Publications by authors named "Hiroko Takahashi"

47 Publications

Acute tubulointerstitial nephritis in a patient with early bronchial tuberculosis.

J Formos Med Assoc 2021 Jul 20. Epub 2021 Jul 20.

Department of Hypertension and Nephrology, NTT Medical Centre Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo 141-8625, Japan.

Patients with chronic kidney disease (CKD) are commonly at high risk of tuberculosis (TB). Conversely, TB rarely causes tubulointerstitial nephritis. A 75-year-old Japanese man who was undergoing periodic follow-ups for CKD stage G3aA3 with membranous nephropathy was diagnosed with acute kidney injury (AKI) (estimated glomerular filtration rate [eGFR]: 15 mL/min/1.73 m) without prerenal AKI. He reported developing recent-onset cough 3 weeks prior to presenting to us. Renal biopsy revealed acute tubulointerstitial nephritis along with known membranous nephropathy. CD4 helper T cells comprised most lymphocytes in the tubulointerstitium. Results of the interferon-gamma release assay, sputum smear test, polymerase chain reaction (PCR), and culture test were positive for TB. Chest computed tomography revealed thickening of the left bronchial wall; therefore, a diagnosis of early bronchial TB was made; his urine culture and PCR were negative for TB. At four months after TB treatment with no immunosuppressive therapy, his eGFR improved to 50 mL/min/1.73 m, and based on this progress, the AKI was diagnosed as tuberculosis-associated tubulointerstitial nephritis (TATIN). Although TATIN typically occurs with chronic or miliary tuberculosis, it is very rare in early bronchial TB. Identification of TATIN is important in kidney diseases of unknown etiology, and treatment with anti-TB drugs is necessary.
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http://dx.doi.org/10.1016/j.jfma.2021.07.010DOI Listing
July 2021

Validation of improved 24-hour dietary recall using a portable camera among the Japanese population.

Nutr J 2021 07 15;20(1):68. Epub 2021 Jul 15.

Department of Health Promotion, National Institute of Public Health, 2-3-6 Minami, Wako, Saitama, 351-0197, Japan.

Background: The collection of weighed food records (WFR) is a gold standard for dietary assessment. We propose using the 24-h recall method combined with a portable camera and a food atlas (24hR-camera). This combination overcomes the disadvantages of the 24-h dietary recall method. Our study examined the validity of the 24hR-camera method against WFR by comparing the results.

Methods: Study subjects were 30 Japanese males, aged 31-58 years, who rarely cook and reside in the Tokyo metropolitan area. For validation, we compared the estimated food intake (24hR-camera method) and weighed food intake (WFR method). The 24hR-camera method uses digital photographs of all food consumed during a day, taken by the subjects, and a 24-h recall questionnaire conducted by a registered dietitian, who estimates food intake by comparing the participant's photographs with food atlas photographs. The WFR method involves a registered dietitian weighing each food item prepared for the subject to consume and any leftovers. Food intake was calculated for each food group and nutrient using the 24hR-camera vs. weighed methods.

Results: Correlation coefficients between the estimated vs. weighed food intake were 0.7 or higher in most food groups but were low in food groups, such as oils, fats, condiments, and spices. The estimated intake of vegetables was significantly lower for the 24hR-camera method compared to the WFR method. For other food groups, the percentages of the mean difference between estimated vs. weighed food intake were -22.1% to 5.5%, with no significant differences between the methods (except for algae, which had a very low estimated intake). The correlation coefficients between the two methods were 0.774 for energy, and 0.855, 0.769, and 0.763 for the macronutrients, proteins, lipids, and carbohydrates, respectively, demonstrating high correlation coefficients: greater than 0.75. The correlation coefficients between the estimated vs. weighed for salt equivalents and potassium intake were 0.583 and 0.560, respectively, but no significant differences in intake were observed.

Conclusions: The 24hR-camera method satisfactorily estimated the intake of energy and macronutrients (except salt equivalents and potassium) in Japanese males and was confirmed as a useful method for dietary assessment.
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http://dx.doi.org/10.1186/s12937-021-00724-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283912PMC
July 2021

Anti-neutrophil cytoplasmic antibody-associated vasculitis accompanied by type II heparin-induced thrombocytopenia resulting in asymptomatic cerebral infarction: a case report.

BMC Nephrol 2021 Jun 14;22(1):220. Epub 2021 Jun 14.

Department of Hypertension and Nephrology, NTT Medical Centre, 5-9-22, Higasi- Gotanda, Shinagawa-ku, 141-8625, Tokyo, Japan.

Background: Heparin-induced thrombocytopenia (HIT) involves platelet activation and aggregation caused by heparin or HIT antibodies associated with poor survival outcomes. We report a case of HIT that occurred after hemodialysis was started for rapidly progressive glomerulonephritis (RPGN), which was caused by anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), and ultimately resulted in asymptomatic cerebral infarction.

Case Presentation: A 76-year-old Japanese man was urgently admitted to our hospital for weight loss and acute kidney injury (serum creatinine: 12 mg/dL). Hemodialysis therapy was started using heparin for anticoagulation. Blood testing revealed elevated titers of myeloperoxidase anti-neutrophil cytoplasmic antibodies, and renal biopsy revealed crescentic glomerulonephritis with broad hyalinization of most of the glomeruli and a pauci-immune staining pattern. These findings fulfilled the diagnostic criteria for microscopic polyangiitis, and the patient was diagnosed with RPGN caused by AAV. Steroid pulse therapy, intermittent pulse intravenous cyclophosphamide, and oral steroid therapy failed to improve the patient's renal function, and maintenance dialysis was started. However, on day 15, his platelet count had decreased to 47,000/µL, with clotting observed in the hemodialysis catheter. Magnetic resonance imaging of the head identified acute asymptomatic brain infarction in the left occipital lobe, and a positive HIT antibody test result supported a diagnosis of type II HIT. During hemodialysis, the anticoagulant treatment was changed from heparin to argatroban. Platelet counts subsequently normalized, and the patient was discharged. A negative HIT antibody test result was observed on day 622.

Conclusions: There have been several similar reports of AAV and HIT co-existence. However, this is a rare case report on cerebral infarction with AAV and HIT co-existence. Autoimmune diseases are considered risk factors for HIT, and AAV may overlap with other systemic autoimmune diseases. To confirm the relationship between these two diseases, it is necessary to accumulate more information from future cases with AAV and HIT co-existence. If acute thrombocytopenia and clotting events are observed when heparin is used as an anticoagulant, type II HIT should always be considered in any patient due to its potentially fatal thrombotic complications.
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http://dx.doi.org/10.1186/s12882-021-02433-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204417PMC
June 2021

Topical Application of Conditioned Medium from Hypoxically Cultured Amnion-Derived Mesenchymal Stem Cells Promotes Wound Healing in Diabetic Mice.

Plast Reconstr Surg 2021 Jun;147(6):1342-1352

From the Departments of Plastic and Reconstructive Surgery and Gastroenterology and Hepatology, Faculty of Medicine and Graduate School of Medicine, and Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University.

Background: Mesenchymal stem cells or their conditioned medium improve chronic wound healing, and their effect is enhanced by hypoxia. Diabetic foot ulcers are chronic wounds characterized by abnormal and delayed healing, which frequently require amputation. The authors evaluated the effect of topical application of conditioned medium from hypoxically cultured amnion-derived mesenchymal stem cells on wound healing in diabetic mice.

Methods: Amnion-derived mesenchymal stem cells were cultured under 21% oxygen to prepare normoxic conditioned medium and under 1% oxygen to prepare hypoxic conditioned medium. Hydrogels containing standard medium, normoxic conditioned medium, or hypoxic conditioned medium were topically applied to excisional wounds of mice with streptozotocin-induced diabetes. Ulcer tissues were harvested on day 9; immunohistochemical and quantitative polymerase chain reaction analyses were performed to analyze angiogenesis, inflammatory cell infiltration, and expression levels of inflammation-related genes.

Results: Hypoxic conditioned medium significantly enhanced wound closure, increased capillary density and epithelization, and reduced macrophage infiltration. It also tended to reduce the infiltration of neutrophils and enhance the infiltration of regulatory T cells; it showed a tendency to downregulate the expression of the inflammation-related genes interleukin-1β, interleukin-6, chemokine ligand 1, and chemokine ligand 2. Normoxic conditioned medium exhibited similar effects, although they were of lesser magnitude than those of hypoxic conditioned medium.

Conclusions: Hydrogels containing hypoxically cultured, amnion-derived mesenchymal stem cell conditioned medium accelerated wound healing in diabetic mice by enhancing angiogenesis, accelerating epithelization, and suppressing inflammation. Therefore, topical application of amnion mesenchymal stem cell-derived hypoxic conditioned medium could be a novel treatment for diabetic foot ulcers.
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http://dx.doi.org/10.1097/PRS.0000000000007993DOI Listing
June 2021

Relationship Between Infection and Arteriosclerosis.

Int J Gen Med 2021 23;14:1533-1540. Epub 2021 Apr 23.

Department of Hypertension and Nephrology, NTT Medical Centre, Tokyo, Japan.

It is reported that () infection may be linked to non-digestive tract diseases, such as arteriosclerosis including dyslipidemia, diabetes, obesity, hypertension, and cardiovascular disease. Therefore, we reviewed recent studies available in PubMed dealing with the mechanisms of arteriosclerosis due to infection and the effects of eradication. Conventional studies suggested that infection may increase the risk of arteriosclerosis. A large interventional study is required to clarify the causal relationships and the effects of bacterial eradication.
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http://dx.doi.org/10.2147/IJGM.S303071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079247PMC
April 2021

The NAD kinase Slr0400 functions as a growth repressor in Synechocystis sp. PCC 6803.

Plant Cell Physiol 2021 Feb 9. Epub 2021 Feb 9.

Graduate School of Science and Engineering, Saitama University , 225 Shimo-Okubo, Sakura-ku, Saitama City, Saitama 338-8570, Japan.

NADP+, the phosphorylated form of nicotinamide adenine dinucleotide (NAD), plays an essential role in many cellular processes. NAD kinase (NADK), which is conserved in all living organisms, catalyzes the phosphorylation of NAD+ to NADP+. However, the physiological role of phosphorylation of NAD+ to NADP+ in the cyanobacterium Synechocystis remains unclear. In this study, we report that slr0400, an NADK-encoding gene in Synechocystis, functions as a growth repressor under light-activated heterotrophic growth conditions and light and dark cycle conditions in the presence of glucose. We show, via characterization of NAD(P)(H) content and enzyme activity, that NAD+ accumulation in slr0400-deficient mutant results in unsuppressed activity of glycolysis and tricarboxylic acid (TCA) cycle enzymes. In determining whether Slr0400 functions as a typical NADK, we found that constitutive expression of slr0400 in an Arabidopsis nadk2-mutant background complements the pale-green phenotype. Moreover, to determine the physiological background behind the growth advantage of mutants lacking slr04000, we investigated the photobleaching phenotype of slr0400-deficient mutant under high-light conditions. Photosynthetic analysis found in the slr0400-deficient mutant resulted from malfunctions in the PSII photosynthetic machinery. Overall, our results suggest that NADP(H)/NAD(H) maintenance by slr0400 plays a significant role in modulating glycolysis and the TCA cycle to repress the growth rate and maintain photosynthetic capacity.
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http://dx.doi.org/10.1093/pcp/pcab023DOI Listing
February 2021

Role of an ancient light-harvesting protein of PSI in light absorption and photoprotection.

Nat Commun 2021 01 29;12(1):679. Epub 2021 Jan 29.

Howard Hughes Medical Institute, Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA.

Diverse algae of the red lineage possess chlorophyll a-binding proteins termed LHCR, comprising the PSI light-harvesting system, which represent an ancient antenna form that evolved in red algae and was acquired through secondary endosymbiosis. However, the function and regulation of LHCR complexes remain obscure. Here we describe isolation of a Nannochloropsis oceanica LHCR mutant, named hlr1, which exhibits a greater tolerance to high-light (HL) stress compared to the wild type. We show that increased tolerance to HL of the mutant can be attributed to alterations in PSI, making it less prone to ROS production, thereby limiting oxidative damage and favoring growth in HL. HLR1 deficiency attenuates PSI light-harvesting capacity and growth of the mutant under light-limiting conditions. We conclude that HLR1, a member of a conserved and broadly distributed clade of LHCR proteins, plays a pivotal role in a dynamic balancing act between photoprotection and efficient light harvesting for photosynthesis.
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http://dx.doi.org/10.1038/s41467-021-20967-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846763PMC
January 2021

Health risk of travel for chronic kidney disease patients.

J Res Med Sci 2020 18;25:22. Epub 2020 Mar 18.

Department of Hypertension and Nephrology, NTT Medical Centre Tokyo, Shinagawa-ku, Tokyo, Japan.

The number of people with chronic kidney disease (CKD) has increased and so has their demand for travel. However, the health risk posed by travel in these patients is unclear. Few reports document the travel risk in CKD and dialysis patients. The aim of this study is to summarize the existing evidence of the influence of travel on risks in CKD patients. We aim to describe the association between the impact of travel risks and patients with CKD. A detailed review of recent literature was performed by reviewing PubMed, Google Scholar, and Ichushi Web from the Japan Medical Abstracts Society. Screened involved the following keywords: "traveler's thrombosis," "venous thromboembolism," "deep vein thrombosis," "altitude sickness," "traveler's diarrhea," "jet lag syndrome," "melatonin," with "chronic kidney disease" only, or/and "dialysis." We present a narrative review summary of the literature from these screenings. The increased prevalence of thrombosis among travelers with CKD is related to a decrease in the estimated glomerular filtration rate and an increase in urine protein levels. CKD patients who remain at high altitudes are at an increased risk for progression of CKD, altitude sickness, and pulmonary edema. Traveler's diarrhea can become increasingly serious in patients with CKD because of decreased immunity. Microbial substitution colitis is also common in CKD patients. Moreover, time differences and disturbances in the circadian rhythm increase cardiovascular disease events for CKD patients. The existing literature shows that travel-related conditions pose an increased risk for patients with CKD.
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http://dx.doi.org/10.4103/jrms.JRMS_459_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213004PMC
March 2020

Efficacy of High-Dose Mycophenolate Mofetil in Multitarget Therapy for Lupus Nephritis: Two Consecutive Case Reports.

Cureus 2020 Jan 31;12(1):e6834. Epub 2020 Jan 31.

Hypertension and Nephrology, NTT Medical Centre Tokyo, Tokyo, JPN.

The complete remission rate for lupus nephritis (LN) is higher with multitarget therapy (MT) using tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids than with steroid plus cyclophosphamide co-therapy. MT is also considered highly safe and is used to treat refractory LN. During MT, MMF is usually administered at a dose of 1 g/day similar to conventional MT; however, it remains unclear whether this is the optimal dose of MMF for Japanese patients, especially those refractories to conventional MT. We report two consecutive cases of refractory LN with conventional MT, case 1 was a 48-year-old woman with LN III (A) and nephrotic syndrome, and Case 2 was a 20-year-old man with LN IV-S (A), nephrotic syndrome, and acute kidney injury. LN was diagnosed by kidney biopsy. Because both these patients were refractory to conventional MT treatment (MMF at a dose of 1.0 g/day) for more than six months, MMF doses of 2.5 and 1.5-2.0 g/day were used as part of MT for cases 1 and 2, respectively. Increasing the MMF dose in MT to 1.5-2.5 g/day without increasing the steroid dose led to complete remission, without any recurrence, and allowed administration of a lower dose of a steroid such as prednisolone (5.5 ± 1.5 mg/day) 18 months after the MMF dose increase. The mean number of days from the start of the higher MMF dose of 1.5-2.5 g/day in MT to complete remission was 129.5 ± 10.5 days. Moreover, lymphopenia, hypogammaglobulinemia, gastrointestinal disturbances, or any infections were not observed as adverse events after increasing the MMF dose in MT. Thus, increasing MMF dose while maintaining the steroid dose in MT may induce complete remission; this will minimize the use of steroids in Japanese patients with refractory LN in conventional MT.
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http://dx.doi.org/10.7759/cureus.6834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996269PMC
January 2020

Non-urate transporter 1, non-glucose transporter member 9-related renal hypouricemia and acute renal failure accompanied by hyperbilirubinemia after anaerobic exercise: a case report.

BMC Nephrol 2019 11 26;20(1):433. Epub 2019 Nov 26.

Department of Nephrology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Background: Renal hypouricemia (RHUC) is an inherited heterogenous disorder caused by faulty urate reabsorption transporters in the renal proximal tubular cells. Anaerobic exercise may induce acute kidney injury in individuals with RHUC that is not caused by exertional rhabdomyolysis; it is called acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE). RHUC is the most important risk factor for ALPE. However, the mechanism of onset of ALPE in patients with RHUC has not been elucidated. The currently known genes responsible for RHUC are SLC22A12 and SLC2A9.

Case Presentation: A 37-year-old man presented with loin pain after exercising. Despite having a healthy constitution from birth, biochemical examination revealed hypouricemia, with a uric acid (UA) level of < 1 mg/dL consistently at every health check. We detected acute kidney injury, with a creatinine (Cr) level of 4.1 mg/dL, and elevated bilirubin; hence, the patient was hospitalized. Computed tomography revealed no renal calculi, but bilateral renal swelling was noted. Magnetic resonance imaging detected cuneiform lesions, indicating bilateral renal ischemia. Fractional excretion values of sodium and UA were 0.61 and 50.5%, respectively. Urinary microscopy showed lack of tubular injury. The patient's older sister had hypouricemia. The patient was diagnosed with ALPE. Treatment with bed rest, fluid replacement, and nutrition therapy improved renal function and bilirubin levels, and the patient was discharged on day 5. Approximately 1 month after onset of ALPE, his Cr, UA, and TB levels were 0.98, 0.8, and 0.9 mg/dL, respectively. We suspected familial RHUC due to the hypouricemia and family history and performed genetic testing but did not find the typical genes responsible for RHUC. A full genetic analysis was opposed by the family.

Conclusions: To the best of our knowledge, this is the first report of ALPE with hyperbilirubinemia. Bilirubin levels may become elevated as a result of heme oxygenase-1 activation, occurring in exercise-induced acute kidney injury in patients with RHUC; this phenomenon suggests renal ischemia-reperfusion injury. A new causative gene coding for a urate transporter may exist, and its identification would be useful to clarify the urate transport mechanism.
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http://dx.doi.org/10.1186/s12882-019-1618-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878684PMC
November 2019

Successful management of visceral disseminated varicella zoster virus infection during treatment of membranous nephropathy: a case report.

BMC Infect Dis 2019 Jul 15;19(1):625. Epub 2019 Jul 15.

Department of Hypertension and Nephrology, NTT Medical Centre Tokyo, 5-9-22, Higasi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.

Background: Visceral disseminated varicella zoster virus (VDVZV) infection is a rare disease with a high mortality rate (55%) in immunocompromised patients, but it is not yet widely recognized in the field of nephrology. We report a case of VDVZV contracted during immunosuppressive therapy for membranous nephropathy.

Case Presentation: A 36-year-old woman was diagnosed with membranous nephropathy and was being treated with immunosuppressive therapy consisting of 60 mg/day prednisolone, 150 mg/day mizoribine, and 150 mg/day cyclosporine. Nephrosis eased; therefore, the prednisolone dosage was reduced. However, 50 days after starting immunosuppressive therapy, the patient suddenly developed strong and spontaneous abdominal pain, predominantly in the epigastric area, without muscular guarding or rebound tenderness. Blood data indicated neutrophil-dominant elevated white blood cell count, reduced platelet count, elevated transaminase and lactate dehydrogenase, slightly increased C-reactive protein, and enhanced coagulability. Abdominal computed tomography revealed a mildly increased enhancement around the root of the superior mesenteric artery with no perforation, intestinal obstruction, or thrombosis. The cause of the abdominal pain was unknown, so the patient was carefully monitored and antibiotic agents and opioid analgesics administered. The following day, blisters appeared on the patient's skin, which were diagnosed as varicella. There was a marked increase in the blood concentration of VZV-DNA; therefore, the cause of the abdominal pain was diagnosed as VDVZV. Treatment with acyclovir and immunoglobulin was immediately started, and the immunosuppressive therapy dose reduced. The abdominal pain resolved rapidly, and the patient was discharged 1 week after symptom onset.

Discussions And Conclusions: This patient was VZV-IgG positive, but developed VDVZV due to reinfection. Abdominal pain due to VDVZV precedes the skin rash, which makes it difficult to diagnose before the appearance of the rash, but measuring the VZV-DNA concentration in the blood may be effective. Saving the patient's life requires urgent administration of sufficient doses of acyclovir and reduced immunosuppressive therapy.
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http://dx.doi.org/10.1186/s12879-019-4193-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632194PMC
July 2019

Overexpression of Orange Carotenoid Protein Protects the Repair of PSII under Strong Light in Synechocystis sp. PCC 6803.

Plant Cell Physiol 2019 Feb;60(2):367-375

Department of Biochemistry and Molecular Biology, Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama, Japan.

Orange carotenoid protein (OCP) plays a vital role in the thermal dissipation of excitation energy in the photosynthetic machinery of the cyanobacterium Synechocystis sp. PCC 6803. To clarify the role of OCP in the protection of PSII from strong light, we generated an OCP-overexpressing strain of Synechocystis and examined the effects of overexpression on the photoinhibition of PSII. In OCP-overexpressing cells, thermal dissipation of energy was enhanced and the extent of photoinhibition of PSII was reduced. However, photodamage to PSII, as monitored in the presence of lincomycin, was unaffected, suggesting that overexpressed OCP protects the repair of PSII. Furthermore, the synthesis de novo of proteins in thylakoid membranes, such as the D1 protein which is required for the repair of PSII, was enhanced in OCP-overexpressing cells under strong light, while the production of singlet oxygen was suppressed. Thus, the enhanced thermal dissipation of energy via overexpressed OCP might support the repair of PSII by protecting protein synthesis from oxidative damage by singlet oxygen under strong light, with the resultant mitigation of photoinhibition of PSII.
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http://dx.doi.org/10.1093/pcp/pcy218DOI Listing
February 2019

Focal segmental glomerulosclerosis lesion associated with inhibition of tyrosine kinases by lenvatinib: a case report.

BMC Nephrol 2018 10 19;19(1):273. Epub 2018 Oct 19.

Department of Hypertension and Nephrology, NTT Medical Centre Tokyo, 5-9-22, Higasi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.

Background: Lenvatinib is a tyrosine kinase inhibitor with novel binding ability. It is considered the standard of care for metastatic thyroid cancer; moreover, whether it is indicated for other malignant tumors has been examined. Lenvatinib increases the risk of kidney injury in some patients. In comparison with sorafenib, which is a conventional tyrosine kinase inhibitor (TKI), lenvatinib results in more side effects, including hypertension and proteinuria. We describe a case of secondary focal segmental glomerulosclerosis (FSGS) that developed following treatment of metastatic thyroid cancer with lenvatinib and reviewed the mechanisms of renal impairment.

Case Presentation: We describe a patient with metastatic thyroid cancer who developed hypertension, nephrotic syndrome, and acute kidney injury after 3 months of lenvatinib treatment. Renal biopsy results revealed that 7 of 16 glomeruli indicated complete hyalinization, and that the glomeruli with incomplete hyalinization showed FSGS due to a vascular endothelial disorder and podocyte damage, which seemed to have been induced by lenvatinib treatment. These findings were similar to those of renal impairment treated with conventional TKIs. Although lenvatinib treatment was discontinued, up to 15 months were required to achieve remission of proteinuria, thus leading to chronic kidney disease with hyalinized lesions.

Conclusions: To the best of our knowledge, this is the first reported case of secondary FSGS by lenvatinib treatment. Renal impairment treated with TKIs is commonly associated with minimal change nephrotic syndrome/FSGS findings, and it is suggested that renal involvement with TKI is different from that with the vascular endothelial growth factor ligand. Overexpression of c-mip due to TKI causes disorders such as podocyte dysregulation and promotion of apoptosis, which cause FSGS. Lenvatinib may result in FSGS by a similar mechanism with another TKI and could cause irreversible renal impairment; therefore caution must be used. It is essential to monitor blood pressure, urinary findings, and the renal function.
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http://dx.doi.org/10.1186/s12882-018-1074-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194623PMC
October 2018

Configuration of Ten Light-Harvesting Chlorophyll / Complex I Subunits in Photosystem I.

Plant Physiol 2018 10 20;178(2):583-595. Epub 2018 Aug 20.

Research Institute for Interdisciplinary Science, Okayama University, Okayama 700-8530, Japan

In plants, the photosystem I (PSI) core complex stably associates with its light-harvesting chlorophyll / complex I (LHCI) to form the PSI-LHCI supercomplex. The vascular plant PSI core complex associates with four distinct LHCI subunits, whereas that of the green alga binds nine distinct LHCI subunits (LHCA1-LHCA9). The stoichiometry and configuration of these LHCI subunits in the PSI-LHCI supercomplex of remain controversial. Here, we determined the stoichiometry of the nine distinct LHCI subunits relative to PSI subunits through uniform labeling of total proteins using C. We separated the nine LHCI polypeptides by three different sodium dodecyl sulfate-polyacrylamide gel electrophoresis systems. Our data revealed that the PSI-LHCI supercomplex contains two LHCA1 proteins and one of each of the other eight LHCI subunits. Subsequently, we identified their cross-linked products by immunodetection and mass spectrometry to determine the configuration of the 10 LHCI subunits within the PSI-LHCI supercomplex. Furthermore, analyses of PSI-LHCI complexes isolated from Δ and Δ mutants and oligomeric LHCI from a PSI-deficient (Δ/) mutant provided supporting evidence for the LHCI subunit configuration. In conclusion, eight LHCI subunits bind to the PSI core at the site of PSAF subunit in two layers: LHCA1-LHCA8-LHCA7-LHCA3 from PSAG to PSAK, in the inner layer, and LHCA1-LHCA4-LHCA6-LHCA5 in the outer layer. The other two LHCI subunits, LHCA2 and LHCA9, bind PSAB between PSAG and PSAH, PSAG-LHCA9-LHCA2-PSAH. Our study provides new insights into the LHCI configuration linked to the PSI core.
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http://dx.doi.org/10.1104/pp.18.00749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181050PMC
October 2018

PROTON GRADIENT REGULATION 5 contributes to ferredoxin-dependent cyclic phosphorylation in ruptured chloroplasts.

Biochim Biophys Acta Bioenerg 2018 Oct 31;1859(10):1173-1179. Epub 2018 Jul 31.

Department of Botany, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan. Electronic address:

Antimycin A-sensitive cyclic electron flow (CEF) was discovered as cyclic phosphorylation by Arnon et al. (1954). Because of its sensitivity to antimycin A, PROTON GRADIENT REGULATION 5 (PGR5)/PGR5-like Photosynthetic Phenotype 1 (PGRL1)-dependent CEF has been considered identical to the CEF of Arnon et al. However, this conclusion still needs additional supportive evidence, mainly because of the absence of definitive methods of evaluating CEF activity. In this study, we revisited the classical method of monitoring cyclic phosphorylation in ruptured chloroplasts to characterize two Arabidopsis mutants: pgr5, which is defective in antimycin A-sensitive CEF, and chlororespiratory reduction 2-1 (crr2-1), which is defective in chloroplast NDH-dependent CEF. We observed a significant reduction in CEF-dependent pmf formation and consequently ATP synthesis in the pgr5 mutant, although LEF-dependent pmf formation and ATP synthesis were not impaired at photosynthetic photon flux densities below 130 μmol m s. In contrast, the contribution of chloroplast NDH complex to pmf formation and ATP synthesis was not significant. Antimycin A partially inhibited CEF-dependent pmf formation, although there may be further inhibition sites. Unlike in the observation in leaves, the proton conductivity of ATP synthase, monitored as g, was not enhanced in ruptured chloroplasts of the pgr5 mutant.
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http://dx.doi.org/10.1016/j.bbabio.2018.07.011DOI Listing
October 2018

A case of ABO-incompatible blood transfusion treated by plasma exchange therapy and continuous hemodiafiltration.

CEN Case Rep 2018 May 31;7(1):114-120. Epub 2018 Jan 31.

Department of Hypertension and Nephrology, NTT Medical Center Tokyo, 5-9-22 Higash-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.

ABO-incompatible blood transfusion is potentially a life-threatening event. A 74-year-old type O Rh-positive male was accidentally transfused with 280 mL type B Rh-positive red blood cells during open right hemicolectomy, causing ABO-incompatible blood transfusion. Immediately after the transfusion, the patient experienced a hypotension episode followed by acute hemolytic reaction, disseminated intravascular coagulation and acute kidney injury. Plasma exchange therapy was performed to remove anti-B antibody and free hemoglobin because they caused acute hemolytic reaction, disseminated intravascular coagulation, and acute kidney injury. Free hemoglobin levels decreased from 13 to 2 mg/dL for 2 h. Continuous hemodiafiltration was used to stabilize hemodynamics. The patient was successfully treated for acute hemolytic reaction, disseminated intravascular coagulation, and acute kidney injury. Plasma exchange therapy and continuous hemodiafiltration are likely to be effective treatments for ABO-incompatible blood transfusion, and further studies are required to assess this effectiveness in future.
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http://dx.doi.org/10.1007/s13730-018-0307-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886938PMC
May 2018

Effects of triclosan on Japanese medaka (Oryzias latipes) during embryo development, early life stage and reproduction.

J Appl Toxicol 2018 04 27;38(4):544-551. Epub 2017 Nov 27.

Center for Health and Environmental Risk Research, National Institute for Environmental Studies, 16-2Onogawa, Tsukuba, Ibaraki, 305-8506, Japan.

Triclosan has been shown to have endocrine-disrupting effects in aquatic organisms. In 2016, the US Food and Drug Administration banned the use of triclosan in consumer soaps. Before the ban, triclosan was reported at low concentrations in the aquatic environment, although the effect of triclosan on reproduction in teleost fish species is yet to be clarified. Here we investigated the effects of triclosan on embryo development and reproduction, and during the early life stage, in Japanese medaka (Oryzias latipes) by using Organisation for Economic Co-operation and Development tests 229, 212 and 210, with minor modifications. In adult medaka, exposure to 345.7 μg l suppressed fecundity and increased mortality but had no effect on fertility. Exposure to 174.1 or 345.7 μg l increased liver vitellogenin concentration in females but decreased liver vitellogenin concentration in males. With triclosan exposure, mortality was increased dose dependently during the embryonic and early larval stages, and a particularly steep increase in mortality was observed soon after hatching. The lowest observed effect concentrations of triclosan in Japanese medaka obtained in the present study (mortality [embryonic and larval stages, 276.3 μg l ; early life stage, 134.4 μg l ; adult stage, 174.1 μg l ], growth [134.4 μg l ], vitellogenin [174.1 μg l ], fecundity [345.7 μg l ] and fertility [>345.7 μg l ]) were at least 55 times (compared with the USA) and up to 13 400 times (compared with Germany) greater than the detected triclosan levels in the aquatic environment. These results suggest that triclosan may not be affecting fish populations in the aquatic environment.
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http://dx.doi.org/10.1002/jat.3561DOI Listing
April 2018

Clostridium paraputrificum Bacteremia in an Older Patient with No Predisposing Medical Condition.

Intern Med 2017 Dec 25;56(24):3395-3397. Epub 2017 Sep 25.

Division of Community Medicine and Career Development, Kobe University Graduate School of Medicine, Japan.

We herein report a rare case of Clostridium paraputrificum bacteremia in an elderly (88-year-old) man without a predisposing medical condition. Although he had a history of anaerobic bacteremia approximately eight months prior to admission, no gastrointestinal disease was discovered. He was treated with intravenous ampicillin/sulbactam. This case suggests that C. paraputrificum bacteremia can result from only minor abnormalities in macroscopically normal mucosal barriers. To our knowledge, this is the first report of C. paraputrificum bacteremia in Japan.
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http://dx.doi.org/10.2169/internalmedicine.8164-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790735PMC
December 2017

Ulceration on an old cervical operative scar: Post-surgical pyoderma gangrenosum induced by recent mastectomy.

J Dermatol 2017 Oct 30;44(10):e244-e245. Epub 2017 May 30.

Department of Dermatology, Sapporo City General Hospital, Sapporo, Japan.

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http://dx.doi.org/10.1111/1346-8138.13929DOI Listing
October 2017

Assessment of the lethal and sublethal effects of 20 environmental chemicals in zebrafish embryos and larvae by using OECD TG 212.

J Appl Toxicol 2017 Oct 29;37(10):1245-1253. Epub 2017 May 29.

Center for Health and Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan.

Fish embryo toxicity tests are used to assess the lethal and sublethal effects of environmental chemicals in aquatic organisms. Previously, we used a short-term toxicity test published by the Organization for Economic Co-operation and Development (test no. 212: Fish, Short-term Toxicity Test on Embryo and Sac-Fry Stages [OECD TG 212]) to assess the lethal and sublethal effects of aniline and several chlorinated anilines in zebrafish embryos and larvae. To expand upon this previous study, we used OECD TG 212 in zebrafish embryos and larvae to assess the lethal and sublethal effects of 20 additional environmental chemicals that included active pharmaceutical ingredients, pesticides, metals, aromatic compounds or chlorinated anilines. Zebrafish embryos (Danio rerio) were exposed to the test chemicals until 8 days post-fertilization. A delayed lethal effect was induced by 16 of the 20 test chemicals, and a positive correlation was found between heart rate turbulence and mortality. We also found that exposure to the test chemicals at concentrations lower than the lethal concentration induced the sublethal effects of edema, body curvature and absence of swim-bladder inflation. In conclusion, the environmental chemicals assessed in the present study induced both lethal and sublethal effects in zebrafish embryos and larvae, as assessed by using OECD TG 212. Copyright © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/jat.3487DOI Listing
October 2017

PETO Interacts with Other Effectors of Cyclic Electron Flow in Chlamydomonas.

Mol Plant 2016 Apr 6;9(4):558-68. Epub 2016 Jan 6.

Institut de Biologie Physico-Chimique, UMR 7141 CNRS-UPMC, 13 rue P et M Curie, Paris 75005, France. Electronic address:

While photosynthetic linear electron flow produces both ATP and NADPH, cyclic electron flow (CEF) around photosystem I (PSI) and cytochrome b6f generates only ATP. CEF is thus essential to balance the supply of ATP and NADPH for carbon fixation; however, it remains unclear how the system tunes the relative levels of linear and cyclic flow. Here, we show that PETO, a transmembrane thylakoid phosphoprotein specific of green algae, contributes to the stimulation of CEF when cells are placed in anoxia. In oxic conditions, PETO co-fractionates with other thylakoid proteins involved in CEF (ANR1, PGRL1, FNR). In PETO-knockdown strains, interactions between these CEF proteins are affected. Anoxia triggers a reorganization of the membrane, so that a subpopulation of PSI and cytochrome b6f now co-fractionates with the CEF effectors in sucrose gradients. The absence of PETO impairs this reorganization. Affinity purification identifies ANR1 as a major interactant of PETO. ANR1 contains two ANR domains, which are also found in the N-terminal region of NdhS, the ferredoxin-binding subunit of the plant ferredoxin-plastoquinone oxidoreductase (NDH). We propose that the ANR domain was co-opted by two unrelated CEF systems (PGR and NDH), possibly as a sensor of the redox state of the membrane.
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http://dx.doi.org/10.1016/j.molp.2015.12.017DOI Listing
April 2016

Biochemical characterization of photosystem I-associated light-harvesting complexes I and II isolated from state 2 cells of Chlamydomonas reinhardtii.

Plant Cell Physiol 2014 Aug 26;55(8):1437-49. Epub 2014 May 26.

The Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama, 700-8530 JapanJapan Science and Technology Agency, CREST

Two photosystems, PSI and PSII, drive electron transfer in series for oxygenic photosynthesis using light energy. To balance the activity of the two photosystems under varying light conditions, mobile antenna complexes, light-harvesting complex IIs (LHCIIs), shuttle between the two photosystems during state transitions. PSI forms a complex consisting of PSI core and its peripheral light-harvesting complex (LHCI) in plants and algae. In a previous study, we isolated a PSI-LHCI-LHCII supercomplex containing both LHCI and LHCII from state 2 cells of Chlamydomonas reinhardtii. In the present study, we isolated a PSI-LHCI-LHCII supercomplex associating with more LHCII complexes under a further optimized protocol. We determined its antenna size by three independent methods and revealed that the associated LHCIIs increased the antenna size by about 70 Chls and transferred light energy to the PSI core. Uniform labeling of total cellular proteins with (14)C indicated that the PSI-LHCI-LHCII supercomplex contains 1.85 copies of LhcbM5 and CP29 and 1.29 copies of CP26. PSI-LHCI-LHCII also stably bound 0.4 copy of ferredoxin-NADP(+) oxidoreductase (FNR) that catalyzes light-induced electron transfer from PSI to NADP(+) in the presence of ferredoxin. We discuss the possible organization of these LHCIIs in the PSI-LHCI-LHCII supercomplex.
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http://dx.doi.org/10.1093/pcp/pcu071DOI Listing
August 2014

Proton gradient regulation 5-mediated cyclic electron flow under ATP- or redox-limited conditions: a study of ΔATpase pgr5 and ΔrbcL pgr5 mutants in the green alga Chlamydomonas reinhardtii.

Plant Physiol 2014 May 12;165(1):438-52. Epub 2014 Mar 12.

Commissariat à l'Energie Atomique, Institut de Biologie Environmentale et Biotechnologie, Lab Bioenerget Biotechnol Bacteries and Microalgues, F-13108 Saint-Paul-lez-Durance, France.

The Chlamydomonas reinhardtii proton gradient regulation5 (Crpgr5) mutant shows phenotypic and functional traits similar to mutants in the Arabidopsis (Arabidopsis thaliana) ortholog, Atpgr5, providing strong evidence for conservation of PGR5-mediated cyclic electron flow (CEF). Comparing the Crpgr5 mutant with the wild type, we discriminate two pathways for CEF and determine their maximum electron flow rates. The PGR5/proton gradient regulation-like1 (PGRL1) ferredoxin (Fd) pathway, involved in recycling excess reductant to increase ATP synthesis, may be controlled by extreme photosystem I acceptor side limitation or ATP depletion. Here, we show that PGR5/PGRL1-Fd CEF functions in accordance with an ATP/redox control model. In the absence of Rubisco and PGR5, a sustained electron flow is maintained with molecular oxygen instead of carbon dioxide serving as the terminal electron acceptor. When photosynthetic control is decreased, compensatory alternative pathways can take the full load of linear electron flow. In the case of the ATP synthase pgr5 double mutant, a decrease in photosensitivity is observed compared with the single ATPase-less mutant that we assign to a decreased proton motive force. Altogether, our results suggest that PGR5/PGRL1-Fd CEF is most required under conditions when Fd becomes overreduced and photosystem I is subjected to photoinhibition. CEF is not a valve; it only recycles electrons, but in doing so, it generates a proton motive force that controls the rate of photosynthesis. The conditions where the PGR5 pathway is most required may vary in photosynthetic organisms like C. reinhardtii from anoxia to high light to limitations imposed at the level of carbon dioxide fixation.
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http://dx.doi.org/10.1104/pp.113.233593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012601PMC
May 2014

Cyclic electron flow is redox-controlled but independent of state transition.

Nat Commun 2013 ;4:1954

Institut de Biologie Physico-Chimique, UMR 7141 CNRS-UPMC, 13 rue P et M Curie, 75005 Paris, France.

Photosynthesis is the biological process that feeds the biosphere with reduced carbon. The assimilation of CO2 requires the fine tuning of two co-existing functional modes: linear electron flow, which provides NADPH and ATP, and cyclic electron flow, which only sustains ATP synthesis. Although the importance of this fine tuning is appreciated, its mechanism remains equivocal. Here we show that cyclic electron flow as well as formation of supercomplexes, thought to contribute to the enhancement of cyclic electron flow, are promoted in reducing conditions with no correlation with the reorganization of the thylakoid membranes associated with the migration of antenna proteins towards Photosystems I or II, a process known as state transition. We show that cyclic electron flow is tuned by the redox power and this provides a mechanistic model applying to the entire green lineage including the vast majority of the cases in which state transition only involves a moderate fraction of the antenna.
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http://dx.doi.org/10.1038/ncomms2954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709502PMC
December 2013

[A retrospective study of oral adverse events with colorectal cancer chemotherapy using bevacizumab].

Gan To Kagaku Ryoho 2011 Jun;38(6):959-62

Dept. of Pharmacy, Tohoku Rosai Hospital.

Purpose: We encountered serious oral mucositis in some patients undergoing colorectal chemotherapy with bevacizumab. We retrospectively investigated the role bevacizumab plays in the occurrence of oral mucositis.

Subjects And Methods: Between January 2008 and December 2009, we encountered 11 patients for whom chemotherapy with bevacizumab had resulted in oral mucositis. The patients included 5 men and 6 women, with a mean age of 67. 9 years(range, 62-76 years). Among the patients, 5 had grade 1 oral mucositis, 3 had grade 2, and 3 had grade 3. We analyzed the risk factors, grades, symptoms, and treatments of oral mucositis in these patients.

Results: In 6 patients, bevacizumab was administered in combination with mFOLFOX6, and in 5 patients, bevacizumab was administered in combination with FOLFIRI. Seven patients had undergone prior treatment without the occurrence of serious oral mucositis. With respect to oral health, 8 patients had periodontal disease, 7 had dental caries, 3 wore dentures, 3 exhibited poor oral self-care, and 2 had diabetes; in addition, 2 patients were smokers. Symptoms of oral mucositis included mucosal reddening in 11 patients, oral mucosal erosion or ulcer in 7, fungus infection in 6, aphtha in 7, pseudomembrane formation in 3, and poor oral intake in 2. All the patients had oral mucositis at the occlusal line of the buccal mucosa. The treatment for oral mucositis included polaprezinc.

Conclusion: Because many factors influence the development of oral mucositis, determining the specific cause of oral mucositis is difficult. Bevacizumabmay possibly decrease the VEGF levels in saliva and delay wound healing in oral mucositis. Therefore, oral mucositis may be caused not only by diabetes and poor oral self-care but by bevacizumab.
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June 2011

Significance of the glutamate-139 residue of the V-type Na+-ATPase NtpK subunit in catalytic turnover linked with salt tolerance of Enterococcus hirae.

J Bacteriol 2011 Jul 20;193(14):3657-61. Epub 2011 May 20.

Integrated Center for Sciences, Ehime University, Matsuyama, Japan1; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.

A Glu139Asp mutant of the NtpK subunit (kE139D) of Enterococcus hirae vacuolar-type ATPase (V-ATPase) lost tolerance to sodium but not to lithium at pH 10. Purified kE139D V-ATPase retained relatively high specific activity and affinity for the lithium ion compared to the sodium ion. The kE139 residue of V-ATPase is indispensable for its enzymatic activity that is linked with the salt tolerance of enterococci.
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http://dx.doi.org/10.1128/JB.01537-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133306PMC
July 2011

Advanced epithelioid malignant peripheral nerve sheath tumor showing complete response to combined surgery and chemotherapy: a case report.

Case Rep Oncol Med 2011 6;2011:705345. Epub 2011 Sep 6.

Department of Plastic and Reconstructive Surgery, Asahikawa-Kosei General Hospital, 1 Jo-dohri 24-chome 111, Asahikawa City, Hokkaido 078-8211, Japan.

Malignant peripheral nerve sheath tumor (MPNST) is a rare high-grade soft tissue sarcoma. The epithelioid variant accounts for 5% or less of MPNSTs; the clinical behavior of this variant is unclear. Reports of approximately 40 cases are available in the English literature; however, most reports addressed clinicopathological features rather than therapeutic procedures or clinical courses. We describe a case of a 62-year-old male with an epithelioid MPNST of the left foot. Multiple lung metastases developed after radical surgery on the primary lesion. The response to adjuvant chemotherapy including doxorubicin and ifosfamide was favorable, and thoracoscopic resection was subsequently performed on the remaining three metastases. No evidence of recurrence or metastasis was observed at the 12-month followup after the first operation. Further followup and chemotherapy may be required.
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http://dx.doi.org/10.1155/2011/705345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350304PMC
August 2012

Micro OS-ELISA: Rapid noncompetitive detection of a small biomarker peptide by open-sandwich enzyme-linked immunosorbent assay (OS-ELISA) integrated into microfluidic device.

Lab Chip 2010 Jan 3;10(1):92-100. Epub 2009 Nov 3.

Department of Bioengineering, School of Engineering, The University of Tokyo, Bunkyo, Tokyo, 113-8656, Japan.

A novel detection system that combines the merits of open-sandwich (OS) enzyme-linked immunoadsorbent assay (ELISA) and a microfluidic sensor chip system, and which enables rapid and noncompetitive immunodetection of small antigens of less than 1000 in molecular weight, has been proposed. Equipped with a sensitive thermal lens microscope, a minute amount of the carboxyl-terminal peptide of human osteocalcin (BGP), a biomarker for bone metabolism, was quantified utilizing antigen-dependent stabilization of an antibody variable region (OS principle). In a short analysis time (approximately 12 min), we could attain a detection limit comparable to that of the microplate-based OS ELISA (1 microg L(-1)). In addition, the effects of several pretreatments for serum-derived samples were investigated: an albumin absorption resin, addition of a protease inhibitor cocktail and heat treatment. Each pretreatment was found to be effective. Consequently, intrinsic BGP and its fragments could be detected in healthy human serum with a superior detection limit and working range compared to those of the conventional competitive ELISA method.
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http://dx.doi.org/10.1039/b915516cDOI Listing
January 2010

Development of a micro-potentiometric sensor for the microchip analysis of alkali ions.

Anal Sci 2009 Dec;25(12):1397-401

Microchemistry Group, Kanagawa Academy of Science and Technology, 3-2-1 Sakado, Takatsu, Kawasaki 213-0012, Japan.

This paper reports on the development of a micro-potentiometric sensor based on external microelectrodes introduced into a microchip. We miniaturized reference and ion-selective electrodes (ISEs) and embedded them into a plastic (PDMS) microchip; the miniaturization of ISE was attained by using a monolithic capillary-based membrane. This sensor was applied to the detection of alkali ions (Na+, K+ and NH4+) in a microflow on the microg/L level.
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http://dx.doi.org/10.2116/analsci.25.1397DOI Listing
December 2009
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