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Biomedical subjects

G Reiner

Publications and source records attributed to G Reiner.

At least 37 records · Page 2Linked to original sources

[Therapy studies of the Austrian Breast Cancer Group (ABC)].

The Austrian Breast Cancer Group (ABC) consisting of more than 60 participating centers in Austria has randomized more than 5800 patients in 11 randomized trials since 1984. At present, roughly 30% of all patients with the diagnosis primary breast cancer are accrued in protocols throughout the country. Due to specific activities, the breast conservation rate raised from an initial 20% to more than 60% in the last years. Multicenter trials are not only the basis for progress in medicine but also tools for quality control and quality improvement.

Antineoplastic Agents, Hormonal↗

Immunosuppression by breast cancer associated p43-effect of immunomodulators.

It has been previously shown that p43- a breast cancer associated antigen-has immunosuppressive properties. The present study was carried out in order to elucidate the pathomechanisms of immunosuppression in breast cancer patients influenced by the expression of p43. Lymphocytes were cultured from blood of 29 women with benign lesions in the breast as well as from 41 female patients with breast cancer. Lymphocyte stimulation was performed by addition of Concanavalin (Con A) in cultures with lymphocytes alone (CONLYM) or in lymphocytes incubated with p43 (CONAg). In other series immunomodulation was tried by addition of indomethacin (INDLYM, INDAg), levamisole (LEVLYM, LEVAg), or interleukin-2 (ILLYM, ILAG). In breast cancer patients, addition of p43 significantly inhibited the activation of lymphocyte proliferation by Con A compared to women with benign tumors. The addition of indomethacin or levamisole did not influence this inhibitory effect of p43 in breast cancer patients. Contrary to these observations, addition of IL-2 resulted in increased proliferation of lymphocytes from patients with benign as well as malignant tumors, which was inhibited after addition of p43. Analysis of the correlation of the immunosuppressive properties of p43 in correlation with prognostic factors for breast cancer showed evidence for a stronger activity of p43 in early stage tumors (i.e. smaller than 2 cm, lymph node negative, histologic grading GI), confirming previous observations of a higher expression of p43 in early stages of breast cancer.

Adjuvants, Immunologic↗

Skeletal muscle sarcoplasmic calcium regulation and sudden death syndrome in chickens.

1. Sudden Death Syndrome (SDS) is a disease of well-developed, predominantly male broiler chickens where death appears to occur because of cardiovascular failure. The role of skeletal muscle sarcoplasmic calcium regulation as a potential cause of SDS has been investigated. 2. Calcium regulation of skeletal muscle sarcoplasmic reticulum was compared between broiler and Leghorn chickens. Calcium regulation matured from the 2nd to the 11th week and, at any age, broiler chickens showed significantly lower calcium transport rates and transport efficiencies. The mechanism of calcium transport in broiler chickens was more energy-consuming than that of the Leghorn chickens. 3. Sarcoplasmic calcium regulation is pivotal for muscle metabolism. As in porcine malignant hyperthermia, weaker calcium regulation might lead to hyperactivation of skeletal muscle, followed by elevated lactic acid concentrations and cardiovascular failure.

Animals↗

[The oxygen consumption of ostrich embryos during incubation].

This work deals with the oxygen consumption of ostrich chicks during incubation. Brood eggs were incubated in a hermetic isolated acrylic-glass cylinder. Reduction of oxygen content in the air surrounding the egg was measured using an oxygen-sensitive electrode. A sigmoid curve could be drawn during incubation, with the steepest phase being around day 26. Maximum oxygen consumption was reached on day 36. It was slightly decreased until day 39, when the embryo switches to lung circulation, followed again by an increase until hatching. Average oxygen consumptions for the whole brood interval were calculated to 63.6 liters. Oxygen volumes consumed on day 36 result in a demand about to 240 liters of fresh air per egg and day. Oxygen consumption of the embryos on day 36 was significantly positive correlated with their vitality. Numb or less vital embryos could be clearly differentiated from others. The higher a chick's oxygen consumption, the earlier and shorter its hatching. Possible applications of the method in regard to the evaluation of incubation parameters or chicken constitution are discussed.

Animals↗

Downregulation of lymphocyte mitogenesis by breast cancer-associated p43.

Placental isoferritin-associated p43 has proven to induce immune suppression during pregnancy in order to avoid rejection of the fetus' alloantigens by maternal lymphocytes. It has been demonstrated previously that p43 is also synthesized by breast cancer cells and can also be found on the surface of a subpopulation of T cells in women with this disease. Therefore, it was the aim of the present study to investigate if breast cancer-associated p43 has immunosuppressive properties. In 40 women undergoing surgical excision of a suspicious lump in their breast, blood was withdrawn and lymphocytes were isolated. Lymphocyte cultures were incubated with p43 antigen and anti-p43 antibody (CM-H-9). In a second series, lymphocyte mitogenesis was activated by addition of concanavalin A (Con A), Con A + p43 and Con A + anti-p43, respectively. While lymphocytes of breast cancer patients (n = 21) and women with benign breast disease (n = 19) incubated with p43 as well as with anti-p43 antibody did not show any difference in terms of incorporation of [3H]thymidine, activation of lymphocytes by addition of Con A was significantly inhibited after addition of p43 antigen in breast cancer patients compared to women with benign breast disease (P = 0.0178). Analysis of prognostic factors for breast cancer showed that inhibition of lymphocyte mitogenesis was dependent on the degree of tumor differentiation and was significantly higher in well differentiated tumors (GI) compared with more dedifferentiated tumors (GIII). The present study shows that breast cancer-associated antigen p43 is able to induce immune suppression in breast cancer patients but not in women with benign breast disease.

Adult↗

Thymidine labeling index and Ki-67 growth fraction in breast cancer: comparison and correlation with prognosis.

In situ determination of proliferative activity was performed on 184 consecutive primary invasive breast cancers. Methods used were monoclonal antibody Ki-67 in immunohistochemistry and thymidine labeling index. Tumor proliferation correlated between both methods (p = 0.0001). For thymidine labeling index and Ki-67, respectively, significant correlations existed with histologic tumour grade and steroid hormone receptors (Tumor grade: TLI p = 0.0001; Ki-67 p = 0.0001. ER-ICA: TLI = 0.0001; Ki-67 p = 0.014. PgR-ICA: TLI p = 0.0001; Ki-67 p = 0.0008). For thymidine labeling index a significant correlation was demonstrated for overall survival (p = 0.001) and recurrence free survival (p = 0.01). No statistical significance was observed for clinical outcome and Ki-67 (overall survival p = 0.18; recurrence free survival p = 0.1). None of the factors, TLI or Ki-67, was an independent prognostic factor as demonstrated by multivariate analysis.

Breast Neoplasms↗

Coexpression of HER-2/neu and p53 is associated with a shorter disease-free survival in node-positive breast cancer patients.

Breast cancer tissue was examined for overexpression of HER-2/neu and p53 oncogene proteins. Samples from 105 breast cancer patients were investigated by Western-blot analysis and their relationship to other established markers and clinical outcome was examined. In 21.0% of the cases HER-2/neu was overexpressed, and in 46.7% the p53 protein level was increased. Expression of these two oncogene products was closely correlated. Overexpression of both oncogenes was associated with larger tumour size and negative hormone receptor. The percentage of HER-2/neu and p53 overexpression was higher in node-positive patients, although statistical evaluation was not significant. While overexpression of HER-2/neu as well as p53 in node-positive patients was associated insignificantly with shorter disease-free survival, a significant difference could be documented when the disease-free survival of patients with overexpression of both oncogene proteins was compared to that of patients with no overexpression.

Breast Neoplasms↗

Induction of tumor necrosis factor alpha gene expression by lipoprotein lipase requires protein kinase C activation.

We have previously found that lipoprotein lipase (LPL) induces tumor necrosis factor alpha (TNF alpha) mRNA expression and TNF alpha protein production in the ANA-1 macrophage cell line and in resident murine macrophages. The present study was designed to elucidate the intracellular signalling pathways involved in the LPL-induced TNF alpha gene expression. Treatment of macrophages with two protein kinase C (PKC) inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine hydrochloride (H7) and calphostin C, suppressed LPL-induced TNF alpha mRNA expression and protein production. In contrast, no inhibition of the TNF alpha mRNA expression occurred when macrophages were exposed to an inhibitor of calmodulin-dependent kinase N-(6-amino-hexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride (W7). Overnight treatment of ANA-1 cells with 100 ng/ml 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) caused the suppression of both PKC activity and LPL-induced TNF alpha mRNA expression. We have also found that LPL treatment increased PKC activity in macrophages and induced a translocation of this enzyme from the cytosol to the membrane. Finally, we have demonstrated that H7 inhibited the enhancement of nuclear protein binding to the NFkB consensus sequence in the promoter of the TNF alpha gene that we observed in LPL-treated macrophages. Moreover, the treatment of macrophages with H7 abolished the stabilization of TNF alpha mRNA in response to LPL. Overall these data demonstrate that LPL induces TNF alpha mRNA expression in a PKC-dependent manner and that the PKC effect involves transcriptional events as well as posttranscriptional modifications.

Animals↗

Antiviral effects of different CD4-immunoglobulin constructs against HIV-1 and SIV: immunological characterization, pharmacokinetic data and in vivo experiments.

The CD4 cell surface antigen belongs to the immunoglobulin superfamily and is the primary receptor for the human immunodeficiency virus 1 (HIV-1). The high affinity interaction between HIV-1 and CD4 is mediated by the viral envelope glycoprotein gp120. Recombinant soluble CD4 (rsCD4) has been shown in vitro to be an effective inhibitor of HIV-1 and HIV-2 propagation in lymphoid cells. A variety of antibody-like molecules were constructed, consisting of different parts of the extracellular domain of CD4 fused to immunoglobulin constant regions. The fusion proteins were expressed in mammalian cell lines and purified via affinity chromatography. The specificity and anti-viral effects of the different CD4-immunoglobulin constructs against HIV were analysed by different immunological tests, i.e., immunofluorescence, neutralisation and in vitro assays. In pharmacokinetic studies, differences were found in serum half-life between the four- and two-domain CD4 constructs in cynomolgus monkeys and between glycosylated and deglycosylated CD4-Fc constructs in rabbits. In two in vivo experiments using the four-domain CD4-Fc in SIV-infected macaques, no beneficial effects were observed.

Animals↗

[The reproductive performance of sows with different malignant hyperthermia syndrome status].

Based on 200 litters descending from 50 sows relations between MHS-genotype and reproductivity were investigated. Breeds used were "Deutsches Edelschwein", German Landrace and a crossbred line. Evaluation of MHS-status was done by Polymerase Chain Reaction. Reproductivity traits were piglet numbers at different ages and litter growth. The sows were not preselected in regard to the halothane gene. MHS-negative sows showed increased reproductivity towards MHS-positives and within the negatives, the homozygote sows were superior to the heterozygotes.

Animals↗

DNA ploidy and other results of DNA flow cytometry as prognostic factors in operable breast cancer: 10 year results of a randomised study.

We evaluated breast cancer specimens from 241 patients of a controlled clinical trial by means of DNA flow cytometry. We report the correlations between DNA index (DNI) and fraction of cells in S-phase (SPF) and other prognostic parameters. Both univariately and in a Cox model, the predictive power of these factors is evaluated after a follow-up of more than 10 years. There are strong correlations between DNI and SPF (P = 0.0001) and between flow cytometry parameters and clinical and histopathological factors such as axillary lymph node involvement, tumour size and histological grade. In univariate analysis DNI fails to provide prognostic information, whereas SPF turns out to be able to differentiate between patients at high and low risk for relapse and death (P = 0.002). In the multivariate Cox model, too, SPF is an important prognostic parameter with respect to patient survival (relative risk: +86%), only surpassed by nodal involvement. DNI, however, turns out to be an independent predictor of relapse free survival and distant recurrence free survival. By combination of DNI and SPF, patients can be divided into three prognostic subgroups. We conclude that data from DNA flow cytometry can be of great importance for the decision on the level of aggressiveness of adjuvant therapy for an individual patient and therefore may help to avoid overtreatment and toxicity.

Adult↗

In-vivo antithrombotic potency of placenta protein 4 (annexin V).

The antithrombotic properties of Placenta Protein 4 (PP4) were investigated in laser or photochemically induced thrombus formation models in rats. In both in-vivo test-systems PP4 displayed a significant antithrombotic effect at dose levels as low as 0.3 and 1.0 mg/kg body weight. Bleeding times, surprisingly, were not prolonged significantly at these dose regimens. Maximal inhibition of thrombus formation in the laser-model was observed 15 min after intravenous administration of PP4, but was not recognizable in a clear-cut reaction in the second model. Determination of PP4 plasma levels in two monkeys revealed a half-life of 11.5 and 14.9 min, respectively. The maximal anticoagulant effect was observed between 15 and 30 min after administration of PP4 as determined functionally by means of thrombelastography.

Animals↗

Coagulation disorders in experimentally induced acute mouse malaria.

The development of coagulation disorders was studied in murine malaria. Plasmodium vinckei was chosen following an initial experiment because onset and duration of parasitemia were more suitable for hemostasiological studies than in the short-lasting infection, caused by P. berghei. Evaluation of the time courses of hematocrit, platelets, antithrombin (AT) III activity, Factor V activity and parasitemia showed a significant decrease in platelets, hematocrit, Factor V and AT III activity during the course of infection. The obtained data strongly suggest the development of a disseminated intravascular coagulation in mice during the terminal phase of murine malaria.

Animals↗

[Steroid hormone receptors in mammary carcinoma. Immunohistochemical detection and prognostic significance].

Estrogen and progesterone receptors were immunohistochemically recorded from 426 cases of primary mammary carcinoma. Immunohistochemical detection was based on monoclonal antibodies to estrogen receptor (H222) and progesterone receptor (KD68). Immunohistochemical and biochemical tests were correlated to each other with significance (p less than 0.0001) for either receptor. Some of the histological parameters exhibited relationships with the immunohistochemical receptor status. Receptor positivity of lobular, mucoid, tubular, and papillary carcinomas was more frequent than that of ductal carcinoma, whereas that of medullary carcinoma fell below ductal cases. A straight forward correlation of statistical significance was found to exist between histological tumor grade and steroid hormone receptor status. Receptor positivity of carcinomas with sizeable stroma components proved to be more frequent than that of carcinomas with lower stroma levels. Steroid hormone receptors can be immunohistochemically identified from cytological specimens, as well, though some limiting factors are implied in the latter. Thirteen percent of fine-needle aspirates provided falsely negative steroid hormone receptor findings, as compared to histological biopsy. This problem was encountered primarily in cases of low receptor positivity and high stroma content of carcinoma, factors for which only minor amounts of cell material could be obtained from puncturing. Clinical follow-up checks and evaluation of survival data revealed the immunohistochemically determined steroid hormone receptor status to be of significant importance to prognostication (ER-ICA p less than 0.00001; PgR-ICA p = 0.004). The prognosis of patients with negative estrogen and progesterone receptors was found to be worse than that of patients with positive receptor status. These studies are likely to confirm immunohistochemical determination of steroid hormone receptors, using monoclonal antibodies, to be a reliable method of great prognostic importance.

Adenocarcinoma↗

[The nutritive effect of avilamycin in swine breeding and fattening].

During a total period of treatment of 141 days, divided into starter grower and fattening period, the efficacy of avilamycin in a dosage of 80 mg/kg (starter grower) and 20 mg/kg (fattening) rsp. 40 mg/kg and 20 mg/kg was investigated in comparison with a negative control group and the additive tylosin. Growth was partially significantly increased by avilamycin at a dosage of 40 mg/kg/20 mg/kg compared to the control. Average daily weight gains of the starter grower period were improved for about 12%, feed conversion ratio for about 14%. In spite of a clear decrease in the efficacy of the additive during fattening period, a superiority of the avilamycin-group over the control- and the tylosin-group could be saved when avilamycin was added till the end of the fattening period. So addition of avilamycin in a dosage of 40 mg/kg during starter grower and 20 mg/kg during fattening period can be recommended.

Animals↗

[The status of lysosomal beta-glucuronidase in liver tissue of swine of different constitution].

This paper deals with cellular-physiological changes in regard to adaptative problems in the pig. As an example for lysosomal catabolism, beta-glucuronidase activity in liver tissue of pigs with different constitution is presented. Male slaughter pigs (n = 120), equally distributed on the breeds Piétrain, German Large White and German Landrace, are used for the investigation. The results show significant variances between, as well as within the breeds. Partly high significant, positive correlations exist between beta-glucuronidase activity and survival rates. The importance of beta-glucuronidase activity and the lysosomes for adaptative constitution and development in the pig is discussed.

Animals↗