Maintenance of CD8+ memory T lymphocytes in the spleen but not in the bone marrow is dependent on proliferation

It is current belief that numbers of CD8⁺ memory T lymphocytes in the memory phase of an immune response are maintained by homeostatic proliferation. Here, we compare the proliferation of CD8⁺ memory T lymphocytes, generated by natural infections and by intentional immunization, in spleen and bone marrow (BM). Fifty percent of CD8⁺ memory T lymphocytes in the spleen are eliminated by cyclophosphamide within 14 days, indicating that numbers of at least 50% of splenic CD8⁺ memory T lymphocytes are maintained by proliferation. The numbers of CD8⁺ memory T lymphocytes in the BM, however, were not affected by cyclophosphamide. This stability was independent of circulating CD8⁺ memory T cells, blocked by FTY720, showing that BM is a privileged site for the maintenance of memory T lymphocytes, as resident cells, resting in terms of proliferation.     

Necrotizing enterocolitis: early conventional and fluorescein laparoscopic assessment

Aim

The clinical and radiological diagnosis of necrotizing enterocolitis (NEC) can be difficult. When radiological evidence is present, severity and complications, such as perforation and full-thickness necrosis, often may not be obvious. This study aims to establish early signs of full-thickness necrosis or perforation by using standard and fluorescein laparoscopy before clinical deterioration of patients occurs.

Patients and Methods

Thirteen patients with preoperative presumed clinical and/or radiological diagnosis of NEC underwent laparoscopy. A 4.7-mm umbilical or left upper quadrant camera port was inserted by using the open method. The abdominal cavity was inspected for bowel ischemia, fibrin, adhesion formation, and presence of free intestinal contents. If necessary, one or two 3-mm working ports were inserted for manipulation of bowel.

Results

Median age of 13 patients was 17 (3-38) days. Their median weight was 1160 (910-2415) g. The first 5 infants had standard laparoscopy only, with the next 8 having fluorescein-aided assessment added to the laparoscopy. Standard laparoscopy identified perforation in 5 patients and gangrenous bowel in 2. One patient was found to have chyle ascites, and 1 patient had no abnormal findings on laparoscopy. Fluorescein identified gangrenous bowel in 3 additional patients. Laparotomy and necessary surgical intervention were performed in all 10 patients with positive laparoscopy findings. Eleven patients survived and were doing well at a median of 9 (range, 6-39) months of follow-up.

Conclusion

Laparoscopy helps to improve assessment of patients with a diagnosis of NEC. It allows for early identification of perforation and necrosis. Where ischemia is suspected, fluorescein laparoscopy may have an added benefit in identifying necrotic segments.     

An awl inflicted chest wound causing acute myocardial infarction

Penetrating chest wounds are frequent. When involving the heart, they usually cause tamponade. In our case, caused by an awl, laceration of the LAD occured without intrapericardial bleeding. The coronary angiography demonstrates the damage to the wall of the LAD.     

An interactive teaching device simulating intussusception reduction

Intussusception is relatively uncommon, occurring in 0.5 to 2.3 cases per 1,000 live births in the USA. Radiology residents, therefore, have few opportunities to participate in intussusception reduction during training, and practicing radiologists encounter it infrequently. Training is essential, as successful reduction avoids surgery. The judgment involved in reducing an intussusception is best gained with experience. We developed a training device that simulates fluoroscopic intussusception reduction with air. The device consists of a doll that contains a cylinder with similar stress and strain characteristics to the human colon. The trainee pumps air into the cylinder through a rectal tube using a standard hand-held air reduction pump. A sensor measures the pressure within the chamber and transmits readings to a computer, which displays images from actual intussusception reductions based on the pressure maintained within the device. A random component in the software gives the user a new experience each time and models uncertainties in the actual reduction process, including perforation. This intussusception reduction simulator can enhance resident education, giving residents the opportunity to practice this technique before employing it on a real patient. The simulator can also help practicing radiologists become more comfortable with intussusception air reduction.     

Effectiveness of a structured diet program in antipsychotic-induced weight gain in patients with schizophrenia

Objective.The aim of this study was to evaluate the effectiveness of a structured diet program in weight loss in patients with schizophrenia. Methods. A total of 38 outpatients diagnosed with schizophrenia according to DSM-IV and who had complaints of weight gain during treatment with various antipsychotic drugs were invited to participate in a 3-month structured diet program. Thirty-two patients and another 40 patients were included as the control group. At the beginning of the diet program, the patients were given a form in order to evaluate their eating habits, and blood samples were taken to measure plasma lipid profile, and fasting blood glucose (FBG) level. Patients’ baseline weight, body mass index (BMI), and basal metabolism rate (BMR) were recorded. Results. Thirty-two patients with schizophrenia, who attended a 3-month structured diet program had mean weight loss of 6.19 kg, whereas patients in the control group gained 1.6 kg. Conclusion. Our findings show that a diet program is effective in managing antipsychotic-induced weight gain. The degree of weight loss seems to be correlated with the duration in which the patient is on the diet program. However; younger patients had less benefit from the diet program.     

TRAIL-R2 promotes skeletal metastasis in a breast cancer xenograft mouse model

Despite improvements in detection, surgical approaches and systemic therapies, breast cancer remains typically incurable once distant metastases occur. High expression of TRAIL-R2 was found to be associated with poor prognostic parameters in breast cancer patients, suggesting an oncogenic function of this receptor. In the present study, we aimed to determine the impact of TRAIL-R2 on breast cancer metastasis. Using an osteotropic variant of MDA-MB-231 breast cancer cells, we examine the effects of TRAIL-R2 knockdown in vitro and in vivo. Strikingly, in addition to the reduced levels of the proliferation-promoting factor HMGA2 and corresponding inhibition of cell proliferation, knockdown of TRAIL-R2 increased the levels of E-Cadherin and decreased migration. In vivo, these cells were strongly impaired in their ability to form bone metastases after intracardiac injection. Evaluating possible underlying mechanisms revealed a strong downregulation of CXCR4, the receptor for the chemokine SDF-1 important for homing of cancers cells to the bone. In accordance, cell migration towards SDF-1 was significantly impaired by TRAIL-R2 knockdown. Conversely, overexpression of TRAIL-R2 upregulated CXCR4 levels and enhanced SDF-1-directed migration. We therefore postulate that inhibition of TRAIL-R2 expression could represent a promising therapeutic strategy leading to an effective impairment of breast cancer cell capability to form skeletal metastases.