Accelerated apoptosis and low Bcl-2 expression associated with neuroendocrine differentiation predict shortened survival in operated large cell carcinoma of the lung

In order to test the hypothesis that increased apoptotic activity is connected with neuroendocrine differentiation and low differentiation degree in large cell carcinoma (LCLC) and is regulated by bcl-2 family proteins, we analysed the extent of apoptosis and tumor necrosis and their relation to the expression of bcl-2, bax, bak and mcl-1 in 35 LCLCs, of which 20 were classified as large cell neuroendocrine lung carcinomas (LCNEC) and 15 as large cell non-neuroendocrine lung carcinomas (LCNNEC). The extent of apoptosis was determined by detecting and counting the relative and absolute numbers of apoptotic cells and bodies using in situ 3′-end labelling of the apoptotic DNA. The extent and intensity of expression of the bcl-2, bax, bak and mcl-1 proteins were studied by immunohistochemistry. Also the relative volume density of necrosis was evaluated and correlated with the other parameters. Finally, all the parameters were evaluated as prognostic markers and correlated with data on the survival of the patients. Relatively high apoptotic indices were seen in both tumor types (average for both 2.53%, range 0.09–27.01%). Significantly higher bcl-2 and bak indices were detected more often in LCNECs than in LCNNECs. Immunohistochemically detected bax, bcl-2 and bak expression was independent of apoptotic index in both tumor types, while there was a statistically significant positive association between mcl-1 expression and apoptotic index in LCNNEC but not in LCNEC. There was a statistically significant association between high apoptotic index and shortened survival in LCLC. However, no association was found between tumor stage and apoptosis. The patients with LCNEC and low bcl-2 protein expression had a significantly shorter survival time than those with high bcl-2 indices. There was also a clear association between shortened survival and necrotic LCNNEC. LCLCs show relatively high apoptotic activity, which is associated with shortened survival. The expression of bcl-2, bak and mcl-1 is associated with neuroendocrine differentiation in LCLC. Finally, our results support some previous reports suggesting that bcl-2 expression in combination with some other markers involved in apoptosis and/or proliferation may be of prognostic value in cases of lung carcinoma with neuroendocrine differentiation. 179-186, 1999)     

Screening migrants for tuberculosis - a missed opportunity for improving knowledge and attitudes in high-risk groups: A cross-sectional study of Swedish-language students in Umeå, Sweden

Background  

Migrants from countries with a high-burden of tuberculosis (TB) are at a particular risk of contracting and developing the disease. In Sweden, new immigrants are routinely offered screening for the disease, yet very little is known about their beliefs about the disease which may affect healthcare-seeking behaviours. In this study we assessed recent immigrant students' knowledge of, and attitudes towards TB, and their relationship with the screening process.     

DNA AMPLIFICATION OF A REPETITIVE SEQUENCE - IS 6110 IN THE EARLY DIAGNOSIS OF EXTRA PULMONARY TUBERCULOSIS

DNA amplification by Polymerase Chain Reaction (PCR) of a repetitive sequence specific for Mycobacterium tuberculosis, from clinical samples of extra pulmonary origin were evaluated. The 123 base pair fragment of the insertion element IS 6110 in Mycobacterium tuberculosis was amplified. A total of 50 samples were analysed by PCR and compared with culture on Lowenstein-Jensen medium (LJ) and the clinical findings of the patient. Out of the total 26 samples were positive by PCR, while only seven grew the bacilli in culture. 24 samples were negative by PCR and culture. All the seven samples that grew the bacilli on culture were positive by PCR. In remaining 19 cases that were positive by PCR but did not grow the bacilli clinical features, radiological findings and Mantoux test were strongly suggestive of M. tuberculosis. All the amplification negative cases had no positive evidence of tuberculosis but were being followed up. When correlated with culture and clinical history the sensitivity of PCR for the diagnosis of active tuberculosis was 100%. However, the specifity was only 55.8% as culture on LJ (Gold Standard) was positive in only 7 samples out of 26 samples that were positive by PCR.KEY WORDS: DNA Amplification, IS 6110, Mycobacterium tuberculosis.     

美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

Xenophagy in Helicobacter pylori‐ and Epstein–Barr virus‐induced gastric cancer

Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd     

Newborn primate infants are entrained by low intensity lighting

At the present time we do not know when the circadian timing system of human infants becomes responsive to light. Because of human study limitations, it is not currently possible to address this issue in clinical studies. Therefore, to provide insights into when the circadian system of humans becomes responsive to light, baboons were studied. We first assessed if the biological clock located in suprachiasmatic nuclei (SCN) is responsive to light at birth. When term newborn infants were exposed to bright light at night (5000 lux), SCN metabolic activity and c-fos mRNA expression increased, indicating the presence of photic responsiveness. When photic entrainment of developing rhythmicity was examined in infants, low intensity (200 lux) cycled lighting was sufficient to entrain circadian phase. However, low intensity lighting was not sufficient to induce changes in SCN metabolic activity or c-fos mRNA expression. Phase–response studies indicated that light exposure (200 lux) before the onset of activity most effectively shifted circadian phase. These data provide direct evidence that the SCN are responsive to visually mediated light information in a primate at birth. Further consideration of lighting conditions that infants are exposed to is therefore warranted.     

Lactation Duration: Influences of Human Milk Replacements and Formula Samples on Women Planning Postpartum Employment

Objective: To examine the influences of i hospital administration of breast milk replacement and receipt of formula samples on lactation duration among women planning postpartum employment.
Design: Prospective design.
Setting: Telephone interviews conducted prenatally and at 6 weeks, 3 months, and 6 months postpartum.
Participants: Sixty-nine participants entered the study; 53 completed all scheduled interviews.
Main Outcome Measures: Incidence and type. of in-hospital human milk replacement, incidence ar sources of formula samples, incidence of breastfeeding at 6 weeks postpartum, and duration of lactation.
Results: During hospitalization, 19% of in fants received formula; the incidence of breastfeeding at 6 weeks and duration of breastfeeding were significantly shorter in these infants compared with infants who were not fed formula. Fifty-nine percent of participants received formula samples from the hospital, 30% received samples from a physician's office, and 51% received samples by mail Receipt of formula samples by mail was associate with reduced incidence of breastfeeding at 6 weeks and shortened duration of lactation.
Conclusions: Early formula feeding and receipt of formula samples by mail may be barriers I lactation in women employed outside the home.