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1.
Microbiol Spectr ; : e0108124, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39320087

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a serious public health concern. At times, MRSA is isolated from the blood along with other pathogens, the significance and consequences of which are not well described. This study aims to outline the clinical characteristics and outcomes of those with polymicrobial MRSA BSI compared with those with monomicrobial MRSA BSI. We conducted a retrospective case-control study of those with and without polymicrobial MRSA BSI from 2014 to 2022 at a single quaternary care center in New York City. Risk factors and outcomes for polymicrobial MRSA BSI were assessed using logistic regression analyses. Of 559 patients with MRSA BSI during the study period, 49 (9%) had polymicrobial MRSA BSI. Gram-positive Enterococcus (23%) was the most common co-pathogen. The presence of urinary (P = 0.02) and gastrointestinal (P < 0.01) devices was significantly associated with polymicrobial MRSA BSI. Polymicrobial MRSA BSI was associated with intensive care unit (ICU) admission after BSI (P = 0.01). Mortality did not differ. While polymicrobial MRSA BSI is relatively uncommon, it complicates an already complex clinical scenario of MRSA BSI.IMPORTANCEStaphylococcus aureus is a common human pathogen associated with severe disease and high mortality rates. Although clinically observed, little is known about the impact of polymicrobial staphylococcal bloodstream infection. This study evaluates polymicrobial methicillin-resistant S. aureus bloodstream infection (BSI), highlighting the increased risk of intensive care unit admission and impact on morbidity. Identifying risk factors for polymicrobial BSI, such as the presence of specific devices, can aid in early recognition and targeted interventions. Clarifying the risks and outcomes of polymicrobial infections can lead to strategies to minimize and manage these infections and explore the potential interactions between pathogens.

2.
Sci Rep ; 14(1): 16391, 2024 07 26.
Article in English | MEDLINE | ID: mdl-39060263

ABSTRACT

Prior to the formation of amyloid fibrils, the pathological hallmark in tau-related neurodegenerative disease, tau monomers aggregate into a diverse range of oligomers. Granular tau oligomers, consisting of approximately 40 tau protein molecules, are present in the prefrontal cortex of patients at Braak stages I-II, preclinical stages of Alzheimer's disease (AD). Antibodies to granular tau oligomers as antigens have not been reported. Therefore, we generated new rat monoclonal antibodies by immunization with granular tau oligomers. Three antibodies from different hybridoma clones showed stronger immunoreactivity to granular tau oligomers and tau fibrils compared with monomeric tau. Of the three antibodies, 2D6-2C6 showed 3000-fold greater immunoreactivity in P301L-tau transgenic (rTg4510) mice than in non-transgenic mice, while MC1 antibody, which detects pathological conformations of tau, showed a 5.5-fold increase. These results suggest that 2D6-2C6 recognizes aggregates more specifically than MC1. In AD subjects, 2D6-2C6 recognized neurofibrillary tangles and pretangles, and co-localized within AT8-positive cells containing phosphorylated tau aggregates. The epitope of 2D6-2C6 is the 423-430 amino acid (AA) sequence of C-terminal regions. Taken together, a novel monoclonal antibody, 2D6-2C6, generated by immunization with granular tau oligomers binds to tau aggregates at the 423-430 AA sequence.


Subject(s)
Alzheimer Disease , Antibodies, Monoclonal , Mice, Transgenic , tau Proteins , tau Proteins/metabolism , tau Proteins/immunology , tau Proteins/chemistry , Antibodies, Monoclonal/immunology , Animals , Humans , Mice , Alzheimer Disease/metabolism , Alzheimer Disease/immunology , Rats , Immunization , Female , Amino Acid Sequence , Epitopes/immunology , Male , Aged , Protein Aggregates , Neurofibrillary Tangles/metabolism
3.
Sleep Med ; 119: 173-178, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38692218

ABSTRACT

BACKGROUND: Although the effects of exercise training (ET) on sleep problem have been reported, the effects according to the components of exercise, including intensity, frequency, and time window, are unknown. Thus, in this study, we aimed to assess the effects of ET on sleep quality in community-dwelling older adults with sleep problems. METHODS: We evaluated individuals aged ≥65 years whose Pittsburgh sleep quality index was >5 points at baseline. The participants were allocated to either the control group or the ET group and underwent interval walking training (IWT) for 5 months. Information regarding intensity, frequency, and time window of ET were obtained using a waist-worn accelerometer. RESULTS: Overall, 63 participants (24 men [mean ± standard deviation age: 75.1 ± 4.6 years] and 39 women [74.7 ± 5.2 years]) and 65 participants (24 men [75.2 ± 4.0 years] and 41 women [73.6 ± 4.2 years]) were included in the ET and control groups, respectively. The change in Pittsburgh sleep quality index was not significantly different between the two groups for both sexes. In the ET group, women who exercised 3-8 h before bedtime, men who did ET > 8 h before bedtime and more than 1 h after waking up, and men who did ET ≥ 5.05 days/week experienced significant improvements compared to the baseline. CONCLUSIONS: IWT does not significantly improve sleep quality. To obtain improvements in sleep quality, it might be necessary to consider the time window of performing ET for both sexes and ET frequency for men.


Subject(s)
Exercise , Independent Living , Sleep Quality , Humans , Male , Female , Aged , Exercise/physiology , Aged, 80 and over , Accelerometry , Time Factors , Exercise Therapy/methods , Walking/physiology
4.
PLoS One ; 18(2): e0281998, 2023.
Article in English | MEDLINE | ID: mdl-36812255

ABSTRACT

This study aimed to characterize patients' symptom severity trajectories and distresses from video-assisted thoracoscopic lung resection to the first post-discharge clinic visit. Seventy-five patients undergoing thoracoscopic lung resection for diagnosed or suspected pulmonary malignancy prospectively recorded daily symptom severity on a 0-10 numeric scale using the MD Anderson Symptom Inventory until the first post-discharge clinic visit. The causes of postoperative distresses were surveyed, and symptom severity trajectories were analyzed using joinpoint regression. A rebound was defined as a statistically significant positive slope after a statistically significant negative slope. Symptom recovery was defined as symptom severity of ≤3 in two contiguous measurements. The accuracy of pain severity on days 1-5 for predicting pain recovery was determined using area under the receiver operating characteristic curves. We applied Cox proportional hazards models for multivariate analyses of the potential predictors of early pain recovery. The median age was 70 years, and females accounted for 48%. The median interval from surgery to the first post-discharge clinic visit was 20 days. Trajectories of several core symptoms including pain showed a rebound from day 3 or 4. Specifically, pain severity in patients with unrecovered pain had been higher than those with recovered pain since day 4. Pain severity on day 4 showed the highest area under the curve of 0.723 for predicting pain recovery (P = 0.001). Multivariate analysis identified pain severity of ≤1 on day 4 as an independent predictor of early pain recovery (hazard ratio, 2.86; P = 0.0027). Duration of symptom was the leading cause of postoperative distress. Several core symptoms after thoracoscopic lung resection showed a rebound in the trajectory. Specifically, a rebound in pain trajectory may be associated with unrecovered pain; pain severity on day 4 may predict early pain recovery. Further clarification of symptom severity trajectories is essential for patient-centered care.


Subject(s)
Lung Neoplasms , Thoracic Surgery, Video-Assisted , Female , Humans , Aged , Aftercare , Patient Discharge , Pain, Postoperative/etiology , Lung Neoplasms/pathology , Pneumonectomy/adverse effects , Lung/pathology , Retrospective Studies
5.
Geriatr Gerontol Int ; 23(2): 103-110, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36608686

ABSTRACT

AIM: To investigate the effects of high-intensity interval exercise training on microvascular endothelial function among community-dwelling older people. METHODS: We analyzed the data from a nonrandomized controlled trial. This study's participants were 48 men (aged 75 ± 5 years; exercise training group, n = 24; control group, n = 24) and 83 women (aged 75 ± 4 years; exercise training group, n = 36; control group, n = 47). The exercise training group underwent a high-intensity interval walking training for 5 months. RESULTS: In the exercise group, 100% and 91.7% of men and women, respectively, achieved brisk walking times ≥50 min/week. The change in the reactive hyperemia index significantly differed between the groups of men, whereas that in the control group was not significant; however, a significant increase was observed in the exercise training group. Among women, changes in the reactive hyperemia index were not significant in either group; however, for women in the exercise training group, these changes negatively and positively correlated with the change in body mass index (Spearman's rho = -0.342; P = 0.041) and baseline body mass index (rho = 0.362, P = 0.030), respectively. Additionally, the distribution of body mass index was broader in women than in men. CONCLUSIONS: Interval walking training increased the reactive hyperemia index in men rather than in women. A higher variation in baseline body mass index may be associated with no statistical increase in reactive hyperemia index in women. Geriatr Gerontol Int 2023; 23: 103-110.


Subject(s)
Hyperemia , Independent Living , Aged , Female , Humans , Male , Endothelium , Exercise , Walking , Aged, 80 and over
6.
J Sports Med Phys Fitness ; 63(3): 492-502, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36239289

ABSTRACT

BACKGROUND: The hypotensive effects of high-intensity interval training have been reported; however, studies on older adults are few. This study aimed to examine whether interval-walking training (IWT), a home-based program of high-intensity interval training, reduces blood pressure (BP) levels when compared with a non-intervention group in community-dwelling older adults. METHODS: An intervention study was conducted with 55 men (age, 75±5 years; IWT/control groups, N.=27/28) and 100 women (75±5 years; N.=47/53). The IWT regimen was as follows: fast (high-intensity) walking at 70-85% of the peak aerobic capacity and normal (light-intensity) walking at approximately 40% of the peak aerobic capacity for 3 min each, ≥5 times/walking day, and ≥4 days/week for 5 months. Systolic, diastolic, and mean arterial BPs (SBP, DBP, and MAP, respectively) were measured in the supine posture. RESULTS: The mean baseline SBP/DBP was 132/78 mmHg in men and 131/72 mmHg in women. Five-month changes in SBP, DBP, or MAP did not significantly differ between the IWT and control groups in either sex. The weekly fast-walking time in the IWT group was negatively correlated with changes in DBP (Spearman's ρ=-0.383, P=0.049) and MAP (ρ=-0.444, P=0.021) only in men. CONCLUSIONS: Though present findings did not indicate significant hypotensive effects of IWT in community-dwelling older adults, men with longer fast-walking times experienced greater BP decreases. Further studies with sufficient sample sizes are needed to determine the factors modulating the effects of the proposed training program.


Subject(s)
High-Intensity Interval Training , Muscle Strength , Walking , Aged , Aged, 80 and over , Female , Humans , Male , Blood Pressure , East Asian People , Walking/physiology
8.
Article in English | MEDLINE | ID: mdl-35483916

ABSTRACT

OBJECTIVE: To examine the effect of apolipoprotein E (APOE) ɛ4 dose on blood-brain barrier (BBB) clearance function, evaluated using an advanced MRI technique and analyse its correlation with brain iron and ß-amyloid accumulation in the early stages of the Alzheimer's continuum. METHODS: In this single-centre observational prospective cohort study, 24 APOE ɛ4 non-carriers, 22 heterozygotes and 20 homozygotes in the early stages of the Alzheimer's continuum were scanned with diffusion-prepared arterial spin labelling, which estimates the water exchange rate across the BBB (kw). Participants also underwent quantitative susceptibility mapping, [11C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional kw of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings. RESULTS: The BBB kw values in the neocortices differed significantly among the groups (APOE ɛ4 non-carriers>heterozygotes>homozygotes). These values correlated with brain iron levels (frontal lobe: r=-0.476, 95% CI=-0.644 to -0.264, p=0.011; medial temporal lobe: r=-0.455, 95% CI=-0.628 to -0.239, p=0.017), ß-amyloid loads (frontal lobe: r=-0.504, 95% CI=-0.731 to -0.176, p=0.015; medial temporal lobe: r=-0.452, 95% CI=-0.699 to -0.110, p=0.036) and neuropsychological scores, after adjusting for age, sex and APOE ɛ4 dose. INTERPRETATION: Our results suggest that an increased APOE ɛ4 dose is associated with decreased effective brain-waste clearance, such as iron and ß-amyloid, through the BBB.

9.
Neurol Sci ; 43(3): 1879-1883, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34398368

ABSTRACT

OBJECTIVE: To investigate the mechanisms underlying the effect of repetitive transcranial magnetic stimulation (rTMS) on post-stroke hemiplegia, we assessed alterations in cerebral glucose metabolism. METHODS: Five post-stroke hemiplegic patients (three targeted for upper limb impairment and two targeted for lower limb impairment) aged 62.6 ± 6.1 years (mean ± standard deviation) with a duration since stroke onset of 3.5 ± 3.8 years participated in this preliminary study. Cerebral glucose metabolism was measured twice-before and after rTMS with intensive rehabilitation-using positron emission tomography with [18F]fluorodeoxyglucose. The Asymmetry Index (AI) was calculated to assess laterality of metabolism between the lesional and contralesional motor areas. The alteration rates of AI (%ΔAI) were compared between participants in whom rTMS was effective and ineffective. RESULTS: Two of the three upper-limb-targeted patients and one of the two lower-limb-targeted patients showed motor function improvements following rTMS treatment. All three patients who responded to rTMS had improved laterality of cerebral glucose metabolism in motor areas, commonly in the precentral gyrus, with an %ΔAI of approximately 10%. In contrast, the two patients who did not respond to rTMS had no improvements in laterality. CONCLUSIONS: These results suggest for the first time that improved glucose metabolism is associated with improved motor function after a combination of rTMS and intensive rehabilitation.


Subject(s)
Stroke Rehabilitation , Stroke , Aged , Glucose , Humans , Middle Aged , Stroke/complications , Stroke Rehabilitation/methods , Transcranial Magnetic Stimulation/methods , Treatment Outcome , Upper Extremity
10.
Kaku Igaku ; 58(1): 19-32, 2021.
Article in Japanese | MEDLINE | ID: mdl-33896894

ABSTRACT

PURPOSE: We developed and validated the accuracy of a method to calculate the arterial input function (AIF) from PET images only, without the need for the arterial blood sampling, in the absolute quantitation of functional parametric values in 15O- gas PET examinations. METHODS: We extended the method reported by Iguchi et al. (2013) to derive the arterial input function, thus absolute quantitative functional parametric images of cerebral perfusion and oxygen metabolism by a reference tissue approach. We compared shapes of the AIF and reproducibility of the absolute functional values. Existing test data that were carried out with the continuous arterial blood sampling were used for this study. RESULTS: The estimated AIF shapes agreed well with those estimated from the continuous arterial blood sampling. The error range of the absolute quantitative values was approximately ±20%, with a fairly well reproducibility in the relative values being less than 3%. CONCLUSION: The AIFs by this method were reproducible. Although the absolute quantitative values varied depending on the assumed functional values in the reference region in individual cases, the relative images showed fairly good agreement with the results from the standard technique that employed the arterial blood sampling. The present technique may provide significant contribution to clinical examination.


Subject(s)
Algorithms , Arteries , Arteries/diagnostic imaging , Reproducibility of Results
12.
J Drug Target ; 29(2): 217-224, 2021 02.
Article in English | MEDLINE | ID: mdl-32997541

ABSTRACT

Guanine-rich oligonucleotide (GRO) can be developed as an effective anticancer agent owing to its high selectivity, affinity and antiproliferative activity in cancer cells. In this study, to increase the potency of GRO29A, a 29-mer GRO aptamer against nucleolin, an overexpressed protein in cancer cells, GRO29A was incorporated into three or six pods of polypod-like structured DNA (polypodna), tripodna or hexapodna, respectively. The polypod-like structured GROs, tri-G3, consisting of one tripodna and three GRO29A, or hexa-G1, hexa-G3 or hexa-G6, each of which comprises one hexapodna and one, three or six GRO29A, respectively, were designed. Tri-G3, hexa-G1 and hexa-G3 were prepared in high yield, except for hexa-G6. Polypod-like structured GROs had quadruplex structures under physiological salt conditions, and degraded at a slower rate in buffer containing serum. Cellular interaction experiments using fluorescently labelled DNA samples showed that the uptake of hexa-G3 by nucleolin-positive MCF-7 cells was more than 2-fold higher than GRO29A, and the interaction was increasingly dependent on the number of GRO29A in the structures. Hexa-G3 inhibited the proliferation of MCF-7 cells in more than 40%, but not of CHO cells. These results indicate that polypod-like structured GROs are useful DNA aptamers with high selectivity and cytotoxicity against nucleolin-positive cancer cells.


Subject(s)
Aptamers, Nucleotide/administration & dosage , DNA/administration & dosage , Guanine/chemistry , Nanostructures , Animals , Breast Neoplasms/genetics , Breast Neoplasms/therapy , CHO Cells , Cell Proliferation/genetics , Cricetulus , Female , Humans , MCF-7 Cells , Phosphoproteins/metabolism , RNA-Binding Proteins/metabolism , Nucleolin
13.
Sci Rep ; 10(1): 17184, 2020 10 14.
Article in English | MEDLINE | ID: mdl-33057015

ABSTRACT

The seed coat of mature black soybean, Glycine max, accumulates a high amount of cyanidin 3-O-glucoside (Cy3G), which is the most abundant anthocyanin in nature. In the pod, it takes two months for the seed coat color change from green to black. However, immature green beans rapidly adopt a black color within one day when the shell is removed. We analyzed the components involved in the color change of the seed coat and detected a new precursor of Cy3G, namely 5,7,3',4'-tetrahydroxyflav-2-en-3-ol 3-O-glucoside (2F3G). Through quantitative analysis using purified and synthetic standard compounds, it was clarified that during this rapid color change, an increase in the Cy3G content was observed along with the corresponding decrease in the 2F3G content. Chemical conversion from 2F3G to Cy3G at pH 5 with air and ferrous ion was observed. Our findings allowed us to propose a new biosynthetic pathway of Cy3G via a colorless glucosylated compound, 2F3G, which was oxidized to give Cy3G.


Subject(s)
Anthocyanins/chemistry , Glycine max/chemistry , Seeds/chemistry , Color
14.
J Phys Act Health ; 17(10): 958-967, 2020 08 31.
Article in English | MEDLINE | ID: mdl-32866945

ABSTRACT

BACKGROUND: Health care providers (HCPs) promoting physical activity (PA) through programs such as Park Prescriptions (ParkRx) are gaining momentum. However, it is difficult to realize provider PA practices and program interest, and differences in program success exist by provider type (eg, primary vs secondary). This study explored HCPs' (1) PA counseling practices, (2) knowledge/interest in ParkRx, (3) barriers and resources needed to implement PA counseling and ParkRx programs, and (4) differences in primary versus secondary HCPs. METHODS: An e-survey administered in Spring/Summer 2018 to HCPs in 3 states examined study objectives. RESULTS: Respondents (n = 278) were mostly primary (58.3%) HCPs. The majority asked about patient PA habits and offered PA counseling (mean = 5.0, SD = 1.5; mean = 4.8, SD = 1.5), but few provided written prescriptions (mean = 2.5, SD = 1.6). Providers were satisfied with their PA counseling knowledge (mean = 3.8, SD = 1.0) but not with prescribing practices (mean = 3.2, SD = 1.1). Secondary HCPs placed higher importance (P = .012) and provided significantly more written PA prescriptions (P = .005). Time was a common barrier to prescribing PA (mean = 3.4, SD = 1.2), though more so for primary HCPs (P = .000). Although few HCPs knew about ParkRx programs, 81.6% expressed interest. Access to park information and community partnerships was an important resource for program implementation. CONCLUSIONS: HCPs underutilize PA prescriptions. Despite little awareness, HCPs were interested in ParkRx programs.


Subject(s)
Exercise , Prescriptions , Counseling , Health Personnel , Humans
15.
J Neurol ; 267(9): 2692-2696, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32440919

ABSTRACT

BACKGROUND: Although pure cerebellar ataxia is usually emphasized as the characteristic clinical feature of spinocerebellar ataxia type 6 (SCA6), parkinsonism has been repeatedly described in patients with genetically confirmed SCA6. METHODS: We conducted a positron emission tomography study using a combination of [18F]fluoro-L-dopa for dopamine synthesis and [11C]raclopride for dopamine D2 receptor function on six genetically confirmed SCA6 patients, both with and without parkinsonism. To the best of our knowledge, this is the first dopamine receptor imaging study of patients with SCA6. RESULTS: Most patients had somewhat decreased dopaminergic function, and this decrease was significant in the caudate nucleus. In addition, one SCA6 patient with parkinsonism had whole striatal dysfunction of both dopamine synthesis and dopamine D2 receptor function. CONCLUSIONS: The pathology of SCA6 may not be restricted to the cerebellum, but may also be distributed across various regions, including in both presynaptic and postsynaptic dopaminergic neurons to some degree. Patients with SCA6 may show apparent parkinsonism after the progression of neurodegeneration.


Subject(s)
Parkinsonian Disorders , Spinocerebellar Ataxias , Dopamine , Humans , Parkinsonian Disorders/diagnostic imaging , Positron-Emission Tomography , Raclopride , Spinocerebellar Ataxias/complications , Spinocerebellar Ataxias/diagnostic imaging
16.
Obstet Gynecol ; 129(5): 844-853, 2017 05.
Article in English | MEDLINE | ID: mdl-28383369

ABSTRACT

OBJECTIVE: To estimate whether the cost of hysterectomy varies by geographic region. METHODS: This was a cross-sectional, population-based study using the 2013 Healthcare Cost and Utilization Project National Inpatient Sample of women older than 18 years undergoing inpatient hysterectomy for benign conditions. Hospital charges obtained from the National Inpatient Sample database were converted to actual costs using cost-to-charge ratios provided by the Healthcare Cost and Utilization Project. Multivariate regression was used to assess the effects that demographic factors, concomitant procedures, diagnoses, and geographic region have on hysterectomy cost above the median. RESULTS: Women who underwent hysterectomy for benign conditions were identified (N=38,414). The median cost of hysterectomy was $13,981 (interquartile range $9,075-29,770). The mid-Atlantic region had the lowest median cost of $9,661 (interquartile range $6,243-15,335) and the Pacific region had the highest median cost, $22,534 (interquartile range $15,380-33,797). Compared with the mid-Atlantic region, the Pacific (adjusted odds ratio [OR] 10.43, 95% confidence interval [CI] 9.44-11.45), South Atlantic (adjusted OR 5.39, 95% CI 4.95-5.86), and South Central (adjusted OR 2.40, 95% CI 2.21-2.62) regions were associated with the highest probability of costs above the median. All concomitant procedures were associated with an increased cost with the exception of bilateral salpingectomy (adjusted OR 1.03, 95% CI 0.95-1.12). Compared with vaginal hysterectomy, laparoscopic and robotic modes of hysterectomy were associated with higher probabilities of increased costs (adjusted OR 2.86, 95% CI 2.61-3.15 and adjusted OR 5.66, 95% CI 5.11-6.26, respectively). Abdominal hysterectomy was not associated with a statistically significant increase in cost compared with vaginal hysterectomy (adjusted OR 1.01, 95% CI 0.91-1.09). CONCLUSION: The cost of hysterectomy varies significantly with geographic region after adjusting for confounders.


Subject(s)
Hysterectomy/statistics & numerical data , Uterine Diseases/surgery , Adult , Costs and Cost Analysis , Cross-Sectional Studies , Demography , Female , Humans , Hysterectomy/economics , Length of Stay , Middle Aged , United States , Women's Health Services/economics , Women's Health Services/statistics & numerical data
17.
Bioconjug Chem ; 26(8): 1782-90, 2015 Aug 19.
Article in English | MEDLINE | ID: mdl-26252905

ABSTRACT

We have been investigating the potential use of cell-penetrating peptide-linked polymers as a novel penetration enhancer. Since previous in vivo studies demonstrated that poly(N-vinylacetamide-co-acrylic acid) bearing D-octaarginine, a typical cell-penetrating peptide, enhanced membrane permeation of biomolecules, its potential as an in vitro transfection tool was evaluated in this study. A plasmid DNA encoding green fluorescent protein (pGFP-C1), ß-galactosidase, and bovine serum albumin (BSA) were used as model biomolecules. Anionic pGFP-C1 interacted electrostatically with cationic d-octaarginine-linked polymers. When the ratio of mass concentration of polymers to that of pGFP-C1 reached 2.5, complexes whose size and zeta potential were approximately 200 nm and 15 mV, respectively, were obtained. GFP expression was observed in cells incubated with complexes prepared under conditions in which the polymer/pDNA concentration ratio exceeded 2.5. The expression level elevated with an increase in the concentration ratio, but physicochemical properties of the complexes remained unchanged. Results suggested that free polymers contributed to pGFP-C1 internalization. Another cell study demonstrated that ß-galactosidase premixed with polymers was taken up into cells in its active tetrameric form. Similar electrostatic interaction-driven complex formation was observed for BSA charged negatively in neutral solution. However, it appeared that the internalization processes of BSA differed from those of pGFP-C1. A mass concentration-dependent increase in internalized BSA was observed, irrespective of the polymer/protein concentration ratio. Due to frail interactions, polymers that were released from the complexes and subsequently immobilized on cell membranes might also contribute to membrane permeation of BSA.


Subject(s)
Green Fluorescent Proteins/metabolism , Oligopeptides/chemistry , Plasmids/administration & dosage , Polymers/chemistry , Serum Albumin, Bovine/metabolism , beta-Galactosidase/metabolism , Animals , Cattle , Cell Membrane Permeability , Drug Carriers/chemistry , Green Fluorescent Proteins/genetics , HeLa Cells , Humans , Serum Albumin, Bovine/genetics , Transfection , beta-Galactosidase/genetics
18.
Proc Natl Acad Sci U S A ; 110(22): 9096-9, 2013 May 28.
Article in English | MEDLINE | ID: mdl-23674671

ABSTRACT

Human herpesvirus-6B (HHV-6B) is a T lymphotropic ß-herpesvirus that is clearly distinct from human herpesvirus-6A (HHV-6A) according to molecular biological features. The International Committee on Taxonomy of Viruses recently classified HHV-6B as a separate species. The primary HHV-6B infection causes exanthem subitum and is sometimes associated with severe encephalopathy. More than 90% of the general population is infected with HHV-6B during childhood, and the virus remains throughout life as a latent infection. HHV-6B reactivation causes encephalitis in immunosuppressed patients. The cellular receptor for HHV-6A entry was identified as human CD46, but the receptor for HHV-6B has not been clear. Here we found that CD134, a member of the TNF receptor superfamily, functions as a specific entry receptor for HHV-6B. A T-cell line that is normally nonpermissive for HHV-6B infection became highly susceptible to infection when CD134 was overexpressed. CD134 was down-regulated in HHV-6B-infected T cells. Soluble CD134 interacted with the HHV-6B glycoprotein complex that serves as a viral ligand for cellular receptor, which inhibited HHV-6B but not HHV-6A infection in target cells. The identification of CD134 as an HHV-6B specific entry receptor provides important insight into understanding HHV-6B entry and its pathogenesis.


Subject(s)
Herpesvirus 6, Human/physiology , Receptors, OX40/metabolism , Viral Fusion Proteins/metabolism , Virus Internalization , Flow Cytometry , HEK293 Cells , Herpesvirus 6, Human/metabolism , Humans , Plasmids/genetics , T-Lymphocytes/metabolism , T-Lymphocytes/virology
19.
Nihon Koshu Eisei Zasshi ; 58(4): 292-9, 2011 Apr.
Article in Japanese | MEDLINE | ID: mdl-21848208

ABSTRACT

OBJECTIVES: Diagnostic criteria for the metabolic syndrome (Mets) in Japan have been set by the Medical Committee of the Japanese Association of Medical Sciences (Med), the National Health and Nutrition Examination Survey (Nat), specific health checkups (Ckup), and second medical examination by Worker's Accident Compensation Insurance System (Wor). The purpose of this study was to compare classification of the metabolic syndrome by different organizational criteria and to investigate underlying differences. METHODS: All faculty members of a university in Osaka, Japan, underwent mandatory health checkups in September 2008. The demographic distribution included 769 males (mean age, 49 +/- 12 years) and 415 females (mean age, 43 +/- 10 years). Using the Med, Nat, Ckup and Wor criteria, individuals were assessed for the MetS and pre-metabolic syndrome (pre-Mets), strongly suspected metabolic syndrome (S-Mets) and assumed pre-metabolic syndrome (A-pre-Mets), as well as a positive support level (PSL) and a motivational support level (MSL). All faculty members were categorized into a morbid group (Mets, S-Mets, PSL, and FB) or a pre-morbid group (pre-Mets, A-pre-Mets, and MSL) based on medical data and smoking habits. The incidence of morbid and pre-morbid individuals was compared across the four criteria and analyzed based on gender and age (under 40 and 40 or over). RESULTS: Male incidences for the morbid and pre-morbid classifications were 17% and 20% with Med, 9% and 23% with Nat, 27% and 14% with Ckup, and 1.4% and 0% with Wor. There were significant differences across criteria sets in both the morbid and pre-morbid groups, with significantly greater numbers of males than females, and higher prevalences in those aged 40 or over than in their younger counterparts. Males aged under 40 classified into the pre-morbid group comprised 18% in Med, 16% in Nat, and 13% in Ckup. CONCLUSION: The different disease incidences found between Med and Ckup data in males aged 40 or over might be attributed to varying criteria for blood glucose levels, while Wor data may be influenced by the higher level of blood pressure set as a criterion with this approach. It will be important to continuously validate currently established criteria to identify the actual prevalence of MetS in Japan. Furthermore, incorporation of waist circumference and BMI for females, and a positive approach for young males, may be critical for future developments.


Subject(s)
Metabolic Syndrome/diagnosis , Adult , Faculty , Female , Humans , Japan , Male , Metabolic Syndrome/classification , Middle Aged
20.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 62(6): 832-9, 2006 Jun 20.
Article in Japanese | MEDLINE | ID: mdl-16799411

ABSTRACT

OBJECTIVES: CT data can be used for both anatomical image and attenuation correction (CTAC) of PET data in PET-CT scanners. The CTAC method is useful for attenuation correction, because the CT scan time is much shorter than the external radionuclide (e.g., (68)Ge) transmission scan time. However, the energy of the X-rays from CT is not monoenergetic and is much lower than that of the external radionuclide source. In this study, we evaluated the differences between emission PET images reconstructed with CT-based and (68)Ge-based attenuation correction. METHODS: CT scans and (68)Ge-Transmission scans were acquired and used for attenuation correction (CTAC, MAC, and SAC). The PET emission scan time was 4 min. CT scans were acquired at 10, 20, 40, 80, and 160 mA. (68)Ge-Transmission scans were acquired at 1, 3, 5, 10, 20, 40, 60, and 300 min. The attenuation-corrected emission image using MAC on a 300 min transmission scan was defined as the reference image. Seven cylinders (30 mm diameter) were filled with (18)F-FDG placed in a heart-liver phantom with simulated pulmonary mass lesions. The PET value [counts/cc] was measured in circular regions of interest (ROI) over the cylindrical mass lesion. Averages [counts/cc], coefficients of variation [C.V.(%)], and ratios of difference [%Diff] from the reference value were calculated for all conditions. RESULTS: In the CT-Transmission, analysis of variance revealed no significant effect of CT current on the average and the C.V. In the (68)Ge-Transmission, the average and the C.V. changed in dependence on the acquisition time. All %Diff using CT-Transmission were small. It was shown that CT-Transmission is more appropriate than (68)Ge-Transmission.


Subject(s)
Gallium Radioisotopes , Germanium , Image Processing, Computer-Assisted/methods , Positron-Emission Tomography/methods , Radioisotopes , Tomography, X-Ray Computed/methods , Phantoms, Imaging , Positron-Emission Tomography/instrumentation , Tomography, X-Ray Computed/instrumentation
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