To elucidate the diagnostic accuracy of macroscopic and histopathological diagnoses of molar pregnancy as compared with cytogenetic diagnosis as the gold standard.
Patients were recruited for the ...molecular diagnostic study of suspected molar pregnancy at Chiba University Hospital between 2007 and 2011. Gynecologists performed macroscopic diagnoses immediately after the evacuation. Pathological diagnoses were then made by pathologists in routine bases without performing p57Kip2 immunostaining. Molecular cytogenetic diagnosis was performed via short tandem repeat (STR) polymorphism analysis. Androgenetic, biparental triploid, and biparental diploid villous tissues determined on STR polymorphism analysis were classified as complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and abortion, respectively.
A total of 86 patients were enrolled. The number of CHMs, PHMs, and abortions on cytogenetic diagnoses were 64, 9, and 13, respectively. The concordance rate between macroscopic and cytogenetic diagnoses was 85% (CHM: 56, PHM: 4, and abortions: 13). The concordance rate between histopathological and cytogenetic diagnoses was 87% (CHM: 59, PHM: 5, and abortions: 10). The complete agreement rate among the 3 categories was 78% (CHM: 55, PHM: 3, and abortions: 10).
Neither macroscopic nor histopathological diagnoses were perfect, but both were quite accurate in a single trophoblastic center.
OBJECTIVE—Chronic inflammatory processes might be involved in the progression and destabilization of atherosclerotic plaques. Therefore, identification of the mechanism underlying arterial ...inflammatory function might lead to the development of novel therapeutic strategies. Angiotensin II (AngII) is implicated in atherogenesis by activating the vascular inflammation system, mainly through monocyte chemotaxis. Therefore, we hypothesized that AngII increases plaque size and promotes destabilization of established atheromas by activating the monocyte chemoattractant protein-1 (MCP-1) pathway.
METHODS AND RESULTS—We report here that 4-week infusion of AngII not only increased plaque size but also induced a destabilization phenotype (ie, increased macrophages and lipids and decreased collagen and smooth muscle cells) of pre-existing atherosclerotic lesions of hypercholesterolemic mice. AngII also enhanced the gene expression of inflammatory cytokines (TNFα, IL-6, etc.) and chemokines (MCP-1, CCR2, etc). Blockade of MCP-1, by transfecting the deletion mutant of the human MCP-1 gene into the skeletal muscles, limited AngII-induced progression and destabilization of established atherosclerotic lesions and suppressed the induction of proinflammatory genes.
CONCLUSIONS—These data suggest that MCP-1 functions as a central inflammatory mediator in the AngII-induced progression and changes in plaque composition of established atheroma.
The aim of this study was to determine the association between hemodialysis (HD) patients’ physical activity (PA) and transportation to HD facilities. Four hundred and one patients from 8 centers ...were divided into 3 groups based on the method of transportation to HD facilities: walking (including public transportation) group, private car group, and shuttle bus group. Physical activity was quantified using the International Physical Activity Questionnaire (IPAQ), short form Japanese version. PA decline was defined as falling into the category of low physical activity (Low). We analyzed the association between PA decline and transportation to HD facilities in all subjects and subgroups based on age. The private car and shuttle bus groups had a higher risk of PA decline than the walking group, even after adjusting for covariates including physical function (private car: odds ratio OR, 1.89 1.00-3.55, p=0.04; shuttle bus: OR, 2.67 1.30-5.46, p=0.01). In subgroup analyses, the private car group was independently associated with the risk of PA decline among middle age adults (<65 years) (p=0.04), and the shuttle bus group was independently associated with the risk of PA decline among the early elderly (65-74 years) (p<0.001), compared with the walking group. On the other hand, there was no significant correlation between PA decline and transportation to HD facilities in the late elderly (≥75 years). Transportation to HD facilities was identified as a factor involved in PA decline in older to early elderly HD patients, independent of the physical function.
Influenza A virus (IAV) recognizes two types of N-acetylneuraminic acid (Neu5Ac) by galactose (Gal) linkages, Neu5Acα2,3Gal and Neu5Acα2,6Gal. Avian IAV preferentially binds to Neu5Acα2,3Gal linkage, ...while human IAV preferentially binds to Neu5Acα2,6Gal linkage, as a virus receptor. Shift in receptor binding specificity of avian IAV from Neu5Acα2,3Gal linkage to Neu5Acα2,6Gal linkage is generally believed to be a critical factor for its transmission ability among humans. Surveillance of this shift of highly pathogenic H5N1 avian IAV (HPAI) is thought to be a very important for prediction and prevention of a catastrophic pandemic of HPAI among humans. In this study, we demonstrated that receptor binding specificity of IAV bound to sialo-glycoconjugates was sensitively detected by quantifying the HA gene with real-time reverse-transcription-PCR. The new assay enabled direct detection of receptor binding specificity of HPAIs in chicken clinical samples including trachea and cloaca swabs in only less than 4 h.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
NS-87/CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. NS-87/CPX-351 exerts antileukemic action by maintaining a synergistic molar ratio of cytarabine to ...daunorubicin of 5:1 within the liposome while in circulation. Patients with high-risk acute myeloid leukemia (AML), which includes therapy-related AML and AML with myelodysplasia-related changes (AML-MRC), have poorer outcomes than those with other AML.
Methodology
This open-label phase 1/2 (P1/2) study was conducted in 47 Japanese patients aged 60–75 years with newly diagnosed high-risk AML to evaluate the pharmacokinetics, safety, and efficacy of NS-87/CPX-351.
Results
In the 6 patients enrolled in the P1 portion, no dose-limiting toxicities (DLTs) were reported, and 100 units/m
2
during the induction cycle was found to be acceptable. Cytarabine and daunorubicin had a long half-life in the terminal phase (32.8 and 28.7 h, respectively). In the 35 patients enrolled in the P2 portion, composite complete remission (CRc; defined as complete remission CR or CR with incomplete hematologic recovery CRi) was achieved in 60.0% (90% CI: 44.7–74.0) of the patients. Adverse events due to NS-87/CPX-351 were well tolerated.
Outcomes
NS-87/CPX-351 can be considered as a frontline treatment option for Japanese patients with high-risk AML.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
It remains unclear whether vascular endothelial growth factor (VEGF) is a proarteriosclerotic or an antiarteriosclerotic factor. We recently reported that long-term inhibition of nitric oxide by ...administering Nomega-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular inflammation and arteriosclerosis.
We used this animal model to investigate the role of VEGF in arteriosclerosis. We blocked VEGF activity in vivo by transfecting with plasmid DNA encoding the murine soluble FLT-1 (sFLT-1) gene into thigh muscle. Soluble FLT-1 can suppress VEGF activity both by sequestering VEGF and by functioning as a dominant-negative inhibitor of VEGF receptors. We observed vascular inflammation associated with increased VEGF expression within 3 days of L-NAME administration, which was prevented by pretreatment with ACE inhibitor, angiotensin II receptor antagonist, or neutralizing monocyte chemoattractant protein-1 antibody. The sFLT-1 gene transfer attenuated the early vascular inflammation and prevented late arteriosclerosis. The sFLT-1 gene transfer also inhibited increased expression of monocyte chemoattractant protein-1 and transforming growth factor-beta, indicating creation of a positive feedback loop to cause arteriosclerosis.
VEGF is necessary in the development of arteriosclerosis by mediating monocyte recruitment and activation in this model.
Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a ...de novo variant in causative gene, GATA3, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis.
Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a de novo variant in causative gene, GATA3, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose
Severe obstructive sleep apnea (OSA) directly impairs left ventricular (LV) diastolic function. Left atrial volume index (LAVI), an independent predictor of future cardiovascular events, is ...also related to OSA severity. This study aimed to assess whether OSA is associated with an increase in LAVI independently of LV diastolic function.
Methods
Two hundred six OSA patients (apnea hypopnea index, AHI ≥ 5/h) without cardiac disease, hypertension, and diabetes were enrolled. They underwent overnight fully attended polysomnography and 2-dimensional echocardiography in order to estimate LA volumes and LV diastolic function which was assessed by the ratio of transmitral early diastolic flow velocity to late diastolic flow velocity (E/A), deceleration time, and mitral annular velocity (e′) which was derived from tissue Doppler imaging. Patients were divided into two groups based on AHI, namely, group M (5 ≤ AHI < 30/h) and group S (AHI ≥ 30/h).
Results
The LAVI value in group S was significantly larger than that in group M (20 ± 5 vs. 23 ± 5 mL/m
2
,
P
< 0.001). E/A in group S was significantly lower than that in group M (
P
< 0.001), whereas the ratio of E to e′ (E/e′) in group S was significantly higher than that in group M (
P
< 0.001). AHI showed a statistically significant correlation with LAVI (
P
< 0.001). On multivariate linear regression analysis, severe OSA was independently related with LAVI even after adjusting for age, sex, systolic blood pressure, body mass index, and measurements of LV diastolic function (
P
= 0.04).
Conclusions
Severe OSA itself might directly increase LAVI, independently of LV diastolic function.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Oxygen 3‐isotope ratios of magnetite and carbonates in aqueously altered carbonaceous chondrites provide important clues to understanding the evolution of the fluid in the asteroidal parent ...bodies. We conducted oxygen 3‐isotope analyses of magnetite, dolomite, and breunnerite in two sections of asteroid Ryugu returned samples, A0058 and C0002, using a secondary ion mass spectrometer (SIMS). Magnetite was analyzed by using a lower primary ion energy that reduced instrumental biases due to the crystal orientation effect. We found two groups of magnetite data identified from the SIMS pit morphologies: (1) higher δ 18 O (from 3‰ to 7‰) and ∆ 17 O (~2‰) with porous SIMS pits mostly from spherulitic magnetite, and (2) lower δ 18 O (~ −3‰) and variable ∆ 17 O (0‰–2‰) mostly from euhedral magnetite. Dolomite and breunnerite analyses were conducted using multi‐collection Faraday cup detectors with precisions ≤0.3‰. The instrumental bias correction was applied based on carbonate compositions in two ways, using Fe and (Fe + Mn) contents, respectively, because Ryugu dolomite contains higher amounts of Mn than the terrestrial standard. Results of dolomite and breunnerite analyses show a narrow range of ∆ 17 O; 0.0‰–0.3‰ for dolomite in A0058 and 0.2‰–0.8‰ for dolomite and breunnerite in C0002. The majority of breunnerite, including large ≥100 μm grains, show systematically lower δ 18 O (~21‰) than dolomite (25‰–30‰ and 23‰–27‰ depending on the instrumental bias corrections). The equilibrium temperatures between magnetite and dolomite from the coarse‐grained lithology in A0058 are calculated to be 51 ± 11°C and 78 ± 14°C, depending on the instrumental bias correction scheme for dolomite; a reliable temperature estimate would require a Mn‐bearing dolomite standard to evaluate the instrumental bias corrections, which is not currently available. These results indicate that the oxygen isotope ratios of aqueous fluids in the Ryugu parent asteroid were isotopically heterogeneous, either spatially, or temporary. Initial water ice accreted to the Ryugu parent body might have ∆ 17 O > 2‰ that was melted and interacted with anhydrous solids with the initial ∆ 17 O < 0‰. In the early stage of aqueous alteration, spherulitic magnetite and calcite formed from aqueous fluid with ∆ 17 O ~ 2‰ that was produced by isotope exchange between water (∆ 17 O > 2‰) and anhydrous solids (∆ 17 O < 0‰). Dolomite and breunnerite, along with some magnetite, formed at the later stage of aqueous alteration under higher water‐to‐rock ratios where the oxygen isotope ratios were nearly at equilibrium between fluid and solid phases. Including literature data, δ 18 O of carbonates decreased in the order calcite, dolomite, and breunnerite, suggesting that the temperature of alteration might have increased with the degree of aqueous alteration.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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