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1.

Objective

The objectives of this study were to analyze the potential correlation between post–liver transplantation survival interval and CD4+ T-cell intracellular ATP (iATP) levels, and to describe the distribution of CD4+ T-cell iATP levels in liver transplant recipients.

Methods

This was a retrospective analysis of clinical data of 273 patients who underwent liver transplantation from July 2010 to October 2012 in our center and achieved long-term stable survival. CD4+ T-cell iATP level was detected using Cylex ImmuKnow assay. Post–liver transplantation survival was analyzed.

Results

CD4+ T-cell iATP level significantly differed among patients with different post–liver transplantation survival intervals. The peak CD4+ T-cell iATP levels typically occurred within the first 3 postoperative months.

Conclusions

Post–liver transplantation survival interval is correlated with CD4+ T-cell iATP levels.  相似文献   

2.

Background

Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation.

Methods

We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 105 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2Ld-restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4+ and CD8+ T cells at various time points.

Results

We found that immunocompetence against tumors depends heavily on cancer-specific CD8+ T-cell responses in a major histocompatibility complex–restricted manner; the evidence was further supported by the increase of interferon-γ–secreting CD4+ T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62LhiCCR7+) as well as effector memory cells (CD62LloCCR7?). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice.

Conclusions

Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment.  相似文献   

3.

Introduction

Isolated microscopic hematuria (IMH) is not uncommon in potential kidney donors.

Aim

The aim was to study the kidney biopsy findings of potential kidney donors with IMH and the impact of the histopathologic diagnoses on the decision to accept or decline such donors from kidney donation.

Methods

In this retrospective study, all the potential kidney donors with IMH were identified from the medical records of patients who underwent kidney biopsies between January 2010 and December 2016.

Results

Forty-five such individuals were identified. The mean age of these potential donors was 32.6 years and 76% were male. All of them had normal blood pressure and no significant proteinuria. Seventeen (38%) biopsies showed histopathologic abnormalities; thin basement membrane disease (n = 13; 28%) was the most common cause followed by immunoglobulin (Ig)A nephropathy (n = 4; 9%). Donors with abnormal biopsy findings were excluded from donation. However, 62% of the potential donors had normal kidney biopsy findings and were accepted for kidney donation.

Conclusion

IMH justifies extensive work-up including kidney biopsy to identify donors who may have underlying significant glomerular pathology excluding them from kidney donation. On the other hand, kidney biopsy also helps in accepting the donors if it does not show significant abnormality.  相似文献   

4.

Background

Both liver natural killer (NK) and NK T cells of the innate immune system play a crucial role in islet graft loss after intraportal islet transplantation, although a relationship between NK and NK T cells in islet loss has not been proven. In this study, we investigated the role of NK cells in the innate immune system in islet graft loss after intraportal islet transplantation.

Methods

To investigate the involvement of liver NK cells in islet destruction, we assessed the differences in graft survival after intraportal islet transplantation between CD1d?/? diabetic mice and NK cell–depleted CD1d?/? diabetic mice.

Results

The transplantation of 400 islets into the liver was sufficient to reverse hyperglycemia in wild-type diabetic mice (100%, 4/4). However, normoglycemia could not be achieved when 200 islets were transplanted (0%, 0/4). In contrast, intraportal transplantation of 200 islets in NK cell–depleted CD1d?/? diabetic mice ameliorated hyperglycemia in 71% of cases (5/7), whereas transplantation of the same number of islets in CD1d?/? diabetic mice did not (0%, 0/4). Histologic findings also confirmed that intact islets were observed in NK cell–depleted CD1d?/? diabetic mice, but were difficult to observe in CD1d?/? diabetic mice.

Conclusions

The involvement of liver NK cells in the innate immune system related to islet graft loss after intraportal islet transplantation is revealed by improved graft survival and function in NK cell–depleted CD1d?/? diabetic mice. Our data reveal that regulation of NK cell activity is particularly important when insufficient islet numbers are used for transplantation.  相似文献   

5.

Background

Mizoribine (MZ) has been developed as an immunosuppressive agent in Japan, but it has a less-potent immunosuppressive effect up to 3 mg/kg/d. In the previous study, a Japanese multicenter study, we reported that high-dose MZ, at 6 mg/kg/d, with a calcineurin inhibitor was effective and safe in reducing the frequency of cytomegalovirus (CMV)-related events in ABO-incompatible (ABO-i) living-related kidney transplantation (LKT). In the present study, therefore, we investigated the effects of high-dose MZ with a CNI in ABO-i LKT recipients in a Japanese multicenter study.

Methods

A total of 37 patients were treated with high-dose MZ (6 mg/kg), a CNI (cyclosporine [CsA] or tacrolimus [Tac]), basiliximab (Bas), rituximab (Rit), and corticosteroids. CsA was started at a dose of 7 mg/kg to maintain blood levels [200 ng/mL (C0), 6000 ng-h/mL (AUC 0–9)]. Tac was started at a dose of 0.2 mg/kg to maintain blood levels [8–10 ng/mL (C0), 100 ng-h/mL (AUC 0–9)]. Bas (20 mg/body) was administrated on day 0 and day 4 after transplantation. Rit (100–200 mg/body) was administrated on day ?14 and day ?7 before transplantation. MZ was adjusted to maintain target C0 levels of 1.5 to 2.0 μg/mL.

Results

Patient and graft survival rates for 2 years were 100% in the CsA group (n = 22) and 93.3% in the Tac group (n = 15) (not significant, NS). Overall incidence of acute rejection for 2 years was 22.7% in the CsA group and 26.7% in the Tac group. Mean serum creatinine levels at 2 years were 1.29 ± 0.2 mg/dL in the CsA group and 1.21 ± 0.34 mg/dL in the Tac group (NS). The incidence of CMV disease was 0% in both groups, and positive rates of CMV antigenemia were 50.0% and 26.7% in the CsA and Tac groups, respectively (NS). Mean serum uric acid levels were 5.5 ± 1.3 mg/dL and 6.4 ± 1.2 mg/dL at 2 years (NS) in the CsA and Tac groups, respectively.

Conclusions

A high-dose MZ regimen including calcineurin inhibitor (CsA or Tac), Bas, Rit, and steroids was effective and safe in reducing the frequency of CMV-related events in ABO-i LKT.  相似文献   

6.

Background

In this study, we investigated the responsiveness of the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) for patient's assessment before and after hallux valgus surgery.

Methods

Patient-reported answers on the SAFE-Q and Short Form-36 (SF-36) before and at a mean of 3–4 and 9–12 months after hallux valgus surgery were analyzed. Data of 100 patients (92 women, eight men) from 36 institutions throughout Japan were used for analysis.

Results

In all subscales of the SAFE-Q, the trend of increased scores after surgery was statistically significant (P < 0.001). Among the patients with available scores both before and at 9–12 months after surgery (n = 66), the largest effect sizes (ESs) were observed for shoe-related (1.60), pain and pain-related (1.05), and general health and well-being (0.84) scales. In the SF-36 (n = 64), the largest ES was observed for the bodily pain scale (0.86). Less notable changes were observed for the remaining SF-36 domains.

Conclusion

The SAFE-Q is the first patient-reported outcome measure which includes a quality of life assessment of shoes. In our cohort, the most remarkable responsiveness was observed for the shoe-related subscale. Based on its responsiveness, the SAFE-Q appears to be sufficient for evaluation of foot-related quality of life before and after surgery.  相似文献   

7.

Background

Hepatic ischemia-reperfusion injury (IRI) is an important determinant of the outcome of hepatic surgery, including re-section and transplantation. Previous studies have shown that nitric oxide (NO) has a protective effect against IRI. Therefore, many studies have examined methods for supplying NO. In this study, we investigated the effect of NO-releasing nanofibers on hepatic IRI in a rat model.

Methods

Male Sprague-Dawley rats were divided into 4 groups: control, IRI only (n = 3); group 1, hepatic IRI and liver-wrapping with nanofiber lacking NO (n = 4); group 2, hepatic IRI and liver-wrapping with NO rapid-releasing nanofiber (n = 4); and group 3, hepatic IRI and liver-wrapping with NO slow-releasing nanofiber (n = 5).

Results

The levels of aspartate aminotransferase and alanine aminotransferase were not significantly different between groups. On the basis of Western blots, Bax/β-actin levels were significantly lower in group 2 than in group 3 (P < .01). Cleaved Caspase-3/β-actin levels were significantly lower in group 2 than in the control, group 1, and group 3 (P < .05, .01, and .01, respectively). However, there were no significant differences in Bcl-2/β-actin between groups.

Conclusions

The liver-wrapping NO rapid-releasing nanofiber downregulated cleaved Caspase-3 and Bax expression. It has a protective effect by reducing apoptosis in hepatic IRI in rats.  相似文献   

8.

Purpose

To evaluate the potential of high-resolution magic angle spinning (HR-MAS) 1H nuclear magnetic resonance (NMR) spectroscopy for metabolite characterization and the differentiation of acute rejection after heart transplantation in rat models.

Methods

We transplanted syngeneic heart grafts from Lewis rats (n = 4) and allogeneic heart grafts from F344 rats (n = 4) heterotopically into Lewis recipients. On day 7 postoperatively, the transplanted hearts were harvested for ex vivo 1H NMR spectroscopy and HR-MAS 1H NMR spectroscopy. 1H NMR spectroscopy and HR-MAS 1H NMR spectroscopy were performed at 4.7 T and 11.7 T, respectively. Metabolomic profiles contributing to the differentiation of allogeneic and syngeneic graft groups were statistically assessed by orthogonal partial least squares discriminant analysis (OPLS/O2PLS-DA). Metabolite concentrations were normalized by total spectral intensities and were compared using Mann-Whitney U tests.

Results

One allogeneic graft that showed extensive necrotic change suggesting graft failure was excluded from the statistical analysis of the NMR spectroscopy. In the 4.7-T 1H NMR spectroscopy, the creatine peak was decreased in the allogeneic group. The PLS-DA and OPLS/O2PLS-DA score plot demonstrated good discrimination of the allogeneic graft group from syngeneic graft group. The concentrations of creatine, myo-inositol, glucose, niacinamide, hypoxanthine, inosine, and glutamine were significantly decreased in the allogeneic graft group, whereas the concentrations of glycine, phosphoethanolamine, xanthine, sn-glycero-3-phosphocholine, leucine, valine, and tyrosine were significantly increased (P < .05).

Conclusions

HR-MAS 1H NMR spectroscopy can metabolically characterize the acute rejection of heart transplantation.  相似文献   

9.

Background

Digital nerve injuries in children are not common, but they are considered to have an excellent prognosis, compared to adults, after nerve injury and repair. In studies including both children and adults age have been found to have an effect on outcome after nerve repair.

Methods

We investigated in a retrospective follow up study the long-time result after digital nerve injury and repair in children, 1–16 years of age (n = 38), and evaluate if age influences outcome. A group with young children, 1–10 years of age (n = 18), was compared with a group with older children, 11–16 years of age (n = 20). A clinical evaluation to evaluate sensation and grip strength was performed and questionnaires were used [Disability of the Arm, Shoulder and Hand (DASH), Cold Sensitivity Severity Scale (CISS), VAS-function and VAS-cosmetic] in median 40 months (range 12–131 months) after the injury and repair.

Results

All patient regained normal sensation. No correlations between age and monofilaments were found. Twenty children (52%) reported some problems with cold intolerance (i.e. CISS), but no other abnormal disability was found (i.e. DASH, VAS); again with no differences between the two groups.

Conclusions

Children have an excellent long-term recovery after a digital nerve repair and without any influence of age.  相似文献   

10.

Objectives

Although soft tissue sarcoma (STS) is rare, its incidence is increasing among older patients. Few studies have compared the outcomes between conservative and surgical treatments for STS patients aged ≥80 years. We assessed the outcomes of both treatments in this population and the association between older age and surgical outcome.

Methods

We recruited consecutive patients with STS aged ≥80 years treated at our institution between January 2006 and May 2014. We recommended surgical resection for all patients without multiple distant metastases. Overall survival and sarcoma-specific survival were assessed using the Kaplan–Meier method.

Results

Of the 39 patients with STS who presented at our institution, 37 were included in this analysis (19 men and 18 women with a median age of 85 [range 80–94] years). Tumors were classified as Stage IB (n = 3), IIA (n = 6), IIB (n = 3) or III (n = 24). Four patients underwent conservative therapy and 33 underwent surgical resection. The most common tumor site was the lower extremity, and the majority of tumors were classified as undifferentiated pleomorphic sarcoma. The follow-up rate was 100%. One-year sarcoma-specific survival rates were 25.0% in the conservative therapy group and 90.9% in the surgical resection group. No associations were found between age ≥85 years and perioperative complications or clinical outcome.

Conclusions

Surgical resection had relatively few complications, given the age group, and improved the prognosis of older patients with STS. Surgical resection of STS with curative intent should be considered in older patients.  相似文献   

11.

Background

Biliary complications are important during liver transplantation because of their effect on recipient and graft survival, incidence, and the long treatment period. These complications are associated with 50% morbidity and 30% mortality rates in recent studies. One of the most important reasons for biliary anastomosis complications is arterial ischemia. We present the results of our telescopic biliary anastomosis technique performed on the mucosa of the main biliary duct.

Patients and Methods

Fifty-six cases of telescopic biliary reconstruction were performed in 203 patients during 2015. Fifty cases and 52 patients who underwent standard reconstruction were chosen and compared. All patients had been scanned retrospectively. Statistical analyses were conducted with χ2 and Mann-Whitney U tests for the complications that occurred during the first 3 months. A P value <.05 was considered significant.

Results

No clinical or demographic differences were detected between the groups. About 90% of both groups were living donor liver transplantation cases. Five (10%) anastomotic leaks occurred in telescopic reconstruction group (n = 50), and 13 (25%) occurred in the standard reconstruction group (n = 52; P < .05).

Conclusion

The arterial blood supply is better if the biliary anastomosis is made on the mucosal side of the main biliary duct. Early period anastomotic leaks may decrease significantly.  相似文献   

12.

Introduction

Studies focusing on the efficacy and safety of ledipasvir (LDV) + sofosbuvir (SOF) therapy in liver transplant (LT) recipients with hepatitis C virus (HCV) recurrence are still limited. Therefore, the aim of our work was to perform a systematic review and meta-analysis to evaluate outcome data of LDV + SOF therapy in LT recipients.

Methods

Multiple databases were systematically searched for eligible studies. We included studies reporting sustained virological response 12 weeks after treatment (SVR12) and treatment-related adverse events (AEs) in LT recipients treated with LDV + SOF ± ribavirin (RBV) for HCV recurrence. All statistical analyses were conducted by using R version 3.3.1 (The R Foundation for Statistical Computing, Vienna, Austria).

Results

Twelve studies with a total of 994 LT recipients were included, most of which were diagnosed with HCV genotype 1 infection. The overall SVR12 reached 96.3% (95% confidence interval [CI]: 94.9%–97.5%) and no significant heterogeneity was observed (Q statistic = 10.63, P = .47; I2 = 0%). No difference was found in SVR12 between treatments for 12 weeks and 24 weeks (P = .18). Patients treated with LDV + SOF + RBV (n = 525) exhibited an SVR12 rate of 95.1% (95% CI 92.8%–96.6%), which showed no difference from the findings in the LDV + SOF treatment group (n = 314) with an SVR12 reaching 94.9% (95% CI 91.5%–97.0%; P = .92). There was a tendency for a higher SVR12 in patients without cirrhosis than those with cirrhosis (P < .05). The most common AEs were listed as following: anemia 41.9% (n = 203 of 484), fatigue 39.1% (n = 207 of 530), headache 24.2% (n = 128 of 530), nausea 21.9% (n = 106 of 484), and diarrhea 19.0% (n = 92 of 484).

Conclusion

LDV + SOF-based treatment is highly effective and well tolerated in LT recipients with HCV reinfection.  相似文献   

13.

Background

Lumbar decompression surgery is often used to treat neurological symptoms of the lower extremity as a result of lumbar disease. However, this method also leads to the improvement of the accompanying low back pain (LBP). We studied the extent of LBP improvement after lumbar decompression surgery without fusion and the associated preoperative factors.

Methods

Patients (n = 140) with lumbar spinal stenosis (n = 90) or lumbar disc herniation (n = 50) were included. To evaluate the change in LBP, VAS scores and the Oswestry disability index scores were measured before surgery and 2 weeks, 3 months, and 6 months after surgery. The predictors of residual LBP were investigated using logistic regression analyses.

Results

In total, 140 patients were examined. The VAS scores for LBP before surgery and 2 weeks, 3 months, and 6 months after surgery were 4.4 ± 3.0 (mean ± standard deviation), 1.1 ± 1.5, 1.3 ± 1.8, and 1.9 ± 2.2, respectively. LBP significantly improved 2 weeks after surgery (P < 0.001), stabilized between 2 weeks and 3 months after surgery, but was significantly aggravated 3–6 months after surgery (P < 0.001). At 6 months after surgery, 67 (47.9%) patients had a VAS score of >1. The predictors of residual LBP included severe preoperative LBP, degenerative scoliosis and the size of the Cobb angle. The independent predictors, determined by multivariate analysis were degenerative scoliosis and the size of the Cobb angle.

Conclusions

LBP was alleviated at 2 weeks after lumbar decompression surgery for lumbar disc herniation and lumbar spinal stenosis. The predictors of residual LBP after decompression included more severe LBP at baseline, degenerative scoliosis and the size of Cobb angle.

Level of evidence

Level 3.  相似文献   

14.

Study Design

Multicenter retrospective study.

Background

Postoperative surgical site infection is one of the most serious complications following spine surgery. Previous studies do not appear to have investigated pyogenic discitis following lumbar laminectomy without discectomy. This study aimed to identify risk factors for postoperative pyogenic discitis following lumbar decompression surgery.

Methods

We examined data from 2721 patients undergoing lumbar laminectomy without discectomy in five hospitals from April 2007 to March 2012. Patients who developed postoperative discitis following laminectomy (Group D) and a 4:1 matched cohort (Group C) were included. Fisher's exact test was used to determine risk factors, with values of p < 0.05 considered statistically significant.

Results

The cumulative incidence of postoperative discitis was 0.29% (8/2721 patients). All patients in Group D were male, with a mean age of 71.6 ± 7.2 years. Postoperative discitis was at L1/2 in 1 patient, at L3/4 in 3 patients, and at L4/5 in 4 patients. Except for 1 patient with discitis at L1/2, every patient developed discitis at the level of decompression. The associated pathogens were methicillin-resistant Staphylococcus aureus (n = 3, 37.5%), methicillin-susceptible Staphylococcus epidermidis (n = 1, 12.5%), methicillin-sensitive S. aureus (n = 1, 12.5%), and unknown (n = 3, 37.5%). In the analysis of risk factors for postoperative discitis, Group D showed a significantly lower ratio of patients who underwent surgery in the winter and a significantly higher ratio of patients who had Modic type 1 in the lumbar vertebrae compared to Group C.

Conclusions

Although further prospective studies, in which other preoperative modalities are used for the evaluation, is needed, our data suggest the presence of Modic type 1 as a risk factor for discitis following laminectomy. Latent pyogenic discitis should be carefully ruled out in patients with Modic type 1. If lumbar laminectomy is performed for such patients, more careful observation is necessary to prevent the development of postoperative discitis.  相似文献   

15.

Background

Systemic inflammation affects kidney function in a wide range of diseases. Even in kidney transplant recipients, higher levels of C-reactive protein (CRP) are invariably associated with both worse short- and long-term graft outcomes. However, little is known about systemic inflammation in kidney donors and, notably, brain death causes a strong systemic inflammatory response.

Objective

To analyze the role of systemic inflammation of brain-dead donors on short-term kidney graft outcomes (ie, delayed graft function [DGF], defined as the need of dialysis during the first week after transplantation).

Materials and methods

Retrospective analysis of clinical and biochemical characteristics of all brain-dead kidney donors generated in the Hospital Clínic of Barcelona in the 2006 to 2015 period (n = 194). Donors who were tested for CRP in the 24 hours before BD declaration were included (n = 97, 50% of initial population). Clinical and biochemical features of their respective recipients (n = 165) were analyzed, comparing recipients who developed DGF (n = 30) with recipients who did not (n = 135).

Results

Donors whose recipients later developed DGF had much higher CRP values (10.58 [5.1-18.21] vs 4.81 [1.42-12.2] mg/dL, P = .025). Other characteristics associated with the development of DGF were renal biopsy score and recipient dialysis vintage (P = .025 and P = .002, respectively). In logistic regression analysis, PCR maintained significance in the non–expanded criteria donor (ECD) group (odds ratio [OR], 1.102; P = .027), but it lost significance in the ECD group (P = .67).

Conclusions

Terminal donor CRP was associated with DGF in kidney transplant recipients and proved to be mostly significant in younger donors.  相似文献   

16.

Objectives

The techniques and outcomes of outflow reconstruction in living donor liver transplantation (LDLT) using cryopreserved homologous veins at the University of Tokyo Hospital are presented.

Methods

We performed 540 LDLTs from January 1996 to March 2015. Graft types included right liver graft (n = 262), left liver graft (n = 196), left lateral sector graft (n = 53), and posterior sector graft (n = 28). We routinely use cryopreserved homologous vein grafts for the hepatic vein reconstructions to secure the large outflow of the graft. In addition to the presentation of our techniques, the cases with symptomatic outflow obstruction and the treatments were also investigated.

Results

The 1-, 3-, and 5-year graft survival rates were 90.6%, 86.1%, and 83.5%, respectively. The incidence of severe complications (Clavien-Dindo grade IIIb and more) was 38%. The overall incidence of outflow obstruction requiring invasive treatment was 1.9% (10/540), including 3 left liver grafts (1.5%, 3/196) and 7 right liver grafts (2.7%, 7/262). Regarding the patency of the reconstructed veins, the left hepatic vein, middle hepatic vein, and right hepatic vein achieved nearly 100% patency. On the contrary, venous tributaries such as V5, V8, and inferior right hepatic vein were frequently occluded in the postoperative course.

Conclusions

Outflow reconstruction is a key for the successful LDLT. Cryopreserved homologous vein graft is useful for the promising hepatic vein reconstruction.  相似文献   

17.

Background

There is very little information on the costs of different surgeries for displaced femoral neck fractures. This study aimed to compare the costs between internal fixation and hemiarthroplasty (HA) in the treatment of displaced femoral neck fracture.

Method

A total of 142 patients aged 65 years or older who had been randomized into internal fixation group (n = 70) or HA group (n = 72) were followed for 2 years. Cost data was collected through hospitalization information, cost diary and telephone interview. Sensitivity analysis was performed for missing diaries. The total costs were collected and compared between the two groups.

Results

All diaries were completed by 69.7% of patients. The mean costs of primary treatment were significantly lower for internal fixation (CNY 21,631) compared with HA (CNY 51,641) (p < 0.001). The mean post-discharge costs were similar for both procedures: CNY 37,377 for internal fixation and CNY 34,981 for HA (p = 0.640). The mean total costs for internal fixation were CNY 59,008, which was significantly lower than the mean total costs of CNY 86,622 for HA (p = 0.002).

Conclusion

Although the post-discharge costs of internal fixation were slightly higher, the total costs were still lower than for HA due to great variance in costs of primary treatment. In China, internal fixation may be less costly than HA for displaced femoral neck fracture treatment.  相似文献   

18.

Background

With the goal of in vivo cultivation of human hepatocytes that have not been sufficient in full differentiation in vitro, the advantage of neonatal thymectomy was verified on expansion of xenogeneic human hepatocyte in the micro-miniature pig (MMP).

Methods

The thymus was excised immediately after the birth of the MMPs via cesarean section. Newborns were fed by artificial feeding under specific pathogen-free conditions. The thymectomized and nonthymectomized littermates were transplanted with human hepatocytes via a portal vein with or without partial hepatectomy at the MMP adult stage.

Results

The growth of thymectomized MMPs and the sham operated littermates was not significantly different; the former weighed 1.98 ± 0.30 kg (average ± standard deviation, n = 4) and the latter weighed 2.28 ± 0.39 kg (n = 4) at 1 month of age, and 17.48 ± 1.92 kg and 16.75 ± 2.68 kg at 12 months of age. Blood thymosin α1 concentrations in the thymectomy group were significantly lower than in the control group (0.22 ± 0.05 ng/mL vs 0.46 ± 0.16 ng/mL; n = 4, 12 months old, P = .029). After human hepatocyte transplantation, human albumin levels were detectable on day 28 in the peripheral blood of the thymectomy plus hepatectomy group (14.3 ± 4.9 ng/mL [± range, n = 2]) but were not detectable even on day 21 in the control group.

Conclusions

Neonatal thymectomy was successfully achieved in infantile MMPs born via cesarean section. These pigs were considered to be an ideal in vivo bioreactor for human hepatocytes.  相似文献   

19.

Background

Chronic back pain is one of the most important complications of postmenopausal osteoporosis. The aim of this study was to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of bisphosphonates (BPs) on pain in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated through an examination of pain-related behavior, as well as immunohistochemical findings. In addition, the effects of alendronate (ALN), a potent osteoclast inhibitor, on these parameters were assessed.

Methods

8-week-old female ddY mice were ovariectomized and assigned to 3 groups: SHAM-operated mice treated with vehicle (SHAM; n = 8); OVX mice treated with vehicle (OVX-V; n = 8); and OVX mice treated with ALN (OVX-ALN; n = 8). Starting immediately after surgery, vehicle or 40 μg/kg ALN was injected subcutaneously twice a week for 4 weeks. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally by μCT. Mechanical sensitivity was tested using von Frey filaments. Transient receptor potential channel vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) expressions in L3-5 dorsal root ganglion (DRG) neurons were examined immunohistochemically.

Results

Ovariectomy induced bone loss and mechanical hyperalgesia in hindlimbs with upregulation of TRPV1 and CGRP expressions in DRG neurons innervating hindlimbs. ALN prevented bone loss and mechanical hyperalgesia in ovariectomized mouse hindlimbs, and it suppressed upregulation of pain markers.

Conclusions

ALN prevented ovariectomy-induced bone loss and mechanical hyperalgesia in hindlimbs, and it suppressed TRPV1 and CGRP expressions in DRG neurons. The results suggest that bone resorption with upregulation of TRPV1 and CGRP expressions is one of the causes of postmenopausal osteoporotic pain.  相似文献   

20.

Background

The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure.

Methods

We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation. The relationship between the clinical severity of liver disease and the phenotype of intrahepatic NK cells in these patients was also evaluated. To estimate the immunological responsiveness of intrahepatic NK cells, phenotypic enhancement after interleukin-2 stimulation was analyzed.

Results

Intrahepatic NK cells from patients with advanced liver failure exhibited down-regulated monomodal expression of NKp46, a major activating molecule. Notably, the expression level of NKp46 decreased depending on the severity of liver disease, Model for End-Stage Liver Disease score, and Child-Pugh score rather than the etiology. After in vitro recombinant interleukin-2 stimulation, the enhancement of expression of cytotoxic molecules, NKp44, and tumor necrosis factor–related apoptosis-inducing ligand was significantly impaired in intrahepatic NK cells from patients with liver failure, concurrently with decreased expression of CD122 and interleukin-2 receptor beta.

Conclusions

Our results suggest that terminal deterioration of liver environments by chronic liver disease impairs the potential of local NK cells, depending on the severity of the deterioration. These influences of advanced liver failure on intrahepatic NK cells may be attributed to multicentric carcinogenesis in patients with liver failure.  相似文献   

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