Publications by authors named "Yuko Shibuya"

23 Publications

  • Page 1 of 1

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

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

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

New chloptosins B and C from an Embleya strain exhibit synergistic activity against methicillin-resistant Staphylococcus aureus when combined with co-producing compound L-156,602.

J Antibiot (Tokyo) 2021 01 14;74(1):80-85. Epub 2020 Aug 14.

Laboratory of Microbiology, Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021, Japan.

Two new dimeric cyclohexapeptides, chloptosins B and C, were discovered from the culture broth of Embleya sp. MM621-AF10 together with the known compounds chloptosin and L-156,602. The structures of the new chloptosins were determined by spectroscopic studies and advanced Marfey's methods. The stereo structure of the constituent isoleucine was determined by C Marfey's analysis. Chloptosins demonstrated potent antimicrobial activity against Gram-positive bacteria including drug-resistant strains of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci with MICs of 0.5-2 µg ml. The antimicrobial activities of chloptosins were enhanced by addition of co-producing compound L-156,602, as shown by checkerboard analysis.
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http://dx.doi.org/10.1038/s41429-020-0361-yDOI Listing
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

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

Membranoproliferative glomerulonephritis-like findings for TAFRO syndrome, associated with an anterior mediastinal tumor: A case report.

Medicine (Baltimore) 2018 Jun;97(24):e11057

Department of Hypertension and Nephrology Department of Diagnostic Pathology, NTT Medical Centre Tokyo, Higasi-Gotanda, Shinagawa-ku, Tokyo, Japan.

Rationale: TAFRO syndrome is a systemic inflammatory disease proposed recently from Japan. The cause of TAFRO syndrome is unclear. Moreover, the disease characteristics and kidney pathology are yet unknown well and there are few cases. Herein, we report a patient with TAFRO syndrome and present the features of the renal histopathology.

Patient Concerns: A 55-year-old woman presented to our hospital with the main complaint of subacute dyspnoea.

Diagnosis: Physical findings included a low-grade fever and generalised oedema. A blood test showed anaemia, coagulation abnormalities, hypoproteinaemia, impaired renal function, proteinuria, and elevated alkaline phosphatase (ALP), C-reactive protein (CRP), interleukin-6 (IL-6). Chest and abdominal computed tomography showed an anterior mediastinal mass and multiple enlarged lymph nodes.

Interventions: Nephrotic syndrome secondary to a malignant mediastinal tumour was suspected; therefore, the patient underwent resection of the anterior mediastinal mass. Histopathological examination of the resected specimen showed lymphocytic proliferation without signs of malignancy. These findings were compatible with hyaline vascular type Castleman disease (CD), and with the associated multiple lymph nodes enlargement, the patient was initially diagnosed with multicenteric CD.

Outcomes: After resection of the whole tumour, all the clinical symptoms improved. However, after resection 6 months passed, the patient developed thrombocytopenia, anaemia, renal dysfunction, further enlargement of the residual lymph nodes, hepatosplenomegaly, and mild myelofibrosis. A diagnosis of TAFRO syndrome (TS) was eventually made. All symptoms improved with initial intravenous pulse steroid therapy followed by oral steroids. Histopathological examination of the renal biopsy samples showed findings resembling membranoproliferative glomerulonephritis (MPGN).

Lessons: In TS, all characteristic signs may not exist from the beginning. The association between TS and CD is not clear. When we compared our findings with previously published cases of TS and CD, we found that the renal pathology findings resembled MPGN in many cases of TS, while only a few cases showed amyloidosis. Recent results suggest that TS may be an independent disease from CD, and given the frequency of renal pathology findings, it may also have a different aetiology. To the best of our knowledge, this case report is rare to demonstrate the renal pathology in a patient with conventional TAFRO syndrome.
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http://dx.doi.org/10.1097/MD.0000000000011057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023668PMC
June 2018

Instability of the 16S rRNA methyltransferase-encoding npmA gene: why have bacterial cells possessing npmA not spread despite their high and broad resistance to aminoglycosides?

J Antibiot (Tokyo) 2018 09 8;71(9):798-807. Epub 2018 Jun 8.

Laboratory of Microbiology, Institute of Microbial Chemistry, Tokyo, Japan.

The NpmA bacterial 16S rRNA methyltransferase, which is identified from Escherichia coli strains, confers high resistance to many types of aminoglycoside upon its host cells. But despite its resistance-conferring ability, only two cases of its isolation from E. coli (14 years apart) have been reported to date. Here, we investigated the effect of the npmA gene on aminoglycoside resistance in Pseudomonas aeruginosa and Klebsiella pneumoniae and its stability in E. coli cells by comparing it with armA, another 16S rRNA methyltransferase gene currently spreading globally. As a result, we found that npmA conferred resistance to all types of aminoglycoside antibiotics we tested (except streptomycin) in both P. aeruginosa and K. pneumoniae, as well in E. coli. In addition, co-expression of armA and npmA resulted in an additive effect for the resistance. However, in return for the resistance, we also observed that the growth rates and the cell survivability of the strains transformed with the npmA-harboring plasmids were inferior than those of the control strains and that these plasmids were easily disrupted by IS10, IS1, and IS5 insertion sequences. We discuss these data in the context of the threat posed by pathogenic strains possessing npmA.
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http://dx.doi.org/10.1038/s41429-018-0070-yDOI Listing
September 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

Structures and biological activities of novel 4'-acetylated analogs of chrysomycins A and B.

J Antibiot (Tokyo) 2017 Nov 6;70(11):1078-1082. Epub 2017 Sep 6.

Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.

Two new 4'-acetylated analogs of chrysomycin were discovered during the screening for antitumor agents from the metabolites of actinomycetes. Their structures and physicochemical properties were determined by standard spectrometric analyses. Their cytotoxicities and antimicrobial activities were evaluated against a panel of cancer cell lines and microbes. While acetylation reinforced the cytotoxicity of chrysomycin B, it weakened the activity of chrysomycin A. Chrysomycin A and its acetylated analog showed high cytotoxicity toward most of the cancer cells with ICs less than 10 ng ml. The 4'-acetyl-chrysomycin A was predominantly observed in nuclei at concentrations where the autofluorescence was observable. Chrysomycins were effective toward Gram-positive bacteria. The 4'-acetylated-chrysomycin A and B had MICs of 0.5-2 μg ml and 2 to greater than 64 μg ml, respectively, toward Gram-positive bacteria including MRSA and VRE.
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http://dx.doi.org/10.1038/ja.2017.99DOI Listing
November 2017

Stability and Bioavailability of Lentztrehaloses A, B, and C as Replacements for Trehalose.

J Agric Food Chem 2016 Sep 14;64(38):7121-6. Epub 2016 Sep 14.

Institute of Microbial Chemistry (BIKAKEN) , 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

Trehalose is widely used as a sweetener, humectant, and stabilizer, but is ubiquitously degraded by the enzyme trehalase expressed in a broad variety of organisms. The stability of the new trehalose analogues lentztrehaloses A, B, and C in microbial and mammalian cell cultures and their pharmacokinetics in mice were analyzed to evaluate their potential as successors of trehalose. Among the 12 species of microbes and 2 cancer cell lines tested, 7 digested trehalose, whereas no definitive digestion of the lentztrehaloses was observed in any of them. When orally administered to mice (0.5 g/kg), trehalose was not clearly detected in blood and urine and only slightly detected in feces. However, lentztrehaloses were detected in blood at >1 μg/mL over several hours and were eventually excreted in feces and urine. These results indicate that lentztrehaloses may potentially replace trehalose as nonperishable materials and drug candidates with better bioavailabilities.
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http://dx.doi.org/10.1021/acs.jafc.6b02782DOI Listing
September 2016

Preoperative estimated glomerular filtration rate as a significant predictor of long-term outcomes after coronary artery bypass grafting in Japanese patients.

Gen Thorac Cardiovasc Surg 2014 Feb 15;62(2):95-102. Epub 2013 Aug 15.

Department of Cardiovascular Surgery, NTT Medical Center Tokyo, 5-9-22 Higashigotanda, Shinagawa-ku, Tokyo, 141-8625, Japan,

Purposes: The aim of this retrospective study was to investigate the effect of chronic kidney disease (CKD) on outcomes after coronary artery bypass grafting (CABG), and to determine whether preoperative estimated glomerular filtration rate (eGFR) can be a predictor of long-term outcomes after CABG.

Methods: 486 Japanese patients who underwent isolated CABG between December 2000 and August 2010 were evaluated. Preoperative eGFR was estimated by the Japanese equation according to guidelines from the Japanese Society of Nephrology. We defined CKD as a preoperative eGFR of less than 60 ml/min/1.73 m(2). 203 patients had CKD (CK group) and 283 patients did not (N group).

Results: During a mean observation time of 53 months, the overall survival rate was significantly lower in the CK group than in the N group (p = 0.0044). Similarly, the CK group had significantly more unfavorable results with regard to freedom from cardiac death, major adverse cardiovascular and cerebrovascular events (MACCE), and hemodialysis. Using multivariate analyses, preoperative eGFR was an independent predictor of all-cause mortality (HR 0.983; p = 0.026), cardiac mortality (HR 0.963; p = 0.006), and incidence of MACCE (HR 0.983; p = 0.002).

Conclusions: The CK group had significantly more unfavorable outcomes than the N group. Preoperative eGFR was an independent predictor of long-term outcomes after CABG in Japanese patients.
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http://dx.doi.org/10.1007/s11748-013-0306-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912374PMC
February 2014

Urinary lipocalin-type prostaglandin D synthase: a potential marker for early gentamicin-induced renal damage?

Ther Drug Monit 2009 Feb;31(1):126-30

Department of Pharmacy, Kanto Medical Center NTT East Corporation, Tokyo, Japan.

Urinary excretion of lipocalin-type prostaglandin D synthase (L-PGDS) has been suggested to be a useful biomarker of early diabetic nephropathy. We studied whether L-PGDS is also a marker of gentamicin (GM)-induced renal damage in the "creatinine-blind" range. A prospective study was conducted in 6 patients who were given long-term intravenous administration of GM (18-42 days in combination with a beta-lactam/carbapenem antibiotic or vancomycin) for the treatment of infective endocarditis. Urinary excretions of L-PGDS, beta2-microglobulin, and N-acetyl-beta-D-glucosaminidase were measured in the early (within 10 days from commencement) and late (thereafter) phases of GM therapy. Systemic clearance of GM (CLGM) and creatinine clearance (CLcr) was also measured concomitantly. CLGM was reduced significantly (P < 0.05) by 10% from the early to late treatment phase, whereas urinary L-PGDS excretion showed a significant (P < 0.05) increase (from 7.3 +/- 4.6 to 8.7 +/- 5.0 mg/g creatinine, mean +/- SD) concomitantly. In contrast, no significant changes were observed for urinary beta2-microglobulin and N-acetyl-beta-D-glucosaminidase concentrations. In conclusion, urinary L-PGDS may be a promising biomarker for the early phase of GM-induced renal impairment.
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http://dx.doi.org/10.1097/FTD.0b013e31819566f1DOI Listing
February 2009

Add-on effect of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning hypertension and left ventricular hypertrophy in patients undergoing long-term amlodipine monotherapy.

Hypertens Res 2007 Nov;30(11):1097-105

Department of Nephrology, Nippon Telegraph and Telephone Corporation (NTT) Kanto Medical Center, Tokyo, Japan.

High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy. The add-on effects of doxazosin at the maximum dose of 6 mg at bedtime on home blood pressure and left ventricular geometry for 1 year were investigated in 49 subjects (37 men and 12 women, aged 57.5+/-9.1 years) with morning hypertension who had been treated with amlodipine alone for more than 1 year. Doxazosin induced a significant decrease in morning blood pressure (145.6+/-5.6/91.5+/-5.4 to 132.4+/-3.7/83.6+/-5.6 mmHg, p
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http://dx.doi.org/10.1291/hypres.30.1097DOI Listing
November 2007

Morning rise of blood pressure assessed by home blood pressure monitoring is associated with left ventricular hypertrophy in hypertensive patients receiving long-term antihypertensive medication.

Hypertens Res 2007 Oct;30(10):903-11

Department of Nephrology, Nippon Telegraph and Telephone Corporation (NTT) Kanto Medical Center, Tokyo, Japan.

To assess the influence of morning rise of systolic blood pressure (SBP) as assessed by home blood pressure monitoring on the left ventricular mass index (LVMI) in relation to the blood pressure control status, we evaluated M-mode cardiac echocardiography in 626 hypertensive subjects (412 men and 214 women; mean age, 61.3+/-10.1 years) who were receiving antihypertensive medication. The subjects were requested to measure their blood pressure at home in the morning and evening over a 3-month period. They were distributed into the following four groups by the average (ME Ave) and the difference (ME Dif) of the morning and evening SBP. The well-controlled hypertensives with a morning rise of SBP (ME Ave<135 mmHg and ME Dif>or=10 mmHg; n=45; 7.2%) had a greater LVMI (122.9+/-22.7 vs. 92.7+/-15.6 g/m2, p<0.001) than the well-controlled hypertensives without a morning rise of SBP (ME Ave<135 mmHg and ME Dif<10 mmHg; n=367; 58.6%). The uncontrolled hypertensives with a morning rise of SBP (ME Ave>or=135 mmHg and ME Dif>or=10 mmHg; n=91; 14.5%) also had a greater LVMI (136.8+/-21.9 vs. 100.2+/-17.5 g/m2, p<0.001) than the uncontrolled hypertensives without a morning rise of SBP (ME Ave>or=135 mmHg and ME Dif<10 mmHg; n=123; 19.6%). A stepwise multivariate regression analysis revealed that the ME Dif was the most important factor related to the LVMI (r2=35.1% for all subjects, p<0001; r2=39.7% for men, p<0.001; and r2=18.7% for women, p<0.001). These results suggest that morning rise of blood pressure is an important factor influencing the development of left ventricular hypertrophy in hypertensive patients on antihypertensive medication.
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http://dx.doi.org/10.1291/hypres.30.903DOI Listing
October 2007

[Two cases of heterozygous Fabry disease].

Nihon Jinzo Gakkai Shi 2006 ;48(5):421-7

Department of Nephrology, Kanto Medical Center NTT EC, Tokyo, Japan.

We report two cases of heterozygous Fabry disease with severe organ damage. Case 1 was a 47-year-old woman. In April 1977, at the age of 27 years, she had proteinuria and edema around the 26th week of her second pregnancy and was diagnosed as toxicosis of pregnancy. She had proteinuria after the delivery. In 1990, a renal biopsy showed zebra bodies under electron microscopic findings, and the patient was diagnosed as Fabry disease. In 1998, a myocardial biopsy showed identical findings. The patient developed severe hypertension and decreased renal function, and alpha-galactosidase enzyme replacement therapy was initiated. However, despite treatment, she was started on dialysis in 2004. Case 2 was a 40-year-old woman. In March 2003, the patient presented with severe hypertension. The patient had cerebral infarction, cardiac hypertrophy, old myocardial infarction and renal failure without diabetes mellitus, hyperlipidemia and collagen disease. The patient was diagnosed as Fabry disease from persistent numbness and pain in the four extremities, a family history of mortality due to heart disease, and skin biopsy findings. She is currently undergoing enzyme replacement therapy. It is generally known that female Fabry disease patients are asymptomatic or mildly symptomatic, as were the present two patients, but some can have marked organ disorders. Hence, even in female patients, it is necessary to consider Fabry disease as a causative disease of chronic renal failure.
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October 2006

Morning rise in blood pressure is a predictor of left ventricular hypertrophy in treated hypertensive patients.

Hypertens Res 2004 Dec;27(12):939-46

Department of Nephrology, Nippon Telegraph and Telephone Corporation (NTT) Kanto Medical Center, Higashigotanda, Tokyo, Japan.

To assess the relationship between home blood pressure and left ventricular mass, we evaluated cardiac echocardiography in 297 hypertensive subjects (188 men and 109 women; mean age, 62.8+/-10.3 years) who were treated with amlodipine monotherapy over 1 year (mean dose, 5.5+/-2.3 mg/day). The morning hypertension group (n=57; 19.2%), who had a morning home systolic blood pressure (HSBP) > or =135 mmHg and an evening HSBP <135 mmHg, had a significantly greater left ventricular mass index (LVMI) concomitant with an increase in the homeostasis model assessment insulin resistance index (HOMA-IR) compared to the good control group (n=174; 58.6%), whose morning and evening HSBP were both <135 mmHg, and had a LVMI roughly equivalent to that of the poor control group (n=63; 21.2%), whose morning and evening HSBP were both > or =135 mmHg. By grouping of subjects according to the difference between morning and evening HSBP (delta HSBP), subjects with a delta HSBP> or =10 mmHg had a significantly greater LVMI than subjects with a delta HSBP <10 mmHg. Increases in LVMI in these patients were still significant after adjustment for age, gender, dose of amlodipine, alcohol consumption, body mass index, office systolic blood pressure, and morning and evening HSBP. In a stepwise multivariate regression analysis, delta HSBP (r2=36.2%, p <0.001), morning HSBP (r2=5.5%, p <0.001), HOMA-IR (r2=1.4%, p=0.016) and age (r2=1.0%, p=0.026) were determined to be significant contributing factors for LVMI. This regression model could explain 44.1% of LVMI variability. These results suggest that morning rise in blood pressure is a dominant predictor of left ventricular hypertrophy.
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http://dx.doi.org/10.1291/hypres.27.939DOI Listing
December 2004

Pravastatin has an additional depressor effect in patients undergoing long-term treatment with antihypertensive drugs.

Am J Hypertens 2004 Jun;17(6):502-6

Department of Nephrology, Nippon Telegraph and Telephone Corporation, Kanto Medical Center, Tokyo, Japan.

Background: Statins have been reported to have direct vascular effects independent of cholesterol reduction. To assess the antihypertensive effect of statins, a crossover study was designed to compare the depressor effect of pravastatin and probucol in hypertensive patients undergoing long-term treatment with antihypertensive drugs.

Methods: The subjects enrolled in this study were 52 hypertensive patients (22 men and 30 women, mean age 62.8 +/- 9.3 years) who were treated with the same antihypertensive drugs for more than 1 year and had serum cholesterol levels of more than 5.69 mmol/L. In 26 subjects, pravastatin at a dose of 10 mg/d was given first for 6 months followed by treatment with probucol at a dose of 500 mg/d, and vice versa in the remaining 26 subjects. Serum lipids, apolipoproteins, glucose, and insulin were measured on the final day of the control period, and pravastatin and probucol treatments. The homeostatic model assessment insulin resistance index (HOMA-IR) was used to assess insulin resistance.

Results: The blood pressure decreased after pravastatin treatment (141.2 +/- 4.7/81.3 +/- 4.9 to 136.5 +/- 5.3/80.6 +/- 5.1 mm Hg, P <.001/.499), but did not decrease after probucol treatment (141.2 +/- 4.7/81.3 +/- 4.9 to 141.4 +/- 4.9/80.8 +/- 4.9 mm Hg, P =.832/.634). Total cholesterol decreased significantly after pravastatin (6.69 +/- 0.69 to 5.23 +/- 0.77 mmol/L, P <.001) and probucol treatment (6.69 +/- 0.69 to 5.53 +/- 0.64 mmol/L, P <.001). The HOMA-IR was decreased by probucol (1.92 +/- 0.78 to 1.57 +/- 0.59, P =.029), whereas pravastatin had no effect on HOMA-IR.

Conclusions: It can be concluded that the depressor effect of pravastatin may have an additional benefit in the treatment of hypertensive patients with hyperlipidemia without any adverse effect on insulin sensitivity.
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http://dx.doi.org/10.1016/j.amjhyper.2004.02.002DOI Listing
June 2004

[Adult onset Still's disease associated esophageal cancer: a case report].

Ryumachi 2003 Jun;43(3):577-82

Department of Nephrology, NTT Kanto Medical Center, Shinagawa-ku, Tokyo.

We report a case of adult onset Still's disease in a 77 year old man, who was diagnosed as a esophageal cancer 9 months after the onset of this disease. At first malignant lesions in any organs were not found and steroid (prednisolone) therapy was begun and the patient was recovered from manifestations. But while tapering prednisolone to 15 mg, fever, arthritis and rash were observed again. Repeated examination revealed that he had suffered from esophageal cancer. This case is considered as a paraneoplastic syndrome of the esophageal cancer. Patients with adult onset Still's disease should be followed as a paraneoplastic syndrome.
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June 2003
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