Nihon Rinsho. Japanese Journal Of Clinical Medicine[JOURNAL]
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200 papers
Cytapheresis.
Yokoyama Y, Kamikozuru K, Nakamura S
Nihon Rinsho · 2017 Mar · PMID 30566785
In the inflammatory bowel disease (IBD) therapeutic settings, leukocytapheresis (LCAP), and Adsorptive Granulocyte/Monocyte Apheresis (GMA) are currently the two major cytapheresis (CAP) strategies approved and are appli...
In the inflammatory bowel disease (IBD) therapeutic settings, leukocytapheresis (LCAP), and Adsorptive Granulocyte/Monocyte Apheresis (GMA) are currently the two major cytapheresis (CAP) strategies approved and are applied to treat patients with IBD, which has become refractory to conventional pharmacological intervention. Further, based on our recently concluded prospective multi-centre studies, we can now report on the therapeutic efficacy, safety and demographic factors, which identify ulcerative colitis (UC) patients as responders, or otherwise as non-responders to CAP. Further, in Crohn's disease (CD) patients, hitherto studies have not identified CAP-responder features. Regarding the maintenance of remission after GMA-induced remission, shorter duration and corticosteroid responder background were significant factors for maintenance of remission, while corticosteroid dependent UC was associating with early relapse. Considering LCAP, intensive therapy was more effective in UC patients with high baseline clinical activity score and a higher biomarker than weekly LCAP. Additionally, we have started assessing the efficacy of CAP in patients with IBD refractory to anti- tumour necrosis factor (TNF)-a biologics, and hope our work may lead to better management of drug refractory IBD. In conclusion, demographic features, which identify a patient as a potential responder to CAP or any given therapeutic intervention should guide to stop futile use of medical resources and shorten morbidity time for non- responder patients who may opt for an alternative therapy.
Enteral nutrition and dietary interventions.
Yamamoto T, Shimoyama T, Maeda S … +1 more , Utsunomiya S
Nihon Rinsho · 2017 Mar · PMID 30566784
Currently, various dietary interventions or supplements, including probiotics and prebiotics, are available for patients with Crohn's disease. Among these interventions or supplements, there is nothing showing significan...
Currently, various dietary interventions or supplements, including probiotics and prebiotics, are available for patients with Crohn's disease. Among these interventions or supplements, there is nothing showing significant efficacy. Although the evidence level is not high, the available data suggest that enteral nutrition is effective in both active and quiescent Crohn's disease. However, the therapeutic efficacy of dietary and nutritional interventions needs to be supported by well-designed trials in large cohorts of patients. Further, a significant limitation of enteral nutrition is inadequate patient compliance due to poor palatability of an elemental diet. One major challenge is to establish practical strategies for increasing patient adherence for long-term enteral nutrition.
Immunomodulator and calcineurin inhibitors on inflammatory bowel disease.
Miura M, Hayashida M, Hisamatsu T
Nihon Rinsho · 2017 Mar · PMID 30566783
Immunomodulator (thiopurines) and calcineurin inhibitors (cyclosporine, tacrolimus) have been used in IBD treatment. Thiopurines such as azathioprine and 6-mercaptopur- ine are used in steroid refractory and steroid depe...
Immunomodulator (thiopurines) and calcineurin inhibitors (cyclosporine, tacrolimus) have been used in IBD treatment. Thiopurines such as azathioprine and 6-mercaptopur- ine are used in steroid refractory and steroid dependent UC patients. They are also concomitant used both in CD and UC with other drugs including anti-TNFa monoclonal Ab mainly as maintenance therapy. Calcineurin inhibitors, cyclosporine and tacrolimus, are used in moderate to severe refractory UC patients. Adverse effects of thiopruine include bone marrow suppression, liver dysfunction, hair loss, and infectious disease. Recently, it was reported that the risk of acute onset leukopenia in thioprine use is associated with NUDT 15 gene variant, especially in Asian population. Renal dysfunction and infectious disease (e. g. pneumocystis) should be concerned in the patientg treated with calcineurin inhibitors.
Biologic drugs for inflammatory bowel disease.
Yanai S, Matsumoto T
Nihon Rinsho · 2017 Mar · PMID 30566782
Biologics have become widely used as an innovative therapy for the management of inflammatory bowel disease (IBD) such as Crohn's disease, ulcerative colitis and intestinal Behcet's disease. Tumor necrosis factor (TNF)-a...
Biologics have become widely used as an innovative therapy for the management of inflammatory bowel disease (IBD) such as Crohn's disease, ulcerative colitis and intestinal Behcet's disease. Tumor necrosis factor (TNF)-a is one of the crucial mediators in these diseases, and biological therapies targeting TNF-a are efficacious for the management of IBD refractory to conventional therapies. Anti TNF-a monoclonal antibodies such as infliximab and adalimumab have been shown to have efficacy in IBD. In addition, biological therapies other than TNF-a antibody, such as ustekinumab, vedolizumab and tofacitinib, are also expected to be used for IBD in the near future in Japan.
Steroid therapy for inflammatory bowel disease.
Saruta M
Nihon Rinsho · 2017 Mar · PMID 30566781
In inflammatory bowel disease (IBD) as represented by ulcerative colitis (UC) and Crohn's disease (CD), UC is characterized by the diffuse inflammation from rectum and the resulting frequent diarrhea and bloody stool, an...
In inflammatory bowel disease (IBD) as represented by ulcerative colitis (UC) and Crohn's disease (CD), UC is characterized by the diffuse inflammation from rectum and the resulting frequent diarrhea and bloody stool, and CD is characterized by scattered inflammation that may affect any part of the gastrointestinal tract from mouth to anus. Both diseases include diarrhea and abdominal cramping or pain, therefore IBD patients lose the quality of life coclusively. In general, salazosulfapyridine and 5-acetylsalicylic acid (5-ASA) are baseline drugs for IBD, but sometimes these drugs are insufficient to suppress their inflammation. Steroid therapy is chosen as an induction treatment at that situation but not as a maintenance therapy. In this session, I would like to show how to use steroid and what are side effects of steroid for the treatment of IBD.
5-Aminosalicylic acid.
Iida T, Onodera K, Nakase H
Nihon Rinsho · 2017 Mar · PMID 30566780
Despite the emergence of new biological therapies that aim for mucosal healing as a new therapeutic target, the importance of 5-ASA formulations in the standard treatment for inflammatory bowel diseases, particularly ulc...
Despite the emergence of new biological therapies that aim for mucosal healing as a new therapeutic target, the importance of 5-ASA formulations in the standard treatment for inflammatory bowel diseases, particularly ulcerative colitis, remains unchanged. With a growing number of patients suffering from inflammatory bowel diseases in Japan, general physicians are also increasingly prescribing 5-ASA formulations. In order to obtain the maximum efficacy of 5-ASA formulations when treating inflammatory bowel diseases, it is essential that the dosage and administration are appropriate.
Imaging (X-ray - CT - MRI - ultrasound).
Katsurada T, Nishida M, Sakamoto N
Nihon Rinsho · 2017 Mar · PMID 30566779
Inflammatory bowel diseases (IBD) require evaluation diagnosis, disease course, location, activity and severity. Endoscopy is well established modality for IBD evaluation but sometimes it is invasive and has some risks....
Inflammatory bowel diseases (IBD) require evaluation diagnosis, disease course, location, activity and severity. Endoscopy is well established modality for IBD evaluation but sometimes it is invasive and has some risks. Radiological imaging techniques are less invasive and complementary to endoscopy. Computed tomography (CT) is an objective and universal imaging method, but there is a problem of radiation exposure. Magnetic resonance imaging (MRI) has similar diagnostic accuracy and indication to CT, but with the advantage of not imparting ionizing radiation. Ultrasound (US) is a well-tolerated and radiation-free imaging method, but has limitation of inter/intra observer variability. These imaging techniques have advantages and disadvantages, so cross-sectional imaging is needed.
Endoscopy for inflammatory bowel disese.
Naganuma M, Kanai T
Nihon Rinsho · 2017 Mar · PMID 30566778
Endoscopy is needed to make a diagnosis for ulcerative colitis (UC) and Crohn's disease (CD). Endoscopy is also useful to make a treatment decision by assessing the severity and extension of inflammations. The endoscopic...
Endoscopy is needed to make a diagnosis for ulcerative colitis (UC) and Crohn's disease (CD). Endoscopy is also useful to make a treatment decision by assessing the severity and extension of inflammations. The endoscopic severity is associated with the long-term prognosis of UC and CD, thus, mucosal healing has raised as treatment goal. The scoring systems for endoscopic severity have been developed, such as Mayo endoscopic score and ulcerative colitis endoscopic index of severity for ulcerative colitis, Crohn's disease index of severity (CDEIS) and simple endoscopic score for Crohn's disease (SESCD). These scoring systems is useful to assess objectively the therapeutic efficacies although CDEIS and CDEIS is not usually used in the clinical setting due to its complexities.
History taking, Biochemical examination, Bacteriological examination.
Nagahori M
Nihon Rinsho · 2017 Mar · PMID 30566777
In the diagnosis of inflammatory bowel disease (IBD), careful history taking based upon available epidemiological data, along with judicious use of biochemical and bacteriological examination is the most powerful and cos...
In the diagnosis of inflammatory bowel disease (IBD), careful history taking based upon available epidemiological data, along with judicious use of biochemical and bacteriological examination is the most powerful and cost-effective technology, particularly to rule out irritable bowel syndrome (IBS). We also have to be careful in evaluating symptomatic IBD patients looking for exacerbating factors such as Clostridium difficile infection, use of NSAIDs, and non-adherence which is revealed only by frank discussion.
The diagnostic criteria and differential diagnosis of IBD.
Suzuki Y
Nihon Rinsho · 2017 Mar · PMID 30566776
Adequate therapy can be done to patients with inflammatory bowel disease just after accurate diagnosis being done speedy. It is necessary to confirm typical symptoms and typical by imaging and to fit them to diagnostic c...
Adequate therapy can be done to patients with inflammatory bowel disease just after accurate diagnosis being done speedy. It is necessary to confirm typical symptoms and typical by imaging and to fit them to diagnostic criteria when a patient is suspected to be IBD. But we have to care about that typical clinical symptoms and typical imaging are not always specific to IBD, other intestinal disease than IBD can present such as symptoms and imaging not rarely. We have to rule out other intestinal disease that can mimic IBD- like symptoms and imaging on the time when we diagnosis IBD accurately.
Pathogenesis of inflammatory bowel disease.
Hibi T, Kobayashi T, Hisamatsu T
Nihon Rinsho · 2017 Mar · PMID 30566775
The causes of IBD (inflammatory bowel disease), ulcerative colitis and Crohn's disease, have not been elucidated. It is thought that the pathogenesis involves genetic predisposition, environmental factors and host immune...
The causes of IBD (inflammatory bowel disease), ulcerative colitis and Crohn's disease, have not been elucidated. It is thought that the pathogenesis involves genetic predisposition, environmental factors and host immune response to food antigens and microbiota. Most of IBD susceptiblity genes are related to function of immune cells, maintenance of homeostasis of epithelial cells, autophagy, ER stress and so on. These genetic abnormalities may induce abnormal immune response to antigens and intestinal bacteria, which are modified by diet habit and hygiene environment. Recently, the interrelationship between intestinal bacteria and hosts has dramatically been elucidated, and breakdown of the homeostatic mechanisms at the cellular level is revealed to have an important role in the onset of IBD.
Definition and epidemiology of inflammatory bowel disease.
Fujii T, Watanabe M
Nihon Rinsho · 2017 Mar · PMID 30566774
Inflammatory bowel disease (IBD) includes two major disorders: ulcerative colitis (UC) and Crohn's disease (CD). Both usually involve severe diarrhea, pain, fatigue and weight loss. IBD can be debilitating and sometimes...
Inflammatory bowel disease (IBD) includes two major disorders: ulcerative colitis (UC) and Crohn's disease (CD). Both usually involve severe diarrhea, pain, fatigue and weight loss. IBD can be debilitating and sometimes leads to life-threatening complications. UC is characterized by relapsing and remitting episodes of inflammation limited to the mucosal layer of the colon. It involves the rectum and typically extends in a proximal of the colon. In CD, inflammation often spreads deep into affected tissues. CD is characterized by transmural inflammation and by skip lesions in the entire gastrointesti- nal tract from mouth to perianal area. The transmural inflammation leads to fibrosis, strictures and microperforations or fistulae. Multiple studies have evaluated the epidemiology of IBD in various geographic regions.
[The cerebral mechanisms of itch and pain].
Mochizuki H, Kakigi R
Nihon Rinsho · 2017 Feb · PMID 30562874
Somatic sensations are indispensable functions to survive everyday life. Thus, when these functions are impaired or do not work normally due to diseases and injuries, it severely influ- ences various activities in daily...
Somatic sensations are indispensable functions to survive everyday life. Thus, when these functions are impaired or do not work normally due to diseases and injuries, it severely influ- ences various activities in daily living as well as the quality of life. Chronic itch and pain are abnormal sensations that can be present in many diseases. Currently, millions of people worldwide suffer from chronic itch and pain. There is a great need to better understand the mechanisms of itch and pain for developing their effective treatments. In this review article, we discuss the cerebral mechanisms of itch and pain with focusing on their similarities and differences.
[Development and application of adjuvant immunotherapy for cancer].
Kitahata Y, Ishii KJ
Nihon Rinsho · 2017 Feb · PMID 30562873
Recent progress in immunology have revealed that the immune system is capable of fight- ing against cancer by not only activation of innate and adaptive immune responses, but also by inhibition of various types of the ca...
Recent progress in immunology have revealed that the immune system is capable of fight- ing against cancer by not only activation of innate and adaptive immune responses, but also by inhibition of various types of the cancer-associated immune suppression. In addition to immune check-point inhibitors and cancer vaccines, many conventional and new generations of vaccine adjuvants are in the limelight, many of which are known as potent immuno- stimulators through specific innate immune receptors and signaling pathways. For example, TLR agonist targeting the tumor microenvironment, or combination of certain TLR agonist with STING ligand can act not only as a potent adjuvant for various modality of cancer vac- cines, but also as a mono-therapeutic agent for various cancer animal models. Their precise mechanisms of action have not been fully elucidated, but evidence suggest that adjuvants mentioned above reverse an immune suppressive tumor microenvironment into an optimal vaccination spot by providing protective tumor (neo) antigens and immunogenic cell death.
[Metformin-dependent metabolic reprogramming contributes to efficient anti-tumor immunity].
Tomonobu N, Eikawa S, Udono H
Nihon Rinsho · 2017 Feb · PMID 30562872
The rate of cancer incidence and mortality of Type 2 diabetes patients who were taking metformin seem to be decreased, comparing with those taking other drugs. We recently pro- vided compelling evidence showing that the...
The rate of cancer incidence and mortality of Type 2 diabetes patients who were taking metformin seem to be decreased, comparing with those taking other drugs. We recently pro- vided compelling evidence showing that the effect might be mediated by immune system, thus, the reversion of exhausted tumor infiltrating CD8T lymphocytes (CD8TIL). Glycolysis is essential in CD8T cell function. However, the metabolism of CD8TIL is locked in a state of oxidative phosphorylation (OxPhos) dominant over glycolysis because of interaction between immune checkpoints and their ligands, and because of extremely low concentration of glu- cose in tumor microenvironment. Metformin increases the glycolysis efficiency, resulting in the conversion of CD8TIL to more active effector memory to fight against cancers.
[Immune cells derived from induced pluripotent stem cells: a new cell source for cancer immunotherapy].
Ueda N, Kaneko S
Nihon Rinsho · 2017 Feb · PMID 30562871
Clinical results have shown promising therapeutic potential of engineered T cell express- ing TCR (T cell antigen receptor) or CAR (chimeric antigen receptor). However, high cost, donor cell availability, complicated pro...
Clinical results have shown promising therapeutic potential of engineered T cell express- ing TCR (T cell antigen receptor) or CAR (chimeric antigen receptor). However, high cost, donor cell availability, complicated procedure of genetic engineering prevent their wider ap- plication. iPSCs (induced pluripotent stem cells) are attractive source of immune cells includ- ing T cells and dendritic cells, and may provide an unlimited cell source for adoptive immune cell therapy. Genetic engineering of iPSCs may confer enhanced anti-tumor activity and ena- ble the escape from immune rejection. Here, we discuss the potential of iPSCs as a novel source of anti-tumor immune cells.
[Invariant NKT cell-based immunotherapy for lung cancer and head and neck cancer].
Ihara F, Motohashi S
Nihon Rinsho · 2017 Feb · PMID 30562870
CD1d-restricted invariant natural killer T (iNKI) cells are the unique lymphocyte subpopu- lation that interacts with glycolipid via the invariant T cell receptor. Ligand activated iNKT cells produce a variety of cytokin...
CD1d-restricted invariant natural killer T (iNKI) cells are the unique lymphocyte subpopu- lation that interacts with glycolipid via the invariant T cell receptor. Ligand activated iNKT cells produce a variety of cytokines, and thus bridging the innate and adaptive immune sys- tems. Since recent studies have highlighted iNKT cells to have potent anti-tumor effects, greater attention are being given to the development of iNKT cell-based immunotherapy for advanced solid tumors. This article summarizes the progress of our recent works on active immunotherapies aiming at the augmentation of iNKT cell function in vivo in patients with non-small cell lung cancer, and discusses the role of iNKT cell-induced immune responses in cancer immunotherapy.
[Natural killer (NK) cell and immunotherapy].
Iino T, Takaishi S
Nihon Rinsho · 2017 Feb · PMID 30562869
Natural killer (NK) cells are innate lymphoid cells important for host defense against patho- gens, and are also thought to play an important role in the immunosurveillance against can- cers. NK cells express surface rec...
Natural killer (NK) cells are innate lymphoid cells important for host defense against patho- gens, and are also thought to play an important role in the immunosurveillance against can- cers. NK cells express surface receptors that interact with target cells and determine their response to infected or transformed cells without prior sensitization or gene rearrangement. Activated NK cells can kill target cells by producing effector molecules and transmit impor- tant information to the rest of the immune system subsequently by producing cytokines. Here, we review the mechanism of cytotoxic function of NK cells and a recent development in NK cell biology, and highlight therapeutic approaches for NK cell-based immunotherapy and targeting NK cells in the treatment of cancer. //.
[γδ T cell-based cancer immunotherapy].
Matsushita H, Kakimi K
Nihon Rinsho · 2017 Feb · PMID 30562868
γδ T cell-based cancer immunotherapy is attracting attention for the treatment of various malignancies because these cells secrete Th1-type cytokines, exert potent cytotoxicity against a variety of cancer cells. We have...
γδ T cell-based cancer immunotherapy is attracting attention for the treatment of various malignancies because these cells secrete Th1-type cytokines, exert potent cytotoxicity against a variety of cancer cells. We have established a large-scale in vitro expansion method for Vγ9Vδ2 T cells using zoledronate and interleukin-2. We conducted phase I clinical trials to evaluate safety and anti-tumor effects of intravenous injection of Vγ9Vδ2 T cells in patients with various cancers, and intraperitoneal injection of Vγ9Vδ2 T cells for the treatment of gas- tric cancer with malignant ascites. γδ T cell therapy trials are being conducted with safety and response results already reported for selected cases. Despite the limited number of patients in the phase I studies, the clinical response is thus far promising and warrants further study.
[Tax-targeted DC vaccine for ATL].
Suehiro Y
Nihon Rinsho · 2017 Feb · PMID 30562867
ATL is a HTLV-1 induced T-cell malignancy with extremely poor prognosis. HTLV-1 Tax which is regulatory protein encoded in the pX region plays a crucial role in HTLV-1 leukemo- genesis and is a major target antigen for C...
ATL is a HTLV-1 induced T-cell malignancy with extremely poor prognosis. HTLV-1 Tax which is regulatory protein encoded in the pX region plays a crucial role in HTLV-1 leukemo- genesis and is a major target antigen for CTL. We conducted a clinical trial of Tax targeted therapeutic vaccine consisting of autologous dendritic cells (Tax-DC). The good quality of lives and long-term treatment-free survival were observed for more than 3 years in two of three patients enrolled in the pilot study. Tax-specific proliferative CTL responses were ob- served in all cases and the sporadic augmented responses also have been detected subse- quently. Tax-DC vaccine might be a well-tolerated and long-lasting maintenance therapy that is acceptable for even elderly patients.
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