Implications of uterine NK cells and regulatory T cells in the endometrium of infertile women

A range of studies have shown that the complex process of implantation and an establishment of a pregnancy also involves immune factors. Disturbances in these underlying immune mechanisms might lead to implantation and pregnancy failure and may be involved in the pathogenesis of unexplained infertility. Several studies have reported that imbalances in uterine NK (uNK) cell abundance are associated with infertility; however, controversies exist. An increased amount of CD56⁺ uNK cells along with a decrease in CD16⁺ uNK cells have been associated with normal fertility in some studies. Very few studies of FoxP3⁺ regulatory T cells (Tregs) in the pre-implantation endometrium have been performed. Results are sparse and controversial, studies reporting both increased and decreased numbers of Tregs, respectively, in women suffering from infertility. In conclusion, studies imply that uNK cells, Tregs and HLA-G carry pivotal roles regarding the establishment of a healthy pregnancy, and that abnormal immune mechanisms involving these parameters may be associated with infertility. However, more research in early phases of the reproductive cycle, such as investigating the conditions in the endometrium before implantation, is needed to further clarify the underlying mechanisms.     

Pulmonary MRI—a new approach for the evaluation of febrile neutropenic patients with malignancies

GOALS OF WORK: Immunocompromised patients with malignant diseases often suffer from pulmonary infections. Early detection of these life-threatening infections is crucial to start effective treatment. The gold standard for the diagnosis of these disorders is high-resolution computed tomography (HR-CT) of the chest. This method, however, has limitations, for instance, in the discrimination of early interstitial infiltrates and the use of X-rays. We conducted a study to determine the feasibility and sensitivity of magnetic resonance imaging (MRI) of the lung compared to HR-CT in immunocompromised patients with persistent fever in neutropenia and suspected pneumonia. MATERIALS AND METHODS: Between January 2003 and July 2004, 50 consecutive neutropenic patients with fever of unknown origin and negative chest X-ray were examined with HR-CT of the lungs. Patients with pulmonary infiltrates were further examined with MRI of the chest within 24 h after HR-CT using a specific lung protocol. In addition, microbiological testing was performed for the characterization of the causative pathogen. RESULTS: Of 50 patients, 35 had pulmonary infiltration according to HR-CT; these were examined with MRI of the lungs. MRI showed a high correlation (91%) with the findings in HR-CT. Both HR-CT and MRI were feasible in 94% of the examined patients. In 12 of 35 patients, fungal pathogens were identified in microbiological testing. CONCLUSIONS: MRI of the lungs is feasible in neutropenic patients with suspected pulmonary infection. Compared to HR-CT, MRI displays a high sensitivity in the detection of pulmonary infiltrates. MRI offers the opportunity of follow-up examinations without repeated X-ray exposure to the patient.     

Preclinical and clinical studies for transplant tolerance via the mixed chimerism approach

Based upon observations in murine models, we have developed protocols to induce renal allograft tolerance by combined kidney and bone marrow transplantation (CKBMT) in non-human primates (NHP) and in humans. Induction of persistent mixed chimerism has proved to be extremely difficult in major histocompatibility complex (MHC)-mismatched primates, with detectable chimerism typically disappearing within 30–60?days. Nevertheless, in MHC mismatched NHP, long-term immunosuppression-free renal allograft survival has been achieved reproducibly, using a non-myeloablative conditioning approach that has also been successfully extended to human kidney transplant recipients. CKBMT has also been applied to the patients with end stage renal disease with hematologic malignancies. Renal allograft tolerance and long-term remission of myeloma have been achieved by transient mixed or persistent full chimerism. This review summarizes the current status of preclinical and clinical studies for renal and non-renal allograft tolerance induction by CKBMT. Improving the consistency of tolerance induction with less morbidity, extending this approach to deceased donor transplantation and inducing tolerance of non-renal transplants, are critical next steps for bringing this strategy to a wider range of clinical applications.     

Aerobic and anaerobic infection associated with malignancy

The goal of this work was to study the microbiology and clinical characteristics of patients with infections associated with malignancy treated over a period of 17 years. A total of 668 specimens were obtained from 605 patients. The malignancies include 224 hematological malignancies and 381 nonhematogenic malignancies. Anaerobic bacteria only were isolated in 201 (30%) specimens, aerobic bacteria in 226 (34%), mixed aerobic–anaerobic bacteria in 231 (35%) and Candida spp. in 10 (1%). A total of 683 anaerobic (1.0 isolates per specimens) and 592 aerobic or facultative (0.9 per specimen) organisms were recovered. The predominant anaerobic bacteria included Bacteroides fragilis group isolates (181), Peptostreptococcus spp. (166), Prevotella spp. (106), Clostridium spp. (70), and Fusobacterium spp. (43). The predominant aerobic bacteria included Escherichia coli (133), Staphylococcus aureus (100), Klebsiella pneumoniae (48), and Pseudomonas aeroginosa (45). The type of infections included abscesses (221), bacteremia (198), wounds (175), including 61 cellulitis, 24 postsurgical wounds and 23 decubitus ulcers), peritonitis (48), empyema (12), cholecystitis (6) and thrombophlebitis (5). S. aureus and Peptostreptococcus spp. were isolated from all sites. However, organisms of the oropharyngeal flora (Prevotella and Fusobacterium spp.) predominated in local infections and bacteremia that originated from this site (head and neck wounds and abscesses and pulmonary infections), and organisms of the gastrointestinal tract flora predominated in infections that originated from this site (peritonitis, abdominal abscesses and decubitus ulcers). This retrospective study demonstrates polymicrobial features of many infections associated with malignancies.     

转化生长因子-β1对瘢痕疙瘩成纤维细胞 SMAD3,7表达的影响

AIM: To study the expression of SMAD3 and SMAD7 of transforming growth factor-β 1 ( TGF-β 1) on keloid- derived fibroblasts. METHODS: The expression of SMAD3 (at 1,2,4,24,48 h)and SMAD7(at 0.5 1,1.5, 2,4,24 h) were detected by using methods of Western blot after 500 pmol/L TGF-β 1 were added to the monolayer culture system.RESULTS: The level of SMAD3 were down regulated at 24 h and the SMAD7 were maximum up regulated at 4 h when TGF-β 1 were used.CONCLUSION: TGF-β 1 may down regulate the expression of SMAD3,but up regulate that of SMAD7 .     

Increased Mortality of Patients With Childhood-Onset Inflammatory Bowel Diseases,Compared With the General Population

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Depressogenic vulnerability and gender-specific patterns of neuro-immune dysregulation: What the ratio of cortisol to C-reactive protein can tell us about loss of normal regulatory control

We examined whether the ratio of cortisol (CORT) to high-sensitivity C-reactive protein (hsCRP), an index that captures the integrity of homeostatic regulation between the hypothalamic–pituitary–adrenal (HPA) axis and inflammatory processes, is associated with vulnerability to depression in a gender specific manner and whether glucocorticoid receptor (GR) sensitivity plays a role in these associations. Fasting blood samples were collected between 08:45 and 09:15 and assayed for CORT, hsCRP, and leukocyte count in 213 healthy, medication-free men and women. The NEO-Personality Inventory was used to assess neuroticism, extraversion and anxiety. We used the Hamilton Depression Interview to assess depressive symptoms, the Buss–Perry anger subscale to measure anger, and the Pittsburgh Sleep Quality Index to evaluate subjective sleep quality and its components. Log-transformed CORT/CRP values were analyzed using multiple regression with Holms’ adjusted p-values and age, body mass index (BMI), and race as covariates. GR sensitivity was estimated using the log-transformed ratio of neutrophils (N)-to-monocytes (M). The log-transformed ratio of CORT/CRP did not differ between men and women but was significantly and negatively associated with age and BMI. Severity of depressive symptoms, extraversion, anxiety, and sleep quality were associated with the CORT/CRP ratio in a gender-specific manner. For women, decreasing CORT/CRP ratios, suggestive of an insufficient release of CORT coupled with a heightened inflammatory state, were associated with increasing severity of depressive symptoms, decreasing quality of sleep, increasing frequency of sleep disturbance, and decreasing extraversion. For men, increasing frequency of daytime disturbance and levels of anxiety were associated with increasing CORT/CRP ratio, suggestive of an enhanced release of CORT relative to attenuated levels of hsCRP. For both genders, increasing anger was associated with decreasing CORT/CRP ratios. Although results suggested GR downregulation in women but not men, such differences did not mediate the observed associations. With the use of the CORT/CRP ratio, we showed that vulnerability factors for depression are associated with a loss of normal regulatory controls resulting in gender-specific patterns of neuro-immune dysregulation. That GR downregulation did not influence these associations suggests that the loss of regulatory controls in at risk individuals is primarily at the level of the hormone. Beyond the individual contribution of each component of the CORT/CRP ratio, disruption of normal neuroimmune regulatory feedback provides a plausible biological framework useful in understanding biobehavioral vulnerabilities to depression in a gender specific manner. The CORT/CRP ratio may be a viable biomarker not only for delineating risk for MDD but also progression and treatment responses among patients with MDD; possibilities that are testable in future studies.