MRI features of extraocular muscle metastases compared to those of other extraocular muscle diseases of non-thyroid origin.

AIM: To identify the magnetic resonance imaging (MRI) features of metastases to the extraocular muscles (EOM metastases). MATERIAL AND METHODS: The MRI features of 19 patients with EOM metastases were compared with those of 24 patients with EOM diseases of non-thyroid origin. MRI was used to assess the number of tumours, morphology, signal intensity on T2-weighted images, enhancement patterns, and apparent diffusion coefficient (ADC) values. RESULTS: Single muscular involvement was observed in 10 patients, and multiple muscular involvement was observed in nine patients. The morphology was focally discrete in nine patients, and diffuse infiltrative in 10 patients; all the nine patients with focal discrete morphology presented with single muscular lesions. On T2-weighted images, the signal intensities were intermediate or low in 15 patients and a mixture of high and intermediate in four patients. In 14 patients for whom contrast-enhanced images were available, ring enhancement (n=5), heterogeneous diffuse enhancement (n=5), and homogeneous enhancement (n=4) were seen. The mean ADC value was 0.98 × 10-3 mm2/s. Compared to other EOM diseases of non-thyroid origin, single muscular presentation, focal discrete morphology, the presence of hyperintensity on T2-weighted images, and ring or heterogeneous enhancement were significantly more frequent in EOM metastases. CONCLUSION: The MRI features of EOM metastases showed two main patterns: a single discrete mass and multiple infiltrative masses. In addition to the presentation as a single discrete mass, the presence of hyperintensity on T2-weighted images and ring or heterogeneous enhancement can aid in the differentiation of EOM metastases from other EOM diseases.

Kinetic Control of the Li0.9Mn1.6Ni0.4O4 Spinel Structure with Enhanced Electrochemical Performance.

The development of more sustainable societies has become an urgent goal worldwide. Electrical batteries are currently seen as one of the most important energy storage technologies for the development of decarbonized societies. However, many lithium-ion battery manufacturers currently utilize cobalt, a toxic and hazardous mineral, in their batteries. Lithium-deficient manganese nickel oxide spinels are considered promising candidates owing to their high potential and environmental friendliness. Their electrochemical performance highly depends on their average and local structures, such as phase purities, lattice parameters, and cation sites. Thus, a synthesis protocol should be designed to control these structural parameters to improve their electrochemical performance. In this study, we controlled the average and local structures of Li0.9Mn1.6Ni0.4O4 spinels obtained by co-precipitation by optimizing their cooling rates. High-resolution techniques, including transmission electron microscopy, synchrotron X-ray diffraction, and Auger-composition analysis combined with density functional theory calculations, X-ray absorption spectroscopy, and electrochemical analysis, were used to understand the average and local structural variations and their effects on the electrochemical properties. As a result, the control of oxygen diffusion at different cooling rates can promote the rearrangement of the structure, resulting in a cation-disordered spinel with minimal variations in lattice parameters and composition. Excellent electrochemical properties were noted in the cation-disordered spinel with high crystallinity and a slightly oxygen-rich surface produced via optimized cooling rates.

An anatomical hypothesis: a "concentric-structured model" for the theoretical understanding of the surgical anatomy in the upper mediastinum required for esophagectomy with radical mediastinal lymph node dissection.

Understanding the surgical anatomy is the key to reducing surgical invasiveness especially in the upper mediastinal dissection for esophageal cancer, which is supposed to have a significant impact on curability and morbidity. However, there is no theoretical recognition regarding the surgical anatomy required for esophagectomy, although the surgical anatomy in abdominal digestive surgery has been developed on the basis of embryological findings of intestinal rotation and fusion fascia. Therefore, we developed a hypothesis of a 'concentric-structured model' of the surgical anatomy in the upper mediastinum based on human embryonic development. This model was characterized by three factors: (1) a concentric and symmetric three-layer structure, (2) bilateral vascular distribution, and (3) an 'inter-layer potential space' composed of loose connective tissue. The concentric three-layer structure consists of the 'visceral layer', the 'vascular layer', and the 'parietal layer': the visceral layer containing the esophagus, trachea, and recurrent laryngeal nerves as the central core, the vascular layer of major blood vessels surrounding the visceral core to maintain the circulation, and the parietal layer as the outer frame of the body. The bilateral vascular distribution consists of the inferior thyroid arteries and bronchial arteries originating from the bilateral dorsal aortae in an embryo. This bilateral vascular distribution may be related to the formation of the proper mesentery of the esophagus and frequent lymph node metastasis observed in the visceral layer around recurrent laryngeal nerves. The three concentric layers are bordered by loose connective tissue called the 'inter-layer potential space'. This inter-layer potential space is the fundamental factor of our concentric-structured model as the appropriate surgical plane of dissection. The peripheral blood vessels, nerves, and lymphatics transition between each layer, thereby penetrating this loose connective tissue forming the inter-layer potential space. Recurrent laryngeal nerves also transition from the vascular layer after branching off from the vagal nerves and then ascend consistently in the visceral layer. We investigated the validity of this concentric-structured model, confirming the intraoperative images and the surgical outcomes of thoracoscopic esophagectomy in a prone position (TSEP) before and after the introduction of this hypothetical anatomy model. A total of 226 patients with esophageal cancer underwent TSEP from January 2015 to December 2016. After the introduction of this model, the surgical outcomes in 105 patients clearly improved for the operation time of the thoracoscopic procedure (160 min vs. 182 min, P = 0.01) and the incidence of recurrent laryngeal nerve palsy (19.0% vs. 36.4%, P = 0.004). Moreover, we were able to identify the concentric and symmetric layer structure through surgical dissection along the inter-layer potential space between the visceral and vascular layers ('viscero-vascular space') in all 105 cases after introduction of the hypothetical model. The concentric-structured model based on embryonic development is clinically beneficial for achieving less-invasive esophagectomy by ensuring a theoretical understanding of the surgical anatomy in the upper mediastinum.

Effect of Te substitution on crystal structure and transport properties of AgBiSe2 thermoelectric material.

Silver bismuth diselenide (AgBiSe2) has attracted much attention as an efficient thermoelectric material, owing to its intrinsically low lattice thermal conductivity. While samples synthesized using a solid-state reaction showed n-type conductivity and their dimensionless figure of merit (ZT) reached ∼1 by electron doping, theoretical calculations predicted that a remarkably high thermoelectric performance can be achieved in p-type AgBiSe2. In this paper, we present the effect of Te substitution on the crystal structure and thermoelectric properties of AgBiSe2, expecting p-type conductivity due to the shallowing of the energy potential of the valence band. We found that all AgBiSe2-xTex (x = 0-0.8) prepared using a solid-state reaction exhibits n-type conductivity from 300 to 750 K. The room-temperature lattice thermal conductivity decreased to as low as 0.3 W m-1 K-1 by Te substitution, which was qualitatively described using the point defect scattering model for the solid solution. We show that ZT reaches ∼0.6 for x = 0.8 at a broad range of temperatures, from 550 to 750 K, due to the increased power factor, although the carrier concentration has not been optimized yet.

Minerals and Trace Elements in Milk, Milk Products, Infant Formula, and Adult/Pediatric Nutritional Formula, ICP-MS Method: Collaborative Study, AOAC Final Action 2015.06, ISO/DIS 21424, IDF 243.

AOAC Final Action Official MethodSM 2015.06 "Minerals and Trace Elements in Milk, Milk Products, Infant Formula and Adult/Pediatric Nutritional Formula, ICP-MS Method" was collaboratively studied. Note that "milk, milk products" has now been added to the title of the Final Action method because whole milk and several dairy ingredients were successfully incorporated into the collaborative study for the purpose of developing an International Organization for Standardization/International Dairy Federation standard (ISO/DIS 21424; in progress). The method determines sodium, magnesium, phosphorus, potassium, calcium, iron, manganese, zinc, copper, chromium, molybdenum, and selenium by inductively coupled plasma (ICP)-MS after microwave digestion. Ten laboratories participated in the study, and data from five different model ICP-MS units were represented. Thirteen products, five placebo products, and six dairy samples were tested as blind duplicates in this study, along with a standard reference material, for a total 50 samples. The overall repeatability and reproducibility for all samples met Standard Method Performance Requirements put forth by the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals, with a few exceptions. Comparisons are made to ICP-atomic emission data from a collaborative study of AOAC Official Method 2011.14 carried out concurrently on these same samples.

Anti-allodynic action of the disease-modifying anti-rheumatic drug iguratimod in a rat model of neuropathic pain.

OBJECTIVE: Patients with rheumatoid arthritis experience nociceptive as well as neuropathic pain. The effect of iguratimod (IGU), a disease-modifying anti-rheumatic drug, on neuropathic pain in a rat model of chronic constriction injury (CCI) was examined in this study. METHODS: CCI was induced by making four ligations on the left sciatic nerve. Rats with stable signs of static allodynia were selected 2 weeks after the surgery and drug treatments were started (day 0). The test drugs were orally administered once daily for 15 days. The threshold of mechanical pain response in the hind paw was evaluated by the von Frey hair test in a blinded manner. To observe histological changes in the spinal cord, the L4 region was subjected to immunohistochemical analysis for the detection of microglial cells. RESULTS: IGU showed an anti-allodynic effect on CCI-induced neuropathic pain at days 6 and 14, but not at 90 min after the first administration of IGU. This effect of IGU was observed until day 21. Furthermore, IGU decreased the number of Iba-1-positive cells, which had been increased at the ipsilateral side of the dorsal horn by CCI. CONCLUSIONS: These results suggest that IGU suppresses neuropathic pain via a different mechanism from that of current therapeutics.

Adsorption efficiency of natural materials for low-concentration cesium in solution.

In this study, several natural materials were investigated in order to clarify their potential use as cesium (Cs) adsorbents in situ. Four materials--carbonized rice hull, beech sawdust, oak sawdust, and charcoal (Japanese cedar)--which were previously shown to have Cs adsorption capabilities, were examined. Cs adsorption experiments were conducted using different initial Cs and adsorbent concentrations. The physical properties, adsorption isotherms, and adsorption processes were then examined, so as to exploit the Cs adsorption characteristics in the field. Based on these findings, carbonized rice hull and beech sawdust were selected as effective Cs adsorbents. It was found that these materials show continuous and stable Cs adsorption rates for different initial Cs concentrations. The adsorption efficiency of these two adsorption materials in combination was considered, and it was shown that the adsorption isotherms for carbonized rice hull and beech sawdust follow the Freundlich model. Furthermore, the beech sawdust adsorption process exhibited better agreement with the calculated values obtained via the adsorption rate model and the adsorption kinetics model than did the carbonized rice hull adsorption.

The influence of season and air temperature on water intake by food groups in a sample of free-living Japanese adults.

BACKGROUND/OBJECTIVES: To examine the influence of season and climate (air temperature and humidity) on water intake by the food group in a sample of free-living Japanese adults. SUBJECTS/METHODS: Four-nonconsecutive-day, semi-weighed dietary records were collected from each of the four seasons in a single 12-month period (16 days in total). The influence of season and climate on individual water intake by the food group was analyzed using a mixed linear model. Participants were 242 healthy adults (121 women aged 30-69 years and 121 men aged 30-76 years) from four areas in Japan. RESULTS: For women and men together, the mean total water intake was 2230 g/day (highest in summer: 2331 g/day; lowest in winter: 2134 g/day). Fifty-one percent of water was derived from foods and the rest from beverages. In a mixed linear model adjusted for sex, age and body mass index, intake of water from foods decreased by 3.1 g/day and that from beverages increased by 8.4 g/day, with an increase in the mean outdoor air temperature on the survey day of 1 °C (both P < 0.0001). The influence of humidity was nonsignificant. CONCLUSIONS: In contrast to previous findings in Western countries, half of water intake in Japanese adults was derived from foods. Water intake from beverages was positively associated with air temperature, whereas that from foods was inversely associated with air temperature.

Acute effect of oral water intake during exercise on post-exercise hypotension.

BACKGROUND/OBJECTIVES: Post-exercise hypotension (PEH) is a sustained reduction in mean arterial blood pressure (MAP) after prolonged exercise. As water drinking is known to elicit a large acute pressor response, we aimed to explore the effect of drinking water during exercise on PEH. SUBJECTS/METHODS: Ten normotensive male volunteers performed the control protocol: 30 min supine rest, 60 min cycling exercise in moderate intensity, and 60 min supine rest recovery. In the water drinking protocol, the same procedure was followed but with water intake during exercise to compensate for exercise-induced body weight lost. Heart rate, MAP, cardiac output and blood flow in the brachial artery were measured pre- and post-exercise. The total vascular conductance (TVC) and the vascular conductance (VC) in the brachial artery were calculated pre- and post-exercise, and the relative change in plasma volume (ΔPV) was also measured. RESULTS: Body weight loss during exercise was 0.65 ± 0.24 kg in the control. ΔPV was not different during recovery in either protocol. MAP in the control was significantly reduced during the latter half of the recovery compared with baseline. In contrast, MAP in the water drinking showed no reduction during recovery, and was significantly higher than in the control. TVC and VC in the brachial artery were lower in the water drinking, in which vasoconstriction was relatively exaggerated. CONCLUSIONS: Prevention of dehydration after exercise by oral water intake, or oral water intake per se has a role in maintaining post-exercise MAP and it may be related to reduction in TVC.

Gasless laparoscopically assisted myomectomy using a wound retraction system.

INTRODUCTION: The purpose of this study was to elucidate the feasibility of gasless laparoscopically assisted myomectomy (LAM) using a wound retraction system. This method treats symptomatic uterine myomas by combining laparoscopy with a mini-laparotomy to enucleate myoma nodules and to close the uterine myometrium. METHODS: This study includes 275 patients who underwent gasless LAM. For patients with fewer than three myoma nodules, the location of the largest nodule was classified as anterior, fundal, or posterior. The operative outcomes, intraoperative and postoperative courses, and complications were examined. RESULTS: All operations were performed satisfactorily, and no conversions to laparotomy were required. None of the patients developed serious complications. The mean blood loss and operating time were 190.3 mL and 152.2 minutes, respectively. The mean myoma size was 8.9 cm, and the mean number of myomas per patient was 2.8. The average postoperative hospital stay was 5.7 days. There were no significant differences in resected myoma size, blood loss, and surgical duration with respect to the location of the largest nodule. CONCLUSION: Gasless LAM with a wound retractor is feasible and allows surgeons to perform myomectomy safely and cost-effectively, without requiring advanced laparoscopic surgical skills and while maintaining minimum invasiveness.

Doxorubicin, cisplatin, and fluorouracil combination therapy for metastatic esophageal squamous cell carcinoma.

The chemotherapy regimen currently used for treating esophageal and gastric carcinoma has been either epirubicin, cisplatin, and fluorouracil (5-FU) or docetaxel, cisplatin, and 5-FU. Here, we report the efficacy and toxicity of doxorubicin, cisplatin, and 5-FU for only esophageal squamous cell carcinoma (ESCC). Between January 2000 and October 2008, a total of 41 ESCC patients with a distant metastasis were enrolled. The most common sites of metastasis were liver (26, 63.4%), lung (9, 22.0%), and bone (8, 19.5%). Doxorubicin was administered on day 1 at 30 mg/m(2) , cisplatin on days 1-5 at 14 mg/m(2)/day, and 5-FU on days 1-5 at 700 mg/m(2)/day. The median number of cycles was 2.0 (range 1-8). The dose intensities of doxorubicin, cisplatin, and 5-FU were 92.9, 92.4, and 92.5%, respectively. The overall response rate was 43.9%; one showed complete response, 17 showed partial response, 13 showed a stable disease, and 10 showed progressive disease (PD). The median survival time was 306 days (95% CI = 74-935) and the 1-year survival rate was 37.6%. Grade 3 neutropenia was seen in seven patients and grade 4 in one patient. Grade 3 fatigue, anorexia, mucositis, and diarrhea were observed in three, two, two, and one patient, respectively. This regimen is effective as a first-line therapy for ESCC with distant metastasis.

AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC.

Activators of 5'-AMP-activated protein kinase (AMPK) 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), metformin, and exercise activate atypical protein kinase C (aPKC) and ERK and stimulate glucose transport in muscle by uncertain mechanisms. Here, in cultured L6 myotubes: AICAR- and metformin-induced activation of AMPK was required for activation of aPKC and ERK; aPKC activation involved and required phosphoinositide-dependent kinase 1 (PDK1) phosphorylation of Thr410-PKC-zeta; aPKC Thr410 phosphorylation and activation also required MEK1-dependent ERK; and glucose transport effects of AICAR and metformin were inhibited by expression of dominant-negative AMPK, kinase-inactive PDK1, MEK1 inhibitors, kinase-inactive PKC-zeta, and RNA interference (RNAi)-mediated knockdown of PKC-zeta. In mice, muscle-specific aPKC (PKC-lambda) depletion by conditional gene targeting impaired AICAR-stimulated glucose disposal and stimulatory effects of both AICAR and metformin on 2-deoxyglucose/glucose uptake in muscle in vivo and AICAR stimulation of 2-[(3)H]deoxyglucose uptake in isolated extensor digitorum longus muscle; however, AMPK activation was unimpaired. In marked contrast to AICAR and metformin, treadmill exercise-induced stimulation of 2-deoxyglucose/glucose uptake was not inhibited in aPKC-knockout mice. Finally, in intact rodents, AICAR and metformin activated aPKC in muscle, but not in liver, despite activating AMPK in both tissues. The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport. On the other hand, although aPKC is activated by treadmill exercise, this activation is not required for exercise-induced increases in glucose transport, and therefore may be a redundant mechanism.

Role of atypical protein kinase C in activation of sterol regulatory element binding protein-1c and nuclear factor kappa B (NFkappaB) in liver of rodents used as a model of diabetes, and relationships to hyperlipidaemia and insulin resistance.

AIMS/HYPOTHESIS: Previous findings in rodents used as a model of diabetes suggest that insulin activation of atypical protein kinase C (aPKC) is impaired in muscle, but, unexpectedly, conserved in liver, despite impaired hepatic protein kinase B (PKB/Akt) activation. Moreover, aPKC at least partly regulates two major transactivators: (1) hepatic sterol receptor binding protein-1c (SREBP-1c), which controls lipid synthesis; and (2) nuclear factor kappa B (NFkappaB), which promotes inflammation and systemic insulin resistance. METHODS: In Goto-Kakizaki rats used as a model of type 2 diabetes, we examined: (1) whether differences in hepatic aPKC and PKB activation reflect differences in activation of IRS-1- and IRS-2-dependent phosphatidylinositol 3-kinase (PI3K); (2) whether hepatic SREBP-1c and NFkappaB are excessively activated by aPKC; and (3) metabolic consequences of excessive activation of hepatic aPKC, SREBP-1c and NFkappaB. RESULTS: In liver, as well as in muscle, IRS-2/PI3K activation by insulin was intact, whereas IRS-1/PI3K activation by insulin was impaired. Moreover, hepatic IRS-2 is known to control hepatic aPKC during insulin activation. Against this background, selective inhibition of hepatic aPKC by adenoviral-mediated expression of mRNA encoding kinase-inactive aPKC or short hairpin RNA targeting Irs2 mRNA and partially depleting hepatic IRS-2 diminished hepatic SREBP-1c production and NFkappaB activities, concomitantly improving serum lipids and insulin signalling in muscle and liver. Similar improvements in SREBP-1c, NFkappaB and insulin signalling were seen in ob/ob mice following inhibition of hepatic aPKC. CONCLUSIONS/INTERPRETATION: In diabetic rodent liver, diminished PKB activation may largely reflect impaired IRS-1/PI3K activation, while conserved aPKC activation reflects retained IRS-2/PI3K activity. Hepatic aPKC may also contribute importantly to excessive SREPB-1c and NFkappaB activities. Excessive hepatic aPKC-dependent activation of SREBP-1c and NFkappaB may contribute importantly to hyperlipidaemia and systemic insulin resistance.

Surface discharge of heavy metals from low farmland.

Runoff heavy metals from farmland were examined using the field data for the summer of 2005. The observation farmland is located on lowland where the irrigation water was contaminated with the drained water from the upstream farmlands. The area of the farmland is 11.2 ha, of which 6.0 ha and 4.5 ha have been used for rice paddy fields and soybean cultivation, respectively. During the observation, heavy metal concentrations at the downstream end were usually found to be higher than those in the irrigation water. That is, the heavy metal concentrations increased due to the passage of the water through the farmland. This increase in the heavy metal concentrations is not equal to the discharge of the heavy metal because the evaporation on the surface of the paddy field and the absorption by plants makes the surface water volume small. The discharged load from the farmland generally indicates the gross surface load from the farmland. When the effects of circulation irrigation on the heavy metal concentrations are estimated, the discharged load from the farmland should be calculated as the net surface load. When the runoff heavy metals from the circulation irrigation farmland are estimated, it is important to consider the inflowing heavy metals with irrigation water. All the heavy metal types observed in this study were discharged from the farmland. The net surface loads of Cr, Fe, Cd, and Pb were 371 microg m(-2) day(-1), 14.9 mg m(-2) day(-1), 0.26 microg m(-2) day(-1), and 3.3 microm( -2) day(-1), respectively.

Application of the Dental Hygiene Human Needs Conceptual Model and the Oral Health-Related Quality of Life Model to the dental hygiene curriculum in Japan.

This paper reports the incorporation of the Dental Hygiene Human Needs Conceptual Model (DHHN) and the Oral Health-Related Quality of Life Model (OHRQL) into a dental hygiene curriculum in Japan. A simulated patient practice was offered to 67 dental hygiene students. In the practice activity, all students were introduced to the use of an OHRQL assessment tool. A DHHN assessment tool was utilized additionally only by the experimental student group. The statistical analysis of the post-practice survey showed that the OHRQL instrument was more helpful in assessment and problem identification than the DHHN instrument. By contrast, text-based analysis of dental hygiene diagnostic statements showed that the experimental group identified more domains of patients' human needs deficits than the control group. This suggested the possibility that the DHHN model helped them to see patients from broader perspectives. However, it was difficult for students to design care plans attending to the domains of the models. Also, in considerations to the cultural issues, the validity and equivalence of the Japanese versions of both models should be further investigated. Within the limitation of the present study, the results suggested that incorporation of the combination of the DHHN and OHRQL models can be useful in a dental hygiene curriculum, as each tool helps students expand the perspective from which they view client. Further improvements in learning strategies should facilitate the effective utilization of these models.

Metformin improves atypical protein kinase C activation by insulin and phosphatidylinositol-3,4,5-(PO4)3 in muscle of diabetic subjects.

AIMS/HYPOTHESIS: Metformin is widely used for treating type 2 diabetes mellitus, but its actions are poorly understood. In addition to diminishing hepatic glucose output, metformin, in muscle, activates 5'-AMP-activated protein kinase (AMPK), which alone increases glucose uptake and glycolysis, diminishes lipid synthesis, and increases oxidation of fatty acids. Moreover, such lipid effects may improve insulin sensitivity and insulin-stimulated glucose uptake. Nevertheless, the effects of metformin on insulin-sensitive signalling factors in human muscle have only been partly characterised to date. Interestingly, other substances that activate AMPK, e.g., aminoimidazole-4-carboxamide-1-beta-D: -riboside (AICAR), simultaneously activate atypical protein kinase C (aPKC), which appears to be required for the glucose transport effects of AICAR and insulin. METHODS: Since aPKC activation is defective in type 2 diabetes, we evaluated effects of metformin therapy on aPKC activity in muscles of diabetic subjects during hyperinsulinaemic-euglycaemic clamp studies. RESULTS: After metformin therapy for 1 month, basal aPKC activity increased in muscle, with little or no change in insulin-stimulated aPKC activity. Metformin therapy for 8 to 12 months improved insulin-stimulated, as well as basal aPKC activity in muscle. In contrast, IRS-1-dependent phosphatidylinositol (PI) 3-kinase activity and Ser473 phosphorylation of protein kinase B were not altered by metformin therapy, whereas the responsiveness of muscle aPKC to PI-3,4,5-(PO(4))(3), the lipid product of PI 3-kinase, was improved. CONCLUSIONS/INTERPRETATION: These findings suggest that the activation of AMPK by metformin is accompanied by increases in aPKC activity and responsiveness in skeletal muscle, which may contribute to the therapeutic effects of metformin.

The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population.

BACKGROUND: Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process. AIMS: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription. SUBJECTS: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis. METHODS: We identified the IL-8 -251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay. RESULTS: IL-8 -251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 -251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in -251A carriers than in T/T carriers. In the in vitro assay, IL-8 -251A showed enhanced promoter activity in response to IL-1beta or tumour necrosis factor alpha. CONCLUSIONS: The IL-8 -251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.

Impaired activation of protein kinase C-zeta by insulin and phosphatidylinositol-3,4,5-(PO4)3 in cultured preadipocyte-derived adipocytes and myotubes of obese subjects.

Insulin resistance in obesity is partly due to diminished glucose transport in myocytes and adipocytes, but underlying mechanisms are uncertain. Insulin-stimulated glucose transport requires activation of phosphatidylinositol (PI) 3-kinase (3K), operating downstream of insulin receptor substrate-1. PI3K stimulates glucose transport through increases in PI-3,4,5-(PO(4))(3) (PIP(3)), which activates atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt). However, previous studies suggest that activation of aPKC, but not PKB, is impaired in intact muscles and cultured myocytes of obese subjects. Presently, we examined insulin activation of glucose transport and signaling factors in cultured adipocytes derived from preadipocytes harvested during elective liposuction in lean and obese women. Relative to adipocytes of lean women, insulin-stimulated [(3)H]2-deoxyglucose uptake and activation of insulin receptor substrate-1/PI3K and aPKCs, but not PKB, were diminished in adipocytes of obese women. Additionally, the direct activation of aPKCs by PIP(3) in vitro was diminished in aPKCs isolated from adipocytes of obese women. Similar impairment in aPKC activation by PIP(3) was observed in cultured myocytes of obese glucose-intolerant subjects. These findings suggest the presence of defects in PI3K and aPKC activation that persist in cultured cells and limit insulin-stimulated glucose transport in adipocytes and myocytes of obese subjects.