Comparison of necrosis in human ovarian tissue after conventional slow freezing or vitrification and transplantation in ovariectomized SCID mice

This paper examines and compares necrosis in human ovarian tissue after conventional slow freezing or vitrification and ensuing xenotranplantation. Slow cryoconserved or vitrified ovarian tissue samples and fresh controls from nine patients were subcutaneously transplanted into SCID mice. The tissue samples were explanted after 6 weeks and the necrotic areas were examined by staining with Lucifer yellow SV. The size of the necrotic areas in parallel cultivated ovarian tissue samples was compared, as was necrosis in cultivated prostate tumour spheroids where the emergence of necrosis and its pathophysiological correlation have been described. Examinations showed no significant rise in the proportion of necrotic areas after slow cryoconservation/transplantation and in the controls (transplanted fresh tissue, not transplanted fresh tissue, long-term culture). The proportion of necrotic areas in the tumour spheroids was significantly higher than in the ovarian tissue. Vitrification could, after these results, be presented as an alternative to conventional slow cryoconservation.     

Inhibition of tumor-induced angiogenesis and matrix-metalloproteinase expression in confrontation cultures of embryoid bodies and tumor spheroids by plant ingredients used in traditional chinese medicine

Tumor-induced angiogenesis is a prerequisite for excessive tumor growth. Blood vessels invade the tumor tissue after degradation of the extracellular matrix scaffold by matrix metalloproteinases (MMPs). Inhibition of MMPs has been therefore suggested to be a useful tool to abolish neoangiogenesis of solid tumors. In the present study, antioxidative plant ingredients used in traditional Chinese medicine were investigated for their capacity to down-regulate MMP expression and to inhibit angiogenesis in embryonic stem cell-derived embryoid bodies and tumor-induced angiogenesis in confrontation cultures consisting of embryoid bodies and multicellular DU-145 prostate tumor spheroids. Embryoid bodies transiently expressed MMP-1, MMP-2, and MMP-9 during the time of differentiation of capillary-like structures. In confrontation cultures, MMP expression was increased compared with control tumor spheroids and embryoid bodies cultivated separately. The increased expression of MMPs in confrontation cultures was a result of elevated levels of reactive oxygen species (ROS) upon confrontation culture and was totally abolished in the presence of the free radical scavenger vitamin E. Incubation of embryoid bodies with baicalein, epicatechin, berberine, and acteoside, which are herbal ingredients used in traditional Chinese medicine, significantly inhibited angiogenesis in embryoid bodies and decreased intracellular ROS levels. Tumor-induced angiogenesis in confrontation cultures was totally abolished in the presence of the free radical scavenger vitamin E. Because herbal ingredients down-regulated MMP expression, we conclude that ROS generated during confrontation culture induce the expression of MMPs that are necessary for endothelial cell invasion into the tumor tissue.     

Physician cesarean delivery rates and risk-adjusted perinatal outcomes

OBJECTIVE: To compare perinatal outcomes in obstetric practices with high and low cesarean delivery rates. METHODS: We conducted a population-based study based on 171295 singleton births in New Jersey in 1996 and 1997. Vital certificate data for each birth were linked to the corresponding hospital discharge records. Nonsubspecialist obstetricians were divided into three groups based on their cesarean delivery rates during the study period: low (less than 18%), medium (18-27%), and high (greater than 27%). Perinatal mortality, rates of birth injury, and uterine rupture were compared among the physician groups after adjustment for differences in patient risks. RESULTS: Physicians in the frequent cesarean delivery group performed more cesarean deliveries for all major indications. Perinatal mortality rates were comparable among the three physician groups. Low and very low birth weight infants delivered by the high-rate physicians did not have a lower risk of mortality. The risk of intracranial hemorrhage was significantly higher for infants delivered by low-rate physicians than for those delivered by medium-rate physicians (adjusted relative risk [RR] 1.53; 95% confidence interval [CI] 1.07, 2.19). Relative to deliveries by medium-rate physicians, deliveries by low-rate physicians were associated with a lower overall risk of uterine rupture (adjusted RR 0.56; 95% CI 0.34, 0.92). Medium- and high-rate groups had similar occurrences of birth injury and uterine rupture. CONCLUSION: Low cesarean delivery rates reduced the rate of uterine rupture and were not associated with increased perinatal mortality. The data suggest a small increase in intracranial hemorrhages in infants delivered by physicians who perform relatively few cesarean deliveries.     

Reported exposures, stressors, and life events among Gulf War Registry veterans

We investigated the association of 15 exposures, 10 stressors, and 18 life events with illness symptoms reported by 978 veterans who believe they suffer from Gulf War-related illnesses. A mail survey was completed by veterans (60% response rate) from the Gulf War Health Registry. Variables most associated with high symptom group membership were reported chemical/biologic warfare (CBW), concerns with infection and faulty equipment, feelings of mistrust in the military, and disability leading to work stoppage within 2 years after the war. These data suggest that belief in CBW exposure, and the experience of war stress and serious negative life events after the war, are important concomitants of Gulf War illness. Models seeking to explain Gulf War symptoms need to incorporate a range of exposure and psychosocial factors to fully account for important influences.     

Ein Kleinhirnsymptom

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Bücherbesprechungen

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Neurologisches aus Nordamerika

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The BCR-ABL1 kinase bypasses selection for the expression of a pre-B cell receptor in pre-B acute lymphoblastic leukemia cells

The BCR-ABL1 kinase expressed in acute lymphoblastic leukemia (ALL) drives malignant transformation of human pre-B cells. Comparing genome-wide gene expression profiles of BCR-ABL1+ pre-B ALL and normal bone marrow pre-B cells by serial analysis of gene expression, many genes involved in pre-B cell receptor signaling are silenced in the leukemia cells. Although normal pre-B cells are selected for the expression of a functional pre-B cell receptor, BCR-ABL1+ ALL cells mostly do not harbor a productively rearranged IGH allele. In these cases, we identified traces of secondary VH gene rearrangements, which may have rendered an initially productive VH region gene nonfunctional. Even BCR-ABL1+ ALL cells harboring a functional VH region gene are unresponsive to pre-B cell receptor engagement and exhibit autonomous oscillatory Ca2+ signaling activity. Conversely, leukemia subclones surviving inhibition of BCR-ABL1 by STI571 restore responsiveness to antigen receptor engagement and differentiate into immature B cells expressing immunoglobulin light chains. BCR-ABL1 kinase activity is linked to defective pre-B cell receptor signaling and the expression of a truncated isoform of the pre-B cell receptor-associated linker molecule SLP65. Also in primary leukemia cells, truncated SLP65 is expressed before but not after treatment of the patients with STI571. We conclude that inhibition of BCR-ABL1 reconstitutes selection for leukemia cells expressing a functional (pre-) B cell receptor.     

Über die sensible Leitung in den vorderen Wurzeln

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