Autooxidation as a basis for altered function by polymorphonuclear leukocytes

To investigate the possibility that human polymorphonuclear leukocytes (PMN) elaborate sufficient amounts of hydrogen peroxide (H2O2) and other radicals of reduced oxygen to be autotoxic and retard directed cell movement and phagocytosis, the rate of ingestion of opsonized lipopolysaccharide-paraffin oil particles and movement through Nuclepore filters were studied. Ingestion rates were increased under anaerobic conditions and in normal aerobic conditions in the presence of extracellular catalase but not superoxide dismutase (SOD) or scavengers of singlet oxygen or hydroxyl radicals. Conversely, ingestion rates were decreased when cells were exposed to H2O2 or a superoxide anion (O2-)-H2O2 generating system of xanthine-xanthine oxidase. Catalase, but not SOD, prevented the effect and also enhanced the directed movement of PMN in normal aerobic conditions. PMN from volunteers administered 1600 U/day of the membrane lipid antioxidant alpha-tocopherol were hyperphagocytic but killed Staphylococcus aureus 502A less effectively than controls, suggesting that less H2O2 was available to damage PMN or kill bacteria. H2O2-dependent stimulation of the hexose monophosphate shunt, H2O2 release from phaogytizing PMN, and fluoresceinated concanavalin A cap formation promoted by H2O2 damage to microtubules were all diminished, but the release of O2- from phagocytizing PMN was not diminished in the vitamin E group. These results support the hypothesis that directed movement and phagocytosis by PMN are attenuated by autooxidative damage to the cell membrane by endogenously derived H2O2 and that the administration in vivo of vitamin E may prevent this damage by scavenging H2O2.     

胃癌相关基因在癌前病变中的表达

目前认为癌的形成过程是多阶段、多过程的,包括多个连续的独立的事件,是多个遗传物质即基因积累改变的结果．与胃癌发生、发展有关的基因有3种：癌基因、抑癌基因、程序死亡基因．原癌基因的激活和抑癌基因的失活可使细胞增生,程序死亡基因的失活可能使细胞永生化,在胃癌的发生、发展的各个阶段,至少有两种以上的基因突变,他们各自发挥不同作用．研究胃癌相关基因在癌前病变中的表达,总结基因改变在癌变过程中的作用和地位．可以从分子水平揭开胃黏膜癌变的本质,进而明确胃癌发生、发展的分子机制．     

Direct comparison by limiting dilution analysis of long-term culture- initiating cells in human bone marrow, umbilical cord blood, and blood stem cells

Limiting-dilution analysis of long-term culture-initiating cells (LTCIC) is a quantitative method of estimating hematopoietic stem cell activity in clinical samples. We compared the numbers of LTCIC in bone marrow (BM), umbilical cord blood, and blood progenitor cells (obtained from patients with solid tumors at leukapheresis after mobilization with induction chemotherapy and filgrastim administration), using a two- stage long-term culture system and a limiting-dilution technique, scoring cobblestone areas of greater than 15 hematopoietic cells weekly for up to 8 weeks. Samples were obtained from 30 normal BMs, 20 human umbilical cords, and 32 leukapheresis products. Direct comparison of LTCIC in the three sources showed that the median proportions of cells generating hematopoietic foci from unfractionated mononuclear cells at 5 and 8 weeks, respectively, were 1:13,314 and 1:33,949 for BM, 1:12,506 and 1:34,546 for umbilical cord blood, and 1:10,302 and 1:12,891 for leukapheresis product. The estimated proportions of LTCIC from unfractionated mononuclear cells and CD34+ cells were similar in experiments with leukapheresis product. Leukapheresis product was superior to umbilical cord blood and cord blood to BM at 5 and 8 weeks of culture (P = .01). In two-stage long-term cultures, more colonies per flask and CD34+ cells were found in assays of leukapheresis product than in BM or umbilical cord blood cultures (P = .0005). Results obtained by this simplified limiting-dilution analysis correlated well with standard long-term cultures and can be used as a measure of the stem cell population. These data suggest that the incidence of putative stem cells in leukapheresis product and umbilical cord blood are at least comparable with that of BM.     

Assessing the potential for improvement of primary care in 34?countries: a cross-sectional survey

Objective

To investigate patients’ perceptions of improvement potential in primary care in 34 countries.

Methods

We did a cross-sectional survey of 69 201 patients who had just visited general practitioners at primary-care facilities. Patients rated five features of person-focused primary care – accessibility/availability, continuity, comprehensiveness, patient involvement and doctor–patient communication. One tenth of the patients ranked the importance of each feature on a scale of one to four, and nine tenths of patients scored their experiences of care received. We calculated the potential for improvement by multiplying the proportion of negative patient experiences with the mean importance score in each country. Scores were divided into low, medium and high improvement potential. Pair-wise correlations were made between improvement scores and three dimensions of the structure of primary care – governance, economic conditions and workforce development.

Findings

In 26 countries, one or more features of primary care had medium or high improvement potentials. Comprehensiveness of care had medium to high improvement potential in 23 of 34 countries. In all countries, doctor–patient communication had low improvement potential. An overall stronger structure of primary care was correlated with a lower potential for improvement of continuity and comprehensiveness of care. In countries with stronger primary care governance patients perceived less potential to improve the continuity of care. Countries with better economic conditions for primary care had less potential for improvement of all features of person-focused care.

Conclusion

In countries with a stronger primary care structure, patients perceived that primary care had less potential for improvement.     

Cardiovascular function and psychological distress in urbanised black South Africans: the SA BPA study

Objective

The increased prevalence of cardiovascular disease risk factors in sub-Saharan Africa has increased the incidence of cardiovascular disease in this region but whether psychological distress contributes to this observed increased risk remains largely unclear.The aim of this study was to investigate the association between cardiovascular function and psychological distress in urbanised black South African men (n = 101) and women (n = 99).

Methods

Resting cardiovascular variables were obtained by making use of the Finometer device and 24-hour ambulatory blood pressure (BP) measurements with the Cardiotens apparatus. Psychological questionnaires assessed the perception of health (General Health questionnaire) and depression status (DSM-IV criteria). The resting ECG (NORAV PC-1200) was used to determine left ventricular hypertrophy (LVH) by making use of the Cornell product. Confounders included age, obesity, alcohol intake, smoking and physical activity.

Results

The hypertensive groups were overweight, with lower vascular compliance and higher LVH (only men) compared to the normotensive groups. In hypertensive men, perception of health (somatic symptoms) was positively associated with blood pressure, while in hypertensive women it was associated with heart rate. Major depression was associated with LVH in hypertensive men and mean arterial pressure in hypertensive women. LVH and depression showed odds ratios of 1.02 (95% CI: 0.997–1.05) and 1.15 (95% CI: 1.01–1.32), respectively, in predicting hypertension in women.

Conclusions

Psychological distress was associated with higher blood pressure in hypertensive African men but also with the development of left ventricular hypertrophy in hypertensive African men and women.