Trends in the serovar and antimicrobial resistance in clinical isolates of Salmonella enterica from cattle and pigs between 2002 and 2016 in Japan.

AIMS: Given the significance of Salmonella enterica in both human and animal health, and a recent global dissemination of Salmonella 4,[5],12:i:-, changes in the prevalent serovars and antimicrobial resistance in clinical isolates of Salmonella from cattle and pigs were investigated in Japan. METHODS AND RESULTS: The serovars and antimicrobial susceptibilities of 1605 Salmonella enterica isolated from cattle (n = 894) and swine (n = 711) between 2002 and 2016 were examined. The most common serovar among all samples was Salmonella Typhimurium. However, its monophasic variant with antigenic structure S. 4,[5],12:i:-, which was first detected in cattle in 2006 and swine in 2010, has been rapidly increasing in incidence and resistance. Resistance rates to cefotaxime and ciprofloxacin were generally low (<10% in the cattle isolates and <5% in the swine isolates); however, isolates resistant to more than five antimicrobials, which often include these antimicrobials, were recently detected in Salmonella Dublin, S. 4,[5],12:i:-, S. Typhimurium, Salmonella Newport, Salmonella Choleraesuis and Salmonella 6,7:c:-. Among them, two S. 4,[5],12:i:- isolates possessed extended-spectrum ß-lactamase-encoding genes; blaSHV-12 or blaCTX-M-55 , respectively, while all the five S. Typhimurium isolates possessed AmpC-type ß-lactamase gene of blaCMY-2 . CONCLUSIONS: S. 4,[5],12:i:- has been rapidly increasing and exhibiting a remarkable change in antimicrobial resistance in Japan. Considering certain serovars are characterized by multidrug resistance including medically important antimicrobials, continuous monitoring and appropriate measures are required to protect public health and veterinary husbandry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a trend in the serovars and antimicrobial resistance in clinical isolates of Salmonella from cattle and pigs in Japan, and showed that there were certain types of Salmonella serovars depending on the animal origin which needs more attention.

Body mass-based exercise in middle-aged and older women.

The present study examined whether the degree to which muscle strength is improved by a body mass-based home exercise program in middle-aged and older women depends on the force-generating capabilities of the muscles prior to the intervention. 75 women (53-76 years) voluntarily participated in a circuit training program consisting of 5 exercises (16 repetitions/exercise, 2 or 3 circuits/day) using only body mass as resistance for 3 months. The subjects performed the training program 6 days a week in their own home and once a week in a local gym. Before and after intervention, isometric torques during maximal voluntary knee extension (KET) and plantar flexion (PFT) were determined and expressed relative to body mass (KET/BM and PFT/BM, respectively). KET/BM and PFT/BM increased significantly after intervention, and their relative changes were negatively correlated to the absolute values before intervention. Most of the subjects whose KET/BM and PFT/BM values before intervention were greater than 2.8 Nm/kg and 1.7 Nm/kg, respectively, did not show increases in strength after intervention. Thus, although body mass-based exercise at home is effective in improving lower limb strength in middle-aged and older women, the magnitude of the improvement is influenced by the force-generating capability before intervention.

Seronegative virus carriers in the infection of rabbits with human T lymphotropic virus type I.

Six HTLV-I-transformed T cell lines were prepared from PBL of three rabbits each of B/J and Chbb:HM strains, and were inoculated into newborn rabbits of these two strains, and of their F1 hybrid. None of three B/J cell lines induced anti-HTLV-I antibody response in newborn B/J rabbits, whereas all three Chbb:HM cell lines did induce a response in newborn Chbb:HM rabbits. These B/J cell lines however could induce antibody response in adult B/J as well as newborn Chbb:HM rabbits, and a Chbb:HM cell line could induce a response in a newborn B/J rabbit. Similar unresponsiveness was observed in (B/J x Chbb:HM)F1 hybrids neonatally inoculated with B/J cells. Unresponsiveness was abrogated by reinoculation of some but not other cell lines. Viral antigen-positive cell lines harboring HTLV-I provirus genomes were established from such seronegative B/J and F1 rabbits. Simultaneous inoculation of HTLV-I-transformed cells and SPV resulted in the induction of papilloma and antibody against SPV, but not antibody against HTLV-I. The present findings thus reveal that neonatal infection of HTLV-I could result in immunological tolerance to the virus antigens, thereby leading to a persistent infection without antibody induction.

Mating preference and the direction of evolution in Drosophila.

Differences in the degree of successful matings between pairs of reciprocal hybrid matings indicate the direction of evolution among related species of Drosophila. Females of a derived species do not mate with males of the ancestral species, whereas females of the ancestral species readily mate with males of the derived species.

Population pharmacokinetics and pharmacodynamics of mycophenolic acid using the prospective data in patients undergoing hematopoietic stem cell transplantation.

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is used to suppress GvHD in patients undergoing hematopoietic stem cell transplantation (HCT). The purpose of this study was to construct a population pharmacokinetic and pharmacodynamic model in HCT patients for individualized MPA therapy. Blood samples were obtained from 49 HCT patients after starting MMF therapy. Population pharmacokinetic and pharmacodynamic parameters were obtained using the program NONMEM. MPA was described via a one-compartment model with a first-order elimination, and 30.9% of MPA glucuronide (MPAG) was found in the enterohepatic circulation. Inosine-5'-monophosphate dehydrogenase (IMPDH) activity was modeled as a maximal inhibitory model with a half-maximal inhibitory concentration (IC50) of 3.59 µg/mL against MPA concentrations. Simulations based on the obtained pharmacokinetic and pharmacodynamic parameters revealed that decreased creatinine clearance increases the MPAG concentration followed by an increased MPA concentration; therefore, IMPDH activity decreases. Diarrhea decreases the enterohepatic circulation of MPAG and consequently reduces MPA concentration. The IC50 for MPA exhibited a positive association with C-reactive protein. Dosage adjustment based on plasma MPA concentration is required especially for patients with renal dysfunction and/or diarrhea.

Human DNA damage induced by 1,2,4-benzenetriol, a benzene metabolite.

Reactivities of benzene metabolites (phenol, catechol, hydroquinone, 1,4-benzoquinone, 1,2,4-benzenetriol) and related polyphenols (resorcinol, pyrogallol, phloroglucinol) with DNA were investigated by a DNA sequencing technique using 32P 5'-end-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene, and the reaction mechanism was studied by UV-visible and electron-spin resonance spectroscopies. 1,2,4-Benzenetriol caused strong DNA damage even without alkali treatment. Alkali-labile sites induced by 1,2,4-benzenetriol were base residues of guanine and adjacent thymine. Catalase, superoxide dismutase and methional inhibited the DNA damage completely, but sodium formate did not inhibit it. 1,2,4-Benzenetriol-induced DNA damage was inhibited by the addition of a Cu(I)-specific chelating agent, bathocuproine, and was accelerated by the addition of Cu(II). The addition of Fe(III) did not create any significant effects on 1,2,4-benzenetriol-induced DNA damage. Electron-spin resonance studies using spin traps demonstrated that addition of Fe(III) increased hydroxyl radical production during the autoxidation of 1,2,4-benzenetriol, whereas the addition of Cu(II) did not. The results suggest that DNA damage was caused by an unidentified active species which was produced by the autoxidation of 1,2,4-benzenetriol in the presence of Cu(II), rather than by hydroxyl radicals. The possibility that 1,2,4-benzenetriol-induced DNA damage is one of the primary reactions in carcinogenesis induced by benzene is discussed.

Hemodynamic simulation study of cerebral arteriovenous malformations. Part 2. Effects of impaired autoregulation and induced hypotension.

The hemodynamic changes occurring during obliteration procedures for arteriovenous malformations (AVM) have not been fully elucidated. Therefore, we undertook a simulation study using a compartmental flow model to investigate the role of altered autoregulatory conditions in the development of hyperperfusion during obliteration of large high-flow AVM. Induced hypotension was also simulated to evaluate its usefulness in reducing the incidence and severity of the event. As the AVM flow was decreased during the obliteration procedures, feeder pressure increased and drainer pressure decreased, with a concomitant increase in the perfusion pressure in the brain tissue surrounding the AVM. Cerebral blood flow (CBF) remained constant at 50 ml 100 g-1 min-1 in the presence of autoregulation and increased to 67 ml 100 g-1 min-1 in its absence. When the lower limit of the autoregulatory pressure range (LAR) was shifted from 60 to 50 or 40 mm Hg, the flow volume increased markedly from 67 to 77 ml 100 g-1 min-1 or to 92 ml 100 g-1 min-1 after complete obliteration. Decrease in LAR would be a cause of the hyperperfusion. Induced systemic hypotension was found to be effective in reducing the magnitude of these hemodynamic changes, when induction was appropriately performed in a stepwise fashion. A simulation study is useful in clarifying the various hemodynamic changes that develop during the treatment of AVM.

Generation of hydrogen peroxide precedes loss of mitochondrial membrane potential during DNA alkylation-induced apoptosis.

Pulsed field gel electrophoresis showed that the initiation time of DNA breakage induced by the DNA alkylating agent duocarmycin A, which is not a redox-cycling agent, was almost the same in the human leukemia cell line HL-60 and its H2O2-resistant clone HP100. Catalase activity of HP100 cells was much higher than that of HL-60 cells. Duocarmycin A-mediated DNA ladder formation in HP100 cells was delayed compared with that in HL-60 cells, suggesting the involvement of H2O2 in duocarmycin A-induced apoptosis. Flow cytometry demonstrated that peroxide formation preceded loss of mitochondrial membrane potential (delta psi m) in cells treated with duocarmycin A. Then, caspase-3 was activated, followed by DNA ladder formation. These findings suggest that DNA damage by duocarmycin A induces H2O2 generation, which causes delta psi m loss and subsequently caspase-3 activation, resulting in apoptosis.

Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds.

DNA damage in cultured cells and in lungs of rats induced by nickel compounds was investigated to clarify the mechanism of nickel carcinogenesis. DNA strand breaks in cultured cells exposed to nickel compounds were measured by using a pulsed field gel electrophoresis technique. Among nickel compounds (Ni(3)S(2), NiO (black), NiO (green), and NiSO(4)), only Ni(3)S(2), which is highly carcinogenic, induced lesions of both double- and single-stranded DNA in cultured human cells (Raji and HeLa cells). Treatment of cultured HeLa cells with Ni(3)S(2) (10 microg/ml) induced a 1.5-fold increase in 8-hydroxy-2'-deoxyguanosine (8-OH-dG) compared with control, whereas NiO (black), NiO (green), and NiSO(4) did not enhance the generation of 8-OH-dG. Intratracheal instillation of Ni(3)S(2), NiO(black), and NiO(green) to Wistar rats increased 8-OH-dG in the lungs significantly. NiSO(4) induced a smaller but significant increase in 8-OH-dG. Histological studies showed that all the nickel compounds used induced inflammation in lungs of the rats. Nitric oxide (NO) generation in phagocytic cells induced by Ni(3)S(2), NiO(black), and NiO(green) was examined using macrophage cell line RAW 264.7 cells. NO generation in RAW 264.7 cells stimulated with lipopolysaccharide was enhanced by all nickel particles. Two mechanisms for nickel-induced oxidative DNA damage have been proposed as follows: all the nickel compounds used induced indirect damage through inflammation, and Ni(3)S(2) also showed direct oxidative DNA damage through H(2)O(2) formation. This double action may explain relatively high carcinogenic risk of Ni(3)S(2).

Effects of verapamil on the contractions of guinea-pig tracheal muscle induced by Ca, Sr and Ba.

A comparison was made of contractions produced by calcium (Ca), strontium (Sr) or barium (Ba) in guinea-pig tracheal smooth muscle after the preparation had been relaxed in Ca-free medium. Most of the experiments were carried out in the presence of indomethacin (5 microM) to inhibit endogenous prostaglandin synthesis. In 40 mM K+ solution, the Ca, Sr and Ba concentrations which produced 50% of maximum tension responses were 0.07 mM, 1 mM and 2 mM, respectively. Maximum tension of a similar size was produced by either 2.4 mM Ca, 9.6 mM Sr or 9.6 mM Ba. The Ca-induced contraction in 5.9 mM K solution, which is probably due to the presence of endogenous prostaglandins, was not significantly affected by verapamil. When the external K concentration was increased to 40 mM, the Ca-induced contraction became susceptible to inhibition by verapamil. Similarly, contractions induced by Sr and Ba in excess K solution were strongly suppressed by verapamil. In the presence of prostaglandin (PG) F2 alpha (1.4 microM) or carbachol (5 microM), Ca, Sr and Ba produced contractions in both the 5.9 mM K and 40 mM K solutions. Contractions produced by PGF2 alpha or carbachol in the presence of Ca were little affected by 10 microM verapamil, whereas those in the presence of Sr or Ba were strongly suppressed by verapamil in both the 5.9 and 40 mM K solutions. 4 A strong suppressant effect of verapamil on the K-induced contraction, but a weak effect on the drug-induced contraction, in the presence of Ca can be explained by assuming that verapamil blocks voltage-operated Ca channels, but not receptor-operated Ca channels. However, this theory cannot account for the effect of verapamil on drug-induced contractions in the presence of Sr or Ba. It may be that susceptibility to verapamil is determined by the relative affinity of'the divalent cations and verapamil for the Ca channels, both for voltage- and receptor-operated channels.

Effect of short-chain fatty acids on Epstein-Barr virus early and viral capsid antigen induction in P3HR-1 cells.

The effects of short-chain fatty acids were assayed for their capacity to induce Epstein-Barr virus (EBV) from the EBV genome-carrying human lymphoblastoid P3HR-1 cells. Not only the n-butyric acid, the activity of which is now well established, but also the n-valeric acid was found to induce EBV-associated early antigen (EA) and viral capsid antigen (VCA) at an appreciable level. Similarly, i-valeric acid showed a considerably lower, but significant, level of this activity, while the i-butyric acid was inactive. All other fatty acids with either a chain shorter than butyric or longer than valeric showed only a marginal effect or none at all. Thus, the decisive factor for EBV-inducing capacity of the fatty acids concerns adequate length and configuration of the basic structure of the molecules.

Similarity of Epstein-Barr virus early polypeptides induced by various tumor promoters.

Epstein-Barr virus (EBV)-harboring non-producer Raji cells were activated to express Epstein-Barr virus early antigen (EA) by the combined use of n-butyrate and various tumor promoters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA), Euphorbiaceae plant extracts and the toxic microbial metabolite, teleocidin. With regard to the structural differences among the inducing agents (promoters), the patterns of EBV early polypeptides were strikingly similar. A common pathway is probably involved in the activation of the latent genomes of the virus in the host cells.

Combined effect of the extracts from Croton tiglium, Euphorbia lathyris or Euphorbia tirucalli and n-butyrate on Epstein-Barr virus expression in human lymphoblastoid P3HR-1 and Raji cells.

The combined usage of n-butyrate and 12-O-tetradecanoylphorbol-13-acetate (TPA) or the oily extracts from Croton tiglium, Euphorbia lathyris or Euphorbia tirucalli exerted a marked effect on induction of Epstein-Barr virus (EBV)-associated early (EA) and viral capsid (VCA) antigens in EBV genome-carrying human lymphoblastoid cell lines. In producer P3HR-1 cells, the enhancing effect of the 2 components was additive both for EA and VCA, while in non-producer Raji cells, a synergistic increase of EA was observed. The possible implication of these findings relating to the cause of EBV-associated diseases is discussed.

Polyclonal increase of HTLV-I provirus-carrying lymphocytes in HTLV-I-carrier rabbits transplanted with Shope carcinoma cells.

Fifteen HTLV-I carrier rabbits of two inbred strains and their F1 hybrid were inoculated with Shope carcinoma cells. The peripheral blood leukocyte counts in all these rabbits increased to 2-4 times the preinoculation level with a concomitant increase in abnormal lymphocytes. Southern blotting analyses of peripheral blood leukocytes revealed the polyclonal integration of HTLV-I proviral genome in all these animals. However, lymphocytic infiltration without any apparent leukemic infiltration was observed in major organs of these animals; a similar but slight lymphocytic infiltration was also observed in non-carrier control animals inoculated with Shope carcinoma cells. These results are interpreted as indicating that the growth of squamous cell carcinoma in HTLV-I carrier rabbits induced the polyclonal expansion of provirus-carrying cells, which may correspond to the intermediate state between healthy carrier and smouldering ATL.

High incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori: impacts of hiatal hernia and corpus gastritis.

BACKGROUND: Although several recent studies have shown that the eradication of Helicobacter pylori provokes reflux oesophagitis, the results are conflicting. AIM: To investigate the prevalence of reflux oesophagitis in patients after eradication of H. pylori and consider its association with hiatal hernia and corpus gastritis. METHODS: A total of 286 patients who underwent H. pylori eradication therapy and 286 age- and disease-matched H. pylori-positive controls who did not undergo eradication therapy were followed prospectively. All patients and controls underwent endoscopy at 1-year intervals or when upper gastrointestinal symptoms recurred. The presence of hiatal hernia and histology of the gastric corpus were evaluated at the time of initial endoscopy. RESULTS: The estimated prevalence of reflux oesophagitis within 3 years was 18% after eradication therapy and 0.3% without therapy. Patients who developed reflux oesophagitis after therapy had a greater prevalence of hiatal hernia (P=0.0008) and more severe corpus gastritis (P=0.0005) before therapy. Cumulative prevalence of reflux oesophagitis was 26% in patients with hiatal hernia, 7.7% in those without hiatal hernia, 33% in those with corpus atrophic gastritis and 13% in those without corpus atrophic gastritis. When patients had both hiatal hernia and corpus gastritis, the prevalence of reflux oesophagitis was 37%. The newly developed reflux oesophagitis was classified as mild in 35 out of 36 (97%) patients who developed reflux oesophagitis after eradication therapy. CONCLUSIONS: Eradication of H. pylori increased the prevalence of reflux oesophagitis in our patient group. The presence of hiatal hernia and corpus gastritis are closely related to the development of reflux oesophagitis after H. pylori eradication therapy.

Neural mechanisms of soleus H-reflex depression accompanying voluntary arm movement in standing humans.

This study have investigated the changes in soleus (Sol) H-reflexes by arm movement during freely standing (FS) and back-supported standing (BS) in healthy subjects. Before the arm movement, there is an anticipatory phase, which includes increased electromyographic (EMG) activity in the biceps femoris (BF) and decreased EMG activity of the Sol muscle. The Sol H-reflex appeared to be inhibited during the anticipatory phase as well as during the time of arm movement. However, the inhibition appeared to be larger in FS than in BS conditions. Vibration applied to the tendon of the BF muscle depressed the Sol H-reflex. This inhibition was attributed to presynaptic inhibition and was reduced during the anticipatory phase, and was not very much changed during arm movements. It is suggested that the depression of the Sol H-reflex induced by voluntary arm movement has two inhibitory components of different origins. Descending motor commands generate the early inhibitory component, while the late component is produced by the presynaptic inhibition that results from peripheral inputs. The inhibition related to anticipatory postural adjustment (APA) indicates that a new-setting of the spinal mechanisms is required and responsible in order to stabilize body equilibrium which is dependent upon different postural conditions.

Posture-dependent modulation of reciprocal inhibition upon initiation of ankle dorsiflexion in man.

The present study tested whether soleus H-reflex depression recorded from normal subjects during isotonic ankle dorsiflexion is due to reciprocal inhibition and this might be modulated by varying postures. The soleus H-reflex amplitude of eight healthy adults was investigated at various times prior to and during tibialis anterior discharge while subjects were seated and when standing. Results showed that the amount of soleus H-reflex depression was significantly larger in the standing than that in the sitting posture in spite of the same dorsiflexion movement. Furthermore, the depression upon initiation of dorsiflexion movement appeared earlier in the standing than in the sitting. The results suggest that increasing amounts of reciprocal inhibition are correlated with and dependent upon the preceding postural conditions for voluntary movement, i.e., modulation of reciprocal inhibition seems to be dictated by the difference in functional demand between sitting and standing posture.

Effects of hypothermia on thrombin-induced brain edema formation.

Recent studies have shown that thrombin plays an important role in brain edema formation after intracerebral hemorrhage (ICH). The possible mechanisms of thrombin-induced brain edema formation include blood-brain barrier (BBB) disruption and inflammatory response involving polymorphonuclear (PMN) leukocyte. Animal experiments have revealed that moderate therapeutic hypothermia improves pathological and functional outcome in various models of brain injury. In this study, we examined the effect of hypothermia on thrombin-induced brain edema formation. Effects of hypothermia on BBB permeability and the accumulation of PMN leukocytes were also determined to clarify the protective mechanism of hypothermia in this model. Anesthetized adult rats received an injection of 10 Units of thrombin into the basal ganglia. Animals were separated into the normothermic and hypothermic groups, which were housed in a room maintained at 25 degrees C and in a cold room maintained at 5 degrees C, respectively, for 24 h after the thrombin injection. The brain temperature in rats housed in a cold room reduced temporarily to approximately 30 degrees C and then gradually recovered to 35 degrees C by the end of the observation. Brain water content in the basal ganglia was significantly reduced in rats treated with hypothermia compared to the normothermic rats (84.3+/-0.2 vs. 82.4+/-0.1%; P<0.01). The decrease of brain water content was accompanied with a significant reduction in BBB permeability to Evan's blue dye and in accumulation of PMN leukocytes. This study indicates that hypothermic treatment significantly reduces thrombin-induced brain edema formation in the rat. Inhibition of thrombin-induced BBB breakdown and inflammatory response by hypothermia appear to contribute to brain protection in this model. Hypothermic treatment may provide an approach to potentially reduce ongoing edema after ICH.

Evidence for facilitation of motor evoked potentials (MEPs) induced by motor imagery.

This study examined the extent to which motor imagery can facilitate to specific pools of motoneurons. Motor commands induced by motor imagery were subthreshold for muscle activity and were presumably not associated with any change in background afferent activity. To estimate excitability changes of flexor carpi radialis (FCR) muscle motoneuron in spinal and cortical level, electric stimuli for recording H-reflex and transcranial magnetic stimulation (TMS) for recording motor evoked potentials (MEPs) were used. During motor imagery of wrist flexion, remarkable increases in the amplitude of the MEP of FCR were observed with no change in the H-reflex. Furthermore, facilitation of antagonist (extensor carpi radialis; ECR) was also observed. Therefore, it is concluded that internal motor command can activate precisely cortical excitability with no change in spinal level without recourse to afferent feedback.

Different mode of action of endothelin-1 in parietal and visceral veins.

The mode of contractile effect of endothelin-1 in venous smooth muscles was evaluated using three isolated veins, the jugular vein, the portal vein and the inferior caval vein of dogs. The contractile responses to endothelin-1 were attenuated by atropine and augmented by neostigmine in the inferior caval and portal veins, but were not affected by either agent in the jugular vein. We conclude that the contractile responses of visceral veins to endothelin-1 are partly mediated via endogenously released acetylcholine.