Detection of current-sheet and bipolar ion flows in a self-generated antiparallel magnetic field of laser-produced plasmas for magnetic reconnection research.

Magnetic reconnection in laser-produced magnetized plasma is investigated by using optical diagnostics. The magnetic field is generated via the Biermann battery effect, and the inversely directed magnetic field lines interact with each other. It is shown by self-emission measurement that two colliding plasmas stagnate on a midplane, forming two planar dense regions, and that they interact later in time. Laser Thomson scattering spectra are distorted in the direction of the self-generated magnetic field, indicating asymmetric ion velocity distribution and plasma acceleration. In addition, the spectra perpendicular to the magnetic field show different peak intensity, suggesting an electron current formation. These results are interpreted as magnetic field dissipation, reconnection, and outflow acceleration. Two-directional laser Thomson scattering is, as discussed here, a powerful tool for the investigation of microphysics in the reconnection region.

High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

Direct observations of pure electron outflow in magnetic reconnection.

Magnetic reconnection is a universal process in space, astrophysical, and laboratory plasmas. It alters magnetic field topology and results in energy release to the plasma. Here we report the experimental results of a pure electron outflow in magnetic reconnection, which is not accompanied with ion flows. By controlling an applied magnetic field in a laser produced plasma, we have constructed an experiment that magnetizes the electrons but not the ions. This allows us to isolate the electron dynamics from the ions. Collective Thomson scattering measurements reveal the electron Alfvénic outflow without ion outflow. The resultant plasmoid and whistler waves are observed with the magnetic induction probe measurements. We observe the unique features of electron-scale magnetic reconnection simultaneously in laser produced plasmas, including global structures, local plasma parameters, magnetic field, and waves.

Intervention of dementia support team pharmacists and its effects for the proper use of rivastigmine.

Pharmacist participation in the medical team is expected in dementia care. We investigated the use of rivastigmine, the intervention of pharmacists for its proper use, and its effects. The number of prescription proposals from the dementia care team pharmacist to the doctor was 87, and the number of acceptances was 57. The content of the proposal was 31/52 for additions/changes (number of acceptances/number of proposals), 21/28 for dose increase, 3/4 for discontinuation of administration, 2/2 for usage changes, and 1/1 for others. In increasing the dose, the number of patients who increased the maintenance dose to 18 mg was significantly higher in the group with the intervention of the pharmacist in the dementia care team than in the group without the intervention (3/12 cases vs. 0/24 cases, p = 0.031). The dose of the brought-in drug also significantly increased with pharmacist intervention compared with that in the non-intervention group (7/12 cases vs. 1/24 cases, p <0.001). The pharmacists of the dementia care team often intervened in the proper use of rivastigmine, which was found to be effective when increasing the dose. Thus, we believe that the active participation of pharmacists is necessary in dementia medication.

Image-guided core biopsy of 2-cm or smaller renal tumors.

PURPOSE: The purpose of this study was to retrospectively evaluate diagnostic yield, risk factors for diagnostic failure, and safety of image-guided core biopsy of renal tumors≤2cm. MATERIALS AND METHODS: Eighty-four biopsies of 84 renal tumors (mean size, 1.5±0.4[SD] cm; range, 0.6-2.0cm) from 84 patients (53 men, 31 women; mean age, 61.7±12.7 [SD] years; age range, 34-87 years) were included. All adverse events (AEs) were evaluated based on the CIRSE classification. The 84 procedures were classified as diagnostic or nondiagnostic. Multiple variables related to the patients, tumors, and procedures were assessed to identify variables associated with diagnostic failure. RESULTS: All 84 biopsies (100%) were technically successful, defined as penetration of the target and acquisition of some specimens. Eighty (80/84; 95.2%) biopsy procedures were diagnostic and four (4/84; 4.8%) procedures were nondiagnostic. Among 80 diagnosed renal tumors, 71/80 (88.8%) tumors were malignant (49 clear cell renal cell carcinomas [RCCs], 14 papillary RCCs, 3 chromophobe RCCs, 3 metastatic renal cancers, 1 lymphoma, and 1 unclassified RCC) and 9/80 (11.2%) lesions were benign (5 angiomyolipomas, 3 oncocytomas, and 1 inflammatory lesion). No significant differences existed in any variables between the two groups. A total of 57 (57/84; 67.9%) procedures resulted in 56 Grade 1, 2 Grade 2, and 1 Grade 3 AEs. CONCLUSION: Image-guided biopsy of renal tumors≤2cm is safe and has a high diagnostic yield.

Percutaneous thermal ablation for renal cell carcinoma in patients with Birt-Hogg-Dubé syndrome.

PURPOSE: The purpose of this study was to analyze the outcome of patients with Birt-Hogg-Dubé (BHD) syndrome who underwent percutaneous thermal ablation of renal cell carcinoma (RCC). MATERIALS AND METHODS: Six patients with genetically proven BHD syndrome who underwent one or more sessions of percutaneous thermal ablation for the treatment of RCC were included. There were 4 men and 2 women, with a mean age of 57.3±7.5 [SD] years (range: 44-67years). A total of 29 RCCs (1-16 tumors per patient) were treated during 20 thermal ablation sessions (7 with radiofrequency ablation and 13 with cryoablation). Outcomes of thermal ablation therapy were assessed, including technical success, adverse events, local tumor progression, development of metastases, survival after thermal ablation, and changes in renal function. RESULTS: Technical success was achieved in all ablation sessions (success rate, 100%). No grade 4 or 5 adverse events were observed. All patients were alive with no distant metastasis during a median follow-up period of 54months (range: 6-173months). No local tumor progression was found. The mean decrease in estimated glomerular filtration rate during follow-up was 10.7mL/min/1.73m2. No patients required dialysis or renal transplantation. CONCLUSION: Radiofrequency ablation and cryoablation show promising results for the treatment of RCCs associated with BHD syndrome. Percutaneous thermal ablation may be a useful treatment option for this rare hereditary condition.

Magnetic reconnection driven by electron dynamics.

Magnetic reconnections play essential roles in space, astrophysical, and laboratory plasmas, where the anti-parallel magnetic field components re-connect and the magnetic energy is converted to the plasma energy as Alfvénic out flows. Although the electron dynamics is considered to be essential, it is highly challenging to observe electron scale reconnections. Here we show the experimental results on an electron scale reconnection driven by the electron dynamics in laser-produced plasmas. We apply a weak-external magnetic field in the direction perpendicular to the plasma propagation, where the magnetic field is directly coupled with only the electrons but not for the ions. Since the kinetic pressure of plasma is much larger than the magnetic pressure, the magnetic field is distorted and locally anti-parallel. We observe plasma collimations, cusp and plasmoid like features with optical diagnostics. The plasmoid propagates at the electron Alfvén velocity, indicating a reconnection driven by the electron dynamics.

Non-traumatic hemorrhage is controlled with REBOA in acute phase then mortality increases gradually by non-hemorrhagic causes: DIRECT-IABO registry in Japan.

PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is now a feasible and less invasive resuscitation procedure. This study aimed to compare the clinical course of trauma and non-trauma patients undergoing REBOA. METHODS: Patient demographics, etiology, bleeding sites, hemodynamic response, length of critical care, and cause of death were recorded. Characteristics and outcomes were compared between non-trauma and trauma patients. Kaplan-Meier survival analysis was then conducted. RESULTS: Between August 2011 and December 2015, 142 (36 non-trauma; 106 trauma) cases were analyzed. Non-traumatic etiologies included gastrointestinal bleeding, obstetrics and gynecology-derived events, visceral aneurysm, abdominal aortic aneurysm, and post-abdominal surgery. The abdomen was a common bleeding site (69%), followed by the pelvis or extra-pelvic retroperitoneum. None of the non-trauma patients had multiple bleeding sites, whereas 45% of trauma patients did (P < 0.001). No non-trauma patients required resuscitative thoracotomy compared with 28% of the trauma patients (P < 0.001). Non-trauma patients presented a lower 24-h mortality than trauma patients (19 vs. 51%, P = 0.001). The non-trauma cases demonstrated a gradual but prolonged increased mortality, whereas survival in trauma cases rapidly declined (P = 0.009) with similar hospital mortality (68 vs. 64%). Non-trauma patients who survived for 24 h had 0 ventilator-free days and 0 ICU-free days vs. a median of 19 and 12, respectively, for trauma patients (P = 0.33 and 0.39, respectively). Non-hemorrhagic death was more common in non-trauma vs. trauma patients (83 vs. 33%, P < 0.001). CONCLUSIONS: Non-traumatic hemorrhagic shock often resulted from a single bleeding site, and resulted in better 24-h survival than traumatic hemorrhage among Japanese patients who underwent REBOA. However, hospital mortality increased steadily in non-trauma patients affected by non-hemorrhagic causes after a longer period of critical care.

IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype.

BACKGROUND: Genetic markers of susceptibility to asthma exacerbations in adults remain unclear. OBJECTIVE: To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype. METHODS: In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis. RESULTS: Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. CONCLUSIONS AND CLINICAL RELEVANCE: IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.

Examination of factors affecting the intraoral perception of object size: a preliminary study.

Oral sensory function is essential for the successful performance of a range of ingestion. Although the perception of object size is important in determining the degree of manipulation, evidence suggests that people does not always perceive the size of the object in oral cavity accurately. The purpose of this study was to investigate the factors affecting the intraoral perception of object size. Twenty-three healthy young volunteers detected the size of cylinders inserted into oral cavity blindly and identified it from the reference set. The diameter of cross section varied from 10 to 14 mm in a gap of 1 mm and had three different temperatures (5, 36, 50 °C) in each. The perceived size was recorded, and the difference with the actual size was assessed. The required time for identification was also measured and compared between gender and between temperatures. The results demonstrated that the direction of size illusion was significantly affected by the required time for identification. Long manipulation led to overestimation, and short manipulation led to underestimation of object size irrespective of temperature and size. Gender was the other factor affecting intraoral size perception. The rate of overestimation was low in female participants comparing with male participants in this experiment, although the number of participants was limited. We therefore concluded that in order to detect the other factors affecting intraoral size perception, regulating oral manipulation time is indispensable.

Surgery for metastatic spine tumors in the elderly. Advanced age is not a contraindication to surgery!

BACKGROUND: With recent advances in oncologic treatments, there has been an increase in patient survival rates and concurrently an increase in the number of incidence of symptomatic spinal metastases. Because elderly patients are a substantial part of the oncology population, their types of treatment as well as the possible impact their treatment will have on healthcare resources need to be further examined. PURPOSE: We studied whether age has a significant influence on quality of life and survival in surgical interventions for spinal metastases. STUDY DESIGN: We used data from a multicenter prospective study by the Global Spine Tumor Study Group (GSTSG). This GSTSG study involved 1,266 patients who were admitted for surgical treatments of symptomatic spinal metastases at 22 spinal centers from different countries and followed up for 2 years after surgery. PATIENT SAMPLE: There were 1,266 patients recruited between March 2001 and October 2014. OUTCOME MEASURES: Patient demographics were collected along with outcome measures, including European Quality of Life-5 Dimensions (EQ-5D), neurologic functions, complications, and survival rates. METHODS: We realized a multicenter prospective study of 1,266 patients admitted for surgical treatment of symptomatic spinal metastases. They were divided and studied into three different age groups: <70, 70-80, and >80 years. RESULTS: Despite a lack of statistical difference in American Society of Anesthesiologists (ASA) score, Frankel neurologic score, or Karnofsky functional score at presentation, patients >80 years were more likely to undergo emergency surgery and palliative procedures compared with younger patients. Postoperative complications were more common in the oldest age group (33.3% in the >80, 23.9% in the 70-80, and 17.9% for patients <70 years, p=.004). EQ-5D improved in all groups, but survival expectancy was significantly longer in patients <70 years old (p=.02). Furthermore, neurologic recovery after surgery was lower in patients >80 years old. CONCLUSIONS: Surgeons should not be biased against operating elderly patients. Although survival rates and neurologic improvements in the elderly patients are lower than for younger patients, operating the elderly is compounded by the fact that they undergo more emergency and palliative procedures, despite good ASA scores and functional status. Age in itself should not be a determinant of whether to operate or not, and operations should not be avoided in the elderly when indicated.

Simultaneous biopsy and radiofrequency ablation of T1a renal cell carcinoma.

OBJECTIVE: The goal of this study was to retrospectively evaluate the outcome, including feasibility, safety, diagnostic yield, and factors affecting the success of computed tomography fluoroscopy-guided biopsy when performed during the same procedure than radiofrequency ablation (RFA) in renal tumors strongly suspected of being T1a renal cell carcinoma (RCC). MATERIALS AND METHODS: Nineteen patients (13 men, 6 women; mean age, 66.7 years) with a total of 19 suspected renal tumors (mean diameter, 1.8cm) underwent computed tomography fluoroscopy-guided biopsy during (n=6) or immediately after (n=13) RFA. All patients were strongly suspected of having RCC on the basis of patient's medical histories and/or the results of imaging investigations. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the 2 groups using univariate analysis. RESULTS: In all tumors, biopsy procedures were technically feasible. No major complications were observed, except for 8 minor post-procedural bleedings. All but one tumor was completely ablated. Local recurrence in the ablation zone as well as tumor seeding in retroperitoneal fat occurred in 1 patient 8.5months after the procedure and were successfully treated with further percutaneous cryoablation. Thirteen tumors were diagnosed as RCC, whereas 6 were ultimately found to contain normal renal tissue (n=5) or connective tissue (n=1). Univariate analysis revealed that none of the variables were significantly different between the diagnostic and non-diagnostic biopsies. CONCLUSION: The performance of renal tumor biopsy and RFA in the same session is feasible and safe. Although pre-treatment pathological diagnosis would be generally desirable, simultaneous biopsy with RFA can be an option for the patients who are not amenable to pre-treatment biopsy.

A Novel Assessment of Vascular Regions Using an Intraoperative Near-Infrared Fluorescence.

INTRODUCTION: The risk of complications and transplant renal function increases in multiple arterial renal transplantations compared with single arterial renal transplantations. Even when multiple arteries are involved, with the introduction of laparoscopic nephrectomy, I mainly choose the left side kidney. Therefore, the number of renal artery reconstructions is increasing, and simultaneous imaging of arterial rebuilding during the donor nephrectomy is important. MATERIAL: Between 2006 and 2015, we performed 132 living donor kidney transplantations at our center and analyzed 32 cases that were diagnosed pre- and intraoperatively. METHOD: We compared the single renal artery (SRA) and multiple renal arteries (MRA) groups and analyzed the number of renal arteries, reconstruction methods, donor and recipient ages, sex, total ischemic times, and 1-month serum creatinine values. RESULT: In the MRA and SRA groups, the average recipient age was 52.3 and 47.0 years, respectively, while the average donor age was 52.9 and 53.1 years, respectively. In SRA and MRA groups, total ischemic time (TIT) was 96.1 and 143.6 min (P < .01). Serum creatinine level 1 month post-transplantation was 1.54 and 1.25, respectively (P < .001). Here we experienced 12 cases of living renal donor nephrectomy with multiple vessels in which the vascular supply territory was first assessed in April 2013 using an intraoperative near-infrared fluorescence camera system. In addition, regarding TIT, it is possible to shorten surgery by using individual anastomosis and ligation. CONCLUSION: By managing multiple donors; arteries by nephrectomy, it is possible to improve kidney transplantation results.

Immunosuppressive Therapy for Elderly Kidney Transplant Recipients.

OBJECTIVES: In elderly kidney transplant (KT) recipients, the incidence of acute rejection is decreased, while that of fatal infections is increased. There are currently no guidelines for an upper age limit for KT, which is very difficult to determine. Here we examined several cases of elderly KT recipients. METHODS: We evaluated 127 KT patients treated at our department between 2003 and 2012 and followed them for 3 years post-transplant. The subjects were divided into two groups by age: ≥60 years (elderly group; n = 24); and <59 years (non-elderly group; n = 103). The presence or absence of acute rejection and infection, dose of immunosuppressive drugs, trough calcineurin inhibitor level, renal function, and graft and patient survival rates were retrospectively examined. RESULTS: Our basic immunosuppressive regimen was a combination of calcineurin inhibitor, methylprednisolone, mycophenolate mofetil, and basiliximab. At 1 year post-transplantation, the average tacrolimus and cyclosporine dose and trough levels were not significantly different. The mean dose of mycophenolate mofetil in the elderly group at 1 year post-transplantation was significantly lower than that of the non-elderly group. The incidences of cytomegalovirus infection and acute rejection during follow-up did not differ significantly between groups. There were no significant differences in creatinine level between the two groups. In the elderly group, the graft survival rates at 1 and 5 years were 100% and 95.4%, respectively, while those in the non-elderly group were 98.1% and 92.5%, respectively. CONCLUSION: Using our current immunosuppressive protocol, the outcomes of patients in the elderly group were considered acceptable.

A patient with elderly-onset atypical hydroa vacciniforme with an indolent clinical course.

Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun-exposed areas without systemic symptoms. HV-like lymphoma (HVLL) is one of the Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T-cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Elderly-onset cases of these diseases are extremely rare, and the clinical features remain unknown. It has been shown that late onset is closely associated with a severe phenotype in EBV-associated LPD including atypical HV. Here we describe a case of elderly-onset atypical HV accompanied by T-cell monoclonality, but with a very indolent clinical course. Our patient indicates a possible case with elderly-onset atypical HV manifesting a favourable course, and that T-cell monoclonality and age of onset cannot always predict the disease severity, and highlights the difficulty of prognosis prediction in elderly-onset atypical HV.

Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study.

BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.

Patient-reported outcome and quality of life after total en bloc spondylectomy for a primary spinal tumour.

Total en bloc spondylectomy (TES) is the total resection of a vertebra containing a tumour. Many authors have investigated patient-reported outcomes after routine spinal surgery and surgery for tumours in general. However, this is the first report of patient-reported outcomes, including health-related quality of life (HRQoL) and satisfaction, after en bloc vertebral resection for a spinal tumour. Of the 54 patients who underwent TES for a primary tumour between 1993 and 2010, 19 died and four were lost to follow-up. In January 2012, a questionnaire was sent to the 31 surviving patients. This included the short form-36 to assess HRQoL and questions about the current condition of their disease, activities of daily living (ADL) and surgery. The response rate was high at 83.9% (26/31 patients). We found that most patients were satisfied and maintained good performance of their ADLs. The mental health status and social roles of the HRQoL scores were nearly equivalent to those of healthy individuals, regardless of the time since surgery. There was significant impairment of physical health in the early post-operative years, but this usually returned to normal approximately three years after surgery.

GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids.

BACKGROUND: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. METHODS: In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. RESULTS: Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/µl) in the high serum periostin group. CONCLUSIONS: A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.

Insulin stimulates the expression of the SHARP-1 gene via multiple signaling pathways.

The rat enhancer of split- and hairy-related protein-1 (SHARP-1) is a basic helix-loop-helix transcription factor. An issue of whether SHARP-1 is an insulin-inducible transcription factor was examined. Insulin rapidly increased the level of SHARP-1 mRNA both in vivo and in vitro. Then, signaling pathways involved with the increase of SHARP-1 mRNA by insulin were determined in H4IIE rat hepatoma cells. Pretreatments with LY294002, wortmannin, and staurosporine completely blocked the induction effect, suggesting the involvement of both phosphoinositide 3-kinase (PI 3-K) and protein kinase C (PKC) pathways. In fact, overexpression of a dominant negative form of atypical protein kinase C lambda (aPKCλ) significantly decreased the induction of the SHARP-1 mRNA. In addition, inhibitors for the small GTPase Rac or Jun N-terminal kinase (JNK) also blocked the induction of SHARP-1 mRNA by insulin. Overexpression of a dominant negative form of Rac1 prevented the activation by insulin. Furthermore, actinomycin D and cycloheximide completely blocked the induction of SHARP-1 mRNA by insulin. Finally, when a SHARP-1 expression plasmid was transiently transfected with various reporter plasmids into H4IIE cells, the promoter activity of PEPCK reporter plasmid was specifically decreased. Thus, we conclude that insulin induces the SHARP-1 gene expression at the transcription level via a both PI 3-K/aPKCλ/JNK- and a PI 3-K/Rac/JNK-signaling pathway; protein synthesis is required for this induction; and that SHARP-1 is a potential repressor of the PEPCK gene expression.