Autoimmunity to citrullinated type II collagen in rheumatoid arthritis

The production of autoantibodies to citrullinated type II collagen and the citrullination of type II collagen were analyzed in rheumatoid arthritis. Autoantibodies to citrullinated type II collagen were detected in 78.5% of serum samples from 130 rheumatoid arthritis patients. Autoantibodies to native noncitrullinated type II collagen were detected in 14.6% of serum samples, all of which were positive for anti-citrullinated type II collagen antibodies. Serum samples were also positive for anti-citrullinated type II collagen antibodies in 1 of 31 systemic lupus erythematosus patients and 2 of 55 patients with osteoarthritis of the knee. In contrast, sera samples from 24 systemic sclerosis patients, 21 dermatomyositis/polymyositis patients, 21 ankylosing spondylitis patients, and 18 psoriatic arthritis patients were all negative for anti-citrullinated type II collagen antibodies. Anti-citrullinated type II collagen antibodies and fragments of citrullinated type II collagen were found in the synovial fluid obtained from affected knee joints of 15 rheumatoid arthritis patients. Moreover, anti-citrullinated type II collagen antibodies were isolated from the synovium of affected knee joints in 8 rheumatoid arthritis patients using antigen/antibody immunocomplex dissociation buffer but not by using standard buffers. These findings indicate that autoantibodies that react with citrullinated type II collagen are specifically produced and that immunocomplexes composed of fragments of citrullinated type II collagen and autoantibodies are deposited in the inflamed articular synovium in rheumatoid arthritis patients. Assaying for the presence of anti-citrullinated type II collagen antibodies may therefore be useful for diagnosing rheumatoid arthritis, and the deposition of these immunocomplexes in the articular synovium may be involved in pathogenesis

Experimental investigation of a control scheme for a tuned resonant sideband extraction interferometer for next-generation gravitational-wave detectors

LCGT plans to use tuned RSE as the optical configuration for its interferometer. A tuned RSE interferometer has five degrees of freedom that need to be controlled in order to operate a gravitational-wave detector, although it is expected to be very challenging because of the complexity of its optical configuration. A new control scheme for a tuned RSE interferometer has been developed and tested with a prototype interferometer to demonstrate successful control of the tuned RSE interferometer. The whole RSE interferometer was successfully locked with the control scheme. Here the control scheme and the current status of the experiment are presented

Construction of Eco-system for NTBFs to Thrive, Grow and Agglomerate (Japanese)

Boston, Massachusetts in the U.S. was able to rejuvenate its economy after WWП through the thrift, growth and agglomeration of MIT-born New Technology-based Firms (NTBFs), which have been categorized as the origin of new venture firms. This paper will explain why some areas like Boston, Silicon Valley, and Austin TX in the U.S. and Cambridge in the UK, were able to construct successful Eco-systems for NTBFs to thrive, grow and agglomerate, while others were unsuccessful, by applying the Eco-system Construction Model deducted from previous studies. Based on the research findings of this paper, we also outline our recommendations for a revision of the U.S. innovation model by clarifying its advantages and disadvantages. The U.S. model was introduced in Japan at the end of the 1990s and prompted a number of new innovation policy projects including the '1000 University Start-up Venture Scheme', the 'Industrial Cluster Project' and the 'Knowledge Cluster Initiative.'

Nutrient-Regulated Antisense and Intragenic RNAs Modulate a Signal Transduction Pathway in Yeast

The budding yeast Saccharomyces cerevisiae alters its gene expression profile in response to a change in nutrient availability. The PHO system is a well-studied case in the transcriptional regulation responding to nutritional changes in which a set of genes (PHO genes) is expressed to activate inorganic phosphate (Pi) metabolism for adaptation to Pi starvation. Pi starvation triggers an inhibition of Pho85 kinase, leading to migration of unphosphorylated Pho4 transcriptional activator into the nucleus and enabling expression of PHO genes. When Pi is sufficient, the Pho85 kinase phosphorylates Pho4, thereby excluding it from the nucleus and resulting in repression (i.e., lack of transcription) of PHO genes. The Pho85 kinase has a role in various cellular functions other than regulation of the PHO system in that Pho85 monitors whether environmental conditions are adequate for cell growth and represses inadequate (untimely) responses in these cellular processes. In contrast, Pho4 appears to activate some genes involved in stress response and is required for G1 arrest caused by DNA damage. These facts suggest the antagonistic function of these two players on a more general scale when yeast cells must cope with stress conditions. To explore general involvement of Pho4 in stress response, we tried to identify Pho4-dependent genes by a genome-wide mapping of Pho4 and Rpo21 binding (Rpo21 being the largest subunit of RNA polymerase II) using a yeast tiling array. In the course of this study, we found Pi- and Pho4-regulated intragenic and antisense RNAs that could modulate the Pi signal transduction pathway. Low-Pi signal is transmitted via certain inositol polyphosphate (IP) species (IP7) that are synthesized by Vip1 IP6 kinase. We have shown that Pho4 activates the transcription of antisense and intragenic RNAs in the KCS1 locus to down-regulate the Kcs1 activity, another IP6 kinase, by producing truncated Kcs1 protein via hybrid formation with the KCS1 mRNA and translation of the intragenic RNA, thereby enabling Vip1 to utilize more IP6 to synthesize IP7 functioning in low-Pi signaling. Because Kcs1 also can phosphorylate these IP7 species to synthesize IP8, reduction in Kcs1 activity can ensure accumulation of the IP7 species, leading to further stimulation of low-Pi signaling (i.e., forming a positive feedback loop). We also report that genes apparently not involved in the PHO system are regulated by Pho4 either dependent upon or independent of the Pi conditions, and many of the latter genes are involved in stress response. In S. cerevisiae, a large-scale cDNA analysis and mapping of RNA polymerase II binding using a high-resolution tiling array have identified a large number of antisense RNA species whose functions are yet to be clarified. Here we have shown that nutrient-regulated antisense and intragenic RNAs as well as direct regulation of structural gene transcription function in the response to nutrient availability. Our findings also imply that Pho4 is present in the nucleus even under high-Pi conditions to activate or repress transcription, which challenges our current understanding of Pho4 regulation

Experimental investigation of a control scheme for a zero-detuning resonant sideband extraction interferometer for next-generation gravitational-wave detectors

Some next-generation gravitational-wave detectors, such as the American Advanced LIGO project and the Japanese LCGT project, plan to use power recycled resonant sideband extraction (RSE) interferometers for their interferometer's optical configuration. A power recycled zero-detuning (PRZD) RSE interferometer, which is the default design for LCGT, has five main length degrees of freedom that need to be controlled in order to operate a gravitational-wave detector. This task is expected to be very challenging because of the complexity of optical configuration. A new control scheme for a PRZD RSE interferometer has been developed and tested with a prototype interferometer. The PRZD RSE interferometer was successfully locked with the control scheme. It is the first experimental demonstration of a PRZD RSE interferometer with suspended test masses. The result serves as an important step for the operation of LCGT.Comment: 6 pages, 9 figrue

Role of hepatic STAT3 in brain-insulin action on hepatic glucose production

SummarySTAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production

Laparoscopic Partial Gastrectomy for Early Gastric Cancers using Plastic T-fasteners for Lifting Gastric Wall

Between September 1992 and July 1996, 2 patients with type I early gastric cancer, 3 with type IIa, and 14 with type IIc, totaling 19 patients underwent laparoscopic partial gastrectomy (gastric wedge resections in 17 and Billroth II distal gastric resection in 2). There were 12 men and 7 women. Mean age was 65.4 years ranging from 44 to 86. Gastric lesions were located on the anterior wall in 7, posterior wall in 8 and lesser curvature in 4. In 15 of 19 patients, we performed laparoscopic surgery by a lesion lifting method using plastic T-fasteners. Average operative time was 164.8±49.6 min (range 85-252) in all, 153.7±46.7 min for the lesion lifting method, and 227 ± 33 min for diatal gastrectomy. Average blood loss was 44.1 ± 57.3 ml, 30.9 ± 43.7 ml, and 97 ± 61 ml, respectively. Mean hospital stay after surgery was 13.6 ± 6.8 (6-30) days. There was no mortality and no postoperative complications. The average size of tumors in type I, IIa and lie was 30 mm, 17.3 mm and 20 mm, respectively. In histologic examination, 16 cases were differentiated carcinoma and the remaining 3 cases were signet cell carcinoma. One of 4 cases diagnosed as SM cancer preoperatively was m (mucosal) cancer, two were sm (submucosal), and one was mp (muscularis propria) cancer histologically, but no one was involved in regional lymph nodes. These results indicate that laparoscopic partial gastrectomy will play an increasing role in the treatment of early gastric cancer without lymph node involvement as well as benign gastric tumors