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91.
Tumour angiogenesis: vascular growth and survival 总被引:3,自引:0,他引:3
Giatromanolaki A Sivridis E Koukourakis MI 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2004,112(7-8):431-440
Angiogenesis starts at the edge of a malignant epithelial tumour concurrently with tumour cell invasion and stromatogenesis, i.e. the formation of specific connective tissue stroma amenable to easy penetration by endothelial and tumour cells. However, as the tumour continues its growth, the edge becomes the inner tumour area, and a new invading tumour front is formed by the multiplying malignant cells which outflank the initial edge. This process, which repeats itself again and again, forms the "relay race" model of tumour vascular growth and regression. At the heart of the tumour unfavourable environmental conditions prevail -- hypoxia, acidity, lack of nutrients, failure of waste removal, and apoptosis rather than proliferation. Blood vessels and tumour cells are greatly decreased, but do not vanish, as tumour cells are shifting to anaerobic glycolysis, and blood vessels are turning into anti-apoptotic pathways -- vascular survival ability (VSA). Thus, assessing vascular density (VD) by simply counting "hot spots" at the edge of a tumour, where conditions are most favourable, is futile; it may reflect tumour angiogenic activity (TAA), but is not representative of genuine tumour vasculature. By combining vessel counts at the invading tumour front with those of the inner tumour areas a complete picture of tumour VD can be achieved. The thus formed four patterns of vascularization, designated as "edvin" (edge vsinner tumour area), are: edvin 1: low TAA/low VSA; edvin 4: high TAA/high VSA; edvin 2: low TAA/high VSA; and edvin 3: high TAA/low VSA. It is expected that this scheme will prove useful in the field of chemoradiotherapy and anti-angiogenic treatment. 相似文献
92.
Vu Thuy Khanh Le-Trilling Jana-Fabienne Ebel Franziska Baier Kerstin Wohlgemuth Kai Robin Pfeifer Aart Mookhoek Philippe Krebs Madita Determann Benjamin Katschinski Alexandra Adamczyk Erik Lange Robert Klopfleisch Christian M. Lange Viktoriya Sokolova Mirko Trilling Astrid M. Westendorf 《European journal of immunology》2023,53(2):2249940
Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis. 相似文献
93.
Nikolaos Athanasiou Katerina Baou Eleni Papandreou Georgia Varsou Anastasia Amfilochiou Elisavet Kontou Athanasia Pataka Konstantinos Porpodis Ioanna Tsiouprou Evangelos Kaimakamis Serafeim-Chrysovalantis Kotoulas Evgenia Katsibourlia Christina Alexopoulou Izolde Bouloukaki Meropi Panagiotarakou Aspasia Dermitzaki Nikolaos Charokopos Kyriakh Pagdatoglou Kallirroi Lamprou Sofia Pouriki Foteini Chatzivasiloglou Zoi Nouvaki Alexandra Tsirogianni Ioannis Kalomenidis Paraskevi Katsaounou Emmanouil Vagiakis 《Journal of sleep research》2023,32(1):e13656
Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer–BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38–54) years and body mass index of 24·84 (22.6–28.51) kg/m2 were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6–7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = −0.178, p < 0.001), poor sleep quality (r = −0.094, p < 0.05), insomnia (r = −0.098, p < 0.05), and nap frequency per week (r = −0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination. 相似文献
94.
Alexandra Schneider-Chaabane David Boschert Sibylle Rau Diana Lorena Guevara Solarte Vera Bleicher Ali Al-Ahmad Karen Lienkamp 《Macromolecular chemistry and physics.》2023,224(5):2200323
Facially amphiphilic polymers carrying cationic and hydrophobic groups on the same repeat unit have shown promising antimicrobial activity and biocompatibility, yet they are prone to suffer from protein adhesion which may induce biofilm formation. To overcome this problem, poly(diitaconate)-based copolymers with cationic/hydrophobic and protein-repellent/charge-neutral repeat units are synthesized. The bioactivity profile of surface-attached polymer networks made from these copolymers depends on the ratio of the cationic and charge-neutral repeat units. In all cases, the protein adhesion is substantially reduced compared to purely cationic polymers. At a 50:50 ratio, the polymer coatings are partially protein-repellent and antimicrobial, yet slightly cell toxic. At an intermediate composition of 30:70, they are still antimicrobial and the cell compatibility is substantially improved. The long-term stability of these materials still has to be determined to judge their suitability for medical applications. 相似文献
95.
Clémence Jacquin Emilie Landais Céline Poirsier Alexandra Afenjar Ahmad Akhavi Nathalie Bednarek Caroline Bénech Adeline Bonnard Damien Bosquet Lydie Burglen Patrick Callier Sandra Chantot-Bastaraud Christine Coubes Charles Coutton Bruno Delobel Margaux Descharmes Jean-Michel Dupont Vincent Gatinois Nicolas Gruchy Sarah Guterman Abdelkader Heddar Lucas Herissant Delphine Heron Bertrand Isidor Pauline Jaeger Guillaume Jouret Boris Keren Paul Kuentz Cedric Le Caignec Jonathan Levy Nathalie Lopez Zoe Manssens Dominique Martin-Coignard Isabelle Marey Cyril Mignot Chantal Missirian Céline Pebrel-Richard Lucile Pinson Jacques Puechberty Sylvia Redon Damien Sanlaville Marta Spodenkiewicz Anne-Claude Tabet Alain Verloes Gaelle Vieville Catherine Yardin François Vialard Martine Doco-Fenzy 《American journal of medical genetics. Part A》2023,191(2):445-458
Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype–phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients. 相似文献
96.
Macular translocation for surgical management of subfoveal choroidal neovascularizations in patients with AMD: first results 总被引:7,自引:0,他引:7
S. Wolf Alexandra Lappas Andreas W. A. Weinberger Bernd Kirchhof 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1999,237(1):51-57
Background: At present no satisfying treatment for subfoveal choroidal neovascularization (CNV) secondary to age-related
macular degeneration (AMD) is available. Visual results after successful surgical removal of subfoveal CNV are disappointing.
This has been explained by a primary dysfunction of the retinal pigment epithelium (RPE) in the macular region and the surgical
trauma to the RPE in patients with AMD. Therefore, Machemer and Steinhorst developed a technique for macular translocation
after surgical removal of subfoveal CNV. We report our first experiences with this technique in patients with subfoveal CNV
secondary to AMD. · Methods: Seven patients aged between 71 and 83 years with subfoveal CNV were included in the study. Visual
acuity of the fellow eyes was below 20/400. All patients underwent pars plana vitrectomy. Retinal detachment was produced
by subretinal infusion of balanced salt solution and a 360° retinotomy at the base of the vitreous was performed. After removal
of the CNV, retinal rotation and reattachment, the retina bordering the retinotomy was coagulated with endolaser photocoagulation.
Silicone oil was used as temporary tamponade. · Results: In all patients the subfoveal CNV was removed and the macula was
translocated by a 15°–45° rotation onto functional RPE. The mean duration of follow-up was 11±3 months. Initial visual acuity
ranged from 20/80 to hand movements. Final visual acuity was 20/100 to 20/400. Initially all patients complained of tilted
vision. During follow-up the rotation of the image regressed and was well tolerated by all patients. Complications included
the development of retinal detachment in three patients after silicone oil removal, development of a macula pucker, and a
significant increase of lens opacity in the phakic eyes. · Conclusion: In our series rapid improvement of visual function
was observed in one patient only, even if the macula appeared ophthalmoscopically and angiographically normal. Vitreoretinal
complications occurred frequently during follow-up.
Received: 2 February 1998 Revised version received: 6 April 1998 Accepted: 29 April 1998 相似文献
97.
Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer’s disease 总被引:4,自引:4,他引:0
To explore further the potential for cognitive enhancement utilizing nicotinic stimulation in Alzheimer’s disease (AD), six
otherwise healthy subjects with moderate AD received placebo and three doses (6, 12, and 23 mg) of the novel selective cholinergic
channel activator (ChCA) (nicotinic agonist) ABT-418 over 6 h in a double-blind, within-subjects, repeated-measures design.
Subjects showed significant improvements in total recall and a decline in recall failure on a verbal learning task. Qualitatively
similar improvements were seen in non-verbal learning tasks such as spatial learning and memory, and repeated acquisition.
No significant behavioral, vital sign, or physical side effects were seen. These results confirm that stimulating central
nicotinic receptors has acute cognitive benefit in AD patients. These findings suggest that selective ChCAs have a potential
therapeutic role in dementing disorders, and that further studies with this or similar agents in AD and/or Parkinson’s disease
are warranted.
Received: 27 February 1998/Final version: 9 September 1998 相似文献
98.
Jinee Rizzo Alexandra M. Levine Geoff R. Weiss Tillman Pearce Maura Kraynak Robert Mueck Susan Smith Daniel D. Von Hoff John G. Kuhn 《Investigational new drugs》1996,14(2):227-234
Summary Mitoguazone is a unique chemotherapeutic agent whose activity is believed to result primarily from the competitive inhibition of S-adenosyl-methionine decarboxylase leading to a disruption in polyamine biosynthesis. Initial clinical trials demonstrated that the dose-limiting toxicities (mucositis and myelosuppression) of Mitoguazone were both dose and schedule dependent. Early pharmacokinetic studies of Mitoguazone in man revealed a prolonged half-life. Concurrent with a recent Phase II trial of Mitoguazone in patients with AIDS related non-Hodgkin's lymphoma, the single dose pharmacokinetics of Mitoguazone were characterized. Twelve patients received 600 mg/m2 of intravenous Mitoguazone over 30 minutes on an intermittent every 2 week schedule. Blood, urine, cerebrospinal fluid (CSF), pleural fluid and tissue samples were collected and analyzed by HPLC. Mitoguazone was cleared from the plasma triexponentially with a harmonic mean terminal half-life of 175 hours and a mean residence time of 192 hours. Peak plasma levels occurred immediately post-infusion, ranged from 6.47 to 42.8 g/ml, and remained (for an extended period) well above the reported concentration for inhibition of polyamine biosynthesis. Plasma clearance averaged 4.73 l/hr/m2 with a relatively large apparent volume of distribution at steady-state of 1012 l/m2 indicating tissue sequestration. Renal excretion of unchanged Mitoguazone accounted for an average of 15.8% of the dose within 48 to 72 hours post-administration. Detectable levels of drug were present in random voided samples eight days post-dose. Mitoguazone levels in CSF ranged from 22 to 186 ng/ml post-dose with CSF/plasma ratios ranging from 0.6% to 7%. The pleural fluid/plasma ratio was approximately 1. Tissue levels of Mitoguazone were highest in the liver followed by lymph node, spleen and the brain. 相似文献
99.
Although Hodgkin's disease (HD) is not usually associated
withcongenital or acquired immunodeficiency disorders, recent
evidencewould suggest a statistically significant increase in HD
amongindividuals infected with human immunodeficiency virus
(HIV).In the setting of underlying HIV infection, clinical and
pathologiccharacteristics of HD may differ from usual
expectations. Thus,70%-100% of HIV-infected
patients with HD present with systemic"B" symptoms.
Likewise, disseminated, stage III or IV diseaseis reported in
approximately 75%-90%. Bone marrow is a commonsite
of extranodal HD, occurring in 40%-50%. Complete
responserates after multiagent chemotherapy range from
approximately45% to 70%, although median survival
has been only in the rangeof approximately 18 months.
Hematologic toxicity from multiagentchemotherapy may be
substantial, even with the use of hematopoieticgrowth factor
support. It is apparent that new strategies oftherapeutic
intervention must be explored. 相似文献
100.
The effect of dimethylnitrosamine on the nucleosomal structure of mouse liver chromatin was studied. After a single oral dose of dimethylnitrosamine (2–75 mg/kg body weight 45 min before sacrifice) liver nuclei were isolated and incubated with micrococcus nuclease. Nucleosomes were separated on sucrose density gradients. There were no differences in nucleosomal sedimentation velocities between preparations from control and dimethylnitrosamine treated animals. The supernatant obtained after centrifugation of the lysed nuclei (2 min at 4,000 g
av) and nucleosomal peak fractions were used for isolation of DNA. DNA was heat denatured in 7 M urea or formamide. After electrophoresis on polyacrylamide gels areas under mononucleosomal DNA and smaller fragments were measured and compared with the total DNA area. The increase in DNA fragmentation was dimethylnitrosamine dose response dependent. When expressed as per cent of controls it amounted to 106% for 2 mg; 115% for 10 mg; 127% for 25 mg; 164% for 75 mg dimethylnitrosamine/kg body weight. A good correlation between mobility and log of chain length of
174 RF DNA-Hae III digest was obtained in nondenaturing 5% polyacrylamide gels and denaturing non-aqueous formamide polyacrylamide gels but not in 12% polyacrylamide gels containing 7 M urea. DNA of mononucleosomal peak fractions contained 200 and that of dinucleosomal peak fractions 400 nucleotides. Fragmentation of DNA was closely related to in vivo dimethylnitrosamine treatment but was not detected in measurements of protein-DNA complexes in the chromatin. It was disclosed on denaturation of DNA followed by polyacrylamide gel electrophoresis.Abbreviations DMN
dimethylnitrosamine
- SDS
sodium dodecyl sulfate
The work was supported by Grant Number 1 R0 1 CA26642-01, awarded to A.v.d.D. by the National Cancer Institute, DHEW 相似文献