Differential requirements for IRF4 in the clonal expansion and homeostatic proliferation of naive and memory murine CD8+ T cells

Interferon regulatory factor 4 (IRF4) has critical roles in immune cell differentiation and function and is indispensable for clonal expansion and effector function in T cells. Here, we demonstrate that the AKT pathway is impaired in murine CD8⁺ T cells lacking IRF4. The expression of phosphatase and tensin homolog (PTEN), a negative regulator of the AKT pathway, was elevated in Irf4^?/? CD8⁺ T cells. Inhibition of PTEN partially rescued downstream events, suggesting that PTEN constitutes a checkpoint in the IRF4‐mediated regulation of cell signaling. Despite the clonal expansion defect, in the absence of IRF4, memory‐like CD8⁺ T cells could be generated and maintained, although unable to expand in recall responses. The homeostatic proliferation of naïve Irf4^?/? CD8⁺ T cells was impaired, whereas their number eventually reached a level similar to that of wild‐type CD8⁺ T cells. Conversely, memory‐like Irf4^?/? CD8⁺ T cells underwent homeostatic proliferation in a manner similar to that of wild‐type memory CD8⁺ T cells. These results suggest that IRF4 regulates the clonal expansion of CD8⁺ T cells at least in part via the AKT signaling pathway. Moreover, IRF4 regulates the homeostatic proliferation of naïve CD8⁺ T cells, whereas the maintenance of memory CD8⁺ T cells is IRF4‐independent.     

Outcomes of pregabalin in lumbar-disease patients with depression

Background

The anti-seizure drug pregabalin is currently used for peripheral neuropathic pain, including degenerative lumbar disease with a neuropathic component. Although there are many reports associated with pregabalin, treatment outcome in low back pain (LBP) patients with depression remains uncertain. This study investigated the outcomes of pregabalin in LBP patients with depression.

Methods

We assessed 64 patients (29 men and 35 women) using a Visual Analogue Scale, a Self-Rating Depression Scale (SDS) and the Oswestry Disability Index (ODI). Mean age was 63.3 years (range 20–81), and mean duration of disease was 69.8 months (range 3–576). The patients were divided into two groups according to SDS: normal (n = 37) and depressed group (n = 27).

Results

Pregabalin significantly reduced both SDS and ODI in the depressed group (p < 0.05). Effect size was larger for both SDS and ODI in the depressed group than in the normal group. Pain was significantly relieved, even in the depressed group (p < 0.01). Pain reduction was achieved by the direct effect of pregabalin, as well as indirect effects attributed to change in depressive symptoms. Although both somnolence and dizziness were detected, the use of hypnotic agents was decreased in half of cases. Somnolence did not influence the analgesic effects of the drug or psychotic state.

Conclusions

This investigation indicated that pregabalin is safe and effective for reducing both LBP and mood disturbance in patients with depression.     

In vivo kinematics of a robot-assisted uni- and multi-compartmental knee arthroplasty

Background

There is great interest in providing reliable and durable treatments for one- and two-compartment arthritic degeneration of the cruciate-ligament intact knee. One approach is to resurface only the diseased compartments with discrete unicompartmental components, retaining the undamaged compartment(s). However, placing multiple small implants into the knee presents a greater surgical challenge than total knee arthroplasty, so it is not certain that the natural knee mechanics can be maintained or restored. The goal of this study was to determine whether near-normal knee kinematics can be obtained with a robot-assisted multi-compartmental knee arthroplasty.

Methods

Thirteen patients with 15 multi-compartmental knee arthroplasties using haptic robotic-assisted bone preparation were involved in this study. Nine subjects received a medial unicompartmental knee arthroplasty (UKA), three subjects received a medial UKA and patellofemoral (PF) arthroplasty, and three subjects received medial and lateral bi-unicondylar arthroplasty. Knee motions were recorded using video-fluoroscopy an average of 13 months (6–29 months) after surgery during stair and kneeling activities. The three-dimensional position and orientation of the implant components were determined using model-image registration techniques.

Results

Knee kinematics during maximum flexion kneeling showed femoral external rotation and posterior lateral condylar translation. All knees showed femoral external rotation and posterior condylar translation with flexion during the step activity. Knees with medial UKA and PF arthroplasty showed the most femoral external rotation and posterior translation, and knees with bicondylar UKA showed the least.

Conclusions

Knees with accurately placed uni- or bi-compartmental arthroplasty exhibited stable knee kinematics consistent with intact and functioning cruciate ligaments. The patterns of tibiofemoral motion were more similar to natural knees than commonly has been observed in knees with total knee arthroplasty. Larger series are required to confirm these as general observations, but the present results demonstrate the potential to restore or maintain closer-to-normal knee kinematics by retaining intact structures and compartments.     

Laparoscopic diagnosis and treatment of a hydrocele of the canal of Nuck extending in the retroperitoneal space: A case report

INTRODUCTION

Hydrocele of the canal of Nuck is a rarely encountered entity. We report a case underwent laparoscopic totally extraperitoneal (TEP) treatment for a hydrocele of the canal of Nuck extending in the extraperitoneal space mainly.

PRESENTATION OF CASE

A 37-year-old woman complained of painless and reducible swelling in her left groin, and referred to our hospital for surgical management against left inguinal hernia with the incarcerated ovary. Ultrasonography and MR images revealed a cystic mass in the retroperitoneal space, and we diagnosed as an unusual type of hydrocele of the canal of Nuck. The patient was scheduled for laparoscopic treatment. Laparoscopic findings on pneumoperitoneum showed an extraperitoneal cystic tumor with no contact with the left ovary. The fascia and peritoneum of the port site were closed, and then an extraperitoneal space was created. The cystic tumor with the round ligament of the uterus was dissected and resected by the TEP technique. The extended deep inguinal ring was repaired with polypropylene mesh. Postoperative course was uneventful.

DISCUSSION

Hydrocele of the canal of Nuck in the adult female is a rare condition. The accurate diagnosis of an inguinal hydrocele in a female is seldom made. Laparoscopic examination provides surgeons with information of inguinal swelling accompanied with retroperitoneal cyst, and consecutive treatment by laparoscopic technique, especially TEP, is useful in regard to minimal damage of the peritoneum.

CONCLUSION

Laparoscopic diagnosis and TEP treatment offers a useful alternative in selected patients with hydrocele of the canal of Nuck.     

α1‐Syntrophin–deficient mice exhibit impaired muscle force recovery after osmotic shock

Introduction: α1‐syntrophin, a member of the dystrophin complex, recruits membrane molecules, including aquaporin‐4, at the sarcolemma. The physiological functions of α1‐syntrophin are poorly understood. Methods: We examined the physiological characteristics of α1‐syntrophin–deficient muscles under osmotic stress conditions to test the possibility that mutant muscles are less tolerant of osmotic shock. Results: Isolated muscle bundles from mutant mice showed markedly reduced force production after hypo‐osmotic shock. In addition, the mutant muscle bundles showed delayed recovery of specific gravity after being exposed to hypo‐osmotic conditions. Two consecutive exercise tests on the treadmill revealed their performance in the second test was significantly lower than for wild‐type mice. Furthermore, mutant mice had higher serum lactate concentrations after treadmill exercise. Conclusions: Although the lack of α1‐syntrophin from the sarcolemma does not lead to muscle degeneration, our results suggest that it may be partly involved in the pathophysiology of dystrophin‐deficient Duchenne muscular dystrophy. Muscle Nerve 49 : 728–735, 2014     

Hepatic pseudolymphoma: imaging–pathologic correlation with special reference to hemodynamic analysis

Objectives

To clarify radiological findings and hemodynamic characteristics of hepatic pseudolymphoma, as compared with the histopathological findings.

Methods

Radiological findings of ten histopathologically confirmed hepatic pseudolymphomas in seven patients were examined using US, CT, and MRI. Six patients also underwent angiography-assisted CT, including CT during arterial portography (CTAP) and CT during hepatic arteriography (CTHA) to analyze hemodynamics.

Results

The nodules were depicted as hypoechoic on US, hypodense on precontrast CT, hypointense on T1-weighted images, and hyperintense on T2-weighted images. On contrast-enhanced CT/MRI, they showed various degrees of enhancement, and sometimes, perinodular enhancement was observed at the arterial dominant and/or equilibrium phase. On CTAP, the nodules showed portal perfusion defects, including some in the perinodular liver parenchyma. On CTHA, irregular bordered enhancement was observed in perinodular liver parenchyma on early phase, and continued until delayed phase. Some nodules had preserved intra-tumoral portal tracts. Histopathologically, the nodules consisted of marked lymphoid cells. In perinodular liver parenchyma, stenosis or disappearance of portal venules, caused by lymphoid cell infiltration in the portal tracts, was observed.

Conclusions

Hepatic pseudolymphoma showed some characteristic radiological findings including hemodynamics on CT, MRI, and angiography-assisted CT. These findings are useful in the differentiation from hepatocellular carcinoma and other tumors.     

Confluent hepatic fibrosis in liver cirrhosis: possible relation with middle hepatic venous drainage

Purpose

Our aim was to retrospectively analyze the location of confluent hepatic fibrosis in relation to the portal and hepatic venous anatomy using multidetector computed tomography (CT) and to clarify the influence of the hepatic venous drainage on confluent fibrosis.

Materials and methods

The study population consisted of 879 patients diagnosed with cirrhosis: 539 men and 340 women (65.9 ± 10.6 years) and 633 with Child-Pugh class A, 161 with class B, and 85 with class C. The cause of cirrhosis was hepatitis C (n = 528) and hepatitis B (n = 122) virus infection, alcoholism (n = 114), and others (n = 115). The confluent fibrosis was diagnosed using CT images according to previous reports and statistically analyzed (p < 0.05).

Results

Thirty-five confluent fibrosis lesions in 30 patients (3.4 %) were identified. The predictive factors were alcoholic cirrhosis [odds ratio (OR), 7.25; p < 0.0001], Child-Pugh class C (OR, 6.95; p < 0.0001), and Child-Pugh class B (OR, 2.91; p < 0.0023). Confluent fibrosis was most frequently seen in the middle hepatic venous drainage area (n = 21) or at the boundary between the medial and anterior segments (n = 17), and each distribution of the location of confluent fibrosis was significantly unequal (p < 0.0001).

Conclusion

Confluent fibrosis was most commonly located in the middle hepatic venous drainage area.     

Cellular and molecular mechanisms of various types of oocyte aging

It is well established that age-related decline of a woman's fertility is related to the poor developmental potential of her gametes. The age-associated decline in female fertility is largely attributable to the oocyte aging caused by ovarian aging. Age-associated oocyte aging results in a decrease in oocyte quality. In contrast to ovarian aging, there is a concept of postovulatory oocyte aging. Postovulatory aging of oocytes, not being fertilized for a prolonged time after ovulation, is known to significantly affect the development of oocytes. Both categories of oocyte aging have similar phenotypes of reproductive failure. However, the mechanisms of the decline in oocyte quality are not necessarily equivalent. An age-dependent increase in aneuploidy is a key determinant of oocyte quality. The reduced expression of molecules regulating cell cycle control during meiosis might be involved in the age-dependent increase in aneuploidy. The mechanism of age-associated oocyte aging might be involved in mitochondrial dysfunction, whose etiologies are still unknown. Alternatively, the mechanism of postovulatory oocyte aging might be involved in reactive oxygen species-induced mitochondrial injury pathways followed by abnormal intracellular Ca²⁺ regulation of the endoplasmic reticulum. We suggest that future research into the mechanism of oocyte aging will be necessary to develop a method to rescue the poor developmental potential of aged oocytes.