Biomedical subjects

Christine Schubert

Publications and source records attributed to Christine Schubert.

5 recordsLinked to original sources

PubMed2005

Influence of factor V HR2 on thrombin generation and clinical manifestation in rare bleeding disorders.

In this study we investigated the influence of the presence of the factor V HR2 haplotype, defined by the factor V gene mutation H1299R (FV(HR2)), on thrombin generation. Measurements were performed in platelet-poor plasma of individuals with factor V(HR2) or factor V(Leiden) in comparison to a control group carrying none of these mutations. Coagulation was triggered by low concentrations of recombinant tissue factor in the presence of activated protein C. Thrombin generation was monitored by a fluorogenic substrate. The endogenous thrombin potential was calculated from the obtained curves. As a result we observed an increased thrombin generation both for individuals heterozygous and homozygous for FV(HR2). The level of endogenous thrombin potential is in the same range as in samples of patients heterozygous or homozygous for FV(Leiden). The results indicate that FV(HR2) plays a role as a risk factor for venous thrombosis in homozygous patients through an increased thrombin generation. The association between different clinical manifestations in individuals with FVII deficiency and endogenous thrombin potential and the presence of FV(HR2) was studied.

Blood Coagulation Disorders↗

PubMed2003

Estrogenic and antiestrogenic regulation of MMP-2 and MMP-13 mRNA in RUCA-I endometrial tumor cells in vitro and in vivo.

We investigated the influence of estrogenic and antiestrogenic treatment on proteolytic activity--especially on MMP-2 and MMP-13--in the RUCA-I transplantable endometrial tumor model. Morphological studies demonstrate that RUCA-I cells are forming highly differentiated gland-like structures by remodelling and invading the underlying ECM. Estrogens upregulate the mRNA levels of MMP-2 and MMP-13 in the rat uterus. Treatment with the pure antiestrogen ICI 182,780 results in the downregulation of MMP-2 and MMP-13 mRNA. The same regulation for MMP-13 mRNA is found in vitro in RUCA-I cells. In contrast, in the transplantation tumor, the mRNA level of MMP-13 is repressed by estrogens and induced by ICI 182,780. MMP-2 mRNA is not regulated by hormones in the transplantation tumor and in RUCA-I cells. The divergent regulation suggests a varying influence of cell-cell-, cell-extracellular matrix interactions and soluble factors.

Adenocarcinoma↗

PubMed2003

Puberty and body composition.

Body composition during puberty is a marker of metabolic changes that occur during this period of growth and maturation, and, thus, holds key information regarding current and future health. During puberty, the main components of body composition (total body fat, lean body mass, bone mineral content) all increase, but considerable sexual dimorphism exists. Methods for measuring body composition (e.g. densitometry and dual-energy X-ray absorptiometry) and degree of maturity will be discussed in this review. Components of body composition show age-to-age correlations (i.e. 'tracking'), especially from adolescence onwards. Furthermore, adipose tissue is endocrinologically active and is centrally involved in the interaction between adipocytokines, insulin and sex-steroid hormones, and thus influences cardiovascular and metabolic disease processes. In conclusion, pubertal body composition is important, not only for the assessment of contemporaneous nutritional status, but also for being linked directly to the possible onset of chronic disease later in life and is, therefore, useful for disease risk assessment and intervention early in life.

Adolescent↗

PubMed2002

Preferential topography of proteins regulating vascularization and apoptosis in a MX1 xenotransplant after treatment with hypoxia, hyperthermia, ifosfamide, and irradiation.

The MX1 xenotransplant growing in nude mice was used as a model for estrogen- and progesterone-receptor-negative breast cancer. The effects of different therapeutic regimens-combinations of hyperthermia, chemotherapy, and irradiation-on the expression of proteins playing a role in tumor vascularization and apoptosis were investigated. Additionally, MX-1 tumors were exposed to hypoxia to investigate changes in protein expression related to angiogenesis. This is of particular importance with respect to antiangiogenic therapies that may be combined with the treatments mentioned before. Endothelial and adhesion factors, extracellular matrix (ECM) factors, apoptosis-regulating factors, and neuronal factors were examined by immunohistochemical techniques. Concerning vascularization, the most prominent changes were seen in the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which increased strongly after hypoxia. The other cytokines, adhesion and ECM molecules, were either little affected or unaffected by the therapy. At the ultrastructural level, the walls of the tumor vessels are of the sinusoidal type, possessing many fenestrations. With regard to the second focus of this investigation, apoptosis, tumor cells again exerted the strongest differences after hypoxia where c-myc was clearly enhanced, whereas the effects on p53, bcl-2, and CD95 were extremely weak or not detectable. Furthermore, the neurotransmitter somatostatin, a possible "external" regulator of apoptosis, did not show treatment-related changes. In summary, it was shown that 1) within the group of apoptosis-regulating proteins c-myc was particularly affected by hypoxia, indicating a possible role for an activation-induced pathway of apoptosis in this context; 2) minor changes seen after treatment combined with hyperthermia point to a more acute vascular reaction (=dilatation), causing an increase of tissue pO2 rather than angiogenesis; and 3) the concentrations of the angiogenic factors VEGF and bFGF rose strongly under hypoxia, thereby possibly exerting counterproductive effects to antiangiogenic therapy but not to thermochemotherapy or irradiation. This supports the concept of a combined antiangiogenic, hyperthermia, chemo- and irradiation therapy.

Animals↗

PubMedDate not supplied

Indications, surgical technique, and long-term experience with laparoscopic closure of the nephrosplenic space in standing horses.

OBJECTIVE: To describe surgical technique and outcome after laparoscopic closure of the nephrosplenic space for treatment of recurrent left dorsal displacement of the left colon (LDDLC) in standing horses. STUDY DESIGN: Retrospective study. ANIMALS: Forty-four horses with LDDLC. METHODS: Laparoscopic portals were located in the left flank region. After administration of etilefrin intravenously to contract the spleen, the dorsal splenic margin was sutured to the nephrosplenic ligament to obliterate the nephrosplenic space. Horses were re-examined (< or = 3 years) for history of recurrence. In addition, medical records of 4,852 horses treated for colic over 16 years were evaluated to establish incidence of LDDLC and recurrence after treatment. RESULTS: Splenic contraction facilitated suture placement and closure of the nephrosplenic space was achieved without complications. LDDLC recurrence did not occur although 5 horses had subsequent episodes of colic; 4 horses had displacement of the ascending colon between the spleen and body wall. Review of medical records revealed an incidence of LDDLC of 6% and recurrence of 21% in a population of horses with signs of colic. CONCLUSION: Laparoscopic closure of the nephrosplenic space, facilitated by etilefrin-induced splenic contraction can be efficiently performed in standing horses. CLINICAL RELEVANCE: Laparoscopic ablation of the nephrosplenic space should be considered in horses that are predisposed to recurrent LDDLC.

Animals↗