Ch. Marth

Rapid reappearance of large granular lymphocytes (LGL) with concomitant reconstitution of natural killer (NK) activity after human bone marrow transplantation (BMT)

The frequency of large granular lymphocytes and their relationship to functional NK‐activity as assessed by the capacity to lyse the K562 tumour target was analysed in five allogenic and two autologous human bone marrow transplant recipients. Date revealed: (i) almost identical disappearence and reconstitution of both parameters further indicating that LGL represent effector cells of spontaneous lysis of K 562 targets; (ii) a long‐lasting suppression of the absolute numbers per ml of blood of both LGL and functional NK activity which we believe was not the consequence of reconstitution with immature effector cells but rather reflected immunosuppressive therapy; (iii) LGL exhibits the fastest reappearance rate subsequent to total body irradiation of all populations of circulating leucocytes.

The Impact of Risk Factors and More Stringent Diagnostic Criteria of Gestational Diabetes on Outcomes in Central European Women

OBJECTIVES In the face of the ongoing discussion on the criteria for the diagnosis of gestational diabetes (GDM), we aimed to examine whether the criteria of the Fourth International Workshop Conference of GDM (WC) select women and children at risk better than the World Health Organization (WHO) criteria. DESIGN AND SETTING This was a prospective longitudinal open study in five tertiary care centers in Austria. PATIENTS AND OUTCOME MEASURES The impact of risk factors, different thresholds (WC vs. WHO), and numbers of abnormal glucose values (WC) during the 2-h, 75-g oral glucose tolerance test on fetal/neonatal complications and maternal postpartum glucose tolerance was studied in 1466 pregnant women. Women were treated if at least one value according to the WC (GDM-WC1) was met or exceeded. RESULTS Forty-six percent of all women had GDM-WC1, whereas 29% had GDM-WHO, and 21% of all women had two or three abnormal values according to WC criteria (GDM-WC2). Eighty-five percent of the GDM-WHO were also identified by GDM-WC1. Previous GDM [odds ratio (OR) 2.9], glucosuria (OR 2.4), preconceptual overweight/obesity (OR 2.3), age 30 yr or older (OR 1.9), and large-for-gestational age (LGA) fetus (OR 1.8) were the best independent predictors of the occurrence of GDM. Previous GDM (OR 4.4) and overweight/obesity (OR 4.0) also independently predicted diabetes postpartum. GDM-WC1 had a higher rate of obstetrical complications (LGA neonates, neonatal hypoglycemia, cesarean sections; P < 0.001) and impaired postpartum glucose tolerance (P < 0.0001) than GDM-WHO. CONCLUSION These results suggest the use of more stringent WC criteria for the diagnosis of GDM with the initiation of therapy in case of one fasting or stimulated abnormal glucose value because these criteria detected more LGA neonates with hypoglycemia and mothers with impaired postpartum glucose metabolism than the WHO criteria.

Transforming growth factor-beta and ovarian carcinoma cells: regulation of proliferation and surface antigen expression

Transforming growth factor-beta (TGF-beta) is a multifunctional peptide regulating several processes in ovarian cells. The growth of ovarian carcinoma cell lines (OVCAR-3, HTB-77, 2780 and CRL-1572) was reduced by TGF-beta in a dose related manner. The antiproliferative activity was not improved by combination with other biological response modifiers. Treatment with TGF-beta augmented the expression of interferon-gamma induced class I and II antigens of the major histocompatibility complex. The presentation of another antigen namely the tumor marker CA-125 on the cell surface was markedly reduced by TGF-beta.

Correlation of Biochemical (Receptors, Endogenous Tissue Hormones) and Quantitative Morphologic (Stereologic) Findings in Normal and hyperplastic Human Prostates

In previous light and electron-microscopic analyses human benign prostatic hyperplasia was shown to be predominantly a stromal disease; the aim of the present study was to correlate the stereological data with the levels of the endogenous tissue hormones (androgens, estrogens, progesterone) in normal (N) and hyperplastic human prostatic tissues (BPH). BPH tissue specimens were obtained by open prostatectomy (n = 25); normal prostatic tissue was obtained from kidney donors (n = 5). No statistically significant difference was found between normal and hyperplastic tissue. Testosterone BPH 0.69 +/- 0.44, N 0.25 +/- 0.12; 5 alpha-dihydrotestosterone BPH 7.0 +/- 2.9, N 4.2 +/- 0.7; progesterone BPH 0.059 +/- 0.022, N 0.058 +/- 0.005; estrone BPH 0.10 +/- 0.03, N 0.14 +/- 0.03; estradiol BPH 0.07 +/- 0.02, N 0.05 +/- 0.02; estriol BPH 0.02 +/- 0.01, N 0.04 +/- 0.02. Using a Spearman rank correlation coefficient a statistical analysis was performed for age, weight of the prostate, absolute stereological data and the endogenous prostatic hormones. As can be seen from the statistical analysis there is a poor correlation for 5 alpha-dihydrotestosterone and the amount of the glandular epithelium; otherwise no correlation of the endogenous tissue hormones with the stereological data investigated was found. These data show that the stromal overgrowth of benign hyperplasia is not reflected in the tissue hormone levels.

Correlation between Steroid Hormone Receptors, Histological and Clinical Parameters in Ovarian Carcinoma

Estrogen (ER) and progesterone (PR) receptors in ovarian tumors of 62 patients (51 carcinomas, 11 benign tumors) were estimated by the dextran-coated charcoal method using Scatchard plot analyses. 63% of carcinomas were ER-positive (greater than 10 fmol/mg cytosol), 38% were PR-positive (greater than 25 fmol/mg cytosol), whereas in benign tumors only 45% were ER-positive and 36% were PR-positive. We found no statistically significant correlation between receptor content and stage of disease, menopausal status or age of the patient. The highest concentration of ER and PR was observed in patients between 61 and 70 years of age. Life table analysis for patients with advanced ovarian carcinomas showed no significant difference in survival time in the group with higher ER and PR content. This study also reports the results obtained in a group of patients with receptor-positive ovarian carcinomas treated with a combination of chemotherapy and antiestrogen therapy. In comparison to treatment with cytotoxic chemotherapy alone, no significant difference in the time of survival or duration of remission could be found.

Vitamin A Status and Retinoid-Binding Proteins in Carcinomas of the Head and Neck Region

The serum levels of retinol, RBP (retinol-binding protein) and PALB (prealbumin) were found to be significantly lower in patients with malignant tumors of the head and neck region than in controls. In tumor tissues as well as in normal laryngeal mucosa, specific binding sites for retinol and retinoic acid were found. Whereas retinol-binding (CRBP = cellular retinol-binding protein) could only be detected in a few cases, binding for retinoic acid (CRABP = cellular retinoic acid-binding protein) was present in all specimens investigated. The presence or lack of binding sites was not dependent on the actual serum retinol levels. With regard to the antineoplastic role of vitamin A, the reduced serum levels are considered as a possible factor in tumor development and growth. CRBP and CRABP are assumed to be mediating factors for the retinol and retinoic acid action. Since the presence of CRABP is a constant finding, we propose that retinoic acid and its synthetic derivatives with high affinity for CRABP could be appropriate antineoplastic drugs in these tissues.

Tumor-associated antigen 90K activates myelomonocytic cell line THP-1

90K is a tumor-associated antigen. Using myelomonocytic cell line THP-1 we determined neopterin production and tryptophan degradation after exposure of cells to 90K in the presence and the absence of interferon-gamma. Interferon-gamma is a well known stimulus for THP-1 cells inducing e.g. neopterin production and tryptophan degradation. Treatment of cells with 50 micrograms/ml 90K induced significant neopterin formation, and the exposure of cells to 90K in addition to 100 U/ml interferon-gamma amplified neopterin production compared to the sole effect of interferon-gamma. In parallel, a significant degradation of tryptophan was observed in culture supernatants leading to the formation of kynurenine. When the cells were treated with the combination of 90K and interferon-gamma the degradation of tryptophan was further enhanced. The data demonstrate that tumor-associated antigen 90K interferes with immunocompetent target cells and is able to induce a biochemical response in monocytic cells.

Cellular retinoic acid binding protein (CRABP) in retinoblastoma

Binding proteins for retinoic acid (cellular retinoic acid binding protein, CRABP) have been demonstrated in various cell types, and display the characteristics of receptors. Three retinoblastomas are described. The clinical diagnosis of retinoblastoma was established by ophthalmoscopic echographic and histological examination. One part of the tumor was frozen in liquid nitrogen immediately after surgery and used for the determination of CRABP. CRABP was present in cells from all three tumors. This may indicate sensitivity of this tumor to retinoic acid or synthetic retinoic acid derivatives with biologic activity.

Calcium Antagonists for Uterine Relaxation

The uterus-relaxant effect of diltiazem, a recently developed calcium antagonist, was investigated in vitro. 24 myometrial strips dissected from the lower uterine segment during cesarean section showed a statistically highly significant (p less than 0.001) decrease of their spontaneous contractility in the presence of Diltiazem 10(-6) M: 82% after 10 min, 100% after 20 and 100% after 60 min (median values). Diltiazem, which is considered to be the most balanced calcium antagonist as far as cardiovascular side effects are concerned, could be of considerable interest also for clinical use.

Retinoic acid- and retinol binding proteins in melanomas and retinoblastomas

Cellular retinoic acid-binding proteins (CRABP) and cellular retinol-binding protein (CRBP) can be found in cells and nuclei. They function in the same way as receptors. CRABP and CRBP were studied in 9 cases of choroidal melanoma and in 3 of retinoblastoma. CRABP was found in 2 cases of melanoma and in 3 cases of retinoblastoma. CRBP was found in 1 melanoma.