Biomedical subjects

R Hildenbrand

Publications and source records attributed to R Hildenbrand.

27 records · Page 2Linked to original sources

PubMed1998

Identification of placental cytokine-producing cells in term and preterm labor.

OBJECTIVE: To determine if the production of proinflammatory cytokines by placentally derived macrophages changes with term and preterm labor and to examine if changes in antigen expression of these cytokines can be detected by immunohistologic methods. METHODS: Enzymatically dispersed placental cell suspensions of the trophoblastic villi, obtained from 16 women with spontaneous term delivery, 16 women with elective cesarean delivery without any labor, and 22 preterm delivering women with labor unresponsive to tocolysis, were fractionated by magnetic-associated-cell-sorting, on the basis of CD11b-antigen expression. Positively and negatively sorted cell fractions were cultured and concentrations of interleukin-6, interleukin-1beta, and tumor-necrosis-factor-alpha were measured in the culture supernatants. Immunohistologic staining was used for identification of cytokine-producing cells within placental tissues. RESULTS: Positively sorted cells obtained from term (median 2027 pg/mL, P = .037) and preterm (median 3628 pg/mL, P = .001) laboring women produced significantly elevated amounts of tumor-necrosis-factor-alpha compared with nonlaboring (median 1088 pg/mL) women at term. Negatively sorted cell fractions obtained from term (median interleukin-1beta 162 pg/mL, P = .031, median interleukin-6 3134 pg/mL, P = .004) and preterm (median interleukin-1beta 934 pg/mL, P = .003, median interleukin-6 5695 pg/mL, P = .001) laboring women produced significantly elevated amounts of interleukin-1beta and interleukin-6 compared with nonlaboring (median interleukin-1beta 29 pg/mL, median interleukin-6 135 pg/mL) women at term. Immunohistologic staining revealed that tumor-necrosis-factor-alpha activity was localized in isolated stromal cells, whereas interleukin-1beta and interleukin-6 were predominantly found in endothelial cells within placental villi. CONCLUSION: The source of labor-associated release of tumor-necrosis-factor-alpha from placental tissues are macrophages, whereas interleukin-1beta and interleukin-6 are released from placental endothelial cells.

Cytokines↗

PubMed1998

Transforming growth factor-beta stimulates urokinase expression in tumor-associated macrophages of the breast.

Recent studies have shown that urokinase (uPA) is an independent prognostic marker in breast cancer. uPA plays a key role in the degradation of tumor matrix and promotes tumor progression. Macrophage expression of uPA appears to be important in this context. Our objective in the present study was to provide evidence that tumor growth factor-beta (TGF-beta) released from breast cancer cells markedly up-regulates uPA expression in tumor-associated macrophages (TAMs). TAMs from 32 breast carcinomas were cultured. Blood monocytes from healthy donors and breast cancer patients as well as tissue macrophages from patients with fibrocystic changes of the breast were also examined. After TGF-beta incubation, uPA levels were tested by ELISA, and uPA mRNA levels were determined by Northern blot analysis. TGF-beta receptor and uPA cell surface fluorescence intensities were determined by flow cytometry; TGF-beta receptors were determined by Western blot analysis. Protein kinase-C dependence was also examined, and immunohistochemical stainings for uPA and TGF-beta were performed. We have demonstrated that TGF-beta markedly up-regulates basal uPA expression (mRNA and protein) in TAMs but only modestly increases uPA production in blood monocytes and tissue macrophages. Exposure of macrophages to TGF-beta1 led to a rapid and sustained increase in uPA mRNA levels, which was independent of de novo protein synthesis and completely inhibited by actinomycin D. H7 markedly reduced the ability of TGF-beta to stimulate uPA expression. Likewise, okadaic acid potentiated the ability of TGF-beta to up-regulate macrophage uPA expression. We suggest that TAMs are more responsive to TGF-beta stimulation than are blood monocytes and tissue macrophages because of different TGF-beta receptor densities. TGF-beta stimulates transcription of the uPA gene, increases uPA-mRNA stability, and activates uPA expression via protein kinase-C-dependent mechanisms. The ability of TGF-beta to induce macrophage uPA expression may provide an indirect mechanism by which this growth factor stimulates angiogenesis. It may be, therefore, that TAMs promote tumor progression and tumor angiogenesis.

Breast Neoplasms↗

PubMed1997

Immune complexes are potent inhibitors of interleukin-12 secretion by human monocytes.

We have studied the effect of immune complexes (IC) on interleukin (IL)-12 secretion by human monocytes in vitro. Two experimental models of IC were used. IC formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum IgG almost completely inhibited IL-12 (p70 and p40) secretion induced by interferon-gamma and lipopolysaccharide in human blood-derived monocytes. Neutralizing anti-IL-10 antibodies plus indomethacin restored IL-12 secretion in the presence of IC to a high extent, indicating that IL-10 and prostaglandin (PG) partially mediate the IC-induced inhibition of IL-12 secretion. However, neutralization of tumor necrosis factor (TNF)-alpha by specific antibodies also incompletely restored IL-12 secretion. Indeed, monocytes secrete high levels of TNF-alpha upon stimulation by IC. We found that exogenously added TNF-alpha caused a profound inhibition of monocytic IL-12 secretion in the absence of IC, again mediated via the induction of IL-10 and PG. In summary, IC inhibit IL-12 secretion via TNF-alpha-induced IL-10 and PG synthesis. We conclude that IC, typically appearing in the course of chronic inflammatory processes, may influence the balance between Th1 and Th2 responses and may thus contribute to a deprivation of cell-mediated immune responses.

Antigen-Antibody Complex↗

PubMed1995

Captopril in acute myocardial infarction. Beneficial effects on infarct size and arrhythmias.

OBJECTIVE: It is known from experiments that angiotensin converting enzyme (ACE) inhibitors can limit infarct size. We examined the effect in patients. METHODS: In a prospective, randomized, placebo-controlled double blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 hours and 18 hours from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. RESULTS: The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV) (p < 0.05). The number of ventricular premature beats at 24 hours from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred 7 times in the placebo group, but did not occur in the captopril group. The creatine kinase (CK) infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). The mean arterial pressure was reduced by 12 mmHg with captopril treatment. CONCLUSIONS: The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.

Arrhythmias, Cardiac↗

PubMed1995

Captopril in acute myocardial infarction: beneficial effects on infarct size and arrhythmias.

It is known from experiments that angiotensin-converting enzyme inhibitors can limit infarct size. In a prospective, randomized, placebo-controlled double-blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 and 18 h from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With the exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV, p < 0.05). The number of ventricular premature beats at 24 h from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred seven times in the placebo group, but did not occur in the captopril group. The creatine kinase infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). Mean arterial pressure was reduced by 12 mmHg with captopril treatment. The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Urokinase plasminogen activator induces angiogenesis and tumor vessel invasion in breast cancer.

Urokinase plasminogen activator (uPA) is a proteolytic enzyme implicated in cancer invasion and tumor progression. Urokinase PA and its inhibitor (PAI-1) appear to be new and independent prognostic markers in breast cancer. To investigate how uPA- and PAI-1-levels correlate with angiogenesis and tumor vessel invasion, we counted microvessels and their tumor invasion and determined the uPA- and PAI-1 levels in 42 primary invasive breast carcinomas. 20 Patients had no lymph node metastasis at the time of surgery, while 22 patients had positive nodes. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for CD31 and Factor VIII. After gaining tumor tissue extracts, we determined the uPA- and PAI-1-levels by ELISA. A positive correlation between microvessel density, angioinvasion and uPA- and PAI-1-levels was found. We speculate that high uPA levels may induce tumor neovascularisation, angioinvasion and may cause tumor progression and metastasis. The degradation of the vessel wall by uPA causes a leak. This wall defect may, on the one hand, be the stimulus for endothelial cell proliferation and formation of new blood vessels and, on the other hand, it may be the place of tumor cell entry.

Breast Neoplasms↗

PubMed1995

Urokinase and macrophages in tumour angiogenesis.

Recent studies have shown that elevated levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) in breast cancer correlate with an increased risk of a reduced relapse-free survival time and shortened overall survival times. Urokinase PA and PAI-1 are independent prognostic indicators for breast cancer. The fact that plasminogen activators are indispensable for tube formation of microvascular cells and that they may induce angiogenesis in vitro strongly suggests a role for uPA and PAI-1 in tumour neovascularisation. Because macrophages and tumour cells produce uPA, we postulate a close collaboration between tumour cells and tumour-associated macrophages in angiogenesis. To investigate how uPA levels and macrophage counts in tumour tissue correlate with angiogenesis, we counted microvessels and determined uPA levels and macrophage content in 42 primary invasive breast carcinomas. Using light microscopy, we highlighted the vessels by staining their endothelium cells immunocytochemically for CD31 and factor VIII and the macrophages for CD68. After obtaining tumour tissue extracts, we determined the uPA and PAI-1 levels by ELISA. A positive correlation between microvessel density, vascular invasion, uPA level, macrophage content and proliferation rate was found.

Breast Neoplasms↗

PubMed1992

[Captopril in acute myocardial infarct: its effect on infarct size and arrhythmias].

The effect of captopril on infarct size and arrhythmias was determined in a prospective, randomized, placebo-controlled double-blind study of 46 patients (9 women, 37 men; mean age 61 [38-86] years). Within 2-18 hours of entry into the study these patients received either a slow intravenous bolus injection of 2.5 or 5.0 mg captopril followed by a continuous infusion of 1.5-2.0 mg/h for a period of 48 hours (n = 22), or of a placebo by the same mode of administration (n = 24). The two groups were comparable as to age, infarct site and time of intervention. All patients, except one in each group, also received nitroglycerin (1.2-6.0 mg/h intravenously). QRS complexes were measured to provide a necrosis index. Q-wave amplitudes decreased under captopril (-0.08 +/- 0.04 mV) while increasing under placebo (+0.15 +/- 0.04 mV; P less than 0.05). The number of ventricular extrasystoles in the first 24 hours after onset of treatment or on placebo was 25/h and 9/h, respectively (P less than 0.02). Ventricular fibrillation occurred in 7 patients of the placebo group, in none of the captopril group. Creatine-kinase infarct weight was 59 and 45 gram-equivalents, respectively (placebo vs treated group: not significant). The mean arterial blood pressure fell by 14 mm Hg during the first hour in the captopril group, but by only 3 mm Hg on placebo (P less than 0.01). These results indicate that captopril has a favourable influence on infarct size and electrical stability which is additional to that provided by standard nitroglycerin treatment.

Adult↗

PubMed1986

[Experiences with a modified nephrostomy instrument kit in ultrasound-guided kidney fistulization].

During a period of 24 months, ultrasound-guided percutaneous nephrostomies were performed in 51 patients in the Hospital at Köln-Merheim. The procedure was carried out with a modified nephrostomy instrument manufactured by Angiomed, Ettlingen, according to our own design. The procedure was successful in 49 patients. In one case it had to be abandoned because of lack of patient co-operation. In one patient a pyonephrosis was found and the patient was treated surgically.

Humans↗