[Leadership behaviour and health - current research state]. / Führungsverhalten und Gesundheit - Zum Stand der Forschung.

The link between leaders' behaviour and health has only recently been the focus of scientific research and the results which already exist on this topic have, to date, not been systematically evaluated or summarized. The objective of this article is to make an attempt to provide a summarised overview of the current state of research. Subject-related databases list 42 publications dealing with the relationship between leaders' behaviour and the state of health and well-being of their employees. The literature discusses leaders' behaviour as being both a stressor (source of stress) and a resource. The publications discussed here also provide the first empirical evidence on the influence of various leadership styles on the health of the employees. In particular, transformational and employee-orientated leadership are considered to be beneficial to health. But the question of how leaders' behaviour influences health has not been satisfactorily explained. In most of the publications included, a direct link was assumed and, in the majority of cases, confirmed empirically. In addition, it also appears that there may be an indirect influence which may be moderated or mediated by, e. g., working conditions or the personality of the individual. The relatively small number of research examinations into the influence of leaders' behaviour on the health and well-being of their staff shows that there is a need for additional research.

[Workplace health promotion through human resources development part I: development and evaluation of qualification programme for prevention of psychic stresses]. / Betriebliche Gesundheitsförderung durch Personalentwicklung Teil I: Entwicklung und Evaluation eines Qualifizierungsprogramms zur Prävention psychischer Belastungen.

Caregivers of the residents in nursing homes are exposed to a high degree of physical and mental stress. The first part of this article deals with the development and evaluation of an intervention programme aiming at the staff's qualification to deal with these stresses. The main purpose of the programme was the improvement of the caregiver's methodical, social and self-care competences. A controlled study design was applied to evaluate the training effects. Seventeen homes for the elderly and nursing homes were involved in the pilot study. All participants of the intervention group (eleven homes) assessed their competences, their job conditions and their mental health status at the beginning and at the end of the training. The participants of the control group (six homes) assessed these aspects at the same time, but had no training in between. Furthermore, the intervention group took part in a third survey about twelve weeks after the intervention had been finished. Among the training participants, particularly the self-care skills improved (p=0.01). In addition, occupational stress could be reduced (p=0.01) and the climate with the residents enhanced (p=0.06). Compared to the changes also observed in the control group, statistically significant effects only confined to the change of the climate with the residents (p=0.01). In sum, the evaluation confirms the programme's success to develop the caregiver's professional competences in order to reduce their job stress. Further follow-up-studies are needed to investigate the long-term influence of behavioural prevention programmes like this on employee's health.

[Workplace health promotion through human resources development part II: practical transfer of qualification programme for prevention of psychic stresses]. / Betriebliche Gesundheitsförderung durch Personalentwicklung Teil II: Praxistransfer eines Qualifizierungsprogramms zur Prävention psychischer Belastungen.

This article is a follow-on from the first article on the development and evaluation of an intervention programme aiming to teach the staff of care facilities how to better deal with the mental strain they are exposed to. After a brief review of the programme's goal of 'increasing in-house health through staff development' and of the pilot study, this report initially shows how the findings from the pilot phase have been integrated into the original programme and what modifications have been carried out. For example, elements that proved to be successful such as the setting up of a 'steering circle' have been kept and, in addition, solutions for acknowledged weak points such as the insufficient transfer of the acquired knowledge to everyday work situations have been developed. In order to adequately support health care facilities during the implementation of the programme, additional courses to train multipliers who are to offer the necessary assistance, were carried out. The article also covers the evaluation of the quality of the development programme and of the accompanying implementation of the programme by the multipliers. At the end, a practical example is used to illustrate the issue and to demonstrate what actual shape the implementation at the different facilities can take.

Morphologic characterization of proliferative cells and virus particles in turkeys with lymphoproliferative disease.

The tumors found in turkeys having lymphoproliferative disease (LPD) are histologically characterized by a pleomorphic population of cells of the lymphoid series. Electron microscopy has shown that, despite marked differences in shape and size, the proliferating cells share basic ultrastructural features, indicating their lymphoid origin. Virus particles morphologically and morphogenetically characteristic of type C oncorna-viruses of Retraviridae were found in different organs and plasma samples of diseased or infected turkeys with LPD. This LPD type C virus resembled members of the reticuloendotheliosis virus group but not members of the avian sarcoma virus group.

Functional interactions between bile acids, all-trans retinoic acid, and 1,25-dihydroxy-vitamin D3 on monocytic differentiation and myeloblastin gene down-regulation in HL60 and THP-1 human leukemia cells.

Bile acids were shown previously to inhibit proliferation and to induce monocytic differentiation in HL60 human acute promyelocytic leukemia cells (A. Zimber et al., Int. J. Cancer, 59: 71-77, 1994). In this report, we hypothesized that bile acids may exert a positive cooperativity with two known inducers of leukemic cell differentiation, all-trans retinoic acid and 1,25(OH)2-vitamin D3. Our results provide evidence that bile acids induced the monocytic differentiation of HL60 and THP-1 human leukemia cells exposed to ineffective concentrations of these inducers. The protein kinase C (PKC) inhibitors H-7 (10 and 20 microM) and staurosporine (5 and 20 nM) modulated the effects of bile acids on HL60 cell differentiation. Most interestingly, bile acids are shown herein to down-regulate the expression of the serine protease myeloblastin gene involved in the differentiation of myeloid hematopoietic cells. In agreement with the recent identification of nuclear receptors for bile acids, our data suggest that functional interactions between nuclear bile acid signaling pathways, PKC, and nuclear receptors for retinoic acid and vitamin D3 are involved in the down-regulation of the myeloblastin gene and the induction of cell differentiation in human leukemic cells.

Bile acids stimulate invasion and haptotaxis in human colorectal cancer cells through activation of multiple oncogenic signaling pathways.

Bile acids are implicated in colorectal carcinogenesis as evidenced by epidemiological and experimental studies. We examined whether bile acids stimulate cellular invasion of human colorectal and dog kidney epithelial cells at different stages of tumor progression. Colon PC/AA/C1, PCmsrc, and HCT-8/E11 cells and kidney MDCKT23 cells were seeded on top of collagen type I gels and invasive cells were counted after 24 h incubation. Activation of the Rac1 and RhoA small GTPases was investigated by pull-down assays. Haptotaxis was analysed with modified Boyden chambers. Lithocholic acid, chenodeoxycholic acid, cholic acid and deoxycholic acid stimulated cellular invasion of SRC- and RhoA-transformed PCmsrc and MDCKT23-RhoAV14 cells, and of HCT-8/E11 cells originating from a sporadic tumor, but were ineffective in premalignant PC/AA/C1 and MDCKT23 cells. Bile acid-stimulated invasion occurred through stimulation of haptotaxis and was dependent on the RhoA/Rho-kinase pathway and signaling cascades using protein kinase C, mitogen-activated protein kinase, and cyclooxygenase-2. Accordingly, BA-induced invasion was associated with activation of the Rac1 and RhoA GTPases and expression of the farnesoid X receptor. We conclude that bile acids stimulate invasion and haptotaxis in colorectal cancer cells via several cancer invasion signaling pathways.

Evidence for the involvement of the Wnt 2 gene in human colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent cancers in humans. It develops via a multistage process involving alterations of both protooncogenes and tumor suppressor genes. In the present report we determined the level of expression of several Wnt genes in CRC by RT-PCR and direct sequencing. While Wnt-1 was not detectably expressed in any colonic tissues, Wnt-5a gene was efficiently expressed both in nontumorous as well as in colonic tumor tissues. In contrast, the Wnt-2 gene, which was expressed at low levels in normal colon, exhibited overexpression in all tumor tissue samples at the different Dukes' stages of CRC progression, including premalignant polyps and liver metastases. Overexpression of the Wnt-2 gene occurred also in other digestive neoplasms such as gastric and esophageal carcinomas, as well as in diverticulitis associated with stenosis or pseudo-tumor.

The arotinoid Ro 40-8757 has antiproliferative effects in drug-resistant human colon and breast cancer cell lines in vitro.

We have examined the antiproliferative effects of the arotinoid Ro 40-8757 in 3 drug-resistant human adenocarcinoma cell lines: the colonic cells HT29-5FU and CaCo2, and the mammary cells MCF-7mdr1. Whereas all-trans retinoic acid had no effect at the concentration of 10(-6) M, Ro 40-8757 was found to exert a high antiproliferative action with similar inhibitory potency (IC50) in drug-resistant and parental cell lines (range, 0.06 x 10(-6) to 0.57 x 10(-6) M). We conclude that: (1) thymidylate synthase is not involved in the mechanism of action of Ro 40-8757; (2) the mdr1 gene product does not recognize this retinoic derivative, and (3) Ro 40-8757, alone or in combinations with other cytotoxic drugs, can be very useful in patients with progressive disease after conventional chemotherapy.

Gs alpha availability to cholera toxin-catalysed ADP-ribosylation is decreased in membranes of retinoic acid-treated leukemic cell lines HL-60 and THP-1. A posttranslational effect.

Retinoic acid (RA) induces HL-60 and THP-1 leukemic cell lines to differentiate into granulocyte-like and monocyte-like cells. Limited data are available concerning the effects of RA on components of the cyclic AMP pathway in human myeloid leukemic cells. We showed previously a decrease in adenylate cyclase activity in the presence of histamine, prostaglandin E1 and forskolin in RA-treated HL-60 cells as compared to untreated cells. We examined the elements of the signal transduction pathway utilized by RA in the human myeloid cell line HL-60 and the human monocytic cell line THP-1. We therefore studied the effect of RA on the activity of the stimulatory G-protein (Gs). We demonstrate that addition of RA to two human myeloid leukemia cell lines, HL-60 and THP-1, does not induce a reduction of the 2 subunit of Gs (Gs alpha) RNA or Gs alpha protein in the plasma membrane but leads to a rapid decrease in the cholera toxin (CTX)-catalysed ADP-ribosylation of Gs alpha. In addition, this effect seems to be specific to RA, since there was no modification in Gs alpha ADP-ribosylation in the membranes of cells treated with dimethyl sulfoxide (DMSO), another inducer of differentiation in HL-60 cells.

The effect of high doses of methyl-CCNU on male and female fertility in SJL/J mice.

Single IP injection of high dose (LD 10) of methyl-CCNU administered to sexually mature male mice resulted in severe inhibition of spermatogenesis and reduction in testicular wet weight, without significant changes in plasma testosterone levels, and with hyperplasia of the interstitum, including Leydig cells, in the testis. These effects were temporary, spermatogenesis and testiculer weight recovered 50 days after treatment. Mating of the treated males with normal females demonstrated absolute sterility at 20 days and full recovery at 50 days after treatment. Administration of a single lethal dose (38 mg/kg, LD70) of methyl-CCNU to immature (25 day-old) male mice also caused severe but temporary inhibition of spermatogenesis, and mating of mice which survived the treatment and reached sexual maturity, with normal females, resulted in 80 to 100% pregnancies at 40 and 70 days after treatment, respectively. Three repeated injections of 30 mg/kg (at 10 day intervals) of methyl-CCNU to 15 day-old male mice resulted in inhibition of spermatogenesis without alteration in plasma testosterone. Ninety days after this treatment, only 40% of matings with normal females resulted in pregnancies. Female mice treated once with 20 mg/kg of methyl-CCNU, 3 days before or 7 days after mating with normal males, showed complete failure to complete pregnancy-resorption of the embryos was demonstrated in those female mice treated 7 days after mating. After a second mating trial with these two treated groups, performed 40 to 55 and 42 days after the first trial, respectively, 80 and 86% of the females delivered offspring. However, average litter size was reduced to 4 in the second group, as compared to 8 in untreated mice. There were no apparent birth defects in the offspring of methyl-CCNU treated male or female mice.

The role of bile acids in carcinogenesis.

Bile acids play a role in colorectal carcinogenesis as evidenced by epidemiological and experimental studies. Some bile acids stimulate growth of normal colonic and adenoma cells, but not of colorectal cancer cells. Moreover, bile acids stimulate invasion of colorectal cancer cells, at least in vitro. One possible mechanism of action is bile acid-induced DNA binding and transactivation of the activator protein-1 (AP-1) by co-operate activation of extracellular signal-regulated kinases (ERKs) and PKC signaling. In the present paper, we review the mechanisms by which bile acids influence carcinogenesis.

Effect of lymphoproliferative disease virus and of niridazole on the in vitro blastogenic response of peripheral blood lymphocytes of turkeys.

Turkeys inoculated at 5 weeks of age with lymphoproliferative disease (LPD) virus developed typical lesions in the spleen, thymus, and pancreas. The in vitro blastogenic response of peripheral blood lymphocytes to the mitogens phytohemagglutinin and concanavalin A was drastically (up to 90%) suppressed in the inoculated turkeys 1 to 4 weeks postinoculation compared with uninoculated controls, and even at 11 weeks the response was about 50% inhibited. A lethal (about LD33) dose of antihelminthic drug niridazole, 100 mg/kg given each day for 3 days to 4-week-old turkeys, caused a transient inhibition of the blastogenic response within 32 days of treatment, which was less pronounced than that observed in turkeys inoculated with LPD virus, whether pretreated with niridazole or not. Virus-associated reverse transcriptase activity in the plasma was significantly higher in the turkeys pretreated with niridazole, and LPD lesions developed to the same extent in the untreated and treated groups, as determined 9 weeks post virus inoculation. A sublethal dose of niridazole, 50 mg/kg given each day for 4 days, did not suppress the blastogenic response to mitogens at any time determined (starting 10 days post-treatment) and did not affect the pathogenesis of LPD and the viremia. Body weights were significantly decreased by virus infection and by treatment with lethal doses of niridazole.

Heterotransplantation of experimentally induced sheep lung adenomatosis into nude mice.

Male ICR nude mice inoculated subcutaneously with minced tissue obtained from pulmonary adenomatosis of sheep which was induced by RNA type-C retrovirus developed a transplant which contained cysts lined by a proliferative epithelium. These cysts showed several characteristics of the epithelial tumour cells of origin, such as high glycogen content and secretion of mucin. Microinvasion of epithelial cells from the adenomatous cysts into the stroma was observed. The stromal tissue demonstrated islets of cartilage. It was concluded that virus-induced pulmonary carcinoma of sheep can be transplanted and grown in nude mice.

Differences in production of solid Landhscütz tumours in BALB/c and ICR mice.

Landschütz tumour cells in the ascitic form injected subcutaneously into BALB/c or ICR mice produce solid tumours which grow progressively in most ICR mice but regress in nearly all BALB/c mice. Solid tumours in the peritoneal wall (produced by intraperitoneal inoculation of ascitic cells and treatment with normal serum) grew in both strains, but were more invasive in ICR mice. Surgical interference in BALB/c mice with these tumours, allowing adhesion of tumour to skin or subcutaneous fascia, resulted in cessation of tumour growth or regression.

Solid intraperitoneal Landschütz tumour in mice: implications in cancer chemotherapy and immunology studies.

Multiple intraperitoneal injections of various normal sera into BALB/c mice inoculated intraperitoneally with Landschütz ascites tumour cells abrogated the development of ascitic syndrome in almost all the animals. In a large proportion of the survivors solid intraperitoneal tumours developed, composed of characteristic ascites tumour cells engulfed and encapsulated in connective tissue. The effect of serum on the development of the solid tumour was diminished if the donor had been immunized against mouse IgG. Inoculated animals treated with serum hyperimmune against mouse IgG showed accelerated ascitic tumour growth. Cyclophosphamide or arabinosylcytosine strongly inhibited growth of solid tumours. Simultaneous administration of arabinosylcytosine and its antagonist cycloheximide did not interrupt tumour growth.

The effect of early treatment with methyl-CCNU on the lymphoid organs and the humoral immune response in chickens.

Presented are data upon the effect of a single or muliple administration of methyl-CCNU (a nitrosourea derivative an alkylating agent, and anticancer drug) to newly-hatched chicks. Lethal and sublethal doses of methyl-CCNU caused temporary damage to the lymphoid organs, of which the bursa was apparently the most sensitive. The decreased weight and the morphological changes observed in the bursa of treated chicks were accompanied by a parallel decrease in serum gamma-globulins level. The humoral immune response of animals treated with me-CCNU to sheep red blood cells and to killed Brucella abortus organisms was impaired in about 30% of the treated animals examined 8-10 weeks following 2 injections of 3 mg me-CCNU (given at the day of hatching and the next day). The thymus recovered rather rapidly from treatment. The time schedule of mortality and the early and late toxic manifestations of the drug as observed in chickens, in this study, are similar to previous reports obtained in mammals. Prolonged effects, however, were noted to some extent on body and spleen weight, and most dramatically, on testicular weight, morphology, and function.

Iron, transferrin, and acid and alkaline phosphatase in healthy turkeys and in turkeys inoculated with the lymphoproliferative disease virus.

Presented are data on iron-binding capacity determinations in the serum of turkeys infected with lymphoproliferative disease (LPD) virus and in healthy males and females (laying eggs and nonlaying) from a breeding flock. Also presented are results of serum and tissue total acid and alkaline phosphatase determinations in turkey poults infected with LPD virus and their uninfected controls and of serum enzyme levels in healthy males and females from the breeding flock. There was no significant alteration in total iron binding capacity (transferrin level) in the serum of turkeys with LPD. Turkey poults inoculated with LPD virus showed a significant decrease in serum alkaline phosphatase activity 4 and 7 weeks postinfection (pi), and a decrease in serum acid phosphatase activity 7 weeks pi. Acid and alkaline phosphatase activity determined in the spleen and pancreas (organs with pronounced tumor involvement) 7 weeks pi did not differ significantly from that of healthy controls, although there was a tendency for both enzymes to decline in the pancreas of the infected turkeys. Healthy laying female turkeys demonstrated marked elevation in serum transferrin level and in acid and alkaline phosphatase activity, as compared with males of the same age. Serum alkaline phosphatase of turkey poults was markedly higher than that of adult turkeys.