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91.
IgG4-related disease (IgG4-RD) is a potentially multiorgan disorder. In this study, clinical and serological features from 132 IgG4-RD patients were compared about organ correlations. Underlying pathologies comprised autoimmune pancreatitis (AIP) in 85 cases, IgG4-related sclerosing cholangitis (IgG4-SC) in 12, IgG4-related sialadenitis (IgG4-SIA) in 56, IgG4-related dacryoadenitis (IgG4-DAC) in 38, IgG4-related lymphadenopathy (IgG4-LYM) in 20, IgG4-related retroperitoneal fibrosis (IgG4-RF) in 19, IgG4-related kidney disease (IgG4-KD) in 6, IgG4-related pseudotumor (IgG4-PT) in 3. Sixty-five patients (49%) had multiple IgG4-RD (two affected organs in 36 patients, three in 19, four in 8, five in 1, and six in 1). Serum IgG4 levels were significantly higher with multiple lesions than with a single lesion (P<0.001). The proportion of association with other IgG4-RD was 42% in AIP, the lowest of all IgG4-RDs. Serum IgG4 level was lower in AIP than in other IgG4-RDs. Frequently associated IgG4-RDs were SIA (25%) and DAC (12%) for AIP; AIP (75%) for IgG4-SC; DAC (57%), AIP (38%) and LYM (27%) for IgG4-SIA; AIP (26%) and LYM (26%) for IgG4-DAC; SIA (75%), DAC (50%) and AIP (45%) for IgG4-LYM; SIA (58%), AIP (42%) and LYM (32%) for IgG4-RF; AIP (100%) and SIA (67%) for IgG4-KID; and DAC (67%) and SIA (67%) for IgG4-PT. Most associated IgG4-RD lesions were diagnosed simultaneously, but IgG4-SIA and IgG4-DAC were sometimes identified before other lesions. About half of IgG4-RD patients had multiple IgG4-RD lesions, and some associations were seen between specific organs.

Graphical Abstract

相似文献   
92.
The effects of aging on inhibitory neuropeptide concentrations and intrinsic inhibitory innervation of circular muscle were investigated using normal descending colon obtained at surgery. Immunoreactive vasoactive intestinal peptide, peptide histidine-methionine, met5-enkephalin, neuropeptide Y, and somatostatin were extracted from specimens of muscularis externa (patient ages: 19–84 years) and measured by radioimmunoassay. Intracellular electrical activity was recorded from strips of circular muscle (patients ages: 49–84 years) using glass microelectrodes; inhibitory junction potentials were evoked by electrical field stimulation. There were no significant differences (t tests:P>0.05) between neuropeptide concentrations in patients<70 years old (N=28) compared to patients70 years old (N=12). However, the amplitude of inhibitory junction potentials declined with increasing patient age (r=–0.58,P=0.02,N=16), with no change in resting membrane potentials (r=0.22;P>0.05). The decline in amplitude in women (r=–0.68,P=0.03,N=9) preceded the decline in men (r=–0.62,P=0.10,N=7). Age-related decline in inhibitory junction potentials could be related to decreased: density of inhibitory nerves, release of inhibitory neurotransmitter, density of binding sites for inhibitory neurotransmitter on smooth muscle, or a combination thereof. Alternatively, this decline might represent a change in interaction of inhibitory neurotransmitter with the smooth muscle membrane, such as a change in coupling of binding site with the potassium channel, decreased number of potassium channels, or altered permeability of the potassium channel.This study was supported in part by the National Institutes of Health (DK 17238 and DK 34988), and by VA Medical Research funds.  相似文献   
93.
In 1999, we began a community-based randomized controlled prevention trial in Chennai, which aims to test the efficacy of HIV prevention messages disseminated through members of an individual's social group called community popular opinion leaders, or CPOLs. We targeted patrons of 100 bars or wine shops in the city of Chennai, India. In this article we report on the process of development of an HIV prevention intervention for wine shop patrons. First, we conducted detailed ethnography to understand social norms and CPOL and social network characteristics, including 41 in-depth interviews among wine shop patrons and gatekeepers. Second, we tailored a generic HIV education training manual to appropriately address the needs of Chennai wine shop patrons. Field-testing involved 16 focus groups with wine shop patrons and 12 sessions of participant observations in wine shops. Finally, we piloted the intervention to determine the appropriateness of the training program and its content among wine shop patrons. Our ethnographic data indicated that wine shops are a common meeting place for men. We were able to identify CPOLs influential in these settings and train them to deliver appropriate prevention messages to their close friends and associates. We found that HIV prevention messages in this population need to dispel misperceptions about HIV transmission, provide strategies and skills to adopt and sustain condom use, and target the role of alcohol in sexual behavior. We outline specific lessons we learned in intervention development in this population.  相似文献   
94.
We have developed hybridization-sensitive fluorescent oligonucleotide probes that, in the presence of quencher strands, undergo efficient fluorescence quenching through the formation of partial DNA/DNA duplexes. In the presence of target RNA, rapid displacement of the quencher strands results in highly enhanced fluorescence.

We have developed hybridization-sensitive fluorescent oligonucleotide probes that, in the presence of quencher strands, undergo efficient fluorescence quenching through the formation of partial DNA/DNA duplexes.

The detection of biomolecules is an important part of any investigation into their biological mechanisms and phenomena. Fluorescence-based methods are particularly useful for providing interpretable signals for various targets (e.g., genes, proteins, small molecules). When nucleic acids are used as probes, they can provide sequence-specific information regarding the binding (through hydrogen bonding) of target nucleic acids. Because of their high sequence-specificity, many fluorescent hybridization probes, including molecular beacons (MBs), have been developed and applied for nucleic acid detection and visualization.1,2In previous studies, we found that a quencher-free molecular beacon (QF-MB) containing the pyrene-modified nucleoside PyU exhibited a high fluorescence enhancement in the presence of trinucleotide repeats, especially for RNA.3,4 Among various fluorescent nucleobase derivatives, uracil derivatives have been particularly useful for selective detection of specific sequences, taking advantage of changes in photoinduced electron transfer between the fluorophore and the neighboring base.3–5 To apply such systems to various other target sequences, here we designed fully complementary sequences and incorporated the internal fluorescent nucleoside PyU in place of a thymine residue, resulting in a significantly increased fluorescence signal based on strand displacement (Fig. 1). Incorporation of a PyU unit in a single strand of the probe sequence and hybridization with a strand partially complementary to the probe strand containing a pyrene unit as a fluorescence quencher can lead to improved discrimination factors.4,6 Such partially double-stranded probes have several attractive features.Open in a separate windowFig. 1(A) Schematic representation of the strand displacement process developed in this present system. (B) Structures of the internal fluorophore PyU.First, the probe sequence does not require an additional sequence in its strand that is not complementary to the target sequence to ensure formation of a secondary structure (e.g., a hairpin). Such additional sequences might interfere with the specific hybridization between the probe and the target sequence. Accordingly, double-stranded fluorescence probes should allow the specific detection of many kinds of targets. Second, the highly quenched initial fluorescence signal, due to the formation of a partial duplex, results in significantly increased fluorescence in the presence of the target; the incorporation of a hybridization-sensitive internal fluorophore provides a stable and sensitive fluorescence signal upon perfect hybridization with the target.Cofilin is a protein that regulates the activity of actin, which is related to the formation of the cytoskeleton in cells. Actin plays a crucial role in the growth and elongation of cells,7 especially in neurons and, therefore, in the control of neurotransmission. We designed probe strands complementary to the 3′-untranslated region (3′-UTR) of target cofilin mRNA and synthesized three kinds of 19-mer probe strands (P1–P3) containing one or two PyU units in each strand (Fig. 2A and S1, ESI). The fluorescence intensities of P1 and P3 increased dramatically after binding with the target RNA T19—by 17.6- and 16.0-fold, respectively. For the probe P2 (in which the PyU residue was located close to the 3′-end), however, the fluorescence enhancement was very low: only 1.8-fold (Table S2, ESI). We assume that terminal modification of the PyU unit in the probe resulted in weak base pairs around the PyU residue than did central modification, resulting in a decrease in fluorescence enhancement (Table S3, ESI).8 Because flanking base pairs around the PyU unit are relatively less rigid compared to central base pairs, the microenvironment of PyU in the duplex formed from P2 and T19 is different from the central modification. Therefore, the fluorescence intensity did not increase significantly compared to the single-stranded P2. The absorption spectrum of P2 in the presence of T19 exhibited a relatively less intense absorption band than that of the duplex formed from P1 and T19—the latter featured an intense signal corresponding to the high fluorescence intensity (Fig. S1, ESI).9,10 Even though two PyU units were incorporated into the single strand P3, its fluorescence enhancement was similar to that of probe P1 containing only one PyU unit. Among other examined probe sequences complementary to other parts of 3′-UTR in cofilin mRNA, P6 (containing two PyU units) also exhibited fluorescence intensity similar to those of P4 and P5, single-PyU – containing probes each modified in the central position (Fig. S2, ESI). These results suggest that single modification of a PyU unit in the probe sequence is more efficient than dual modification, in terms of inducing high fluorescence enhancement with target RNA.Oligonucleotide sequences of probe and target strands
NameSequence
P15′-GGT GCC PyUAG GAC GGG ACT T-3′
P25′-GGT GCC TAG GAC GGG ACPyU T-3′
P35′-GGT GCC PyUAG GAC GGG ACPyU T-3′
U53′-CA CGG PyUTC CTG-5′
U63′-CCA CGG PyUTC CTG C-5′
T19a5′-a agu ccc guc cua ggc acc-3′
T19-Ua,b5′-a agu ccc guc cu ggc acc-3′
T19-Ga,b5′-a agu ccc guc cu ggc acc-3′
T19-Ca,b5′-a agu ccc guc cu ggc acc-3′
Open in a separate windowaTarget RNA sequence.bUnderlined letter indicates a single mismatched base.Open in a separate windowFig. 2(A, B) Fluorescence emission spectra of (A) the probes P1–P3 with T19 and (B) the probe P1 with U5 and U6. (C) Fluorescence enhancements (F/F0) at 432 nm of P1 in the presence of U5 and U6 upon binding with T19; 1.0 μM of samples in 100 mM Tris-HCl buffer (pH 7.2), 100 mM NaCl and 10 mM MgCl2; annealing: 90 °C; excitation wavelength: 380 nm; excitation/emission slit: 5 nm/5 nm; F: fluorescence intensity at 432 nm of the probe P1 with the target RNA T19 in the absence or presence of a quencher strand U5 and U6; F0: fluorescence intensity at 432 nm of the probe P1 in the absence or presence of a quencher strand U5 and U6.Next, to improve the fluorescence enhancement in the presence of the target, the background signal of the probe was decreased by mixing it with a pyrene-modified short oligonucleotide, a so-called “quencher strand”, capable of quenching the fluorescence of the PyU unit. Two pyrene units on the opposite side in the duplex resulted in fluorescence quenching because pyrene moieties are stacked each other and located in a highly polar environment.4,9 Such duplexes containing probe and quencher strands would have to undergo displacement of the quencher strand prior to hybridization of the target strand. First, we tested the effects of a PyU residue located in the quencher strand at the central position, opposite the PyU residue in the probe strand, potentially minimizing the fluorescence of the PyU residue in the probe strand through π-stacking of the two pyrene units in the duplex.4,11 We synthesized the quencher strands U5 and U6, each containing a PyU residue, and examined the relationship between the quenching efficiency and stable hybridization of the probe/quencher duplexes upon varying the length of the quencher strand (Fig. 2B). The more stable the partial duplex is formed, the more effective stacking interaction between pyrene moieties close to each other can be possible.12 In the presence of the PyU-modified quencher strands, the quenching efficiency of the probe at 435 nm was 65% for U5 and 80% for U6. As a result, the enhancements in fluorescence for the probe in the presence of the target T19 were 51.5- and 66.7-fold for U5 and U6, respectively (Fig. 2C and S7, ESI) much higher than that for P1 alone. Notably, these fluorescence signals were generated not only from the probe/target duplexes but also from the released quencher strands (i.e., the single-stranded quencher strands also exhibited fluorescence to some degree). Therefore, the actual fluorescence signal arising from hybridization of the probe with the target was slightly lower than that observed in the fluorescence spectra; we estimated that the additional signals due to the release of U5 and U6 increased the fluorescence intensity by 7% (Fig. S7, ESI). In other words, the released quencher strands added to the fluorescence enhancement of the DNA/RNA duplex. Moreover, we also tested the effect of incorporating a dabcyl derivative, DabU, as a typical fluorescence quencher on the quencher strand and compared its effects with those of the quencher strand containing a PyU unit (Table S4, Fig. S4, ESI). The PyU-modified quencher strands provided the probe with similar quenching in fluorescence as did DabU-modified quencher strands of the same length (Fig. S8 and S9, ESI). The melting temperatures (Fig. S10, Table S5, ESI) of the duplexes of the PyU-modified quencher strands and P1 (for U5 and U6 with P1: 60.1 and 66.0 °C, respectively) were higher than those of the natural strands and P1 (for N5 and N6 with P1: 46.8 and 56.0 °C, respectively); the former were stabilized through π-stacking of the PyU units (Fig. S5 and S6, ESI). The formation of duplexes from the probe and quencher strands was evident also in circular dichroism (CD) and polyacrylamide gel electrophoresis (PAGE) experiments (Fig. S11 and S12, ESI).To confirm the effective strand displacement of the quencher strand from the probe strand, we conducted time-dependent fluorescence experiments after addition of the target RNA T19 to probe/quencher duplexes (Fig. 3). After addition of the target strand to the single strand of P1, hybridization was complete within 30 min (i.e., the increase in fluorescence at 435 nm was minor thereafter). In contrast, the fluorescence intensity of P1 in the presence of the 11-mer quencher strand U5 was relatively rapid, reaching equilibrium after 20 min; for the 13-mer strand U6, however, equilibrium was reached within 35 min. Thus, compared with the single-stranded probe P1, the hybrid of P1 with U5 reacted more rapidly with the target T19, but the reaction time of the hybrid of P1 with U6 responding to the target T19 was slightly slower than that of P1 in the absence of a quencher strand. We suspect that the probe strand in the absence of a quencher strand was stabilized by stacking of the nucleobases; the probe would take some time to hybridize with the target RNA, requiring unfolding of its stacked bases. For the partially hybridized duplexes, however, the non-bonded sequence of the probe would be exposed, facilitating hybridization with the target strand. As a result, the response of P1 in the presence of U5 toward the target RNA was slightly faster than that of single-stranded P1 alone. Thus, as the length of the non-bonding sequence of P1 in the partial duplex decreased by increasing the length of quencher strand, the rate of strand displacement decreased accordingly.13–16 Indeed, the reaction time for the probe strand in the presence of the 15-mer strand U7 was much longer than those in the presence of the 11- and 13-mer quencher strands, because only a four-nucleotide sequence was available for hybridization of the target stand T19 (Fig. S13, ESI); in addition, the equilibrium of the reaction shifted to the left, in conjunction with a smaller enhancement in fluorescence.Open in a separate windowFig. 3Time-dependent fluorescence of P1 in the presence of U5 and U6 after addition of T19; 1.0 μM of samples in 100 mM Tris-HCl buffer (pH 7.2), 100 mM NaCl and 10 mM MgCl2; excitation wavelength: 380 nm; emission wavelength: 435 nm; excitation/emission slit: 5 nm/5 nm; temperature: 20 °C.We also tested the selectivity of the probe P1 itself against single-base-mismatched target RNA (Fig. 4, Open in a separate windowFig. 4Fluorescence emission spectra of P1 in the presence of single-base-mismatched target RNA; 1.0 μM of sample in 100 mM Tris-HCl buffer (pH 7.2), 100 mM NaCl and 10 mM MgCl2; annealing: 90 °C; excitation wavelength: 380 nm; excitation/emission slit: 5 nm/5 nm.In conclusion, we have developed a double-stranded duplex that functions as a universal probe that is highly specific for the sequence of its target RNA—in this case, for cofilin mRNA. When the PyU-modified probe strand was partially hybridized with quencher strands containing a PyU unit, the fluorescence intensity decreased dramatically as a result of π-stacking of the PyU units. The probe/quencher hybrids provided even greater fluorescence enhancements after stable binding of the target RNA strand with the additional signal from the released quencher strand further improving the fluorescence detection of the target RNA.  相似文献   
95.

Introduction

We compared laparoscopic Toupet fundoplication (LTF) and laparoscopic Nissen fundoplication (LNF) in neurologically normal children.

Methods

Forty neurologically normal children who were followed up for more than 3 years after LTF (n = 22) or LNF (n = 18) were reviewed retrospectively. LTF and LNF were performed between 2006 and 2012.

Results

There were no significant differences in gender (LTF, 15 male and 7 female patients; LNF:, 12 male and 6 female patients), mean age at surgery (LTF vs LNF: 2.5 vs 2.3 years), mean weight at surgery (LTF vs LNF: 9.6 vs 8.9 kg), preoperative symptoms, preoperative pH monitoring (pH <4) (LTF vs LNF: 26.7% vs 21.8%), mean operative time (LTF vs LNF: 117 vs 126 min), postoperative recommencement of enteral feeding (LTF vs LNF: 3.7 vs 3.8 days), or duration of hospitalization (LTF vs LNF: 5.5 vs 6.3 days). Intraoperative complications were esophageal trauma (LTF; n = 1; 4.5%) and liver trauma (LNF; n = 1; 5.6%) (P = 0.70). Post‐LTF complications were wrap stenosis (n = 1; 4.5%), and post‐LNF complications were wrap stenosis (n = 1; 5.5%) and gastric outlet obstruction (n = 1; 5.5%) (P = 0.43); all were managed conservatively. No case required conversion to open repair. There was no recurrence after LTF, but there were three cases (16.7%) after LNF (P = 0.08). Reoperation was performed at 4, 11, and 13 months, respectively.

Conclusion

Despite LTF and LNF appearing to be equally effective, three LNF cases required reoperation.  相似文献   
96.
We successfully treated a case of mitral regurgitation due to chest trauma in Barlow's disease. A 71‐year‐old man was admitted with severe mitral regurgitation after blunt compression of the chest by a heavy object 5 months earlier. Preoperative examination revealed wide chordae tendineae rupture and myxomatous changes to the bileaflets. Neo‐chordae reconstruction of the anterior mitral leaflet using loop technique, triangular resection of the posterior mitral leaflet, and ring annuloplasty was performed via surgical robot. Robotic mitral valve plasty for severe mitral regurgitation due to chest trauma in Barlow's disease was achieved safely with good clinical and excellent cosmetic results.  相似文献   
97.
Fixed pericardial tissue is commonly used for commercially available xenograft valve implants, and has proven durability, but lacks the capability to remodel and grow. Decellularized porcine pericardial tissue has the promise to outperform fixed tissue and remodel, but the decellularization process has been shown to damage the collagen structure and reduce mechanical integrity of the tissue. Therefore, a comparison of uniaxial tensile properties was performed on decellularized, decellularized‐sterilized, fixed, and native porcine pericardial tissue versus native valve leaflet cusps. The results of non‐parametric analysis showed statistically significant differences (p < .05) between the stiffness of decellularized versus native pericardium and native cusps as well as fixed tissue, respectively; however, decellularized tissue showed large increases in elastic properties. Porosity testing of the tissues showed no statistical difference between decellularized and decell‐sterilized tissue compared with native cusps (p > .05). Scanning electron microscopy confirmed that valvular endothelial and interstitial cells colonized the decellularized pericardial surface when seeded and grown for 30 days in static culture. Collagen assays and transmission electron microscopy analysis showed limited reductions in collagen with processing; yet glycosaminoglycan assays showed great reductions in the processed pericardium relative to native cusps. Decellularized pericardium had comparatively low mechanical properties among the groups studied; yet the stiffness was comparatively similar to the native cusps and demonstrated a lack of cytotoxicity. Suture retention, accelerated wear, and hydrodynamic testing of prototype decellularized and decell‐sterilized valves showed positive functionality. Sterilized tissue could mimic valvular mechanical environment in vitro, therefore making it a viable potential candidate for off‐the‐shelf tissue‐engineered valvular applications.  相似文献   
98.
99.
Purpose: To examine factors in the fear-avoidance model, such as pain, pain catastrophizing, fear-avoidance beliefs, physical disability, and depression and their relationships with physical and psychological quality of life in patients with rheumatic diseases.

Materials and methods: The data were obtained from 360 patients with rheumatic diseases who completed self-report measures assessing study variables. Structural equation modeling was used to examine the hypothesized relationships among factors specified in the fear-avoidance model predicting physical and psychological quality of life.

Results: Final models fit the data well, explaining 96% and 82% of the variance in physical and psychological quality of life, respectively. Higher pain catastrophizing was related to stronger fear-avoidance beliefs that had a direct negative association with physical disability and depression, which, in turn, negatively affected physical quality of life. Pain severity was also directly related to physical disability. Physical disability also affected physical quality of life indirectly through depression. The hypothesized relationships specified in the model were also confirmed for psychological quality of life. However, physical disability had an indirect association with psychological quality of life via depression.

Conclusion: The current results underscore the significant role of cognitive, affective, and behavioral factors in perceived physical disability and their mediated detrimental effect on physical and psychological quality of life in patients with rheumatic diseases.

  • Implications for rehabilitation
  • The fear-avoidance model is applicable to the prediction of quality of life in patients with rheumatic diseases.

  • As pain-catastrophizing and fear-avoidance beliefs are important factors linked to physical disability and depression, intervening these cognitive factors is necessary to improve physical function and depression in patients with rheumatic diseases.

  • Considering the strong association between depression and physical and psychological quality of life, the assessment and treatment of the former should be included in the rehabilitation of patients with rheumatic diseases.

  • Interventions targeting physical function and depression are likely to be effective in terms of improving physical and psychological quality of life in patients with rheumatic diseases.

  相似文献   
100.

Objectives

Since the Cabinet’s decision concerning the Basic Policies 2005, the Japanese government has implemented specific measures to suppress increases in national medical care expenditure. However, we believe that the economic significance of medical care should be quantified in terms of its economic impact on national medical care expenditure. No one has examined the economic impact of all medical institutions in Japan using data from a statement of profits and losses. We used an input–output analysis to quantitatively estimate economic impact of medical care and examined its estimation range with a probabilistic sensitivity analysis.

Methods

To estimate the economic impact and economic impact multipliers of all medical institutions in Japan, an input–output analysis model was developed using an input–output table, statement of profits and losses, margin rates, employee income rates, consumption propensity and an equilibrium output model. Probabilistic sensitivity analysis was conducted using a Monte Carlo simulation.

Results

Economic impact of medical care in all medical institutions was ¥72,107.4 billion ($661.5 billion). This impact yielded a 2.78-fold return of medical care expenditure with a 95 % confidence interval ranging from 2.74 to 2.90.

Conclusion

Economic impact of medical care in Japan was two to three times the medical care expenditure (per unit). Production inducement of medical care is comparable to other industrial sectors that are highly influential toward the economy. The contribution to medical care should be evaluated more explicitly in national medical care expenditure policies.  相似文献   
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