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Biomedical subjects

O Dapunt

Publications and source records attributed to O Dapunt.

At least 37 records · Page 2Linked to original sources

Activated cellular immunity and decreased serum tryptophan in healthy pregnancy.

We analyzed plasma samples from 45 randomly selected healthy pregnant women and from 20 healthy nonpregnant female controls of corresponding age. Tryptophan and kynurenine concentrations were measured by reverse-phase high performance liquid chromatography. The kynurenine per tryptophan ratio was calculated to allow a more accurate estimate of tryptophan degradation. In addition, neopterin was measured by radioimmunoassay. There were significantly lower tryptophan concentrations in pregnant women compared to nonpregnant controls. Kynurenine per tryptophan ratios were increased in pregnant women in the 3rd trimester. Significant correlations existed between neopterin increase and tryptophan decrease as well as kynurenine increase and tryptophan decrease. Also significant correlations between week of pregnancy and lower tryptophan and higher kynurenine per tryptophan ratio were found (p < 0.01). From our data, cellular immune activation is likely to be the cause of enhanced tryptophan degradation during pregnancy.

Biopterins↗

Decreased plasma tryptophan in pregnancy.

OBJECTIVE: To examine levels of serum tryptophan and its degradation product kynurenine in uncomplicated pregnancy, according to the week of pregnancy and the concentrations of neopterin. METHODS: Plasma was analyzed from 45 healthy pregnant women (15 in each trimester), 15 healthy puerperas, and 20 nonpregnant controls. Tryptophan and kynurenine were measured by reverse-phase, high-performance liquid chromatography, and neopterin by radioimmunoassay. RESULTS: In healthy pregnant women, tryptophan values decreased (median first trimester: 72 mumol/L; second trimester: 51 mumol/L; third trimester: 46 mumol/L; P < .001) in a manner correlated with the duration of pregnancy (Spearman rank correlation coefficient ra = -0.771, P < .001) and normalized in the puerperium (median 60 mumol/L). No change in kynurenine, a tryptophan degradation product, was observed, but the ratio of kynurenine to tryptophan increased during pregnancy and correlated positively with gestational age (ra = 0.714, P < .001). In addition, an inverse correlation existed between neopterin and tryptophan concentrations (ra = -0.566, P < .001), as well as a positive one between neopterin and the kynurenine to tryptophan ratio (ra = 0.660, P < .001). CONCLUSION: Tryptophan levels decrease during normal pregnancy and the decrease may be related to immune activation phenomena.

Biopterins↗

[Immunostimulating protein 90K in ovarian carcinoma].

Protein 90K is a tumor-associated antigen, which is able to enhance the cytotoxic activity in lymphokine-activated and natural killer cells as well as the IL-2 release in peripheral blood lymphocytes. In our in vitro experiences we observed a stimulatory effect by IFN-alpha and IFN-gamma on 90K-specific mRNA expression and protein release in ovarian cancer cells, and 90K was furthermore found to be a potent stimulator of macrophage activity. Protein 90K seems to be involved in tumor immunology; it may represent a critical link between tumor and immune system.

Adjuvants, Immunologic↗

[Role of the immune parameter neopterin in adnexitis].

Neopterin is a sensitive marker of macrophage activity, and elevated urine excretion has been observed in viral and bacterial infections. Including 48 patients, we investigated whether neopterin could be a valid parameter for classification of PID. Urinary Neopterin was determined pretherapeutically and throughout the follow-up by means of high pressure liquid chromatography. In about one third of the patients elevated levels of neopterin were observed and these were characterized by higher PID-scores, accelerated erythrocyte sedimentation rate and higher levels of C-reactive protein. The results indicate that in patients with PID macrophages are regularly activated. Neopterin may give additional information for classification of PID although because of lack of sensitivity and specificity it may not be helpful for differential diagnosis or follow-up of these patients.

Adolescent↗

Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells.

Retinoids and gamma-interferon (IFN-gamma) have been demonstrated to synergistically amplify growth inhibition in cultured breast cancer cells. Since IFN-gamma enhances effects mediated by retinoids more than vice versa, we focused our investigations on the mRNA expression of cellular retinoic acid-binding proteins (CRABPs) and retinoic acid receptors (RARs), since these are the key molecules that mediate retinoid action. Synergistic inhibition of cell proliferation under treatment with 9-cis-retinoic acid and IFN-gamma was detected in the three breast cancer cell lines MCF-7, SKBR-3, and even in the RA-resistant BT-20 cells. RAR-alpha and RAR-gamma mRNA were observed in all cell lines, whereas RAR-beta was not detectable. CRABP I message was expressed in MCF-7 cells only, but CRABP II was found in all three breast cancer cell lines. IFN-gamma (10 ng/ml) increased RAR-gamma expression but had no influence on RAR-alpha, whereas RAR-beta was not detectable in any of the cell lines. RA (1 microM)-mediated CRABP II increase was suppressed by IFN-gamma (10 ng/ml). These observations indicate that IFN-gamma-mediated increase in RAR-gamma and suppression of RA-mediated CRABP II activation may play a role in synergistic inhibition of proliferation in breast cancer cell lines.

Breast Neoplasms↗

[Value of the TAG-72 (CA 72-4) tumor marker in primary diagnosis of ovarian carcinoma. A comparison with the established CA-125 marker].

The value of the TAG-72 (CA 72-4) serum marker in primary diagnosis was investigated in 110 patients with histologically diagnosed ovarian cancer. A reference group consisted of 103 patients with benign pelvic masses. Compared to the well-established CA-125, TAG-72 showed a low sensitivity of 42% in the detection of ovarian cancer. By contrast, when the cut-off level for TAG-72 was set at 6 U/ml, it showed a very high specificity of 99%. When the measurement of TAG-72 was combined to that of CA-125, improvements in both the specificity (as compared to a single CA-125 determination) and the sensitivity (as compared to a single TAG-72 assay) were observed. In such a combined assay, our results suggest that the best predictive value (positive and negative) was obtained if CA-125 is assigned a relatively high cut-off value (65 U/ml) in conjunction with a low cut-off level (3.2 U/ml or 4 U/ml) for TAG-72. In the present study, at threshold values of 65 U/ml respectively, a sensitivity of 86%, a specificity of 83% and a positive and negative predictive value of 85% were obtained. In mucinous carcinomas of the ovary, however, the additional TAG-72 determination did not lead to a better predictive power than did CA-125 measurement alone.

Adenocarcinoma, Clear Cell↗

Serum IgG, IgM, and IgA reactivity to human papillomavirus types 11 and 6 virus-like particles in different gynecologic patient groups.

Serum samples from several groups of patients attending a gynecology clinic were analyzed by ELISA for specific antibodies recognizing surface epitopes on intact human papillomavirus (HPV) types 6 and 11 L1 virus-like particles (VLPs) that were synthesized in vitro. In these samples, positive IgG and IgM reactivities to HPV-11 L1 VLPs were, respectively, 12% and 6% for 87 controls, 46% and 67% for 79 condyloma patients, 30% and 64% for 72 cervical intraepithelial neoplasia patients, 16% and 19% for 63 pregnant women at time of delivery, and 5% and 0 in their 63 newborns. IgA reactivities were low and not significantly different. The prevalence of IgG-positivity in HPV-6/11 DNA-positive patients increased from 46% with HPV-11 L1 VLPs to 76% when the sera were additionally screened with HPV-6 L1 VLPs. These data show that HPV-6 and -11 L1 VLPs are effective antigens for serologic studies and they detect type-specific antibodies.

Adolescent↗

IUD-associated pelvic actinomycosis: a report of five cases.

Five cases of intrauterine device (IUD)-associated tuboovarian actinomycosis are presented. The patients' ages ranged from 33 to 49 years and their IUD usage from 2 to 12 years. Clinical features of the cases included stenosis of the sigmoid colon in 4 cases, ureteric or bladder obstruction in two cases, and rectal fistula in a further instance. All patients were successfully treated postoperatively with penicillin or ampicillin. An initial diagnosis of ovarian carcinoma was considered in all cases. Although Actinomyces is difficult to differentiate histopathologically from microorganisms and other substances that cause the Splendore-Hoeppli phenomenon, morphological diagnosis permits a quicker and more practical approach than bacterial cultures in the establishment of postoperative antibiotic treatment. Intraoperative frozen-section diagnosis of an acute inflammatory process permits the surgeon to make an immediate decision in order to avoid extensive surgery when ovarian carcinoma is suspected.

Actinomyces↗

Increased production of immune activation marker neopterin by colony-stimulating factors in gynecological cancer patients.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been introduced in the treatment of chemotherapy-induced neutropenia. Effects of these CSFs on the cellular immune system were evaluated in 38 neutropenic gynecological cancer patients during chemotherapy. In addition to restoring the leukocyte count, GM-CSF--to a greater extent than G-CSF--also induced neopterin, a sensitive marker of macrophages activated by interferons. This effect was confirmed in vitro by investigating the effects of these CSFs on interferon-gamma-mediated pathways in THP-I human myelomonocytic cells. The results suggest activation of immune effector cells by GM-CSF.

Adult↗

Significance of thrombocytosis in patients with epithelial ovarian cancer.

OBJECTIVES: Our objective was to determine the relevance of a preoperative platelet count in ovarian cancer. Special interest was directed to a possible prognostic significance of thrombocytosis in this disease. STUDY DESIGN: Charts of 130 patients with epithelial ovarian cancer were reviewed retrospectively. Survival analyses were performed with the Kaplan-Meier method. Differences in survival were examined according to Mantel and Breslow. Platelet counts were furthermore correlated to other clinical parameters. For this purpose the Spearman rank test and a stepwise logistic regression model were used. Data comparison was accomplished with the Mann-Whitney U test and the chi 2 test. RESULTS: Prevalence of thrombocytosis was 38%. No differences in survival between patients with or without thrombocytosis was found. Volume of ascites and hemoglobin concentrations were independently associated with thrombocytosis (p = 0.002 and p = 0.004, respectively). CONCLUSIONS: Thrombocytosis is not a useful prognostic factor in ovarian cancer. Elevated platelets are predominantly associated with the presence of ascites and marked anemia.

Adult↗

[Interaction of interferon with retinoic acid].

Lippman and coworkers recently reported striking response rates achieved in patients with cervical cancer using a combined treatment with 13-cis-retinoic acid and interferon-alpha. In vitro studies demonstrated a synergistic amplification of proliferation inhibition by retinoids and interferon in malignant cells. Comparing all-trans- with 9-cis-retinoic acid, the latter was more effective in inhibiting tumor cell growth and in inducing synergism with interferon-gamma. Combination of retinoic acid with interferon-gamma increased the down-regulation of specific binding sites of interferon-gamma. Expression of MHC class II antigens induced by interferon-gamma was not further enhanced by retinoic acid. These results indicate that interferon seems to modulate the retinoic acid system.

Breast Neoplasms↗

Progesterone receptors in routinely paraffin-embedded primary breast carcinomas and lymph node metastases.

Described here is an immunohistochemical technique using the commercially available monoclonal progesterone receptor (PR) antibody KD 68 in routinely fixed and paraffin-embedded breast carcinomas and lymph node metastases. The authors' technique is compared with several incubation variations. The method applying the primary antibody in a dilution of 1:10 overnight followed by a biotinylated second antibody showed the best results when Triton X-100 was added to the buffer. Using this method, comparison with the results on frozen sections of 34 breast carcinomas yielded a significant concordance of 94%. Correlation between the results on paraffin sections and those obtained by the standard dextran-coated charcoal cytosol assay was 80%. The value of the method for predicting endocrine therapy response was shown in 20 patients. Thus the reliability of the method has been demonstrated and was applied on 151 lymph node metastases and the corresponding primary breast carcinomas from 50 patients. Generally PR content in the metastases was lower than in the primary tumors (p < 0.001). This finding indicates that evaluation of PR in lymph node metastases should be included in the decision for endocrine therapy of breast cancer.

Breast Neoplasms↗

The prognostic value of nuclear roundness and neopterin in ovarian cancer.

The prognostic value of clinical factors, morphometric features and neopterin, a marker for macrophage activation, was investigated retrospectively in 68 ovarian carcinoma patients. Nuclear roundness was a good predictor of patient survival. About 50% of our patients showed neopterin concentrations above the cut-off level of 275 mumol/mol creatinine. Interestingly, those patients with elevated urinary neopterin concentration, and thus displaying a sign of activation of cell-mediated immunity, had a shorter survival than those with normal concentration. Applying a multivariate Cox regression analysis, the only independent parameters predicting patient survival were FIGO stage, residual disease, nuclear roundness and neopterin.

Adult↗

Tumor marker CA-125 in tissues of the female reproductive tract and in serum during the normal menstrual cycle.

OBJECTIVE: To further elucidate the origin of the physiological CA-125 amounts that lead to cyclic changes in CA-125 serum levels in normally menstruating women. DESIGN: Fifty-three normal endometria, 13 fallopian tubes, 25 ovaries, and nine isolated corpora lutea were prospectively investigated for their CA-125 content in a sandwich solid-phase RIA and by immunohistochemistry. In addition, endometrial CA-125 tissue content was compared with the actual CA-125 serum levels of the study patients. RESULTS: Cytosolic CA-125 concentrations were 20-fold and twofold higher in the endometrium than those measured in the ovary and the fallopian tube, respectively. Moreover, only in the endometrium did CA-125 content show significant cyclic changes, with the highest concentrations during the early proliferative and middle secretory phase. The lowest tissue concentrations were measured during the early secretory phase. Furthermore, during the early and middle secretory phases cytosolic CA-125 was negatively associated with CA-125 serum levels. In immunohistochemistry, marked distributional changes in OC-125 reactivity were revealed in the basalis and the functionalis throughout the menstrual cycle and the postovulatory loss of CA-125 expression was found to be strongly connected with early secretory transformation of glandular epithelium. CONCLUSION: Our findings indicate that the CA-125 amounts responsible for cyclic changes in serum levels in normally menstruating women seem to be a product of normal endometrium.

Adult↗

[The value of etoposide (VP-16) in the therapy of refractory ovarian cancer].

In analogy to Kühnle et al. (1984) the role of etoposide in patients with cisplatin-refractory ovarian cancer was evaluated. 45 patients were treated with 150-200 mg of etoposide per sa. m. on days 1-3. Acute toxicity was tolerable except alopecia grade III. Remarkable, however, was the induction of two fatal cases of leukaemia following etoposide treatment. The first patient, who was 27 years old, with FIGO stage IIb serous cystadenocarcinoma, which was treated with cisplatin/epirubicin and after a latent period of 45 months, a local recurrence was treated with 8 cycles of etoposide. Twenty-three months after discontinuation of etoposide therapy, the patient showed acute myelogenous leukaemia (AML) of M5b-subtype according to the FAB classification. Two days after diagnosis, the patient died of the disease. The second patient, a 55-year old woman with FIGO stage IIa serous cystadenocarcinoma, was treated with cisplatin/cytoxan; 8 cycles of etoposide were given as a second line therapy. This patient, 21 months after discontinuation of etoposide therapy showed a pre-pre-B-acute lymphocytic leukaemia with coexpression of the myeloid antigens. Two months after diagnosis, the patient died of the disease. In 4 out of 38 patients, a complete and in 7 patients a partial remission was induced by etoposide treatment and survival of these responding patients was prolonged in comparison with the nonresponder. The survival was also dependent on CA-125 serum level and the cumulative dose of etoposide administered. Etoposide treatment is an acceptable option as salvage therapy in refractory ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗