CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza

Summary: We have outlined the carefully orchestrated process of CD4⁺ T‐cell differentiation from naïve to effector and from effector to memory cells with a focus on how these processes can be studied in vivo in responses to pathogen infection. We emphasize that the regulatory factors that determine the quality and quantity of the effector and memory cells generated include (i) the antigen dose during the initial T‐cell interaction with antigen‐presenting cells; (ii) the dose and duration of repeated interactions; and (iii) the milieu of inflammatory and growth cytokines that responding CD4⁺ T cells encounter. We suggest that heterogeneity in these regulatory factors leads to the generation of a spectrum of effectors with different functional attributes. Furthermore, we suggest that it is the presence of effectors at different stages along a pathway of progressive linear differentiation that leads to a related spectrum of memory cells. Our studies particularly highlight the multifaceted roles of CD4⁺ effector and memory T cells in protective responses to influenza infection and support the concept that efficient priming of CD4⁺ T cells that react to shared influenza proteins could contribute greatly to vaccine strategies for influenza.     

Tales of tails: regulation of telomere length and telomerase activity during lymphocyte development, differentiation, activation, and aging

Summary: Telomerase activity and the regulation of telomere length are factors which have been implicated in the control of cellular replication. These variables have been examined during human lymphocyte development, differentiation, activation, and aging. It was found that telomere length of peripheral blood CD4⁺ T cells decreases with age as well as with differentiation from naive to memory cells in vivo , and decreases with cell division in vitro. These results provide evidence that telomere length correlates with lymphocyte replicative history and residual replicative potential. In contrast, telomere length appears to increase during tonsil B-cell differentiation and germinal center (GC) formation in vivo. It was also found that telomerase activity is highly regulated during T-cell development and B-cell differentiation in vivo , with high levels of telomerase activity expressed in thymocytes and GC B cells, and low levels of telomerase activity in resting mature peripheral blood lymphocytes. Finally, resting lymphocytes retain the ability to upregulate telomerase activity upon activation, and this capacity does not appear to decline with age. Although the precise role of telomerase in lymphocyte function remains to be elucidated, telomerase may contribute to protection from telomere shortening in T and B lymphocytes, and may thus play a critical role in lymphocyte development, differentiation and activation. The future study of study telomerase and its regulation of telomere length may enhance our understanding of bow the replicative lifespan is regulated in lymphocytes.     

北京地区精神分裂症患者家属情感表达测查报告

目的;探讨北京地区的住院精神分裂症患者家属情感表达方式及测查方法的实用性、测查工具应用的一致性。方法：经过训练的研究人员,采用费氏修订的ＣＦＩ－ＣＶ访谈提纲,对１７１例住院精神分裂症患者家庭的２８４位家属进行访谈和录音,并将录音打印成文字资料。     

An acute pleuropneumonia in a pig caused by Chromobacterium violaceum

A 2.5-month-old, 30 kg Duroc pig died 10 days after showing clinical signs of dyspnoea and diarrhoea. Acute necrotizing and fibrinous pleuropneumonia with locally extensive lesions was found. Chromobacterium violaceum was isolated from pneumonic lung tissues and intratracheal inoculation of a pure culture into two SPF pigs reproduced lesions similar to those found in the natural infection.     

Protein synthesis inhibition blocks the late-phase LTP of C-fiber evoked field potentials in rat spinal dorsal horn

Previous studies have demonstrated that in the hippocampus the maintenance of long-term potentiation (LTP) requires de novo protein synthesis. To investigate the role of protein synthesis in the maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn, which may be relevant to hyperalgesia, protein synthesis inhibitor (either cycloheximide or anisomycin) was applied locally to the recording segments of spinal cord in anesthetized rats, 30 min prior to tetanic stimulation to the sciatic nerve. We found that both cycloheximide and anisomycin selectively inhibited late-phase maintenance of the spinal LTP but affected neither LTP induction nor baseline responses of C-fiber evoked field potentials. In the presence of cycloheximide, LTP of C-fiber evoked field potentials was 281.5 +/- 16.5% (n = 6) of baseline 1 h after tetanic stimulation and the potentiation significantly decreased to 235.5 +/- 18.5% at 145 min after tetanic stimulation (P < 0.05). Afterward, LTP of C-fiber evoked field potentials decreased continuously and at 270 min after tetanic stimulation reached 130.8 +/- 18.0%, which was no longer different from baseline (P > 0.05). Spinal application of anisomycin at 30 min before tetanic stimulation yielded similar results (n = 6). These results suggest that protein synthesis may be crucial for the late-phase maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn.     

Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways

We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS-associated coronavirus (SARS-CoV). In the present study, we used a murine monoclonal antibody specific for SARS-CoV nucleoprotein, and probes specific for a SARS-CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS-CoV systematically in tissues from patients who died of SARS. SARS-CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS-CoV may also be targets of SARS-CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS-CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS-CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS-CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS.     

Comparison of risk estimates using life-table methods

Risk estimates promulgated by various radiation protection authorities in recent years have become increasingly more complex. Early "integral" estimates in the form of health effects per 0.01 person-Gy (per person-rad) or per 10(4) person-Gy (per 10(6) person-rad) have tended to be replaced by "differential" estimates which are age- and sex-dependent and specify both minimum induction (latency) and duration of risk expression (plateau) periods. These latter types of risk estimate must be used in conjunction with a life table in order to reduce them to integral form. In this paper, the life table has been used to effect a comparison of the organ and tissue risk estimates derived in several recent reports. In addition, a brief review of life-table methodology is presented and some features of the models used in deriving differential coefficients are discussed. While the great number of permutations possible with dose-response models, detailed risk estimates and proposed projection models precludes any unique result, the reduced integral coefficients are required to conform to the linear, absolute-risk model recommended for use with the integral risk estimates reviewed.     

Research trends of prostatitis over past 20 years: A bibliometric analysis

In the past two decades, thousands of documents in the field of prostatitis have been published. This bibliometric analysis aimed to assess the characteristics, hotspots and frontiers trend of global scientific output on prostatitis. With the trend of moderate growth, altogether 2,423 papers were reviewed. The leading role of the United States in global prostatitis research was obvious, while China had developed rapidly in recent years. Queen's University and JOURNAL OF UROLOGY were the most prolific affiliation and journal respectively. Nickel, J. C made the greatest contribution to the field of prostatitis. Five hotspots have been confirmed: (a) male infertility associated with prostatitis and the molecular mechanisms; (b) diagnosis and treatment of prostatitis; (c) inflammation, pain and bladder irritation symptoms; (d) relationship between chronic prostatitis/chronic pelvic pain syndrome, benign prostatic hyperplasia and prostate cancer; (e) epidemiology, complications of prostatitis and improvement of acupuncture. This bibliometric analysis reveals that the international cooperation was becoming more and more close. Hotspot analysis shows that the molecular mechanism of prostatitis will be a hotspot in the future, mainly focussing on inflammatory immunity and oxidative stress.     

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.