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The glycoprotein Prominin‐1 and the carbohydrate Lewis X stage‐specific embryonic antigen 1 (LeX‐SSEA1) both have been extensively used as cell surface markers to purify neural stem cells (NSCs). While Prominin‐1 labels a specialized membrane region in NSCs and ependymal cells, the specificity of LeX‐SSEA1 expression and its biological significance are still unknown. To address these issues, we have here monitored the expression of the carbohydrate in neonatal and adult NSCs and in their progeny. Our results show that the percentage of immunopositive cells and the levels of LeX‐SSEA1 immunoreactivity both increase with postnatal age across all stages of the neural lineage. This is associated with decreased proliferation in precursors including NSCs, which accumulate the carbohydrate at the cell surface while remaining quiescent. Exposure of precursors to bone morphogenetic protein (BMP) increases LEX‐SSEA1 expression, which promotes cell cycle withdrawal by a mechanism involving LeX‐SSEA1‐mediated interaction at the cell surface. Conversely, interference with either BMP signaling or with LeX‐SSEA1 promotes proliferation to a similar degree. Thus, in the postnatal germinal niche, the expression of LeX‐SSEA1 increases with age and exposure to BMP signaling, thereby downregulating the proliferation of subependymal zone precursors including NSCs. StemCells2017;35:2417–2429 Interfering with endogenous BMP signalling and fucose removal, both decrease LeX‐SSEA1 expression and rescue proliferation in the adult subependymal zone. Photomicrographs illustrate that in organotypic slice cultures 24‐hour treatment with either BMP antagonist noggin or fucosidase (Fuca) 1, similarly decrease LeX‐SSEA1 (green) expression while increasing the number of Ki67 (red) immunopositive nuclei (blue).

Cancer stem cells (CSCs) are a challenge in cancer treatment due to their therapy resistance. We demonstrated that enhanced Notch signaling in breast cancer promotes self-renewal of CSCs that display high glycolytic activity and aggressive hormone-independent tumor growth in vivo. We took advantage of the glycolytic phenotype and the dependence on Notch activity of the CSCs and designed nanoparticles to target the CSCs. Mesoporous silica nanoparticles were functionalized with glucose moieties and loaded with a γ-secretase inhibitor, a potent interceptor of Notch signaling. Cancer cells and CSCs in vitroand in vivoefficiently internalized these particles, and particle uptake correlated with the glycolytic profile of the cells. Nanoparticle treatment of breast cancer transplants on chick embryo chorioallantoic membranes efficiently reduced the cancer stem cell population of the tumor. Our data reveal that specific CSC characteristics can be utilized in nanoparticle design to improve CSC-targeted drug delivery and therapy.

Aim To describe mothers’ perceptions of what characterized mothers’ groups that continued over many years and to explore how the mothers benefitted from participating.Background Scarce knowledge about mothers’ groups in a long term perspective.Methods A qualitative research design was applied. Data were obtained by focus group discussions in three mothers’ groups that had lasted for 13, 16 and 21 years, respectively. Data was analysed using a phenomenographic approach.Findings The analysis revealed three descriptive categories and nine sub-categories. The categories were: Structure and contents over the years; Diverse backgrounds and views, with respect; and Revitalization, continuation and outcome of the groups. The underlying structure was found to be that the mothers’ groups had developed from baby-oriented to life-oriented forums and constituted a free space built upon confidentiality and trust, and with respect for differences.Conclusion The study concludes that mothers’ groups may result in social support and new coping strategies. Health professionals should encourage established groups to continue on their own. More research on the drop-outs from the groups is needed.

The purpose of this study was to examine if family structure and family relations were associated with children's perceived outcome of the contact with the school nurse.Methods: Danish school survey (1998) with a study population of 11-, 13- and 15-year-olds, response rate 88.0%, n=5,205, data collection by the internationally standardised HBSC questionnaire. Independent variables were family structure and confident relations with father and mother; outcome measures were student-reported outcomes of the dialogue.Results: The OR for having discussed the health dialogue with parents was 0.63 (0.51–0.78) among boys who did not have confident relations with their mother and 0.43 (0.35–0.52) for girls who had no confident relations with their mother.Discussion and conclusion: Lack of confident relations with parents were associated with less positive outcome of the dialogue with the school nurse. The practical implications of the study are that school nurses organise their health promotion efforts in order to support students and their families in develop mutual positive relations.

Aim:to examine if students who smoke and drink alcohol report more or less benefit from an annual health dialogue with a school nurse than students without this risk behaviour.Method:The study was one of the Danish contributions to the international collaborative Health Behaviour in School-aged Children (HBSC) study. A random sample of students in the fifth, seventh, and ninth grade (on average 11.8, 13.8 and 15.8 years of age) in schools in Denmark, answered a questionnaire, (response rate 87%, n=5 205). The independent variables were ‘How often do you smoke at present?’ and a combined variable of overall frequency of drinking. Perceived outcome of the dialogue was measured as: reflected on the dialogue; discussed the content with parents; followed the advice of the nurse; visited the nurse again.Results:Risk behaviour (smoking, drinking alcohol, and having experience with being drunk) is associated with lower odds for reflecting about the content of the dialogue with the school nurse, discussion of the content with parents, and for following the school nurse’s advice. However, risk behaviour is associated with higher odds for visiting the school nurse again but only in relation to smoking behaviour.

Introduction and aim: This paper examines whether students with common symptoms perceive positive outcome of the health dialogue with the school health nurse.Methods and study population: This study included all students in the fifth, seventh and ninth grade classes (average age 11.8, 13.8 and 15.8 years) in a random sample of schools in Denmark, response rate 87%, n=5.205. The data collection took place in the classroom by a standardised questionnaire. The dependent variables were four aspects of perceived outcome of the health dialogue with the school health nurse and the independent variables were eight common symptoms.Results: The majority of the students had thought about the health dialogue, discussed it with their parents, and had followed the advice from the nurse. A minority also visited the nurse again. Students with frequent physical and psychological symptoms had more often than other students thought about the health dialogue, followed the advice and visited the nurse again. Conclusion: The study suggests that students with high symptom load perceive more benefit from the dialogue with the school health nurse.

Abstract The developmental mechanism of tubulointerstitial fibrosis in diabetic nephropathy (DN) has not been elucidated. Tubulointerstitial fibrosis, as well as glomerulosclerosis, occurs in DN. Myofibroblasts which overproduce extracellular matrix are present in the renal interstitium in diabetics, although they are almost never seen in normal kidneys. The myofibroblasts appear to originate from interstitial fibroblasts. In addition, transforming growth factor-β1 (TGF-β1), which can evoke myofibroblast transformation, is detected in interstitial cells in the diabetic kidney, but not in the normal kidney. Taken together, these findings led us to speculate that TGF-β1 induces the transformation of interstitial fibroblasts into myofibroblasts, followed by tubulointerstitial fibrosis. Based on this speculation, we discuss the developmental mechanism of tubulointerstitial fibrosis in this review.

In the present study, the three-dimensional architecture of retinal vasculature was studied in KK mice, by combined use of resin injection, chemical treatment and scanning electron microscopy (SEM). In particular, Mercox/methylmethacrylate resin-injected eye tissues were subjected in sequence to NaClO immersion, ultrasonication and HCl treatment. The present technological innovation made possible SEM visualization of deeper retinal vasculature. In KK mice, the tunica media of stem arterioles and of first and second order branches consisted of a single layer of spindle-shaped smooth muscle cells provided with spine-like cytoplasmic processes. In addition, there occurred small triangular smooth muscle cells provided with slender cytoplasmic processes. The processes, giving off tiny secondary processes, overlapped with each other, thus forming assemblages around branching sites. Such a structure was particularly prominent for those branching sites where parent arterioles gave rise to their branches in a side arm-like pattern. The third (and occasionally fourth) order branche were surrounded by atypical smooth muscle, cells, with considerable dimension of endothelial surface remaining uncovered. Capillary pericytes consisted of fusiform cell bodies and slender cytoplasmic processes. Smooth muscle cells of retinal venules differed from those of arterioles. They were stellate in shape, exhibiting several cytoplasmic processes.
Keywords:smooth muscle cell, pericyte, retinal blood vessel, KK mouse, SEM

The metabolic activity of the brain has not been evaluated during physical exercise. In six volunteers substrate uptake by the brain was determined during graded exercise and recovery from maximal exercise by measuring the arterial‐internal jugular venous concentration differences(a–v differences).The a–v difference for lactate increased from 0.02 ± 0.08 mmol l−1at rest to 0.39 ± 0.13 mmol l−1during exercise and remained positive during 30 min of recovery (P< 0.05).The a–v difference for glucose (0.55 ± 0.06 mmol l−1at rest) did not change significantly during exercise, but during the initial 5 min of recovery it increased to 0.83 ± 0.10 mmol l−1(P< 0.05). The O2a–v difference at rest of 3.11 ± 0.30 mmol l−1remained stable during exercise, then increased during the initial 5 min of recovery (3.77 ± 0.52 mmol l−1) and remained high during the subsequent 30 min recovery period (3.62 ± 0.64 mmol l−1; P< 0.05). Thus the O2/glucose uptake ratio did not change during exercise (pre‐exercise 5.95 ± 0.68; post‐exercise 6.02 ± 1.39) but decreased to 4.93 ± 0.99 during the initial 5 min of recovery (P< 0.05). When lactate uptake was included, the resting O2/carbohydrate uptake ratio of 5.84 ± 0.73 was reduced to 4.42 ± 0.25 during exercise and decreased further during the recovery phase (to 3.79 ± 0.30; P< 0.05).In contrast, in the resting and immobilised rat, lactate infusion to a level similar to that obtained during maximal exercise in humans did not affect the a–v difference for lactate.The large carbohydrate uptake by the brain during recovery from maximal exercise suggests that brain glycogen metabolism is important in the transition from rest to exercise, since this would explain the significant post‐exercise decrease in the O2/carbohydrate uptake ratio.

There is differential resolution of mucosal infiltration with neutrophils and mononuclear cells following successful Helicobacter pylori eradication. We investigated the effects of H. pylori eradication on mucosal interleukin-8 (IL-8) and IL-6 activity in relation to the resolution of H. pylori-associated gastritis. Eighty-one duodenal ulcer patients with H. pylori infection received dual- or triple-treatment eradication therapy, and mucosal biopsy specimens obtained at the initial and follow-up endoscopic examinations were cultured in vitro for 24 h. The levels of IL-8 and IL-6 were measured by enzyme-linked immunosorbent assays. In the 42 patients in whom H. pylori eradication failed, there was little change in the numbers of neutrophils and mononuclear cells infiltrating the mucosa and in IL-8 and IL-6 activity. In the 39 patients in whom H. pylori was eradicated, there was normalization both in the numbers of infiltrating neutrophils and in mucosal IL-8 activity, which was evident within 1 month following therapy. In contrast, there was a gradual resolution of mononuclear cell infiltration over a 6-month period, accompanied by a gradual normalization in IL-6 levels. Addition of H. pylori to cultures of mucosal tissues induced a significant increase in IL-8 activity in both uninfected control subjects and patients from whom H. pylori was eradicated. However, this introduction yielded a significant increase in IL-6 activity only in the latter group. This study indicates a dichotomy in the changes of mucosal IL-8 and IL-6 activity after H. pylori eradication. The rapid normalization of IL-8 after H. pylori eradication and the ability of H. pylori cells to stimulate IL-8 in control tissues indicate that IL-8 induction is a part of the innate (nonimmune) responses to this organism. In contrast, the results of experiments analyzing IL-6 activity in cultured mucosal tissues suggest that the gradual resolution of mucosal IL-6 activity and mononuclear infiltration after successful eradication observed in vivo may reflect gradually diminishing residual immune responses against H. pylori.

Background & Aims: Interleukin (IL)-15 has been found to share many immunoregulatory activities in lymphocytes with IL-2. The aim of this study was to investigate IL-15 activity in organ cultures, localization of IL-15 messenger RNA (mRNA), and proliferation of lamina propria mononuclear cells (LPMCs) in response to recombinant IL-15 using the mucosal tissues obtained from patients with inflammatory bowel disease (IBD). Methods: The contents of IL-15, tumor necrosis factor @a, and IL-2 in the culture supernatant of the rectal mucosal tissues were determined by an enzyme-linked immunosorbent assay. Expression of IL-15 mRNA was analyzed by in situ hybridization, and proliferative response of LPMCs to recombinant IL-15 was determined by [^3H]thymidine incorporation into DNA. Results: Significantly greater IL-15 activity was detected in active IBD, and this elevation was also observed in inactive ulcerative colitis. In contrast, greater tumor necrosis factor @a activity was observed only in active IBD, and IL-2 was not detected in organ cultures. In situ hybridization showed IL-15 mRNA in macrophages and epithelial cells in active IBD specimens, and recombinant IL-15 induced a dose-dependent proliferative response in LPMCs. Conclusions: Mucosal IL-15 may be involved in the pathogenesis of IBD as one of the important mediators in activation of mucosal immune cells. GASTROENTEROLOGY 1998;114:1237-1243

Phagostimulant activity of glycerolipids such as digalactosyldiacylglycerol (DGDG), 6-sulfoquinovosyldiacylglycerol (SQDG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), etc., have been examined using the Avicel plate method for three kinds of marine herbivorous gastropods, the abaloneHaliotis discus, the turban shellTurbo cornutus, and the topshellOmphalius pfeifferi. DGDG showed strong activity for all the test animals. SQDG was much less active than the other glycerolipids for abalone. The turban shell and the top shell responded more or less sensitively to all tested glycerolipids at doses of 10–20µg/sample zone.

Methanol extracts of the green algaUlva pertusa contain four kinds of glycerolipids that are active as feeding-stimulants for marine herbivorous gastropods. These compounds are digalactosyldiacylglycerol (DGDG), 1,2-diacylglycerly-4'-O-(N,N,N-trimethyl)-homoserine (DGTH), 1-monoacylglyceryl-4'-O-(N,N,N-trimethyl)-homoserine (MGTH), and 6-sulfoquinovosyldiacylglycerol (SQDG). The various gastropods exhibit marked specificity, however, as young abaloneHaliotis discus respond to DGDG and DGTH at minute dosages of 20–30 µg/sample zone, but do not respond to 300 µg of SQDG, which is a phagostimulant for two other kinds of gastropods,Turbo comutus andOmphalius pfeifferi.

The purpose of the paper is to analyse the associations between learning health promotion from the health dialogue and sociodemographic and psycho-social variables. The theoretical framework is based on empowerment and health promotion and on experiential learning theory. The study is the Danish contribution to the WHO-collaborative study Health Behaviour in Schoolchildren. In 1991, a nationwide random sample of pupils 11, 13, 15-year-olds (n=1860) answered a standardised questionnaire about perceived health, health behaviour, social situation as well as the health dialogue with the school health nurse. Pupils from lower social classes reported a high proportion of learning health promotion. Among the study population, 31% had learned health promotion, mostly the 11-year-old pupils, and more girls than boys. Learning health promotion was associated with school satisfaction, unhappiness, nervousness, tiredness, physical exercise, puberty-related issues, headache and backache. Weekly recurring needs predicted the highest proportion of learning health promotion. Headache was the main reason for spontaneous contact. The second reason was problems with social relations. Pupils who were inclined to spontaneous visits had a positive attitude to school. Age, school satisfaction and headaches may be essential predictors of learning health promotion. Three steps in a learning spiral were applied: concrete experience (CE), reflective observation (RO), abstract conceptualization (AC).

BACKGROUND & AIMS: Microvascular endothelial cells mediate leukocyte homing, angiogenesis, and inflammation and healing and show tissue- specific adhesion molecules and functions. The activation of human intestinal mucosal microvascular endothelial cells (HIMECs) was studied in vitro to uncover possible abnormalities associated with inflammatory bowel disease. METHODS: HIMECs were isolated from normal and inflammatory bowel disease mucosa and assessed for phenotypic and morphological features, proliferative response, leukocyte binding capacity, and adhesion molecule expression. RESULTS: Basal proliferation by HIMECs was less than that of human umbilical vein endothelial cells (HUVECs) but increased proportionally more in response to vascular endothelial growth factor. Proinflammatory stimuli induced an activated, spindle-shaped morphology in HIMEC monolayers. Compared with HUVECs, unstimulated HIMECs showed less adhesiveness for U937 and MOLT4 cells and neutrophils, but cytokines and lipopolysaccharide substantially increased the binding capacity of HIMECs. HIMECs derived from inflammatory bowel disease mucosa showed a markedly greater leukocyte-binding capacity than normal mucosal HIMECs. Patterns of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and E-selectin messenger RNA expression were distinct in HIMECs, HUVECs, and mucosal mesenchymal cells. CONCLUSIONS: HIMECs represent differentiated endothelial cells with unique functional properties. Their dramatically enhanced capacity to bind leukocytes in inflammatory bowel disease suggests that HIMECs play an important role in initiating or maintaining inflammation. (Gastroenterology 1997 Jun;112(6):1895-907)

Analysis of cytokine production and function is an indispensable tool to study Crohn's disease and ulcerative colitis. This analysis has generated a tremendous amount of data, but a clear interpretation of results has been hampered by limited attention paid to several patient‐ and sample‐related pitfalls. These include: clinical parameters; the relative value of circulating vs. intestinal cytokine levels; the selection of tissue specimens and their processing method; the specific cellular source of each cytokine; the effect of cytokine inducers; and the technique utilized to obtain qualitative or quantitative data on cytokine protein or mRNA. Once all of these crucial variables are taken into proper perspective, a better understanding will emerge of the true role of cytokines in the pathogenesis of inflammatory bowel disease.

Deoxyribonucleic acid-dependent ribonucleic acid (RNA) polymerase (EC 2.7.7.6) was purified from the dimorphic bacterium Caulobacter crescentusat three stages in development. Enzyme from pure populations of stalked cells, as well as populations enriched in swarmer and predivisional cells, appeared identical in subunit structure and template requirements. The molecular weights of the enzyme subunits were 165,000, 155,000, 101,000, and 44,000, respectively. By analogy with RNA polymerase from other bacterial sources, they are considered to be components of the C. crescentusholoenzyme, β′, β, σ, and α, respectively. The C. crescentusenzyme appeared similar to the Pseudomonas aeruginosaenzyme and unlike the Escherichia colienzyme with respect to subunit molecular weights and failure to separate into core and sigma components upon phosphocellulose chromatography. In addition, the effects of ionic strength on the time course of polymerization varied both with the sources of bacterial polymerase and bacteriophage DNA.

Resistance plasmids were transferred in urine from a multi-drug-resistant Serratia marcescensto Escherichia coli. Transfer of resistance to kanamycin, tetracycline, chloramphenicol, streptomycin, ampicillin, and carbenicillin occurred readily after 4 h of incubation at room temperature (25°C). The urinary catheter collection bag is postulated as a potential site for extraintestinal resistance plasmid transfer in the Enterobacteriaceae, especially for pathogens such as Serratia, which do not frequently colonize the intestinal tract.

Background & Aims: The efficacy of hormonal therapy for recurrent bleeding from gastrointestinal angiodysplasia remains uncertain. We investigated the efficacy of long-term estrogen-progestagen therapy in the prevention of rebleeding from gastrointestinal angiodysplasia. Methods: Seventy-two noncirrhotic patients bleeding from gastrointestinal angiodysplasia confirmed by endoscopy or angiography were randomized to receive in double-blind conditions treatment with ethinylestradiol (0.01 mg) plus norethisterone (2 mg) (1 tablet/d), or placebo (1 tablet/d) for a minimum period of 1 year (range: 1-2 years). Results: Four patients could not be assessed because they did not attend the first follow-up visit. Failure of treatment occurred in 13 of 33 (39%) patients in the treatment group and in 16 of 35 (46%) patients in the placebo group (P = NS). No significant differences between groups were found according to number of bleeding episodes (0.7 +/- 1.0 vs. 0.9 +/- 1.5) and transfusional requirements (0.9 +/- 1.9 vs. 0.7 +/- 1.5 units). Treatment received was not an independent predictor for rebleeding prevention in the multivariate regression analysis. Severe adverse events (2 vs. 1) and mortality (0 vs. 1 patient, respectively) were similar between the treatment and placebo groups. Conclusions: Continuous estrogen-progestagen treatment is not useful in the prevention of rebleeding from gastrointestinal angiodysplasia.

In the present study, the three-dimensional architecture of retinal vasculature was studied in KK mice, by combined use of resin injection, chemical treatment and scanning electron microscopy (SEM). In particular, Mercox/methylmethacrylate resin-injected eye tissues were subjected in sequence to NaClO immersion, ultrasonication and HCl treatment. The present technological innovation made possible SEM visualization of deeper retinal vasculature. In KK mice, the tunica media of stem arterioles and of first and second order branches consisted of a single layer of spindle-shaped smooth muscle cells provided with spine-like cytoplasmic processes. In addition, there occurred small triangular smooth muscle cells provided with slender cytoplasmic processes. The processes, giving off tiny secondary processes, overlapped with each other, thus forming assemblages around branching sites. Such a structure was particularly prominent for those branching sites where parent arterioles gave rise to their branches in a side arm-like pattern. The third (and occasionally fourth) order branche were surrounded by atypical smooth muscle, cells, with considerable dimension of endothelial surface remaining uncovered. Capillary pericytes consisted of fusiform cell bodies and slender cytoplasmic processes. Smooth muscle cells of retinal venules differed from those of arterioles. They were stellate in shape, exhibiting several cytoplasmic processes. Keywords:smooth muscle cell, pericyte, retinal blood vessel, KK mouse, SEM