but IncH2 was detected from domestic pigeons (1 lot) and kite (1 lot). IncI alpha was detected from feral pigeons (1 lot) and kite (1 lot). The potential transfer of R plasmids between Salmonella and E. coli, and of dissemination of the plasmids among the free-flying birds, animals and humans is discussed.