Changes in mouse submaxillary glands after injection of isoproterenol in intact and depancreatized animals

The changes in the relative weight, cell area and ultrastructure of the submaxillary glands (SMG) of CBA/C57BL mice and those in the content of immunoreactive insulin-like protein (IRILP) occurring in the organ were studied. The changes were examined on day 6 after isoproterenol (ISP) injection (23 mg/100 g bw) to healthy animals (group I), on day 13 after pancreatectomy and on day 6 after injection of the indicated dose of ISP (group II), and on day 13 after pancreatectomy without ISP injection (group III). Intact animals served as control. In all the three experimental groups, the ratio between the SMG weight and the total weight of animals showed a tendency towards increase. The highest increase was recorded in group II, where the weight of the SMG was 46.1% higher than the control value. In groups II and III, the area of acinar cells increased by 49.1 and 12.5%, respectively. The area of salivary tube granular ducts decreased by 12.6% in group II and slightly increased (by 4.7% much greater than in group III. Electron microscopy demonstrated that secretory activity of the granular duct cells was enhanced in all the three groups and that secretory extrusion occurred via the apocrine (in group II animals via the holocrine as well) cells. The radioimmunoassay data suggest that IRILP content in the SMG of controls and animals entering groups I-III was 685 +/- 50, 1125 +/- 125, 914 +/- 120 and 302 +/- 66 mu units/g weight, respectively. It is concluded that the synthesis and accumulation of IRILP in the SMG after ISP injection are activated and that the formation and extrusion of IRILP after ISP injection to diabetic animals are overtly activated. Presumably ISP injection to diabetic mice facilitates the stimulation of the compensatory function of the SMG as an IRILP-producing organ.     

immunocytochemical localization of urokinase-type plasminogen activator in lewis lung carcinoma

The invasively growing and metasizing Lewis lung carcinoma consistently contained urokinase-type plasminogen activator (u-PA) enzyme activity. When investigated immunocytochemically with antibodies against u-PA, different parts of individual tumors showed a pronounced heterogeneity in staining intensity. Strong staining was found in areas with invasive growth and degradation of surrounding normal tissue, while other areas were completely devoid of staining. Immunoreactivity occurred both with a perinuclear cytoplasmic localization in tumor cells and associated with apparently extracellular material. SDS PAGE of tumor extracts, under both reducing and nonreducing conditions, followed by immunoblotting, showed only one immunocytochemically stainable band with an electrophoretic mobility corresponding to that of purified proenzyme to u-PA, while no two-chain u-PA was detected. This indicates that the major part of the activator in Lewis lung carcinoma is present as one-chain pro-u-PA.     

Mouse splenocyte sensitization to normal tissue antigens and natural killer activity. III. The effect of partial hepatectomy

Partial hepatectomy leads to both increasing of natural cell-mediated activity and sensibilization level (SL) of splenocytes of hepatectomized mice towards antigens of the syngeneic liver. The wave-like variability of SL was shown with sharp increase at 3, 6 and 9 days after operation. Natural killer activity was elevated on the 2nd and 10th days with a significant decrease on the 3-4th days after operation. It is assumed that the variability in the functional activity of splenocytes under study may characterized splenocytes of different populations.     

Prognostic value of non-MHC-restricted killer cell activity in lung cancer

The prognostic value of peripheral blood non-MHC-restricted cytotoxicity against the myeloid leukaemic line K562 in lung cancer patients was studied. At the time of diagnosis and before operation, 57 patients with lung cancer were tested for cytotoxicity and subsequently followed for up to 4 years. In addition, 145 lung cancer patients, 30 patients with non-neoplastic lung diseases and 76 healthy donors were tested for cytotoxicity without the follow-up, in order to correlate the stage of lung cancer and the growth rate of tumours to the level of non-MHC-restricted cytotoxicity. On average, lung cancer patients had similar non-MHC-restricted cytotoxicity to the controls. However, patients with stage II–IV diseases showed an impaired activity, stages III and IV differing significantly from the controls. This result shows that the decline in natural killer (NK) activity is associated with tumour burden. Patients with slowly growing neoplasms had stronger cytotoxic activity than patients with fast or moderately progressing disease. In the follow-up study, the whole material of 57 patients showed only a slight correlation between cytotoxicity and survival: 42% of the patients with strong activity survived for more than 2.5 years, whereas 6% of the patients with weak activity did so. In stage I patients there was no correlation between cytotoxicity and survival, nor was there a correlation in patients with stages II–IV of the disease. Hence, in our group of patients the determination of cytotoxicity preoperatively yielded no prognostic information beyound that already available from staging. However, those stage II–IV patients that survived for 1 year or more after the diagnosis and cytotoxicity tests, showed a significant correlation between cytotoxicity and survival.     

Immunomodulating effect of cyclophosphamide on cytotoxic activity of rat and mouse splenocytes

The goal of this work consisted in study of the immunomodulating action of the cytostatic drug cyclophosphamide (CP) on the natural cytotoxic activity of rat and mice splenocytes. The cytotoxicity of effector cells (EC) with respect to monolayer cell lines of the Zajdela rat hepatoma and the HTC rat hepatoma and of the MH-22a mouse hepatoma was determined with the aid of morphometric analysis. CP at a dose of 100 mg/kg 48 h after administration to animals has been shown to produce an immunomodulating effect on cytotoxicity of splenocytes—a suppressive one with respect to cell-targets (CT) of Zajdela hepatoma and an immunopotentiating one with respect to CT of HTC and MH-22 hepatomas. Possible mechanisms of the CP immunopotentiating action are discussed.     

Post-construction avian mortality monitoring at Project West Wind

Abstract

Post-construction avifauna investigations were undertaken at Project West Wind, Meridian Energy Limited's 62-turbine wind farm on the Wellington south coast. These investigations were required in accordance with the resource consent conditions to quantify the level of avian mortalities occurring at the wind farm, particularly in regard to New Zealand falcon (Falco novaeseelandiae), kākā (Nestor meridionalis) and kererū (Hemiphaga novaeseelandiae). This is the first comprehensive study at a New Zealand operating wind farm. The methods included three field components necessary to calculate annual estimates of mortalities across the wind farm site: routine turbine searches; carcass detection trials; and carcass removal trials. Results from years 1 and 2 of a three-year programme are presented. To date, mortalities have been recorded for 17 taxa at 18 of the 24 study turbines. There have been no recorded mortalities of falcon, kākā or kererū. Australasian harrier (Circus approximans) has been the species for which the most mortalities have been recorded. Overall estimated annual mortality rates for years 1 and 2 were calculated to be approximately six and five birds per turbine respectively.     

Genetic architecture of survival and fitness-related traits in two populations of Atlantic salmon

The additive genetic effects of traits can be used to predict evolutionary trajectories, such as responses to selection. Non-additive genetic and maternal environmental effects can also change evolutionary trajectories and influence phenotypes, but these effects have received less attention by researchers. We partitioned the phenotypic variance of survival and fitness-related traits into additive genetic, non-additive genetic and maternal environmental effects using a full-factorial breeding design within two allopatric populations of Atlantic salmon (Salmo salar). Maternal environmental effects were large at early life stages, but decreased during development, with non-additive genetic effects being most significant at later juvenile stages (alevin and fry). Non-additive genetic effects were also, on average, larger than additive genetic effects. The populations, generally, did not differ in the trait values or inferred genetic architecture of the traits. Any differences between the populations for trait values could be explained by maternal environmental effects. We discuss whether the similarities in architectures of these populations is the result of natural selection across a common juvenile environment.     

The influence of tumor growth on natural cytotoxicity and activity of some lysosomal enzymes of human effector cells and the C3HA mouse splenocytes

In the course of malignant growth processes in patients with lung cancer, a decrease of natural cytotoxic activity of peripheral blood lymphocytes was observed. This process was accompanied by changes of activities of two lysosomal enzymes, arylsulfatase and acid phosphatase, suggesting participation of these enzymes in manifestation of effector functions of lymphocytes in cancer patients. The level of activity of granular enzyme, beta-glucuronidase, remained unchanged at all stages of disease. A study of natural killer activity of C3HA mice splenocytes after inoculation of transplantable hepatoma 22-a cells revealed a relative stability of the level of their cytotoxicity, and of the activities of lysosomal enzymes--arylsulfatase, acid phosphatase, alpha-mannosidase, acid lipase, N-acetyl-beta-D-glucosidase, and beta-galactosidase, beginning from the 3rd day after hepatoma implantation.     

Effect of immunosuppressors cyclophosphane and 5-fluorouracil on natural cytotoxicity and activity of lysosomal enzymes of splenocytes in C3HA mice

Effects of two immunosuppressors, cyclophosphane abd 5-fluorouracyl, used in clinical practice for treatment of oncological diseases, were assessed in respect to cytotoxicity and activity of several lysosomal enzymes located in splenocyte granules of C3HA mice. 48 h after a single intraperitoneal injection, both preparations produced a marked decrease in their cytotoxic activity, which was accompanied by a pronounced splenopathy. Both preparations were shown to decrease activity of arylsulfatase. Administration of cyclophosphane brought about the rise of activity of acid lipase as compared to control. Activities of acid phosphatase, alpha-mannosidase, beta-galactosidase, and N-acetyl-beta-D-glucosidase did not change after administration of the used immunosuppressors. It may be suggested that only arylsulfatase and acid lipase are involved in performance and(or) manifestation of the natural killer activity in splenocytes of the C3HA mice after their administration with cyclophosphane or 5-fluorouracyl.     

Leptin activation of mTOR pathway in intestinal epithelial cell triggers lipid droplet formation,cytokine production and increased cell proliferation

Accumulating evidence suggests that obesity and enhanced inflammatory reactions are predisposing conditions for developing colon cancer. Obesity is associated with high levels of circulating leptin. Leptin is an adipocytokine that is secreted by adipose tissue and modulates immune response and inflammation. Lipid droplets (LD) are organelles involved in lipid metabolism and production of inflammatory mediators, and increased numbers of LD were observed in human colon cancer. Leptin induces the formation of LD in macrophages in a PI3K/mTOR pathway-dependent manner. Moreover, the mTOR is a serine/threonine kinase that plays a key role in cellular growth and is frequently altered in tumors. We therefore investigated the role of leptin in the modulation of mTOR pathway and regulation of lipid metabolism and inflammatory phenotype in intestinal epithelial cells (IEC-6 cells). We show that leptin promotes a dose- and time-dependent enhancement of LD formation. The biogenesis of LD was accompanied by enhanced CXCL1/CINC-1, CCL2/MCP-1 and TGF-β production and increased COX-2 expression in these cells. We demonstrated that leptin-induced increased phosphorylation of STAT3 and AKT and a dose and time-dependent mTORC activation with enhanced phosphorilation of the downstream protein P70S6K protein. Pre-treatment with rapamycin significantly inhibited leptin effects in LD formation, COX-2 and TGF-β production in IEC-6 cells. Moreover, leptin was able to stimulate the proliferation of epithelial cells on a mTOR-dependent manner. We conclude that leptin regulates lipid metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on activation of the mTOR pathway, thus suggesting that leptin-induced mTOR activation may contribute to the obesity-related enhanced susceptibility to colon carcinoma.