A large intermediate domain of vertebrate REV3 protein is dispensable for ultraviolet-induced translesion replication.

DNA polymerase ζ (pol ζ) is involved in translesion replication (translesion synthesis, TLS) and plays an essential role in embryogenesis. In adults, pol ζ triggers mutation as a result of error-prone TLS and causes carcinogenesis. The catalytic subunit of pol ζ, REV3, is evolutionarily conserved from yeast and plants to higher eukaryotes.

Preproghrelin gene polymorphisms in obese Japanese women. Minor homozygotes are light eaters, do not prefer protein or fat, and apparently have a poor appetite.

Preproghrelin gene single-nucleotide polymorphisms are possible predisposing factors to obesity and other metabolic syndromes. To study the correlation between genotypes and obesity, we recruited 117 obese Japanese women (BMI, 25.0-41.

Caffeine abolishes the ultraviolet-induced REV3 translesion replication pathway in mouse cells.

When a replicative DNA polymerase stalls upon encountering a photoproduct on the template strand, it is relieved by other low-processivity polymerase(s), which insert nucleotide(s) opposite the lesion. Using an alkaline sucrose density gradient sedimentation technique, we previously classified this process termed UV-induced translesion replication (UV-TLS) into two types. In human cancer cells or xeroderma pigmentosum variant (XP-V) cells, UV-TLS was inhibited by caffeine or proteasome inhibitors.

NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol η-dependent translesion DNA synthesis.

Translesion DNA synthesis, a process orchestrated by monoubiquitinated PCNA, is critical for DNA damage tolerance. While the ubiquitin-conjugating enzyme RAD6 and ubiquitin ligase RAD18 are known to monoubiquitinate PCNA, how they are regulated by DNA damage is not fully understood. We show that NBS1 (mutated in Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 to sites of DNA damage.

Rev1, Rev3, or Rev7 siRNA Abolishes Ultraviolet Light-Induced Translesion Replication in HeLa Cells: A Comprehensive Study Using Alkaline Sucrose Density Gradient Sedimentation.

When a replicative DNA polymerase stalls upon encountering a lesion on the template strand, it is relieved by other low-processivity polymerase(s), which insert nucleotide(s) opposite the lesion, extend by a few nucleotides, and dissociate from the 3'-OH. The replicative polymerase then resumes DNA synthesis. This process, termed translesion replication (TLS) or replicative bypass, may involve at least five different polymerases in mammals, although the participating polymerases and their roles have not been entirely characterized.

Preproghrelin gene polymorphisms in obese Japanese: Association with diabetes mellitus in men and with metabolic syndrome parameters in women.

Preproghrelin gene polymorphisms (SNPs) are possible predisposing factors to obesity and metabolic syndrome. We analysed SNPs in obese Japanese individuals and studied the correlation with diabetes and metabolic syndrome. We recruited 235 subjects (BMI > 28.

Proteasome inhibitors remarkably prevent translesion replication in cancer cells but not normal cells.

When a replicative DNA polymerase encounters a lesion on the template strand and stalls, it is replaced with another polymerase(s) with low processivity that bypasses the lesion to continue DNA synthesis. This phenomenon is known as translesion replication or replicative bypass. Failing this, the cell is increasingly likely to undergo apoptosis.

Epidemiological approach to nosocomial infection surveillance data: the Japanese Nosocomial Infection Surveillance System.

Surveillance of nosocomial infection is the foundation of infection control. Nosocomial infection surveillance data ought to be summarized, reported, and fed back to health care personnel for corrective action. Using the Japanese Nosocomial Infection Surveillance (JANIS) data, we determined the incidence of nosocomial infections in intensive care units (ICUs) of Japanese hospitals and assessed the impact of nosocomial infections on mortality and length of stay.

Comparison of contamination between conventional three-way stopcock and needleless injection device: a randomized controlled trial.

Background: Intraluminal contamination of catheter hubs has been recognized as the most frequent cause of catheter-related blood stream infections. We have investigated the efficacy of a new hub device, Planecta SC(R) (PNSC), in preventing endoluminal catheter contamination, compared to a conventional three-way stopcock.

Material/methods: Adults patients requiring an intravascular catheter placement for at least 48 hours in intensive care units were randomly assigned to receive either the infusion device with the newly designed hub, PNSC (P group, n=89), or with a conventional three-way stopcock (C group, n=73).

Measurement of DNA synthesis and strand breaks using alkaline sucrose density gradient centrifugation.

Alkaline sucrose density gradient (ASDG) centrifugation is probably an only method to detect elongation of "pulse-labeled" replication products in cells. If the cells are pulse-labeled after being exposed to some DNA-damaging agents, their "post-replication repair" can be measured by ASDG technique. With non-damaged cells, normal replication in replicon size can be observed, too.

Hyperlactemia can predict the prognosis of liver resection.

Although hyperlactemia is known to accompany hepatic failure and metabolic acidosis, few reports examined the relationships between lactate concentrations and outcome after liver resection. We examined the ability of arterial plasma lactate concentration to predict the patient outcome after hepatectomy. The relationships of arterial lactate and base excess (BE) measured on admission to the intensive care unit (ICU) after hepatectomy to postoperative outcome were investigated in 151 consecutive patients.

Impact of intensive-care-unit(ICU)-acquired ventilator-associated pneumonia(VAP) on hospital mortality: a matched-paired case-control study.

The effect of ICU-acquired ventilator-associated pneumonia (VAP) on hospital mortality is still a controversial issue in many countries. The aim of this study was to evaluate the effect of ICU-acquired VAP on hospital mortality in a Japanese university hospital. Our study population was comprised of patients aged 16 years or older who were admitted to our ICU and received mechanical ventilation for more than 48 hours during a period of 42 months as of December 2003.

Incidence and outcomes of ventilator-associated pneumonia in Japanese intensive care units: the Japanese nosocomial infection surveillance system.

Objectives: To determine the incidence of ventilator-associated pneumonia (VAP) among intensive care unit (ICU) patients in Japan and to assess the impact of VAP on patient outcomes, including mortality, length of stay, and duration of mechanical ventilation.

Design: Multicenter cohort study.

Setting: Twenty-eight ICUs in multidisciplinary Japanese hospitals with more than 200 beds.

[Use of PCR based diagnosis for common invasive fungal infections in the intensive care unit].

Deep-seated Candida infections and invasive aspergilloma are becoming a serious problem for individuals who need intensive care. The laboratory diagnosis of such infections is sometimes delayed due to relatively slow growth of these yeasts from clinical specimens. Several studies seem to indicate that early detection of deep-seated and invasive fungal infections is possible using genomic amplification methods.

Incidence and outcome of sepsis in Japanese intensive care units: The Japanese nosocomial infection surveillance system.

Objectives: To determine the incidence of sepsis in Japanese intensive care units (ICUs) and to evaluate the impact of sepsis on mortality and length of stay (LOS).

Methods: Using the JANIS database for the period between June 2002 and June 2004, 21,895 eligible patients aged ≥16 years, hospitalized in 28 participating ICUs for ≥24 hours, were monitored until ICU discharge. Adjusted hazard ratio (HR) with 95% confidence interval (CI) for the incidence of sepsis was calculated using Cox's proportional hazard model.

A novel Rad18 function involved in protection of the vertebrate genome after exposure to camptothecin.

In Saccharomyces cerevisiae, Rad18 functions in post-replication repair pathways, such as error-free damage bypass involving Rad30 (Poleta) and error-prone damage bypass involving Rev3/7 (Polzeta). Chicken DT40 RAD18(-/-) cells were found to be hypersensitive to camptothecin (CPT), while RAD30(-/-) and REV3(-/-) cells, which are defective in translesion DNA synthesis, were not. RAD18(-/-) cells also showed higher levels of H2AX phosphorylation and chromosomal aberrations, particularly chromosomal gaps and breaks, upon exposure to CPT.

Time to change diagnostic criteria of ARDS: towards the disease entity-based subgrouping.

Because of high mortality and morbidity, acute respiratory distress syndrome (ARDS) continues to be one of the clinical challenges for intensivists. The diagnostic criteria for ARDS published by the American-European consensus conference were over simplified and made it possible to conduct large-scale randomized controlled trails (RCTs). Thus, many RCTs have been conducted in attempts to evaluate new treatment modalities, but many have reported negative results, in part because this definition was too broad to be used as diagnostic criteria.

[Polymorphisms related to SIRS and inflammatory response].

Recently, susceptibility and outcome of disease are proved to depend on some gene polymorphisms. Here, we review of gene polymorphisms and its contributions to systemic inflammatory response syndrome (SIRS) and inflammation. The relationships of many polymorphisms, such as TNF, IL-1, PAI-1, TLR, etc.

[Nutritional therapy in acute pancreatitis].

In this review, systematic search of literatures for acute pancreatitis and nutrition was performed. Eleven randomized controlled trials (RCT) were found. Eight of them are about parenteral or enteral nutrition, 2 are about immunomodulated nutrition, and one is nutritional method in postoperative period.

Association between APACHE II score and nosocomial infections in intensive care unit patients: A multicenter cohort study.

Objective: To examine whether nosocomial infection risk increases with APACHE II score, which is an index of severity-of-illness, in intensive care unit (ICU) patients.

Methods: Using the Japanese Nosocomial Infection Surveillance database, 8,587 patients admitted to 34 participating ICUs between July 2000 and May 2002, aged 16 years or older, who had stayed in the ICU for 2 days or longer, had not transferred to another ICU, and had not been infected within 2 days after ICU admission, were followed until ICU discharge, Day 14 after ICU admission, or the development of nosocomial infection. Adjusted odds ratios with their 95% confidence intervals for nosocomial infections were calculated using logistic regression models, which incorporated sex, age, operation, ventilator; central venous catheter, and APACHE II score (0-5, 6-10, 11-15, 16-20, 21-25, 26-30, and 31+).

Comparison of proportional hazard model and neural network models in a real data set of intensive care unit patients.

There has been increased interest in using neural network model (NNM) for prognosis tasks. However, the performance of NNM has seldom been compared with that of traditional statistical models such as proportional hazard model (PHM) in real data sets. We conducted a comparative study of PHM and two types of NNM, that is, aggregate single point model (ASPM) and multiple point model (MPM), using a real data set of intensive care unit patients.

Impact of intensive care unit-acquired infection on hospital mortality in Japan: A multicenter cohort study.

Objectives: To elucidate factors associated with hospital mortality in intensive care unit (ICU) patients and to evaluate the impact of ICU-acquired infection on hospital mortality in the context of the drug resistance of pathogens.

Methods: By using the Japanese Nosocomial Infection Surveillance (JANIS) database, 7,374 patients who were admitted to the 34 participating ICUs between July 2000 and May 2002, were aged 16 years or older, and who stayed in the ICU for 48 to 1,000 hours, did not transfer to another ICU, and did not become infected within 2 days after ICU admission, were followed up until hospital discharge or to Day 180 after ICU discharge. Adjusted hazard ratios (HRs) with the 95% confidence intervals (CIs) for hospital mortality were calculated using Cox's proportional hazard model.

Translesion replication in cisplatin-treated xeroderma pigmentosum variant cells is also caffeine-sensitive: features of the error-prone DNA polymerase(s) involved in UV-mutagenesis.

Patients with xeroderma pigmentosum variant (XP-V) have a higher risk to skin cancer and XP-V cells are extremely mutable by ultraviolet (UV). The defective gene encodes a DNA polymerase (Poleta) which catalyzed relatively accurate translesion synthesis past the cyclobutane dimer of UV-lesions instead of the replicative polymerase(s) that stalled just before the lesion. Pulse-chase studies have shown that translesion replication in XP-V cells is delayed, but does not completely cease.

[Current guideline for hospital infection control in Japan].

The Committee for Prevention of Nosocomial Infection organized by national university hospitals has developed guideline for preventing hospital acquired infections. This was developed after intensive and systematic reviews of the existing scientific papers, followed by a consensus meeting with presence of the infection control specialists. The guideline consisted of following categories: standard precaution, causality organism, urinary tract infection, ventilator associated pneumonia, surgical site infection, catheter related bloodstream infection, and accidental contamination by needles.