Ubiquitin-like protein MNSFß regulates glycolysis and promotes cell proliferation with HSC70 assistance.

Monoclonal non-specific suppressor factor ß (MNSFß) is a universally expressed ubiquitin-like protein that has multiple biological functions. MNSFß modifies its target molecules through covalent conjugation. Most recently, we identified a molecular chaperone, HSC70, that facilitates the stabilization of aggregable MNSFß. In the current study, we determined the role of HSC70 in stabilizing unstable MNSFß. HSC70 promoted the correct folding of MNSFß both in vitro and in vivo. We also examined the regulatory function of MNSFß in cell proliferation and glycolysis. MNSFß siRNA and HSC70 siRNA treatment attenuated lactate release from Raw264.7 macrophage-like cells. MNSFß siRNA inhibited glucose uptake in Raw264.7 cells. We found that glucose transporter 1 (GLUT1) is an important membrane protein involved in the regulatory function of MNSFß during glycolysis. MNSFß siRNA inhibited the increased GLUT1 expression in LPS-stimulated cells, suggesting that MNSFß controls the inflammatory response through GLUT1 regulation. We identified several important molecules, including lactate dehydrogenase A, which are regulated by MNSFß and involved in glucose metabolism. Here we firstly report that MNSFß regulates glycolysis and promotes cell proliferation.

Treatment of Chronic Bony Mallet Fingers by Dorsal Extension Block Pinning with Percutaneous Curettage.

Dorsal extension block pinning is a commonly performed surgical technique for acute bony mallet fingers. However, the treatment of chronic bony mallet finger remains controversial. We investigated the use of dorsal extension block pinning with percutaneous curettage for chronic bony mallet fingers. Seven patients with chronic bony mallet fingers were treated by dorsal extension block pinning with percutaneous curettage. The average age was 17 (range, 12-23) years, and the average time from injury to surgery was 20 (range, 7-49) weeks. Bone union was achieved in all patients. None of the patients experienced pain after bone union. The average loss of distal interphalangeal joint extension was 6 (range, 5-20) degrees, and the average flexion was 59 (range, 40-80) degrees. The Crawford functional score was excellent in three patients, good in two, and fair in two. Dorsal extension block pinning with percutaneous curettage could be a useful treatment for chronic bony mallet fingers.

The analgesic efficacy of ultrasound-guided transversus abdominis plane block with mid-axillary approach after gynecologic laparoscopic surgery: A randomized controlled trial.

BACKGROUND AND AIMS: The transversus abdominis plane (TAP) block is widely used in clinical practice as a part of the multimodal analgesic regimen after abdominal surgery. The analgesic efficacy of ultrasound (US)-guided TAP block with the mid-axillary approach was investigated in patients undergoing laparoscopic gynecologic surgery in a randomized controlled clinical trial. MATERIALS AND METHODS: Adult patients (n = 119) undergoing laparoscopic gynecologic surgery were randomized to undergo either TAP block with ropivacaine (Group A, n = 60) or that with saline (Group B, n = 59), in a blinded manner. Following general anesthesia, TAP block was performed bilaterally by infusion of either 20-mL 0.375% ropivacaine/one side in Group A or 20-mL saline/one side in Group B, under US guidance with a mid-axillary approach. Patient-controlled analgesia (PCA) was performed postoperatively with tramadol. The analgesic effect was postoperatively evaluated using a four-grade pain score and the prince Henry pain scale (PHS) at 0, 6, 12, and 24 h. Postoperative tramadol PCA consumption and vomiting/nausea were recorded. Statistical analyses were performed using the Mann-Whitney U-test or Fisher's exact probability test. A P < 0.05 was considered significant. RESULTS: There was no statistically significant difference in background characteristics. The dose of remifentanil was significantly higher in Group B (P = 0.01). The pain score (P = 0.02) and PHS (P = 0.01) were significantly lower in Group A at 0 h. Tramadol PCA consumption in the period of 0-6 h (P = 0.01) and postoperative nausea (P = 0.04) were significantly less in Group A. CONCLUSION: Postoperative pain/nausea and PCA consumption were significantly lower in patients with TAP block in the early postoperative stage. TAP block with a mid-axillary approach holds considerable promise as a part of a balanced postoperative analgesic regimen following laparoscopic gynecologic surgery.

Soy and Soy Products Intake, All-Cause Mortality, and Cause-Specific Mortality in Japan: The Jichi Medical School Cohort Study.

Soy and soy products are popular ingredients in the Japanese diet. This study aimed to determine whether soy or soy products intake was associated with all-cause mortality in a community-based cohort in Japan. A total of 11 066 participants were obtained from an annual community-based health examination program. A self-administered questionnaire was used to collect information concerning soy and soy products intake and potential confounding factors. Associations between soy and soy products intake and all-cause mortality were assessed using hazard ratios (HRs). After adjusting for all factors, morality was significantly higher in men with infrequent soy intake (HR = 1.53; 95% confidence interval [CI] = 1.13-2.07) and with almost daily intake (HR = 1.55; 95% CI = 1.19-2.03) compared with intake 1 to 2 times per week. Cancer mortality was higher among men who reported rarely eating soy (HR = 1.74; 95% CI = 1.08-2.79). Soy products intake was not statistically significantly associated with all-cause mortality in both sexes.

Usefulness of distal motor latency measurement after palmar stimulation in advanced carpal tunnel syndrome.

The measurement of distal motor latency (DML) after palmar stimulation distal to the carpal tunnel (Palmar-DML) was investigated before carpal tunnel release (CTR) in 48 advanced carpal tunnel syndrome (CTS) with thenar atrophy and absence of motor and sensory responses after wrist stimulation. This allowed measurement of the direct effects of stimulation, in assessing the pathologic condition of the median nerve. Palmar-DML was measurable in 47 of 48 hands preoperatively, which responded to CTR with improvement of thenar atrophy at 1 year postoperatively. Also, electrophysiologic recovery presenting reappearance of DML after wrist stimulation was shown in 43 hands of those 47 hands. Furthermore, sensory nerve conduction velocity was measurable in 24 hands. In contrast, in one hand with the absence of Palmar-DML, CTR neither relieved thenar atrophy nor induced measurable Palmar-DML. This study demonstrated that Palmar-DML was measurable in most advanced CTS, which suggested the major abnormality was focal demyelination. This was confirmed by electrophysiologic and clinical improvement obtained after CTR. Palmar-DML measurement was useful to elucidate the median nerve condition in advanced CTS.

Carpal tunnel syndrome associated with a fracture of a silicone implant for Kienböck's disease: two case reports.

In this report, two cases presenting with CTS including a fracture of the silicone implant for Kienböck's disease after replacement over 20 years postoperatively where CTR ceased the symptoms of CTS. The major symptom characteristic was the median nerve impairment with less emphasis on the limited range of motion of the wrist or wrist pain due to a fracture of the silicone implant. There was an unlikely association between the fracture of the implant and CTS, which was confirmed by the operative findings of tenosynovitis and thickness of the degenerated transverse ligament without a significant protrusion of the silicone implant.

[Influence of general anesthesia in pregnant patients for gynecologic surgery].

BACKGROUND: Surgery during pregnancy is suspected to have various harmful influences to pregnant patients and fetuses. Although laparoscopic surgery has been recently reported to have some advantages over open surgery in this condition, it often requires general anesthesia. METHODS: The influence of general anesthesia was retrospectively investigated in 12 patients having undergone gynecologic surgery during pregnancy in comparison with 18 with surgery under lumbar and epidural anesthesia. RESULTS: Patients receiving general anesthesia required less pain relief compared with those receiving lumbar and epidural anesthesia. Pregnancy was adequately maintained after surgery in all patients. No abortions or preterm deliveries occurred. There was no significant difference in influence on mother and babies between these two patient groups. CONCLUSIONS: General anesthesia during pregnancy is not necessarily associated with harmful influences on mother and babies compared with lumbar and epidural anesthesia if selected appropriately.

[Trends of HIV patients operated at International Medical Center of Japan].

BACKGROUND: HIV-infected patients are on the increase in Japan, and anti-HIV therapy improved their prognosis. It is expected that the number of operations in HIV patients will increase. METHODS: We surveyed the prevalence of HIV 30,188 patients operated at International Medical Center of Japan, a major, HIV/AIDS hospital, from 2001 to 2007. RESULTS: The number of HIV-positive cases was 389 in 7 years, and the prevalence of HIV seropositivity was 1.3% in total, 1.0% in scheduled, and 2.0% in emergent cases. The prevalence of male (2.0%) was higher than female (0.7%) patients and the prevalence was highest (9.2%) in male patients in their 30's. They were parallel with the HIV occurrence trend of Japan. The prevalence was the highest (2.4%) in the division of general surgery, as well as in obstetric and gynecology. The number of major surgery in HIV patients has been increasing. CONCLUSIONS: We assume that the perioperative management in each hospital has become more important. The annual trend of the number of the operations performed in HIV-positive patients at our hospital did not show annual changes.

[Effects of rikkunshito on the postoperative nausea and vomiting (PONV) after laparoscopic gynecological surgery].

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of unignorable complications after general anesthesia. The aim of this study was to examine prophylactic effects of TSUMURA rikkunshito (TJ-43), a herbal medicine consisting of eight herbs, on PONV after laparoscopic surgery. METHODS: One hundred and forty-two female patients undergoing gynecological laparoscopic surgery (ASA-PS1-2) were randomly allocated to one of two groups receiving rikkunshito (n = 91) and control (n = 51). The oral administration of 2.5 g of TJ-43 was commenced the night before surgery and was continued for 3 days after surgery. The suppository form containing 1.5 g of TJ-43 was used during surgery. RESULTS: There were no significant differences of the incidence of PONV between the two groups. The patterns of change in the degree of PONV were similar between the two groups, although TJ-43 group showed slightly earlier reduction in symptom scores. The patients with TJ-43 showed earlier postoperative recovery of oral meal intake. CONCLUSIONS: Perioperative administration of TJ-43 showed a possible effectiveness to reduce the severity of PONV and to promote earlier recovery of oral meal intake after gynecological laparoscopic surgery.

[Diagnosis and transfusion algorithm for the management of perioperative coagulopathy].

The present article reviewed the management of coagulopathy in the perioperative setting, following the Japanese practical guidelines for the blood component therapy, edited by the Ministry of Health, Labour and Welfare of Japan in 2005. The threshold concentrations of platelets, prothrombin time international normalized ratio (PT-INR) and activated partial thromboplastin time (APTT) were optimized for the perioperative critical care under active and/or microvascular bleeding, based on currently available randomized controlled trials. Discontinuation or modification of anticoagulants as well as antiplatelets is essential for the safe perioperative care. Several factors, including normothermia, normovolemia, as well as the maintenance of plasma calcium levels within normal range, are important for the management of coagulopathy. Platelet counts, PT, APTT, and if possible, other point-of-care testing including thromboelastography and its modified techniques should be performed following visual inspection of abnormal bleeding. The transfusion algorithms based on causal diagnosis of coagulopathy optimize the risk/ benefit ratio of perioperative transfusion therapy.

Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis.

Oxidative stress is a persistent threat to the genome and is associated with major causes of human mortality, including cancer, atherosclerosis, and aging. Here we established a method to generate libraries of genomic DNA fragments containing oxidatively modified bases by using specific monoclonal antibodies to immunoprecipitate enzyme-digested genome DNA. We applied this technique to two different base modifications, 8-hydroxyguanine and 1,N6-propanoadenine (acrotein-Ade), in a ferric nitrilotriacetate-induced murine renal carcinogenesis model. Renal cortical genomic DNA derived from 10- to 12-week-old male C57BL/6 mice, of untreated control or 6 hours after intraperitoneal injection of 3 mg iron/kg ferric nitrilotriacetate, was enzyme digested, immunoprecipitated, cloned, and mapped to each chromosome. The results revealed that distribution of the two modified bases was not random but differed in terms of chromosomes, gene size, and expression, which could be partially explained by chromosomal territory. In the wild-type mice, low GC content areas were more likely to harbor the two modified bases. Knockout of OGG1, a repair enzyme for genomic 8-hydroxyguanine, increased the amounts of acrolein-Ade as determined by quantitative polymerase chain reaction analyses. This versatile technique would introduce a novel research area as a high-throughput screening method for critical genomic loci under oxidative stress.

Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis

Oxidative stress is a persistent threat to the genome and is associated with major causes of human mortality, including cancer, atherosclerosis, and aging. Here we established a method to generate libraries of genomic DNA fragments containing oxidatively modified bases by using specific monoclonal antibodies to immunoprecipitate enzyme-digested genome DNA. We applied this technique to two different base modifications, 8-hydroxyguanine and 1,N6-propanoadenine (acrotein-Ade), in a ferric nitrilotriacetate-induced murine renal carcinogenesis model. Renal cortical genomic DNA derived from 10- to 12-week-old male C57BL/6 mice, of untreated control or 6 hours after intraperitoneal injection of 3 mg iron/kg ferric nitrilotriacetate, was enzyme digested, immunoprecipitated, cloned, and mapped to each chromosome. The results revealed that distribution of the two modified bases was not random but differed in terms of chromosomes, gene size, and expression, which could be partially explained by chromosomal territory. In the wild-type mice, low GC content areas were more likely to harbor the two modified bases. Knockout of OGG1, a repair enzyme for genomic 8-hydroxyguanine, increased the amounts of acrolein-Ade as determined by quantitative polymerase chain reaction analyses. This versatile technique would introduce a novel research area as a high-throughput screening method for critical genomic loci under oxidative stress.

Tissue distribution of Thorotrast and role of internal irradiation in carcinogenesis.

Carcinogenesis in Thorotrastosis has been assumed due to direct bombardment by alpha-particle with high linear energy transfer during decay of 232Th. To revisit the mechanism of carcinogenesis by Thorotrast (THR), we examined the tissue distribution of THR granules and two-dimensional distribution of radioactivity in the organs of Thorotrastosis patients and studied their spatial relationship to histopathological changes. The high radioactivity in the patients' organ was predominantly derived from decay of Thorium series and showed unique distribution, while the far lower natural radioactivity was mainly from Uranium series decay and fairly evenly distributed. It was found that a large majority of THR granules were phagocytized by macrophages and were embedded in extensive fibrosis. Cancer was rarely in the center of THR deposition but rather at a distance from the deposits. These observations may indicate that the predominant feature of THR deposition is the tissue damage by direct hit of alpha-particles and subsequent fibrosis. The effect of THR resembles action of toxic chemical agents, as several authors have pointed out. We therefore assume that carcinogenesis in Thorotrastosis is a combination of events, such as regeneration of liver tissue after radiation damage, emission of secondary electrons, ionization of the surrounding tissue, and beta- or gamma-ray from daughter nuclei of Thorium (Th). In this context, the role of alpha-particle is important but more intriguing.

Diabetes attenuates the hemodynamic stabilizing effects of oral clonidine during off-pump coronary artery bypass surgery.

STUDY OBJECTIVE: To investigate the influence of diabetes mellitus on the hemodynamic-stabilizing effect of clonidine during off-pump coronary artery bypass (OPCAB) surgery. DESIGN: Prospective study. SETTING: Public, university-affiliated hospital. PATIENTS: 40 patients (32 male, 8 female) scheduled for OPCAB surgery. INTERVENTIONS AND MEASUREMENTS: Patients were divided into equal groups of diabetic and nondiabetic patients. All patients were given 150 microg oral clonidine 1 hour before induction. Anesthesia was induced and maintained with fentanyl, propofol, and sevoflurane. Propranolol was administered intermittently to maintain an adequate heart rate (HR; 50 to 70 bpm). Preoperative demographic data (fasting blood glucose concentration and hemoglobin A1c), dose of intraoperative drugs (propofol and propranolol), and outcome data (duration of intubation and duration of hospital stay after surgery) were analyzed. MAIN RESULTS: In the diabetic and nondiabetic groups, the mean (+/-SD) plasma glucose values were 7.8 +/- 2.3 mmoL. L(-1) and 5.4 +/- 0.7 mmoL. L(-1), respectively (p < 0.05), and the mean (+/-SD) HbA1c values were 7.1 +/- 1.3% and 5.2 +/- 0.4%, respectively (p < 0.05). The mean propofol infusion rate was 2.8 +/- 0.9 mg. kg(-1). h(-1) in diabetic patients and 3.1 +/- 1.0 mg. kg(-1). h(-1) in nondiabetics (NS, p > 0.05). The total requirement for propranolol was 5.1 +/- 2.4 mg in diabetic patients and 1.6 +/- 1.1 mg in nondiabetics (p < 0.05). CONCLUSIONS: Diabetes attenuates the hemodynamic stabilizing effects of preanesthetic oral clonidine in the clinical setting.