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1.
Overview of the Properties of Glutamic Peptidases That Are Present in Plant and Bacterial Pathogens and Play a Role in Celiac Disease and Cancer.
Oda, K, Wlodawer, A
Biochemistry. 2023;(3):672-694
Abstract
Seven peptidase (proteinase) families─aspartic, cysteine, metallo, serine, glutamic, threonine, and asparagine─are in the peptidase database MEROPS, version 12.4 (https://www.ebi.ac.uk/merops/). The glutamic peptidase family is assigned two clans, GA and GB, and comprises six subfamilies. This perspective summarizes the unique features of their representatives. (1) G1, scytalidoglutamic peptidase, has a β-sandwich structure containing catalytic residues glutamic acid (E) and glutamine (Q), thus the name eqolisin. Most family members are pepstatin-insensitive and act as plant pathogens. (2) G2, preneck appendage protein, originates in phages, is a transmembrane protein, and its catalytic residues consist of glutamic and aspartic acids. (3) G3, strawberry mottle virus glutamic peptidase, originates in viruses and has a β-sandwich structure with catalytic residues E and Q. Neprosin has propyl endopeptidase activity, is associated with celiac disease, has a β-sandwich structure, and contains catalytic residues E-E and Q-tryptophan. (4) G4, Tiki peptidase, of the erythromycin esterase family, is a transmembrane protein, and its catalytic residues are E-histidine pairs. (5) G5, RCE1 peptidase, is associated with cancer, is a transmembrane protein, and its catalytic residues are E-histidine and asparagine-histidine. Microcystinase, a bacterial toxin, is a transmembrane protein with catalytic residues E-histidine and asparagine-histidine. (6) G6, Ras/Rap1-specific peptidase, is a bacterial pathogen, a transmembrane protein, and its catalytic residues are E-histidine pairs. This family's common features are that their catalytic residues consist of a glutamic acid and another (variable) amino acid and that they exhibit a diversity of biological functions─plant and bacterial pathogens and involvement in celiac disease and cancer─that suggests they are viable drug targets.
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2.
Molecular genetics of cytoplasmic male sterility and restorer-of-fertility for the fine tuning of pollen production in crops.
Kitazaki, K, Oda, K, Akazawa, A, Iwahori, R
TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik. 2023;(7):156
Abstract
Cytoplasmic male sterility (CMS) is an increasingly important issue within the context of hybrid seed production. Its genetic framework is simple: S-cytoplasm for male sterility induction and dominant allele of the restorer-of-fertility gene (Rf) for suppression of S. However, breeders sometimes encounter a phenotype of CMS plants too complex to be explained via this simple model. The molecular basis of CMS provides clue to the mechanisms that underlie the expression of CMS. Mitochondria have been associated with S, and several unique ORFs to S-mitochondria are thought to be responsible for the induction of male sterility in various crops. Their functions are still the subject of debate, but they have been hypothesized to emit elements that trigger sterility. Rf suppresses the action of S by various mechanisms. Some Rfs, including those that encode the pentatricopeptide repeat (PPR) protein and other proteins, are now considered members of unique gene families that are specific to certain lineages. Additionally, they are thought to be complex loci in which several genes in a haplotype simultaneously counteract an S-cytoplasm and differences in the suite of genes in a haplotype can lead to multiple allelism including strong and weak Rf at phenotypic level. The stability of CMS is influenced by factors such as the environment, cytoplasm, and genetic background; the interaction of these factors is also important. In contrast, unstable CMS becomes inducible CMS if its expression can be controlled. CMS becomes environmentally sensitive in a genotype-dependent manner, suggesting the feasibility of controlling the expression of CMS.
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3.
Membranous nephropathy associated with multicentric Castleman's disease that was successfully treated with tocilizumab: a case report and review of the literature.
Saiki, R, Katayama, K, Hirabayashi, Y, Oda, K, Fujimoto, M, Murata, T, Nakajima, A, Dohi, K
BMC nephrology. 2021;(1):216
Abstract
BACKGROUND Multicentric Castleman's disease is a life-threatening disorder involving a systemic inflammatory response and multiple organ failure caused by the overproduction of interleukin-6. Although renal complications of Castleman's disease include AA amyloidosis, thrombotic microangiopathy, and membranoproliferative glomerulonephritis, membranous nephropathy is relatively rare. We experienced a case of secondary membranous nephropathy associated with Castleman's disease. CASE PRESENTATION The patient was a 43-year-old Japanese man who had shown a high zinc sulfate value in turbidity test, polyclonal hypergammaglobulinemia, anemia, and proteinuria. A physical examination revealed diffuse lymphadenopathy, an enlarged spleen and papulae of the body trunk. A skin biopsy of a papule on the patient's back showed plasma cells in the perivascular area and he was diagnosed with multicentric Castleman's disease, plasma cell variant. Kidney biopsy showed the appearance of bubbling in the glomerular basement membranes in Periodic acid methenamine silver stain and electron microscopy revealed electron dense deposits within and outside the glomerular basement membranes. Since immunofluorescence study showed predominant granular deposition of IgG1 and IgG2, he was diagnosed with secondary membranous nephropathy associated with Castleman's disease. He was initially treated with prednisolone alone, however his biochemical abnormalities did not improve. After intravenous tocilizumab (700 mg every 2 weeks) was started, his C-reactive protein elevation, anemia, and polyclonal gammopathy improved. Furthermore, his urinary protein level declined from 1.58 g/gCr to 0.13 g/gCr. The prednisolone dose was gradually tapered, then discontinued. He has been stable without a recurrence of proteinuria for more than 6 months. CONCLUSIONS Tocilizumab might be a treatment option for secondary membranous nephropathy associated with Castleman's disease.
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4.
Hard Metal Lung Disease with Favorable Response to Corticosteroid Treatment: A Case Report and Literature Review.
Chiba, Y, Kido, T, Tahara, M, Oda, K, Noguchi, S, Kawanami, T, Yokoyama, M, Yatera, K
The Tohoku journal of experimental medicine. 2019;(1):51-58
Abstract
Hard metal lung disease (HMLD) is a pneumoconiosis caused by occupational exposure to hard metals such as tungsten carbide and cobalt, but the treatment strategies for HMLD have not been well established. A 68-year-old Japanese man with occupational history as a grinder of hard metals for 18 years referred to our hospital because of dry cough and dyspnea. A chest computed tomography (CT) on admission revealed centrilobular micronodules, ground-glass opacities, and reticular opacities in the peripheral zone of both lungs. Mineralogic analyses of lung tissues detected components of hard metals, such as tungsten, titanium and iron, and the same metals were also detected in the sample of the dust of his workplace. Thus, the patient was diagnosed as having HMLD based on occupational exposure history and radiologic and mineralogic analyses of the lung. Corticosteroid therapy was initiated, which resulted in partial improvements in his symptoms, radiological and pulmonary functional findings. In a review of the 18 case reports of HMLD treated with corticosteroids, including our case, the majority of patients (77.8%) showed favorable responses to corticosteroid treatment. Furthermore, the presence of fibrotic changes, such as reticular opacity, in radiological examinations was associated with the resistance to corticosteroids. In conclusion, the majority of patients with HMLD are expected to favorable response to corticosteroid treatment, whereas chest CT findings such as fibrotic changes may be predictive of the resistance of corticosteroid treatment. Lastly, proper prevention of hard metal exposure is most important as the first step.
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5.
Clinical features of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: a review of human studies.
Oda, K, Uto, H, Mawatari, S, Ido, A
Clinical journal of gastroenterology. 2015;(1):1-9
Abstract
Most cases of hepatocellular carcinoma (HCC) in Japan develop in the background of chronic liver disease caused by hepatitis C virus (HCV). Recently, however, HCV-associated HCC has been shown to be decreasing, while non-B and non-C HCC (NBNC-HCC), which is negative for HCV and hepatitis B virus infection, has increased. The main cause of NBNC-HCC is alcoholic liver disease, but the recent increase of NBNC-HCC is thought to be due to an increase in patients with nonalcoholic fatty liver disease (NAFLD). Approximately 10% of NAFLD cases involve nonalcoholic steatohepatitis (NASH), and NASH can progress to liver cirrhosis and its associated complications such as HCC. There are no accurate data on the percentage of NASH-related HCC among all-cause HCC in Japan, because no large-scale investigation has been performed. However, the rate is thought to be about 3% of overall HCC, which is lower than that in the United States. The incidence of HCC in patients with NASH-related cirrhosis is thought to be 2% per year, which is lower than that in HCV-related cirrhosis. Risks for NASH-related HCC include advanced hepatic fibrosis, older age, and being male. NAFLD that includes NASH is associated with metabolic syndrome, which includes obesity and diabetes, and metabolic syndrome is a risk factor for HCC. Genetic factors and dietary patterns may also be related to NASH-related HCC. Thus, regular HCC surveillance, as performed for patients with viral chronic liver disease, is required for patients with NAFLD, and diagnostic markers are required for simple, rapid and specific detection of NASH-related HCC.
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6.
[A case of Stage IV sigmoid colon cancer cured with radical combined modality therapy].
Babaya, A, Fukunaga, M, Yamamoto, T, Oda, K, Nakata, K, Ohzato, H
Gan to kagaku ryoho. Cancer & chemotherapy. 2013;(12):1956-8
Abstract
The patient was a 54-year-old man who had undergone resection of the sigmoid colon for unresectable sigmoid colon cancer with multiple liver( H1), lymph node, and lung metastases at the previous hospital. Chemotherapy with 5-fuorouracil, Leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab was initiated after surgery. The outcome was partial response. The patient was introduced to our hospital because he had relocated. Based on the findings of the patient's computed tomography( CT) and positron emission tomography( PET)-CT scans, we decided to perform radical resection. We performed partial hepatectomy( S7 and S8) and pancreatoduodenectomy for metastases to the hepatoduodenal ligament lymph node. After confirming that there was no recurrence, he underwent right partial pneumonectomy. Currently, the patient shows no signs of recurrence. The therapy for colon cancer should include aggressive radical surgery to control metastasis.
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7.
[Systematic review of complications for proper informed consent (9) periprocedural complications of carotid artery stenting: a review article].
Asai, T, Miyachi, S, Izumi, T, Matsubara, N, Yamanouchi, T, Ota, K, Oda, K, Wakabayashi, T
No shinkei geka. Neurological surgery. 2013;(8):719-29
Abstract
BACKGROUND Carotid artery stenting(CAS)is a common procedure for the treatment of high surgical risk patients with carotid artery stenosis. Recent clinical study failed to show the non-inferiority of CAS to carotid endarterectomy(CEA)because of higher complication rates of CAS. However the result of a multicenter case study in Japan with tailored application of adequate devices including stents and protection devices revealed the safety of CAS in Japan. In this article the overall review in the previous reports of CAS are reviewed focusing on the complications and clinical outcome. METHOD Five randomized controlled trials concerning CAS versus CEA and 14 case series of CAS were reviewed, and the rates of periprocedural complications of CAS including death, stroke, myocardial infarction, hypotension and bradycardia, cranial nerve palsy, major vascular injury, cholesterol crystal embolization and hyperperfusion syndrome were summarized. RESULT Mortality within 30 days of procedures was 0.9%. The rate of any stroke was 6.0% from the five RCT results, but a recent 14-case series reported any stroke rate at 3-4% and severe stroke rate at 1-2% respectively. The rates of acute myocardial infarction, hypotension, and bradycardia were 1%, 4%, and 4-12% respectively. The rate of bleeding complication of the access root was about 2% and non-bleeding was 1-2%. Cholesterol crystal embolization occurred in 0.2%. Incidence of hyperperfusion syndrome occurred in 1.5%, and intracranial hemorrhage in 0.8%. CONCLUSION Historically, the rapid improvement of devices and technical skills have contributed to the better clinical results. Also the lessons from complication cases have led to more appropriate indication and perfect protection to avoid adverse events. Therefore the rate of complication is always improving and those written in this article may not reflect the present real number. This article should be quoted with the previous reference as well as the newest data according to the operator's own experiences on taking informed consent.
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8.
Robustness trade-offs and host-microbial symbiosis in the immune system.
Kitano, H, Oda, K
Molecular systems biology. 2006;:2006.0022
Abstract
The immune system provides organisms with robustness against pathogen threats, yet it also often adversely affects the organism as in autoimmune diseases. Recently, the molecular interactions involved in the immune system have been uncovered. At the same time, the role of the bacterial flora and its interactions with the host immune system have been identified. In this article, we try to reconcile these findings to draw a consistent picture of the host defense system. Specifically, we first argue that the network of molecular interactions involved in immune functions has a bow-tie architecture that entails inherent trade-offs among robustness, fragility, resource limitation, and performance. Second, we discuss the possibility that commensal bacteria and the host immune system constitute an integrated defense system. This symbiotic association has evolved to optimize its robustness against pathogen attacks and nutrient perturbations by harboring a broad range of microorganisms. Owing to the inherent propensity of a host immune system toward hyperactivity, maintenance of bacterial flora homeostasis might be particularly important in the development of preventive strategies against immune disorders such as autoimmune diseases.
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9.
Cancer targets in the Ras pathway.
Rodriguez-Viciana, P, Tetsu, O, Oda, K, Okada, J, Rauen, K, McCormick, F
Cold Spring Harbor symposia on quantitative biology. 2005;:461-7
Abstract
Ras proteins play a direct causal role in human cancer and in other diseases. Mutant H-Ras, N-Ras, and K-Ras occur in varying frequencies in different tumor types, for reasons that are not known. Other members of the Ras superfamily may also contribute to cancer. Mutations also occur in downstream pathways, notably B-Raf, PTEN, and PI 3' kinase: These pathways interact at multiple points, including cyclin D1, and act synergistically. In some cases mutations in Ras and effectors are mutually exclusive; in other cases, they coexist. Drugs blocking elements of the pathway are in different stages of clinical development. One of these, the Raf kinase/VEGF-R2 inhibitor Sorafenib, has already been approved for treatment of renal cancer and is being tested in other indications. However, therapeutic targets in the Ras pathway have not yet been fully validated as bona fide targets.
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10.
Effect of the supplemental use of antioxidants vitamin C, vitamin E, and coenzyme Q10 for the prevention and treatment of cancer.
Shekelle, P, Hardy, ML, Coulter, I, Udani, J, Spar, M, Oda, K, Jungvig, LK, Tu, W, Suttorp, MJ, Valentine, D, et al
Evidence report/technology assessment (Summary). 2003;(75):1-3