Community-acquired methicillin-resistant

Autophagy, a major bulk proteolytic pathway, contributes to intracellular protein turnover, together with protein synthesis. Both are subject to dynamic control by amino acids and insulin. The mechanisms of signaling and cross-talk of their physiological anabolic effects remain elusive. Recent studies established that amino acids and insulin induce p70 S6 kinase (p70 S6k ) phosphorylation by mTOR, involved in translational control of protein synthesis. Here, the signaling mechanisms of amino acids and insulin in macroautophagy in relation to mTOR were investigated. In isolated rat hepatocytes, both regulatory amino acids (RegAA) and insulin coordinately activated p70 S6k phosphorylation, which was completely blocked by rapamycin, an mTOR inhibitor. However, rapamycin blocked proteolytic suppression by insulin, but did not block inhibition by RegAA. These contrasting results suggest that insulin controls autophagy through the mTOR pathway, but amino acids do not. Furthermore, micropermeabilization with Saccharomyces aureus ␣-toxin completely deprived hepatocytes of proteolytic responsiveness to RegAA and insulin, but still maintained p70 S6k phosphorylation by RegAA. In contrast, Leu 8 -MAP, a non-transportable leucine analogue, did not mimic the effect of leucine on p70 S6k phosphorylation, but maintained the activity on proteolysis. Finally, BCH, a System L-specific amino acid, did not affect proteolytic suppression or mTOR activation by leucine. All the results indicate that mTOR is not common to the signaling mechanisms of amino acids and insulin in autophagy, and that the amino acid signaling starts extracellularly with their "receptor(s)," probably other than transporters, and is mediated through a novel route distinct from the mTOR pathway employed by insulin.

Compliance with therapy is the single most important factor in Helicobacter pylori (H. pylori) eradication. Poorer levels of compliance with therapy are associated with significantly lower levels of eradication. Numerous factors can contribute to achieving good levels of compliance. These include the complexity and duration of treatment. It is also important that the physician is motivated to ensure eradication is confirmed and the patient is sufficiently informed to empower him or her to achieve high levels of compliance. Compliance is also contingent on medication regimes that are simple, safe, tolerable and efficacious. The opportunity to improve compliance exists at every point of contact between the patient and the medical services. Experts and opinion leaders in the field can play a role by ensuring that physicians are educated and motivated enough to encourage and support compliance with H. pylori eradication therapy. Both patients and physicians need to be aware of the importance of the bacterium in causing disease. The importance of the doctorpatient relationship is paramount. Pragmatic strategies that may be of assistance may come in the form of polypills, combined Blister Packs, adjuvant therapies and modified release compounds. Colleagues such as pharmacists and nurse specialists can also play an important role and should be actively engaged. Structured aftercare and follow up offers the best chance for ensuring compliance and subsequent eradication of the H. pylori pathogen.

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The motility of Helicobacter pylori was maximum at 37°C and at pH 6. A newly developed proton pump inhibitor, rabeprazole (RPZ), and its thioether derivative (RPZ-TH) markedly inhibited the motility of H. pylori. The concentrations of the drug necessary to inhibit 50% of the motility were 0.25, 16, 16, and >64 g/ml for RPZ-TH, RPZ, lansoprazole, and omeprazole, respectively. No such inhibitory effects were observed with H 2 blockers or anti-H. pylori agents. The motilities of Campylobacter jejuni and C. coli-but not those of Vibrio cholerae O1 and O139, Vibrio parahaemolyticus, Salmonella enterica serovar Typhimurium, and Proteus mirabilis-were also inhibited. Prolonged incubation with RPZ or RPZ-TH inhibited bacterial growth of only H. pylori, except for a turbid colony mutant. The results indicate that RPZ and RPZ-TH have a characteristic inhibitory effect against the motility of H. pylori (spiral-shaped bacteria), which is distinguished from that against bacterial growth.Helicobacter pylori, which colonizes the gastric mucosa, is closely associated with gastritis and peptic ulcers (7,17) and is even a bacterial risk factor for gastric cancer (9,10,24,25,27 (1,6,11,14,15,23) as well as urease activity (16,19,26) in vitro.H. pylori is a spiral-shaped, gram-negative bacterium with one or two turns along its axis. It has multiple (four to six) polar flagella, and exhibits strong motility (13). The motility conferred by the flagella is necessary for colonization of the gastric mucosa and development of gastritis by H. pylori (3,4). In this study, we examined the effects of a newly developed PPI, rabeprazole (RPZ), and its thioether derivative (RPZ-TH) on the motility of H. pylori. MATERIALS AND METHODSBacterial strains. H. pylori strains used (seven strains) were isolates from gastric biopsy specimens of patients with gastritis and peptic ulcers. The primary cultures of each isolate were stored frozen at Ϫ80°C in 3% skim milk (Difco Laboratories, Detroit. Mich.) supplemented with 5% glucose (Difco). The following motile, gram-negative bacteria were also employed: Campylobacter jejuni and Campylobacter coli for spiral-shaped bacteria; Vibrio cholerae O1 biotype El Tor strain EO8 (28), V. cholerae O1 biotype classical strain CI3 (28), and V. cholerae O139 strain T16 (30) for curved rods; and V. parahaemolyticus (e.g., strain 100B [29]), Salmonella enterica serovar Typhimurium, and Proteus mirabilis for rods. All bacterial strains except for P. mirabilis were isolates from patients with diarrhea. Media and bacterial growth. H. pylori, C. jejuni, and C. coli were grown on blood agar plates (Trypticase soy agar supplemented with 5% sheep blood; Becton Dickinson, Tokyo, Japan) for 2 (for C. jejuni and C. coli) to 4 (for H. pylori) days at 37°C in a microaerophilic atmosphere (10% O 2 and 10% CO 2 ). The colonies developed were then suspended in brain heart infusion (BHI) broth (Difco) containing 10% fetal bovine serum (FBS) (Gibco, Gaithersburg, Md.), followed by incubation for 18 to 20 h at 37°C in a microaerophilic a...

SUMMARY BackgroundHelicobacter pylori infection is eradicated with antimicrobial agents and drug-resistant strains make successful treatment difficult. Geographical variations in virulence-factor genotype also exist.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) with Panton-Valentine leukocidin (PVL) genes is increasing worldwide. Nosocomial outbreak-derived (hospital-acquired) MRSA (HA-MRSA) in Japan in the 1980s was also largely PVL + . PVL + HA-MRSA and CA-MRSA shared the same multi-locus sequence type (ST30) and methicillin resistance cassette (SCCmecIV), but were divergent in oxacillin resistance, spa typing, PFGE analysis or clfA gene analysis. PVL + HA-MRSA, which probably originated in PVL + S. aureus ST30, was highly adhesive (carrying cna and bbp genes), highly-toxic (carrying luk PV and sea genes) and highly drug-resistant. PVL + HA-MRSA was once replaced by other PVL À HA-MRSA (e.g., ST5), and is re-emerging as CA-MRSA.

Biopsy specimens of the antrum and corpus were obtained from four Helicobacter pylori-infected members of a family and from the same boy (son 1) in whom the infection reappeared after simultaneous successful eradication treatment of three family members, excluding the mother. A total of 18 to 60 H. pylori isolates were obtained from each specimen and subjected to rRNA gene restriction pattern analysis. The father's isolates and the initial isolates from son 1 showed the same HindIII type, which was divided into three HaeIII subtypes. Isolates from the mother and a brother (son 2) and posttreatment isolates from son 1 showed a distinct HindIII type (with one minor subtype), which was divided into six HaeIII subtypes. All subtypes of the initial isolates from son 1 were present in the father's isolates, and all subtypes of the posttreatment isolates from son 1 were present in the mother's isolates but not in son 2's. Electron microscopic analysis of the biopsy specimens demonstrated extremely high levels of H. pylori colonization in the father's gastric mucosa. H. pylori adherence with a ruffle formation was also demonstrated. The findings suggest that son 1 was infected initially with the H. pylori strain of the father and son 2 was infected with the H. pylori strain of the mother and that after eradication therapy son 1 was reinfected with the H. pylori strain of the mother, who did not undergo eradication therapy.Helicobacter pylori colonizes the gastric mucosa via an oral route, and around 60% of individuals worldwide are infected with H. pylori (5). Children are at high risk for H. pylori infections (21, 34). H. pylori infection may persist for years or be lifelong (30,35), although spontaneous clearance is also common in childhood (15,19). H. pylori infection is closely associated with gastritis and peptic ulcers (14, 25), and it is also a bacterial risk factor for gastric cancer (16) and mucosa-associated lymphoid tissue lymphoma (2).The precise mechanisms of H. pylori transmission are not yet known. Previous investigations by Drumm et al. in 1990 (8), Malaty et al. in 1991 (18), and Oderda et al. in 1991 (27) suggested intrafamilial clustering of H. pylori infections. Molecular DNA analyses of familial strains of H. pylori were then performed by Nwokolo et al. in 1992 (26) and by Bamford et al. in 1993 (1), demonstrating intrafamilial infections due to a single H. pylori strain (or a common source of infection within the family). Now, transmission among family members is considered to constitute the main route of H. pylori infection (6).In intrafamilial H. pylori infection, the infected parents, particularly infected mothers, have been considered likely to play a key role in the transmission of H. pylori (4, 28). In contrast, in developing countries, environmental factors may be more important than intrafamilial transmission (29, 32).Those epidemiological studies, however, are not based on molecular biological analysis of H. pylori strains. In this study, we investigated the molecular basis of H. pylor...