c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes

The mechanisms of podocyte disorders in cases of idiopathic nephrotic syndrome (INS) are complex and remain incompletely elucidated. The abnormal regulation of NF-κB may play a key role in the pathophysiology of these podocyte diseases, but at present, NF-κB has not been thoroughly investigated. In this study, we report that induction of c-mip in podocytes of patients with INS is associated with a down-regulation of RelA, a potent antiapoptotic factor that belongs to the NF-κB family. Overexpression of c-mip in differentiated podocytes promotes apoptosis by inducing caspase-3 activity and up-regulating the proapoptotic protein Bax, whereas the overall levels of the antiapoptotic protein Bcl-2 was concomitantly decreased. The associated overexpression of RelA prevented the proapoptotic effects of c-mip. In addition, the targeted induction of c-mip in podocytes in vivo inhibited the expression of the RelA protein and increased the Bax/Bcl-2 ratio. The expression of both c-mip and active caspase-3 increased in focal and segmental glomerulosclerosis biopsies, and both proteins displayed a close spatial relationship. These results suggest that alterations in NF-κB activity might result from the up-regulation of c-mip and are likely to contribute to podocyte disorders in cases of INS.     

Human natural killer T cells (NKT), NK and T cells in pulmonary tuberculosis: potential indicators for disease activity and prognosis

One third of the world's population is infected with Mycobacterium tuberculosis (MTB). However, active disease can develop only in a small percentage, when the immunity is weakened. The acquired immune response to MTB is primarily mediated by T cells. Natural killer (NK) cells play a central role in innate immunity to microbial pathogens. Human NKT cells have characteristics of both T and NK cells and also exhibit antimycobacterial activity. This work aimed to enumerate T, NK and NKT cells in active pulmonary TB compared with healthy controls and to study the correlation between these cells with different factors affecting prognosis of pulmonary TB as disease severity, complications or associated diseases, antitubrculosis chemotherapy, and age & gender. Of the 22 active tuberculosis patients examined, 17 were recent cases and 5 recurrent. Healthy controls were divided into 14 individuals with detectable reaction to purified protein derivative (PPD+) and 14 individuals without detectable reaction to PPD-. The percentages of T, NK and NKT cells in erythrocyte-lysed whole blood samples were determined using flowcytometry. The percentage of NKT cells was significantly higher among the recently diagnosed MTB cases as compared with both PPD+ (P < 0.01) and PPD- (P < 0.01) healthy controls, while no significant difference could be found in the percentages of T or NK cells among these groups. However, comparing recurrent cases with recently diagnosed cases showed a significant difference only in the percentage of T cells (P < 0.01). There was also a significant difference in the percentage of T cells according to severity of disease (P < 0.01) and in the association of diabetes mellitus (P < 0.01). Age, gender and treatment with antituberculosis chemotherapy had no effect on the percentages of T, NK or NKT cells. It is concluded that T and NKT cells play an important role in immunity against TB. In active pulmonary tuberculosis, increased T cell count points to severity of the disease, while their reduced count predicts bad prognosis. Human NKT cell count is a marker of disease activity. Enumeration of these cells in peripheral blood can be used as a non-invasive prognostic indicator for patients with active pulmonary TB.     

Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells

Abnormalities in CD4(+)CD25(+)Foxp3(+) regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that expression of CD127, the alpha chain of the interleukin-7 receptor, allows an unambiguous flow cytometry-based distinction to be made between CD127(lo) T reg cells and CD127(hi) conventional T cells within the CD25(+)CD45RO(+)RA(-) effector/memory and CD45RA(+)RO(-) naive compartments in peripheral blood and lymph node. In healthy volunteers, peripheral blood CD25(+)CD127(lo) cells comprised 6.35 +/- 0.26% of CD4(+) T cells, of which 2.05 +/- 0.14% expressed the naive subset marker CD45RA. Expression of FoxP3 protein and the CD127(lo) phenotype were highly correlated within the CD4(+)CD25(+) population. Moreover, both effector/memory and naive CD25(+)CD127(lo) cells manifested suppressive activity in vitro, whereas CD25(+)CD127(hi) cells did not. Cell surface expression of CD127 therefore allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases.     

Getting it right: Educating professionals to work together in improving health and health care

Dedication

This paper is based on a lecture given by LAH as the 2nd John Horder lecture at Imperial College, London on 11 April 2006. Dr. Horder has been influential in improving patient outcomes in multiple ways, including his contributions to professional education. He was instrumental in the development of the Royal College of General Practitioners, serving as president from 1979–1982 and acting as a key leader in establishing post-graduate training for general practitioners in the United Kingdom. Dr Horder went on to found the Centre for the Advancement of Interprofessional Education, in part because of what he observed about the power of interprofessional collaboration in his own primary care practice. It was an honor to give a lecture in tribute to Dr John Horder. It was an opportunity to reflect on what we know about educating health professionals in training about the improvement of health care, including work I've helped to lead in the United States (where I now serve as the Senior Associate Dean for Education at the University of Missouri-Columbia School of Medicine). This paper also is dedicated to Dr. Horder.     

Effectiveness of HIV/STD sexual risk reduction groups for women in substance abuse treatment programs: results of NIDA Clinical Trials Network Trial

CONTEXT: Because drug-involved women are among the fastest growing groups with AIDS, sexual risk reduction intervention for them is a public health imperative. OBJECTIVE: To test effectiveness of HIV/STD safer sex skills building (SSB) groups for women in community drug treatment. DESIGN: Randomized trial of SSB versus standard HIV/STD Education (HE); assessments at baseline, 3 and 6 months. PARTICIPANTS: Women recruited from 12 methadone or psychosocial treatment programs in Clinical Trials Network of National Institute on Drug Abuse. Five hundred fifteen women with >or=1 unprotected vaginal or anal sex occasion (USO) with a male partner in the past 6 months were randomized. INTERVENTIONS: In SSB, five 90-minute groups used problem solving and skills rehearsal to increase HIV/STD risk awareness, condom use, and partner negotiation skills. In HE, one 60-minute group covered HIV/STD disease, testing, treatment, and prevention information. MAIN OUTCOME: Number of USOs at follow-up. RESULTS: A significant difference in mean USOs was obtained between SSB and HE over time (F = 67.2, P < 0.0001). At 3 months, significant decrements were observed in both conditions. At 6 months, SSB maintained the decrease and HE returned to baseline (P < 0.0377). Women in SSB had 29% fewer USOs than those in HE. CONCLUSIONS: Skills building interventions can produce ongoing sexual risk reduction in women in community drug treatment.     

Primary adrenocortical sarcomatoid carcinoma: case report and review of literature

Adrenocortical carcinoma (AC) mixed with a sarcoma or sarcoma-like component is exceptional, and only six cases have been detailed in the literature, three including osteo-, chondro-, or rhabdomyosarcoma components, and three others only showing a malignant spindle cell component. These histological subtypes, respectively called adrenal carcinosarcomas and sarcomatoid AC, represent poorly differentiated and extremely aggressive forms of carcinoma, with locoregional recurrence and metastases rapidly arising from the sarcomatous or sarcomatoid component, and death occurring in a few months. We report a case of AC in a 31-year-old man presenting as a nonfunctional tumor, with a histological biphasic pattern combining few areas of differentiated AC and extensive areas of sarcomatoid spindle cell proliferation. The patient died 3 months of locoregional and distant recurrences after surgery despite apparently total tumor resection and VP16-cisplatinum chemotherapy. This case underlines the necessity to identify and isolate these carcinoma’s subtypes with worse prognosis and the difficulties to distinguish them from metastatic carcinomas and retroperitoneal sarcomas, in relation to the particular adrenal cortex immunoprofile. According to the World Health Organization principles of terminology, we suggest these tumors be collectively classified as “adrenal sarcomatoid carcinomas,” a designation that tends to unify all carcinomas with “pleomorphic, sarcomatoid, or sarcomatous elements.”     

Detection of <Emphasis Type="BoldItalic">Cryptosporidium parvum</Emphasis> and <Emphasis Type="BoldItalic">Cryptosporidium hominis</Emphasis> in human patients in Cairo,Egypt

Cryptosporidium is a significant cause of diarrheal disease in developing and industrialized nations. Cryptosporidium hominis and Cryptosporidium parvum are the main agents of cryptosporidiosis in humans. In Egypt, very little is known about genetic structure of Cryptosporidium spp. Therefore, this study was designed to examine samples from sporadic cases of cryptosporidiosis in Egyptians in order to identify the species involved in infection as well as the transmission dynamics and distribution of the parasite in the Great Cairo area. A total of 391 human faecal samples were collected, between May 2008 and March 2009, from ten public hospitals in Great Cairo. Initial screening by immunochromatographic detection kit “the Stick Crypto-Giardia; Operon” showed 23 possible positive cases. Twenty of them were confirmed by microscopic examination. PCR was performed by amplification of the oocyst wall protein (COWP) gene where 18 out of 23 samples were positive, one not detected by microscopy. Cryptosporidium genotyping was performed by RFLP analysis of PCR products of the diagnosis PCR. Only 15 samples rendered a digestion pattern. The genotyping distribution was nine cases showing C. hominis genotype, three showing C. parvum genotype and three showing mixed infection by C. hominis and C. parvum. The data showed an elevated prevalence of C. hominis (80.0%), the most anthroponotic species, suggesting a human–human transmission. Furthermore, the presence of up to 40% of samples infected with C. parvum shows that further investigations are required to determine the subgenotypes of C. parvum to clarify the mode of transmission in order to improve the control measures.     

Use of Polycaprolactone Electrospun Nanofiber Mesh in a Face Mask

Electrospun nanofiber mesh has previously been used as an air filtration device. However, the qualification of polycaprolactone (PCL) nanofiber mesh cloth in face masks to protect individuals against airborne particles carrying microorganisms has yet to be investigated. The long-term goal of this study is to develop methods to use PCL nanofiber mesh to provide better protection against microorganisms. To achieve this goal, we observed the morphology, water droplet absorption, thermal (differential scanning calorimetry), mechanical, and airborne particle filtering capabilities, and also the microbial activities of a PCL cloth, to evaluate whether it is suitable to act as a filter in a face mask. We have produced a polycaprolactone (PCL) nanofiber cloth after electrospinning it onto a drum for 3 and 10 min, referred to hereafter as PCL-3 and PCL-10, respectively. Our study found that the middle protection layer (control) of the Henry Schein Earloop Procedure Mask contains pores (average diameter = 5.72 ± 0.62 µm) which are 48 times larger than the diameter of a microorganism an average diameter of ~120 nanometers. However, PCL-10 nanofiber membranes show pores with an average diameter of 1.42 ± 0.34 µm. Our contact angle measurement tests found that all the samples were very hydrophobic (contact angle values varied between 120 and 150 degrees). However, both PCL cloths’ contact angle values were lower compared to the control. The produced PCL cloths showed a lower water droplet absorption compared to the control. Thermal studies found that PCL is stable in extreme conditions and no plasticizing effect occurs due to the presence of a solvent. Mechanical tests showed that PCL-10 cloth had higher strength and modulus compared to the control and PCL-3 under tension loading conditions. A vacuum experiment found that the PCL-10 fiber cloth could withstand a negative pressure of 18 Psi without any signs of breakage, and the mask was able to capture airborne particles and microorganisms. The feasibility of immobilizing anti-bacterial nanoparticles with PCL during electrospinning creates the future potential of producing an anti-bacterial face mask using PCL.