Fire cycles in North American interior grasslands and their relation to prairie drought.

High-resolution analyses of a late Holocene core from Kettle Lake in North Dakota reveal coeval fluctuations in loss-on-ignition carbonate content, percentage of grass pollen, and charcoal flux. These oscillations are indicative of climate-fuel-fire cycles that have prevailed on the Northern Great Plains (NGP) for most of the late Holocene. High charcoal flux occurred during past moist intervals when grass cover was extensive and fuel loads were high, whereas reduced charcoal flux characterized the intervening droughts when grass cover, and hence fuel loads, decreased, illustrating that fire is not a universal feature of the NGP through time but oscillates with climate. Spectral and wavelet analyses reveal that the cycles have a periodicity of approximately = 160 yr, although secular trends in the cycles are difficult to identify for the entire Holocene because the periodicity in the early Holocene ranged between 80 and 160 yr. Although the cycles are evident for most of the last 4,500 yr, their occasional muting adds further to the overall climatic complexity of the plains. These findings clearly show that the continental interior of North America has experienced short-term climatic cycles accompanied by a marked landscape response for several millennia, regularly alternating between dual landscape modes. The documentation of cycles of similar duration at other sites in the NGP, western North America, and Greenland suggests some degree of regional coherence to climatic forcing. Accordingly, the effects of global warming from increasing greenhouse gases will be superimposed on this natural variability of drought.

Synthesis, characterization, and activity of metabolites derived from the cyclooxygenase-2 inhibitor rofecoxib (MK-0966, Vioxx).

Metabolites of the COX-2 inhibitor rofecoxib (MK-0966, Vioxx) were prepared by synthetic or biosynthetic methods. Metabolites include products of oxidation, glucuronidation, reduction and hydrolytic ring opening. Based on an in vitro whole blood assay, none of the known human metabolites of rofecoxib inhibits COX-1 nor contributes significantly to the inhibition of COX-2.

Characterization of human copine III as a phosphoprotein with associated kinase activity.

The copines, first described by Creutz et al. [(1998) J. Biol. Chem. 273, 1393-1402], comprise a two C2 domain-containing protein family and are known to aggregate phosphatidylserine membranes in a calcium-dependent manner. No enzymatic function has been attributed to copines yet. Due to a cross-reacting activity of Mikbeta1, an antibody to the IL-2Rbeta chain, we were able to serendipitously purify, partially microsequence, and clone human copine III. The 5 kb copine III transcript is expressed ubiquitously as determined by a multitissue Northern blot analysis. Phosphoamino acid analysis revealed phosphorylation of copine III on serine and threonine residues. In vitro kinase assays were performed with immunoprecipitated endogenous copine III, chromatography-purified endogenous copine III, and recombinant copine III expressed in Saccharomyces cerevisiae. The exogenous substrate myelin basic protein was phosphorylated in all in vitro kinase assays containing copine III immunoprecipitate or purified copine III. A 60-kDa band was observed in corresponding in gel kinase assays with staurosporine-activated cells. Cell lines expressing high levels of copine III protein had correspondingly high kinase activity in copine III antiserum immunoprecipitate. However, the copine amino acid sequences lack the traditional kinase catalytic domain. Therefore, the data suggest copine III may possess an intrinsic kinase activity and represent a novel unconventional kinase family.

Coping, life attitudes, and immune responses to imagery and group support after breast cancer treatment.

BACKGROUND: The pilot study used clinical trial methodology to differentiate the effects of imagery and support on coping, life attitudes, immune function, quality of life, and emotional well-being after breast cancer. METHODS: Women (N = 47) who completed treatment for primary breast cancer, excluding stage IV, were randomly assigned to standard care (n = 15) or six weekly support (n = 16) or imagery (n = 16) sessions. Self-report measures included Ways of Coping-Cancer, Life Attitude Profile, Quality of Life (FACT-B), Profile of Mood States, and Functional Support. Immune measures included natural killer cell activity, plasma neopterin, interferon-gamma, interleukins 1 alpha, 1 beta, and 2, and beta-endorphin levels. Differences between groups over time were tested using general linear models, adjusted for pretest score and covariates (age, stage, and months posttreatment). RESULTS: For all women, interferon-gamma increased, neopterin decreased, quality of life improved, and natural killer activity remained unchanged. Compared with standard care, both interventions improved coping skills (seeking support) and perceived social support, and tended to enhance meaning in life. Support boosted overall coping and death acceptance. When comparing imagery with support, imagery participants tended to have less stress, increased vigor, and improved functional and social quality of life. CONCLUSION: Although imagery reduced stress and improved quality of life, both imagery and support improved coping, attitudes, and perception of support. The clinical implications of these changes warrant further testing.

Molecular analysis of a silent polymorphism in the PDZ domain of p55, the major palmitoylated erythrocyte membrane protein.

Two independently published cDNA sequences of p55, the X-linked major palmitoylated erythrocyte membrane protein, revealed a discrepancy between G and T at position 358 (Genbank: M64925). This results in codon 85, in exon 3 in the PDZ (PSD-95, discs-large, Z0-1) domain, being either ACG or ACT. As both ACG and ACT code for threonine, this represents a silent polymorphism. Polymerase chain reaction (PCR), single-stranded conformational polymorphism (SSCP), and direct-sequencing analysis of exon 3 of the p55 gene was performed in 98 subjects of African and European origin. Of the 70 females studied, the frequency of G versus T at position 358 was 0.76:0.24, while of the 28 males, 16 had a G and 12 a T at position 358 (0.57:0.43). In subjects of African origin, the frequency of G versus T at position 358 was 0.78:0.22; in subjects of European origin the ratio was 0.63:0.37.

Sequential TNF and TGF-beta regulation of expansion and induction of cytotoxicity in long-term cultures of lymphokine-activated killer cells.

Therapeutic use of lymphokine-activated killer (LAK) cells frequently requires higher numbers of effector cells than can be produced in short-term cultures. Extended stimulation of these cells by interleukin-2 (IL-2) past 2 weeks leads to a decrease in cytolytic activity and cell proliferation. To determine how known regulatory cytokines are involved in the mechanism responsible for loss lf IL-2 responsiveness, adherent LAK (A-LAK), nonadherent LAK (NA-LAK), monocyte-depleted (MD-LAK), and unmanipulated LAK (UN-LAK) cells derived from human peripheral blood were stimulated with high-dose IL-2 for 4 weeks, and cytokine production was measured serially. Despite continued supplementation with IL-2, cell number plaeaued at 2 weeks with a 2.5-3.0 log increase in A-LAK cultures and a 1.0 log increase in NA-LAK, MD-LAK, and UN-LAK cultures. Cytolytic activity had decreased significantly in all four culture systems after only 14 days of stimulation with IL-2 as assessed by the chromium release assay using K562, Daudi, and RP-mel tumor cell lines as targets, and LAK activity was barely detectable after 28 days of stimulation. Bioactive tumor necrosis factor (TNF) was present in concentrations of 15-55 U/ml during the first week of culture and at less than 10 U/ml thereafter. Bioactive transforming growth factor-beta (TGF-beta) was detected at 1-36 U/ml from 5 to 14 days of culture and decreased thereafter. Immunoreactive TGF-beta 2 was still present at concentrations of 20-90 pg/ml after 21 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

[Therapy of ballistic hyperkinesia (case report)]. / Zur Therapie ballistischer Hyperkinesen (Falldarstellung).

Discussing the example of two cases of patients suffering from mixed choreic-hemiballistic hemi-hyperkinesia, the authors report on successes they obtained in long-term therapy after surgical stereostactic treatment (high-frequency coagultation) in the thalamus or subthalamus. The discussion deals with indications of the etiology, the supposed pathophysiology and pathomorphology of the disease pictures in question.