Marked post-18th century environmental change in high-arctic ecosystems.

Paleolimnological data from three high-arctic ponds on Cape Herschel, Ellesmere Island, Canada, show that diatom assemblages were relatively stable over the last few millennia but then experienced unparalleled changes beginning in the 19th century. The environmental factors causing these assemblage shifts may be related to recent climatic warming. Regardless of the cause, the biota of these isolated and seemingly pristine ponds have changed dramatically in the recent past and any hopes of cataloging natural assemblages may already be fruitless.

Impacts of climatic change and fishing on Pacific salmon abundance over the past 300 years.

The effects of climate variability on Pacific salmon abundance are uncertain because historical records are short and are complicated by commercial harvesting and habitat alteration. We use lake sediment records of delta15N and biological indicators to reconstruct sockeye salmon abundance in the Bristol Bay and Kodiak Island regions of Alaska over the past 300 years. Marked shifts in populations occurred over decades during this period, and some pronounced changes appear to be related to climatic change. Variations in salmon returns due to climate or harvesting can have strong impacts on sockeye nursery lake productivity in systems where adult salmon carcasses are important nutrient sources.

The effect of dietary fiber level on milk fat concentration and fatty acid profile of cows fed diets containing low levels of polyunsaturated fatty acids.

The objective of this study was to investigate the effect of dietary fiber level on milk fat concentration, yield, and fatty acid (FA) profile of cows fed diets low in polyunsaturated fatty acid (PUFA). Six rumen-fistulated Holstein dairy cows (639 +/- 51 kg of body weight) were used in the study. Cows were randomly assigned to 1 of 2 dietary treatments, a high fiber (HF; % of dry matter, 40% corn silage, 27% alfalfa silage, 7% alfalfa hay, 18% protein supplement, 4% ground corn, and 4% wheat bran) or a low fiber (LF; % of dry matter, 31% corn silage, 20% alfalfa silage, 5% alfalfa hay, 15% protein supplement, 19% ground wheat, and 10% ground barley) total mixed ration. The diets contained similar levels of PUFA. The experiment was conducted over a period of 4 wk. Ruminal pH was continuously recorded and milk samples were collected 3 times a week. Milk yield and dry matter intake were recorded daily. The rumen fluid in cows receiving the LF diet was below pH 5.6 for a longer duration than in cows receiving the HF diet (357 vs. 103 min/d). Neither diet nor diet by week interaction had an effect on milk yield (kg/d), milk fat concentration and yield, or milk protein concentration and yield. During wk 4, milk fat concentration and milk fat yield were high and not different between treatments (4.30% and 1.36 kg/d for the HF treatment and 4.31% and 1.33 kg/d for the LF treatment, respectively). Cows receiving the LF diet had greater milk concentrations (g/100 g of FA) of 7:0; 9:0; 10:0; 11:0; 12:0; 12:1; 13:0; 15:0; linoleic acid; FA

Development of a flow cytometric assay to quantify lymphocyte adhesion to cytokine-stimulated human endothelial and biliary epithelial cells.

The adhesive interaction between T lymphocytes and parenchymal cells is of importance for many processes of the cellular immune response. This adhesion is regulated by the activation status of the T cell and by cytokines in the microenvironment which can alter adhesion molecule expression by endothelial and epithelial cells. In this study results from an isotopic adhesion assay were compared with those from a flow cytometric assay in order to determine which was most appropriate for the investigation of lymphocyte adhesion to human umbilical vein endothelial cells (HUVEC) and intrahepatic biliary epithelial cells (HIBEC). Treatment of both these cell types with the proinflammatory cytokines interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) significantly upregulated expression of intercellular adhesion molecule-1 (ICAM-1). Treatment with TNF-alpha also induced endothelial cells to express vascular cell adhesion molecule-1 (VCAM-1). The isotopic assay demonstrated increased adhesion of lymphoblasts to HUVEC which had been stimulated with cytokines for 15 h but failed to detect major changes in adhesion following 72 h of cytokine treatment of HUVEC or HIBEC. However, the flow cytometric assay reproducibly demonstrated increased adhesion following cytokine treatment for both these time periods; these increases corresponded with the changes in adhesion molecule expression by cytokine-stimulated HUVEC and HIBEC targets. The differences in apparent adhesion measured by the two assays after cytokine stimulation for 72 h may be explained by cytokine-induced changes in the morphology and confluency of cultured cells. Results of the isotopic assay are proportional to the total number of lymphoid cells bound by the cultured target cells and will be distorted by changes in effective target cell area. The flow cytometric assay measures the mean number of lymphoid cells bound by each target cell and is independent of the total binding area. It is concluded that the flow cytometric assay is more suitable than the isotopic technique for following time-dependent changes in the adhesion of leukocytes to cytokine-stimulated target cells.

Prevalence and stability of social skill deficits in schizophrenia.

The prevalence of social skill deficits in schizophrenia was examined by comparing patients assessed over a 1 year period with a group of non-patient controls recruited from the community. Social skills were assessed using a role play test and were considered deficient when they were below the range of the control sample. Approximately 50% of the patients were consistently unskilled over the one year, whereas 11% were consistently skilled. Deficits in specific social skills were relative rare. Consistent deficits were present for only one of six specific skills: 14% of the patients were consistently less appropriate in their conversational turn-taking (Meshing) than the controls. Patients' social skills were relatively stable over time. The implications of these results for the assessment and remediation of social skill impairments in schizophrenia are discussed.

Assessment of enduring deficit and negative symptom subtypes in schizophrenia.

The clinical importance of subtypes based on enduring deficit or negative symptoms was examined in a group of schizophrenic patients who were assessed twice over a 1-year period. Subgroups of patients with high levels of enduring negative or deficit symptoms, based on the Scale for the Assessment of Negative Symptoms and the Quality of Life Scale, had a poorer prognosis and were consistently worse in social adjustment, quality of life, and thought disorder over the year than were patients with less severe negative symptoms. Subtypes based on Andreasen's negative schizophrenia classification and on enduring thought disorder were only weakly related to other symptoms and social adjustment. Social-skill deficits were weakly related to the enduring negative symptom subtype and Andreasen's negative schizophrenia. The results suggest that enduring negative and deficit symptoms may be associated with a poor outcome in schizophrenia, including more severe positive symptoms, lower levels of social adjustment, and a poorer quality of life.

Prediction of social skill acquisition in schizophrenic and major affective disorder patients from memory and symptomatology.

Memory and symptomatology were examined as predictors of social skill acquisition in psychiatric inpatients participating in a social skills training program. Poor memory was related to pretreatment social skill impairments and slower rates of skill improvement during the intervention for patients with schizophrenia or schizoaffective disorder, but not affective disorder. Symptomatology was not consistently related to pretreatment social skill or changes in skill for either schizophrenic or affective disorder patients. The results suggest that cognitive deficits in schizophrenia are associated with impairments in social skill and that such deficits may limit the rate of skill acquisition and clinical response to social skills training interventions.

Nurses' perspectives on unconventional therapies.

Unconventional therapies have become increasingly popular with health care consumers in recent years. As patients seek information and attempt to make decisions about unconventional therapies, they often turn to nurses, asking the nurse's opinion about certain therapies. The nurse's attitudes and beliefs about unconventional therapies quite likely will influence the response to the patient's inquiries. This article represents the findings of interviews with 20 nurses regarding their perspectives on unconventional therapies. Without exception, all nurses who were interviewed emphasized that information regarding unconventional therapies needs to be available readily for both patients and health care professionals. Other themes identified in the interviews included the following: Various people use unconventional therapies; people seek unconventional therapies for a variety of reasons; communication about unconventional therapies needs to be open, and a place should be found for unconventional therapies. The interviewees saw a clearly defined role for nurses regarding unconventional therapies.

Oncology nurses' perspectives on unconventional therapies.

Unconventional therapies have become increasingly popular with health care consumers in recent years. As patients seek information and attempt to make decisions about unconventional therapies, they often turn to nurses, asking their opinion about certain therapies. The nurse's attitudes and beliefs about unconventional therapies very likely will influence the response to the patient's inquiries. This work represents the findings of interviews with 48 nurses regarding their perspectives on unconventional therapies. Without exception, all nurses interviewed emphasized the need for information regarding unconventional therapies to be readily available for patients and health care professionals. The other themes identified in the interviews included the following: various people use unconventional therapies; people seek unconventional therapies for a variety of reasons; communication about unconventional therapies needs to be open; and conventional and unconventional practitioners ought to work collaboratively. The participants interviewed saw a clearly defined role for nurses regarding unconventional therapies.

Physician perspectives on unconventional cancer therapies.

The popularity of unconventional therapies has grown dramatically in recent years. This paper reports on the results of a pilot study investigating the perspectives of physicians involved with cancer care regarding their reactions to this trend and their ways of trying to meet associated challenges. Nine oncologists, nine general practitioners, and one surgeon were interviewed over the telephone, employing open-ended questions. The physicians were unanimously interested in having information available about unconventional therapies. They also expressed a desire to be supportive of patient choices in this area, provided conventional therapy was not compromised. However, there was little interest in initiating communication about unconventional therapies, with most seeing such discussions as a poor use of their time. Suggestions for future research, as well as educational and policy strategies, are addressed.

Teaching conflict resolution skills to the chronically mentally Ill. Social skills training groups for briefly hospitalized patients.

Previous research on social skills training has demonstrated its usefulness as an adjunct treatment for a variety of psychiatric disorders. At the Medical College of Pennsylvania at Eastern Pennsylvania Psychiatric Institute, an acute-care psychiatric hospital, a social skills training group has been in operation for over 3 years. The group is unique in its format in several ways that are described in this article. Data collected over the 3-year period are also presented. The major findings indicate that even over a very brief period of time during an acute hospitalization, patients can learn basic conflict resolution skills. Some predictors of skill acquisition were also identified.

Partnerships between self-help networks and health care facilities: the case of the Bayview Support Network.

This article discusses the role of patients and their families as peer support providers to other patients, and as decision makers within organizations. We use as a model the Bayview Support Network, a self-help network at the Toronto-Sunnybrook Regional Cancer Centre. We review the benefits of partnership, costs, limitations and risks. A list of features that contribute to effective partnership is also provided.

Monocyte chemotaxis and chemotactic cytokine release after exposure to hydroxyethyl starch.

Hydroxyethyl starch (HES) is commonly used in leukapheresis and infused as an alternative to blood components for the treatment of hypotension due to hemorrhage and trauma. Its prolonged intravascular persistence and retention in tissue raise concerns about possible effects on humoral and cell-mediated immunity and white cell (WBC) locomotion, particularly in volunteer WBC donors or in severely burned individuals with immunologic depression and increased risk for infection. This study evaluated the effect of HES on human monocyte migration and chemotaxis and the production of antigen- and mitogen-induced WBC-derived chemotactic cytokine. A bioassay was developed to quantitate the neutrophil chemotactic activity of a cytokine generated by mononuclear WBCs stimulated in vitro by phytohemagglutinin or tuberculin protein. The time- and dose-dependent generation of the chemotactic cytokine was not affected by the presence of HES. HES by itself did not induce the generation of this cytokine, nor were human monocyte chemotaxis and spontaneous migration significantly changed by exposure to HES. These results, with those of other investigators, suggest that HES is a safe red cell-sedimenting agent for leukapheresis and an alternative to the use of blood components in shock resuscitation.

Examination of the mechanism by which heparin antagonizes activation of a model endothelium by interferon-gamma (IFN-gamma).

IFN-gamma increases the potential immunogenicity of vascular endothelial cells by up-regulation of intercellular adhesion molecule-1 (ICAM-1) and class I MHC antigen expression and by induction of class II MHC antigens and certain chemokines. In this study the mechanism by which the glycosaminoglycan (GAG) heparin antagonizes the activation of a model endothelium by IFN-gamma was investigated. Radioligand binding assays demonstrated that total binding of 125I-IFN-gamma to the EAhy.926 endothelial hybridoma cell line was reduced in the presence of heparin or heparan sulphate (HS); the structurally dissimilar GAG chondroitin sulphate had no effect. Treatment of the cells with chlorate, a metabolic inhibitor of GAG sulphation, was found to reduce both the subsequent binding of IFN-gamma and its ability to induce expression of class II MHC antigens. Treatment with heparinase II dramatically reduced the binding of IFN-gamma, while chondroitin ABC lyase had no effect. A cationic peptide from the C-terminal region of IFN-gamma was also found to reduce binding of intact IFN-gamma to the cells. These results appear to demonstrate that IFN-gamma is sequestered at the surface of endothelial cells by electrostatic interaction between specific basic amino acid residues and sulphated domains on HS, the most abundant endothelial GAG. This interaction is competitively inhibited by heparin, which is structurally related to HS. These observations are consistent with the model that IFN-gamma is bound by membrane-associated HS before engagement with the high-affinity receptor and signal transduction. Inhibition of the interaction between proinflammatory cytokines and membrane-associated GAG molecules may provide a mechanism for inducing clinically useful immunosuppression.

Endothelial production of MCP-1: modulation by heparin and consequences for mononuclear cell activation.

Heparin is a polyanionic glycosaminoglycan (GAG) that can bind with high affinity to a range of cytokines including interferon-gamma (IFN-gamma) and members of the chemokine superfamily. This GAG also possesses immunomodulatory activity in vivo and can antagonize the capacity of IFN-gamma to induce class II MHC antigen expression, and to up-regulate intercellular adhesion molecule-1, by cultured endothelial cells. Previous studies have shown that binding to cell-surface heparan sulphate is essential for optimal activity of IFN-gamma and that free heparin competitively inhibits this sequestration process. The present study was performed to increase our understanding of the immunosuppressive activity of heparin by investigation of potential antagonism of the production and function of monocyte chemotactic peptide-1 (MCP-1), a chemokine important for mononuclear leucocyte recruitment across vascular endothelium. It was found that mixture of heparin with IFN-gamma inhibited up-regulation of the signal transducer and activator of transcription protein, STAT-1 produced normally by treatment of endothelial cells with IFN-gamma. An inhibition of MCP-1 production was observed that was specifically caused by mixture of IFN-gamma with heparin-like, and therefore cytokine-binding, GAGs. It was also shown that mixture of heparin-like GAGs with MCP-1 inhibited the rapid tyrosine phosphorylation of phosphatidylinositol 3-kinase which is normally produced by treatment of mononuclear leucocytes with this chemokine. Blockade of this intracellular signalling event was associated with a reduction in the normal transendothelial migration response towards MCP-1. Results from this study indicate that soluble, heparin-like GAGs can block IFN-gamma-dependent up-regulation of MCP-1 production by cultured endothelial cells, and can also antagonize the leucocyte-activating and migration-promoting properties of pre-existing MCP-1. These activities may contribute to the immunomodulatory properties of heparin.

Role of glycosaminoglycans (GAGs) in regulation of the immunogenicity of human vascular endothelial cells.

Heparan sulphate is a common glycosaminoglycan component of proteoglycans present on the luminal surface of vascular endothelium. It has been proposed that an important function of these molecules is the sequestration of a range of proinflammatory and proadhesive cytokines. Such cytokines play a vital role during lymphocyte recruitment from the blood at sites of inflammation. In this study it is shown that the effects of interferon-gamma (IFN-gamma), but not of tumour necrosis factor-alpha (TNF-alpha), are inhibited by treatment with soluble heparin. Specifically, heparin was shown to inhibit the induction of class II MHC antigens and the up-regulation of intercellular adhesion molecule-1 (ICAM-1) produced by treatment of cultured human endothelial cells with IFN-gamma. Furthermore, it was shown that heparin blocked the enhanced adhesion of T lymphocytes to IFN-gamma-treated endothelial cells. Investigation of the inhibitory effects of other GAG molecules demonstrated a requirement for heparin-like structural domains as chondroitin sulphate was unable to inhibit the function of IFN-gamma. These results may explain reported immunosuppressive properties of heparin, and are consistent with the model that heparin may compete with cell surface GAGs to bind IFN-gamma, thereby reducing effective biological activity.

Cryoprotectant toxicity and cryoprotectant toxicity reduction: in search of molecular mechanisms.

Cryoprotectant toxicity is a fundamental obstacle to the full potential of artificial cryoprotection, yet it remains in general a poorly understood phenomenon. Unfortunately, most relevant biochemical studies to date have not met the basic criteria required for demonstrating mechanisms of toxicity. A model biochemical study of cryoprotectant toxicity was that of Baxter and Lathe, which demonstrated that alteration of a specific enzyme (fructose diphosphatase, or FDPase) was the cause of impaired glycolysis after treatment with and removal of dimethyl sulfoxide (D). FDPase alteration by D was reported to be preventable by the simultaneous presence of amides. This protection could be due to a "counteracting solute" effect similar to that employed by nature, but we find no meaningful correlation between the general protein stabilizing or destabilizing tendency of the cryoprotectant medium and its toxicity. Baxter and Lathe postulated that the effect of D arises from hydrogen bonding between D and the epsilon amino groups of surface lysine residues on FDPase, and it was found that molecules which resembled this group could block the alteration induced by D, presumably by competing with lysine residues for association with D. However, we find that the interaction between D and lysine in the presence of water is actually thermochemically repulsive, and that the presence of formamide does not affect the interaction between D and lysine, implying no useful complex formation between formamide and D. We were also unable to demonstrate that the blocking compounds consistently reduce toxicity when added to D rather than substituting for D, contrary to predictions based on complex formation between blocking compounds and D. In summary, it seems that present concepts of cryoprotectant toxicity are in need of serious revision.

A strategy for informing patients and health professionals about unconventional cancer therapies.

BACKGROUND: A Guide to Unconventional Cancer Therapies was produced by the Ontario Breast Cancer Information Exchange Project with the intention of meeting needs of patients, family members, and health professionals for information about unconventional therapies. Concerns raised by health professionals during the development of the guide serve as a focus for considering its impact on cancer patients who purchased it. MATERIALS AND METHODS: Purchasers of the guide were sent a survey questionnaire inquiring about their access to, use of, and attitudes toward it. RESULTS: A total of 634 individuals responded to the survey, including cancer patients, health professionals, and family members. The guide was rated moderately helpful overall, and health professionals found it significantly more helpful than did cancer patients. A minority of patients were influenced to try an unconventional therapy as a result of reading the guide. Those who did try a new therapy typically chose ones that are most popular and have few potential negative effects. CONCLUSIONS: As an informational strategy, the Guide to Unconventional Cancer Therapies has been successful. Concerns expressed by some health professionals about potential harm through implementing the strategy have been shown to be largely unwarranted, at least for study respondents.