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Biomedical subjects

D C Fischer

Publications and source records attributed to D C Fischer.

42 records · Page 3Linked to original sources
PubMedDate not supplied

A large keratan sulfate proteoglycan present in human cervical mucous appears to be involved in the reorganization of the cervical extracellular matrix at term.

OBJECTIVE: To elucidate the function of keratan sulfate proteoglycan (KS-PG) in the human uterine cervix, we analyzed its distribution with respect to physiologic conditions. METHODS: Immunohistochemistry was used to localize KS bearing proteoglycans (mAb 5D4) and decorin (mAb 6B6) in the lower uterine segment. Proteins present in cervical mucous were labeled with biotin, glycosaminoglycan chains were digested enzymatically, and the samples were analyzed by Western blot. RESULTS: Decorin was detected throughout the extracellular matrix, in tissues from menstruating nonpregnant women, in early pregnancy, from women who had cesarean at term, at postpartum hysterectomy, and from postmenopausal women. In menstruating nonpregnant women, in early pregnancy (first trimester), and in postmenopausal women, KS-PG was detectable only in epithelial, mucous-producing cells. Interestingly, in samples obtained either at the time of cesarean at term (lower uterine segment) or after postpartal hysterectomy, KS-PG was detectable throughout the extracellular matrix, indicating that the expression of KS-PG is associated with reorganization of the tissue. Biochemical analysis of the KS present in mucous revealed a core protein in the range of 220 kDa, suggesting an identity with the large KS-PG described previously. CONCLUSION: At parturition, a large KS-PG, which is virtually exclusively present in the cervical mucous of either early or nonpregnant women, was detected in the extracellular matrix. This finding indicates that cervical ripening is accompanied not only by quantitative but also by qualitative changes in the composition of the extracellular matrix.

Adult↗
PubMedDate not supplied

Histologic and immunohistochemical analysis of tissue response to adenovirus-mediated herpes simplex thymidine kinase gene therapy of ovarian cancer.

Herpes simplex virus (HSV) thymidine kinase (tk) gene incorporated into adenovirus was delivered intraperitoneally (ip) followed by an antiherpetic prodrug and topotecan in patients with recurrent epithelial ovarian cancer. Tissue response was evaluated. Ten patients underwent secondary debulking with subsequent delivery of ADV-HSV-tk therapy. Two patients each were treated at dose level 1 (2 x 10(10) vector particles = VP), 2 (2 x 10(11) VP), and 3 (2 x 10(12) VP); four patients were treated at dose level 4 (2 x 10(13) VP). Five patients underwent second-look surgery about one month after gene therapy (GT). Treatment response, presence of vector DNA, protein expression of steroid hormone receptors, p53, c-erbB2 and Ki67 protein were analyzed. At second-look, two out of five patients were tumor-free and none of their peritoneal biopsies showed vector DNA. After GT, the vital tumor mass was smaller, desmoplastic reaction had increased, and tumors were less differentiated with an increase of Ki67 expression. There was no change in expression of hormone receptors, p53, or c-erbB2. ADV-HSV-tk GT appears to eliminate cells with higher differentiation first and might induce fibrosis. Dedifferentiation might render residual cells more sensitive to chemotherapy secondary to their subsequent higher mitotic activity.

Adenoviruses, Human↗
PubMedDate not supplied

[Cytokine concentrations and expression of adhesion molecules in the lower uterine segment during parturition at term: relation to cervical dilatation and duration of labor].

OBJECTIVE: To determine the concentrations of tumor necrosis factor (TNF)alpha, interleukin (IL)beta, IL-6 and IL-8 and the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the lower uterine segment during parturition at term and to investigate correlations with the stage of cervical dilatation and with the duration of labor. PATIENTS AND METHODS: Biopsy specimens were taken from the lower uterine segment of 59 women undergoing non-elective cesarean sectin at term at different stages of cervical dilatation (< 2 cm, n = 17; 2-3 cm, n = 12; 4-6 cm, n = 13; > 6 cm, n = 17) after varying length of the time in labor (1-6 h, n = 18; > 6-12 h, n = 16; > 12-24 h, n = 15; > 24 h, n = 10). The concentrations of TNF alpha, IL-1 beta, IL-6 and IL-8 in protein extracts of these specimens were determined by enzyme linked immunosorbent assays and the expression of ELAM-1 and VCAM-1 was studied by immunohistochemistry. Staining was considered negative if < 5% of the endothelial cells were stained and positive if > or = 5% were stained. RESULTS: At < 2 cm dilated cervix the median concentrations of TNF alpha, IL-1 beta, IL-6 and IL-8 were 8.0 pg/mg total protein (TP), 1.3 pg/mg TP, 12.6 pg/mg TP and 17.2 pg/mg TP, respectively. At 4-6 cm dilatation the median concentrations were increased (TNF alpha: 22.2 pg/mg TP [P = 0.05], IL-1 beta: 22.2 pg/mg TP [P < 0.05], IL-6: 1226 pg/mg TP [P < 0.05], IL-8: 2081 mg/mg TP [P < 0.05]). At > 6 cm dilatation no further increase was observed. The expression of ELAM-1 and VCAM-1 was significantly greater at > 6 cm dilatation than < 2 cm dilatation (P < 0.001 and 0.05, respectively). With increasing duration of labor, the concentrations of IL-1 beta, IL-6 and IL-8 (but not of TNF alpha) increased and were significantly higher at > 6 cm dilatation than at < 2 cm (P < 0.05). Expression of ELAM-1 and VCAM-1 did not vary with duration of labor. CONCLUSIONS: These first investigations of cytokines and cell adhesion molecules in the lower uterine segment at both different stages of cervical dilatation and different duration of labor support the decisive role of cytokines for normal cervical dilatation. Local changes in the lower uterine segment independent from the effects of labor (e.g. increase of endothelial adhesivity) seem to be of special importance in this process.

Cell Adhesion Molecules↗