Inhibitory effect of isomaltodextrin on tyrosine metabolite production in rat gut microbiota.

We examined the effect of isomaltodextrin (IMD), a soluble dietary fiber, on production of putrefactive products by intestinal bacteria using a tyrosine load test to measure phenol production in IMD-treated rats. We observed a significant increase in phenol and p-cresol concentrations in rats administered with only tyrosine, but not for rats co-administered tyrosine and IMD. To elucidate the mechanism of this effect, we analyzed the intestinal microbiota in each group and found that although IMD had no direct effect on the proportion of bacteria known to produce phenols, it did alter the balance of intestinal microbiota. The results suggested that changes in the intestinal microbiota composition reduced the metabolic capacity for tyrosine and in turn suppressed production of phenol or p-cresol, putrefactive products in the intestine.

Bioaccumulation Patterns of Perfluoroalkyl Acids in an Estuary of the Ariake Sea, Japan.

To evaluate the bioaccumulation potential of perfluoroalkyl acids (PFAAs) in an aquatic food web, we measured the concentrations of nine PFAAs in the water and aquatic organisms from an estuary of the Omuta River, Japan. Average log bioaccumulation factors for all PFAAs ranged from 2.0 to 2.8. There was no positive correlation observed between PFAA carbon chain length and there was no evidence of trophic magnification demonstrated among the sample types collected. These results differed from the findings of previous studies in enclosed bodies of water, perhaps because river mouth-estuarine ecotones are more variable spatially and temporally and include some fish that are highly migratory. Further investigations of bioaccumulation factors will be needed to elucidate the tendency of amphiphilic chemicals to bioaccumulate in these river mouth-estuarine ecotones.

Respiratory Uptake and Depuration Kinetics of Perfluorooctanesulfonate (PFOS) in a Marine Sandworm Species.

We determined the respiratory uptake and depuration kinetics of perfluorooctanesulfonate (PFOS) in Perinereis wilsoni, a polychaete sandworm used as a model species to investigate the fate of chemical pollutants in coastal environments. The sandworms were kept in gravel-packed containers, and the water levels were varied cyclically to mimic the tides. We used seawater kept at 17.1°C. A 7-day exposure period was followed by a 9-day depuration period. The dissolved PFOS concentration averaged 28 ng/L during the exposure period. Sandworm samples were collected regularly for analysis of PFOS concentrations, and a first-order-kinetics model was applied to the concentrations. The respiratory absorption efficiency of PFOS was estimated to be 11% that of oxygen, which is higher than the corresponding estimates reported for several fish species. The estimated depuration half-life of 15 days was comparable to previously reported estimates for fish and oligochaete species. The bioconcentration factor was 470.

Cervical Posterior Spinal Artery Syndrome: A Case Report and Literature Review.

We report a case of left upper cervical posterior spinal artery (PSA) syndrome caused by atherosclerosis of the left vertebral artery. A 70-year-old female experienced sudden dizziness and paralysis of the left upper and lower limbs. Diffusion-weighted magnetic resonance imaging (DWI) of the brain showed high signal intensity at the vermis and lower left hemisphere of the cerebellum, and magnetic resonance angiography showed that the entire left vertebral artery was thin. The patient was treated with an intravenous infusion of tissue plasminogen activator 2 hours after symptom onset and made a full recovery. Repeat DWI, fluid-attenuated inversion recovery images, and T2-weighted images showed high signal intensity in the left upper cervical PSA area from the lower medulla oblongata to the C2 level in addition to the cerebellum. Previously reported cases of cervical posterior artery syndrome are reviewed.

Evaluation of the pharmacokinetic equivalence and 54-week efficacy and safety of CT-P13 and innovator infliximab in Japanese patients with rheumatoid arthritis.

OBJECTIVES: To demonstrate the pharmacokinetic equivalence of CT-P13 and its innovator infliximab (IFX) in Japanese patients with rheumatoid arthritis (RA), and to compare the efficacy and safety of these drugs, administered for 54 weeks. METHODS: In a randomized, double-blind, parallel-group, multicenter study, 3 mg/kg of CT-P13 or IFX, in combination with methotrexate (MTX) (6-16 mg/week), was administered for 54 weeks to Japanese active RA patients with an inadequate response to MTX, to demonstrate the pharmacokinetic equivalence, based on the area under the curve (AUC(τ)) (weeks 6-14) and C(max) (week 6) of these drugs, and to compare their efficacy and safety. RESULTS: The CT-P13-to-IFX ratios (90% confidence intervals) of the geometric mean AUC(τ) and C(max) values in patients negative for antibodies to infliximab at week 14 were 111.62% (100.24-124.29%) and 104.09% (92.12-117.61%), respectively, demonstrating the pharmacokinetic equivalence of these drugs. In the full analysis set, CT-P13 and IFX showed comparable therapeutic effectiveness, as measured by the American College of Rheumatology, Disease Activity Score in 28 joints, the European League Against Rheumatism, and other efficacy criteria, at weeks 14 and 30. The incidence of adverse events was similar for these drugs. CONCLUSION: CT-P13 and IFX, administered at a dose of 3 mg/kg in combination with MTX to active RA patients, were pharmacokinetically equivalent and comparable in efficacy and safety.

Loss of cellular cohesion in cytology composes a special subgroup of breast tumors - analysis of 37 cases.

OBJECTIVE: We analyzed smears by fine needle aspiration (FNA) from 37 cases that displayed numerous dissociated cells and correlated the results with histological findings. STUDY DESIGN: Between 1996 and 2005, 1,583 patients underwent breast FNA and resection. Loss of cellular cohesion was observed in 37 of these cases. RESULTS: From the cytological findings, we classified cases into 3 groups according to cell size and shape. Type A: numerous isolated spindle cells with a necrotic background. Four cases were classified into this group (3 cases of intraductal papilloma and 1 case of adenomyoepithelioma). Type B: lymphocytes and large isolated cells such as medullary carcinoma. Five cases were classified into this group [1 case of classic medullary carcinoma, 1 case of ductal carcinoma in situ (DCIS) and 3 cases of invasive carcinoma of no special type (NST)]. Type C: numerous uniform small round cells. Twenty-eight cases were classified into this group (2 cases of lobular carcinoma, 1 case of DCIS, 22 cases of invasive carcinoma NST, and 3 cases of solid papillary carcinoma). CONCLUSION: Numerous isolated cells are sometimes seen in both benign and malignant cytology.

Erratum: Attenuation of postprandial blood glucose in humans consuming isomaltodextrin: carbohydrate loading studies.

[This corrects the article DOI: 10.1080/16546628.2017.1325306.].

Corticosteroid therapy in a patient with cerebral amyloid angiopathy-related inflammation.

We studied longitudinal changes of the levels of anti-amyloid ß (anti-Aß) antibody, amyloid ß (Aß) protein, and interleukin 8 (IL-8) in cerebrospinal fluid (CSF) of a patient with cerebral amyloid angiopathy-related inflammation (CAA-ri) in whom steroid treatment resulted in clinical improvement. The diagnosis of CAA-ri was established with brain biopsy. Levels of anti-Aß 42 antibody, Aß 40, Aß 42 and IL-8 in CSF were measured in the CAA-ri patient at 23 time points in the 8-month clinical course. These CSF samples were divided into 2 groups: those obtained before (n = 12) and those after (n = 11) oral corticosteroid therapy was started. We compared these levels between CSF samples obtained before and after therapy. The mean levels of anti-Aß 42 antibody and IL-8 were significantly higher in CSF samples of the CAA-ri patient before oral corticosteroid therapy than those after therapy. A positive correlation was noted between levels of anti-Aß 42 antibodies and IL-8 in CSF of this patient. There were no significant differences of mean levels of Aß 40 and Aß 42 between CSF samples obtained before and after oral corticosteroid therapy. It was possible that the autoinflammatory process with anti-Aß 42 antibodies and IL-8 may have been involved in the pathogenesis of CAA-ri, and that corticosteroid therapy directly affected levels of anti-Aß 42 antibody and IL-8. In summary, CAA-ri encephalopathy is a relapsing or progressive disorder and may be treatable by adequate immunosuppressive therapy. The anti-Aß 42 antibody in CSF is a useful biological marker for therapeutic monitoring of CAA-ri.

Extrapyramidal syndromes of chronic kidney disease and dialysis (diabetic uremic syndrome) with reversible parkinsonism and lentiform fork sign: A case report and literature review including metformin-induced encephalopathy.

Diabetic uremic syndrome has been rarely reported in patients on maintenance dialysis for diabetic nephropathy who present subacutely with neurological symptoms and bilateral basal ganglia lesions. There are also a few reports on metformin-induced encephalopathy, which is clinically similar to diabetic uremic syndrome. Because some patients with each of these diseases also have metabolic acidosis, it is speculated that these two diseases may have the same pathology. Recently, the term "extrapyramidal syndromes of chronic kidney disease and dialysis" (EPS-CKDD), with associated diagnostic criteria, has been proposed to describe these conditions, and metformin use is considered a risk factor for developing these syndromes. We report a case of a patient on maintenance hemodialysis for diabetic nephropathy who was taking metformin and developed subacute parkinsonism and bilateral basal ganglia lesions that rapidly improved after discontinuation of metformin with continued maintenance hemodialysis. We should ascertain whether patients with EPS-CKDD are taking metformin because it may be inappropriately prescribed for end-stage renal disease. If metformin has been prescribed, it should be discontinued immediately; its discontinuation may lead to rapid symptom recovery and improved prognosis.

Elevated anti-heat shock protein 60 antibody titer is related to white matter hyperintensities.

BACKGROUND: There are many reports that the antibody against heat shock protein 60 (Hsp60) is present in most patients with coronary artery disease and atherosclerosis, and that its titer correlates with disease severity. However, few reports have described the association between anti-Hsp60 antibody and cerebrovascular disease. METHODS: We determined the anti-Hsp60 antibody titer in patients with neurologic diseases and healthy subjects using enzyme-linked immunosorbent assay (ELISA) and evaluated their findings of brain magnetic resonance imaging (MRI) of the white matter. White matter hyperintensities (WMHs) on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images were classified into 2 categories: periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). The lesions in each category were then divided into 4 grades (grades 0-3) according to the Fazekas rating scale. RESULTS: There were no significant differences in the titer between patients with neurologic diseases and healthy subjects. The mean grade of DWMHs (mean ± SD, 1.56 ± 0.70) was significantly higher in 18 subjects in the high-titer group (≥39.8 ng/mL; mean titer + 2 SD in sera from 23 healthy subjects) than in 86 subjects (mean ± SD, 0.09 ± 0.76) in the normal-titer group (<39.8 ng/mL; P < .003). The mean grade of PVHs (mean ± SD, 1.50 ± 0.71) was also significantly higher in the high-titer group than in the normal-titer group (mean ± SD, 1.17 ± 0.62; P < .02). CONCLUSIONS: A significant correlation was noted between anti-Hsp60 antibody titer and the severity of WMHs on brain MR images. We suggest that an elevated titer of the anti-Hsp60 antibody could be a risk factor for cerebral small-vessel disease.

[Bi-weekly nab-paclitaxel and trastuzumab therapy effective against recurrent breast cancer with multiple lung metastases in elderly patient who had previously undergone two chemotherapeutic regimens for treatment of metastatic disease-a case Report].

We herein report a 75-year-old patient with recurrent hormone-nonresponsive, HER2-positive breast cancer who presented with multiple lung metastases. She had undergone a mastectomy followed by adjuvant chemotherapy with FEC, CMF, and UFT. Forty-six months after the surgery, multiple lung, liver, and bone metastases were observed. Docetaxel and trastuzumab were administered as first-line chemotherapy for 13 months. A partial response and stable disease were observed, but progressive disease in the lung and brain was subsequently revealed. The patient then underwent g-knife treatment for brain metastasis. Lapatinib and capecitabine treatment was administered as second-line chemotherapy for 9 months. Stable disease was observed, but progressive disease in the lung metastases with clinical symptoms including cough, exertional dyspnea, and general malaise was revealed. As third-line chemotherapy, the patient was administered low-dose, bi-weekly nab-paclitaxel(150mg/m2)and trastuzumab therapy. Four weeks after beginning the nab-paclitaxel and trastuzumab treatment, the cough disappeared; 2 months after beginning the therapy, a partialresponse in the lung metastases was seen. The patient is well and the treatment has been continued for 50 weeks. No progression has been seen. Bi-weekly nab-paclitaxel treatment appears to have few side effects and might be an effective treatment option for patients with recurrent breast cancer.

Spatial distribution and benthic risk assessment of cyclic, linear, and modified methylsiloxanes in sediments from Tokyo Bay catchment basin, Japan: Si-based mass profiles in extractable organosilicon.

We investigated the spatial distribution, mass profiles, and benthic risk assessment of a wide range of methylsiloxanes (MSs), including 7 cyclic MSs (CMSs; D3-D9; the number refers to the number of SiO bonds), 13 linear MSs (LMSs; L3-L15), and 15 modified and other MSs (MMSs) in sediments from the Tokyo Bay catchment basin, Japan. We observed widespread distribution of MSs (ΣCMS, ΣLMS, and ΣMMS) in the sediment samples, with concentrations of 1.0-6180 ng/g dry weight (dw), 1.8-10,100 ng/g dw, and < 0.31-210 ng/g dw, respectively. Our study is the first to measure various MMSs modified with hydrogen, vinyl, or phenyl groups; however, only methyltris(trimethylsiloxy)silane and phenyltris(trimethylsiloxy)silane were detected with high occurrence frequency. Notably, no elevated concentrations of MSs were observed downstream of silicone manufacturers, whereas the sediment was characterized by a specific D4/D5 ratio. With the Si-based mass profiles in extractable organosilicon (EOSi), the measured CMSs, LMSs, and MMSs accounted for 5.4%, 7.8%, and 0.2%, respectively. Unidentified EOSi (unknown fraction) constituted a major proportion of the EOSi in the sediment, with a mean of 87%, suggesting that the organosilicon environmental emissions were more than the measured MSs. In risk assessment of the adverse effects of D4, D5, and D6 in sediment on benthic organisms, the respective distributions indicated no overlap between the 95th percentile field sediment concentration and the 5th percentile chronic sediment no-effect concentration in organic carbon-normalized concentration. Although the hazard quotient compared with the predicted no-effect concentration for D5 and D6 exceeded the threshold level (hazard quotient ≥1), the results of probabilistic risk assessment for the three CMSs were not high enough to indicate a threat to benthic organisms in the study area.

Transfer of polychlorinated biphenyls from marine sediment to a benthic fish (Pleuronectes yokohamae).

We examined the transfer of polychlorinated biphenyls (PCBs) from suspended and bottom sediments to a benthic fish species (Pleuronectes yokohamae) by conducting laboratory experiments and determined the distribution of PCBs in the fish tissues. The mean total PCB concentrations in individual tissues and whole body of the fish exposed to bottom sediment (including suspended sediment) in the bottom sediment tank for 28 days increased to levels 3-5 times the initial concentrations, whereas those in the fish exposed only to suspended sediment in the suspended sediment tank did not increase. The congeners #52/#69, #70, #66, #101, #120/#110, [corrected] and #153 were the most abundant congeners in the fish from the bottom sediment tank, reflecting the congeners that were abundant in the water and sediment in addition to those abundant in the fish in the control tank. The proportional distribution of the PCB burden to different tissues of the fish was similar in all the treatment groups, and within each treatment group, the proportion of the congeners and their homologues was relatively consistent among all tissues. Results of a mass-balance analysis indicated that in the fish exposed to bottom sediments, the sediment contributed to an average of 0% (#138) to 81% (#132) of the increase in 13 congeners (penta- and hexa-CBs).

Spatial distribution and partitioning of polychlorinated biphenyls in Tokyo Bay, Japan.

Spatial distributions and partitioning of polychlorinated biphenyls (PCBs) in Tokyo Bay, Japan, were evaluated by measuring the concentrations of all 209 PCB congeners in surface and bottom waters and bottom sediment at 10 locations. The dissolved + particulate summed congener concentrations (SigmaPCB [sum of the concentrations of all 209 PCB congeners]) in surface and bottom waters ranged from 120 to 1100 pg L(-1) (median 250 pg L(-1)) and from 83 to 910 pg L(-1) (median 230 pg L(-1)), respectively. The concentrations did not statistically differ between the two layers, possibly because of vertical mixing of the water column. SigmaPCB concentrations in sediment ranged from 2.7 to 110 ng g(-1)-dry weight. The highest SigmaPCB concentrations in both water and sediment were found at stations in the northern bay. Logarithms of field-observed organic carbon-normalized partition coefficients (K(OC)) increased linearly as the log octanol-water partition coefficients (K(OW)) increased, up to a log K(OW) of about 6.5, and then decreased for log K(OW) > 6.5 (mostly hexa- and hepta-chlorinated biphenyls). Furthermore, log K(OC) values of congeners having log K(OW) < 6.5 were higher by about 1 than values predicted by a published empirically derived equation, suggesting that application of K(OC) values determined in laboratory experiments with soil or sediment samples to fate prediction models may result in overestimation by about one order of magnitude of the concentrations of PCBs with log K(OW) < 6.5 in the dissolved phase in the water column.

Dementia with Lewy Bodies with Pure Agraphia for Kanji (Japanese Morphograms).

A 70-year-old dextral woman was admitted to a hospital with agraphia for kanji (Japanese morphograms). She had a history of severe constipation, nightmares, and visual hallucinations. Neurological examinations revealed no obvious Parkinson's disease symptoms. She showed poor skills in writing the kanji for looking at picture objects, [e.g., writing the Japanese word "inu" (which means dog) when she saw a drawing of a dog] or dictated words. A reduced striatal uptake of [123I]-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) on single-photon-emission computed tomography and reduced meta-iodobenzylguanidine (MIBG) cardiac uptake on myocardial scintigraphy were detected. The accumulation of amyloid beta in the bilateral cerebral cortices was observed on amyloid-positron emission tomography. We herein report a case of Lewy body dementia with pure agraphia for kanji with underlying Alzheimer's disease pathology.

[Nineteen years postoperatively, anastrozole, UFT and cyclophosphamide combination therapy remained effective against recurrent hormone responsive breast cancer with intraabdominal lymphnode, pleural, skin and bone metastases in old age following sixteen-year tamoxifen treatment - a case report].

We report an 89-year-old patient with recurrent hormone-responsive breast cancer who presented with pleural, skin and bone metastases. Nineteen years previously, she had undergone a mastectomy and then for 16 years received adjuvant hormone therapy. The patient was orally administered a combination therapy of anastrozole, UFT and cyclophosphamide. A remarkable response was seen after 5 months, and no side effects were observed. The patient became well and the treatment was continued without relapse at 8 months. Oral anti-cancer treatments in combination with hormone therapy appear to have few side effects and might be an effective treatment option for recurrent breast cancer patients.

Comparison of trophic magnification factors of PCBs and PBDEs in Tokyo Bay based on nitrogen isotope ratios in bulk nitrogen and amino acids.

Trophic positions (TPs) are key parameters for determining trophic magnification factors (TMFs) of environmental pollutants. We used compound-specific nitrogen isotope analysis of amino acids (CSIA-AA), with which we expected to obtain precise TPs, to estimate the TMFs of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the pelagic and benthic food webs of Tokyo Bay. The objective of the present study was to evaluate the difference between TMFs derived from TPs estimated by CSIA-AA (TPGlu/Phe) and TMFs derived from TPs estimated by bulk stable isotope analysis (TPbulk). TPGlu/Phe tended to be lower than TPbulk for many pelagic and benthic fishes. In the pelagic food web, the slopes for the relationships between PCB concentrations and TPGlu/Phe exceeded those between PCB concentrations and TPbulk for many congeners in samples from December 2014, and TMFGlu/Phe values (0.89-6.9) were higher than TMFbulk values (0.92-3.8). However, there were no statistically significant differences between the slopes of the relationships between PCB and PBDE concentrations and TPbulk or TPGlu/Phe for any of the congeners (analysis of covariance, P ≥ 0.08). In the benthic food web, PCB concentrations correlated with TPGlu/Phe for 9 PCB congeners in the samples collected during December 2014, although the concentrations of none of the PCB congeners correlated with TPbulk. A decrease of TMFGlu/Phe and TMFbulk values from December 2014 to May 2015 suggested that variation of PCB and PBDE concentrations in the organisms had more effect than TPs on the TMFs.

Georeferenced multimedia environmental fate of volatile methylsiloxanes modeled in the populous Tokyo Bay catchment basin.

We investigated the multimedia fate of decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6) in the densely populated catchment basin of Tokyo Bay, Japan, by using a georeferenced multimedia model. We estimated the daily per person consumption rate of these compounds in Japan according to literature. Emissions to the atmosphere accounted for almost all of the emissions of these compounds to the environment. The majority of these compounds was predicted to be distributed in the atmosphere (about 60%) and sediment (about 40%). The advective flows in and out of the atmosphere over the Tokyo Bay catchment basin dominated the flows of these compounds. The sewerage systems contributed considerably to the transport and fate of D5 and D6 in water. They transported these compounds from households to discharge outlets of sewage treatment plants (STPs), which in turn accounted for approximately one quarter of the emission of these compounds to rivers and to Tokyo Bay. The wastewater treatment plants also effectively removed these compounds from the wastewater. The overall persistence of D5 and D6 in the catchment basin was estimated to be 3.8-9.5 days. The horizontal distributions of these compounds were similar among environmental compartments; high concentrations were generally observed in populated areas. A sensitivity analysis demonstrated that the D5 discharge rate to Tokyo Bay excluding the direct discharge from STPs and the D5 mass in the river compartment were sensitive to changes of the organic-carbon-water partition coefficient. Comparison with the concentrations in rivers measured recently in the target area showed that the model captured overall trends of low to high concentrations in rivers. However, there was some variability and a bias toward underprediction. The model provided a better fit to measurements for D5 than for D6. One potential factor contributing to the bias toward underprediction was underestimation of the consumption rates.

A Case of Crossed Logopenic Primary Progressive Aphasia in a Dextral Patient with Underlying Frontotemporal Dementia.

A 61-year-old dextral woman was admitted to the hospital with difficulty finding words. Neurological examinations confirmed that her speech was affected by frequent pauses and occasional phonological paraphasia without cognitive deficits. We detected atrophy, hypoperfusion, and hypometabolism in the right perisylvian and parietal regions, expanding to the right anterior temporal lobes and right inferior frontal gyrus (opercular region) by magnetic resonance imaging, single-photon emission computed tomography, and fluorodexyglucose-positron emission tomography (PET), respectively. Amyloid-PET did not identify the accumulation of amyloid beta (Aß) in the bilateral cerebral cortices. We herein report a case of crossed aphasia with Aß-negative logopenic primary progressive aphasia that was likely the result of frontotemporal lobar degeneration.