OM Treatment Research Articles

Current status of oriental medicine in treating Korean allergy patients

To evaluate the prevalence, compliance, pattern of use, and economic cost of OM in Korean allergy patients. A total of 647 allergy patients were enrolled from 10 general hospitals, and were surveyed by the questionnaire. It consisted of 12 items and regarded the prescription rates, reasons for referring, their opinions for the efficacy of OM, and economic costs. A total of 259 (40.5%) patients had used OM, and 35.5% of these patients experienced two or more kinds of these practices. A patients' income or education level did not affect the prescription rates of OM. Of the patients that used OM, 34.6% of them were satisfied with the effect of OM treatment, and 40.9% of them were inclined to continue with their OM treatments. The most frequent reasons for choosing OM were the patient's belief that OM can predispose 'allergic constitution to normal' (30.2%), worries about the possible adverse reactions of the long-term administration of the proven drugs (20.2%), and the safety of OM (15.6%). However, 18.9% of these patients experienced perceived adverse events to their OM treatment such as skin rashes, gastrointestinal discomfort, and hepatitis. The patients that have used OM spent on average $915 US dollars annually for OM treatment. Many Korean allergy patients are cliental to OM. Some patients experienced a satisfactory treatment effect from OM, however, others had no treatment effect, even adverse event. Therefore, it is important to educate people to use OM appropriately to make harmony with modern medicine.

Interim Analysis of Randomized Phase II Study of Recombinant Human Epidermal Growth Factor on Oral Mucositis Induced by Intensive Chemotherapy with Stem Cell Transplantation for Hematologic Malignancies

AbstractAbstract 905Oral mucositis (OM) develops in 40–80% of patients undergoing intensive chemotherapy with stem cell transplantation (SCT) which is often debilitating and influences the quality of life (QoL). A novel drug, recombinant human epidermal growth factor (rhEGF), recently demonstrated promising efficacy and minimal toxicity in the prevention of OM in patients with head and neck cancer receiving radiotherapy (Wu HG et al, Cancer 2009). To evaluate the efficacy and safety of rhEGF for prevention and treatment of OM during SCT, a prospective randomized double-blind placebo-controlled phase II study is being performed (ClinicalTrials.gov identifier, NCT00845819). In this report, results of the scheduled interim analysis are presented. Patients for whom the procedure of SCT for hematologic malignancies was planned were eligible for this study. Patients were randomly assigned to either the rhEGF group or the placebo group, at a 1:1 ratio. Patients were instructed to spray either the 50 μg/mL rhEGF or the placebo over their entire oral mucosa twice daily and to swallow the residual. The rhEGF was administered at the start of intensive chemotherapy until the time of their recovery from neutropenia (absolute neutrophil count >1000 /μL for 3 consecutive days) and disappearance of OM. The severity of OM was assessed daily using the World Health Organization (WHO) scale. Patients also completed an Oral Mucositis Daily Questionnaire (OMDQ) to assess patient-reported QoL (Stiff PJ et al, J Clin Oncol 2006). A total of 138 patients are planned to be enrolled in this study. This interim analysis was performed after the acquisition of data on the 58 patients who were enrolled between March 2009 and June 2010. Twenty-nine patients were assigned to each group. Patient median age in the rhEGF group was 56 (range, 18–63) years and 51 (range, 19–65) years in the placebo group. Autologous SCT was performed on 26 patients (89.7%) from each group, and allogeneic SCT, in the rest (10.3%). Baseline characteristics were not significantly different between the 2 groups. The difference in the incidence of grade 3 or 4 OM between the 2 groups was not significant (p=0.283). The duration of OM in patients with grade 3 or 4 OM tended to be shorter, however, in the rhEGF group than in the placebo group (8.0 [range, 2.0–23.0] days vs. 18.5 [range, 2.0–34.0] days; p=0.108). This result is also supported by the significantly shorter duration of medication use in patients with grade 3 or 4 OM in the rhEGF group than in the placebo (28.0 [range, 17.0–44.0] days vs. 39.5 [range, 17.0–61.0] days; p=0.050). The OMDQ analysis using area-under-the-curve calculation (with a lower score for milder limitation) for patients with grade 3 or 4 OM also showed that rhEGF significantly reduced limitations in swallowing (26.0 [range, 8.0–75.0] vs. 51.5 [range, 19.0–92.0]; p=0.039) and drinking (25.0 [range, 7.0–73.5] vs. 55.5 [range, 20.0–86.0]; p=0.042) compared to placebo. The duration of administration of total parenteral nutrition (TPN) was significantly shorter in the rhEGF group than in the placebo group (7.0 [range, 0.0–25.0] days vs. 16.5 [range, 10.0–32.0] days; p=0.012) in patients with grade 3 or 4 OM. A similar result was observed for the duration of opioid analgesics use (6.0 [range, 0.0–25.0] days vs. 17.0 [range, 0.0–48.0] days; p=0.117). In patients with grade 3 or 4 OM, the rhEGF group showed a significantly shorter length of hospitalization than the placebo group (27.0 [range, 18.0–65.0] days vs. 41.5 [range, 27.0–94.0] days; p=0.022). Adverse events between the 2 groups were not statistically significant. The adverse events in the rhEGF group were nausea (n=2, 6.9%), oral pain (n=1, 3.4%), and taste alteration (n=1, 3.4%). No grade 3 or 4 adverse events developed. To summarize, in patients who received SCT for hematologic malignancies, rhEGF tended to reduce the duration of grade 3 or 4 OM and significantly reduced limitations in swallowing and drinking. In addition, rhEGF significantly reduced the duration of TPN use and hospitalization, and tended to reduce the duration of opioid analgesics use. The rhEGF was generally well tolerated with a favorable safety profile. The results of this interim report demonstrate that rhEGF has a role in the treatment of OM induced by intensive chemotherapy with SCT, and improves QoL. This study is still ongoing, and the final results are expected to be available within 2 years. Disclosures:Off Label Use: Recombinant human epidermal growth factor is a novel drug, which is officially approved for treatment of diabetic foot in Korea. This drug is currently not approved for treatment of oral mucositis by both the US FDA and the Korean FDA yet. In the present study, we used this drug to evaluate efficacy and safety of this drug for prevention and treatment of oral mucositis induced by intensive chemotherapy with stem cell transplantation.

Subcutaneous Omacetaxine (OM) Treatment of Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Patients Following Multiple Tyrosine Kinase Inhibitor (TKI) Failure

AbstractAbstract 2290 Introduction:Multiple TKI failure is a growing problem in a subset of CML patients. Treatment with a third TKI after two have failed often yields poor results. New treatment options are needed for this patient population. OM is a first-in-class cetaxine with demonstrated activity as a single agent in CML. It inhibits the production of short-lived oncoproteins (such as Mcl-1) involved in cancer cell survival via a mechanism independent of Bcr-Abl binding. Several studies have suggested that OM has a favorable toxicity profile when given to patients with CML via the subcutaneous route. We explored OM efficacy and safety in a subset of patients who had received therapy with multiple prior approved TKI. Methods:We analyzed a subset of adult CML-CP patients who had received two or more TKI (imatinib, dasatinib, nilotinib), from a combined interim dataset of two prospective Phase 2 studies (CML-202, for patients with the T315I kinase domain mutation, and CML-203, for patients with failure to ≥2 TKI) utilizing OM in the treatment adult patients with all phases of CML who had failed TKI. TKI failure was defined as no complete hematologic response (CHR) by 12 weeks (wk), no cytogenetic response by 6 months (mo), no major cytogenetic response (MCyR) by 12 mo, loss of CHR or MCyR, or progressive leukocytosis. The focus of this analysis was to assess the CHR and MCyR response rates as well as the overall safety of OM in these patients. Adverse events presented are Grade 3/4 events that occurred in ≥ 5% of patients (regardless of causality). Results:A total of 73 of the 93 CML-CP patients from these two studies had received two or more TKI prior to OM treatment. Median time from initial CML diagnosis to first dose of OM was 74.4 months. Mutations of any kind were seen in 48% of the patients, whereas 29% had no identified mutation and 23% had no available data on mutation status. Sixty (82%) of these 73 patients achieved or maintained (twelve patients were in CHR at study entry) a CHR and 17 (23%) achieved a MCyR (9 complete and 8 partial). The median duration of MCyR was 4.4+ months (range 1.2–14.1+). Median overall survival for patients treated with OM after failure of 2 or more TKI has not yet been reached [95% Confidence Interval (CI) 22.9, NA months] (Figure 1). Eleven patients had a treatment—emergent adverse event leading to death, and two deaths were probably related to study drug. Median progression-free survival was 11.1 months (95% CI 6.5, 13.8 months). Median follow-up time was 7.5 months for all patients with twenty-five patients remaining on study at the time of this data cut. A total of 36 of the 93 CP patients from these two studies had been treated with three or more TKI; 27 (75.0%) achieved or maintained a CHR and 7 (19.4%) achieved a MCyR (4 complete and 3 partial) on OM treatment. The median duration of MCyR in this group was 4.0+ months (range 1.2–11.5+) at the time of data cut-off. The primary Grade 3/4 adverse events in patients who received OM after failure of 2 or more TKI were hematologic, including thrombocytopenia (64%), neutropenia (48%) and anemia (40%) most commonly, followed by febrile neutropenia (12%), bone marrow failure (12%), pancytopenia (7%) and febrile bone marrow aplasia (6%). These events were dosing schedule dependent. Clinical sequelae were uncommon and managed with transient treatment interruptions and dose adjustments. Grade 3/4 non-hematologic adverse events were infrequent, with only fatigue (6%) occurring ≥5% of patients. Conclusions:OM, through a mechanism of action independent of Bcr-Abl, may offer a clinically viable option for patients who have progressed on multiple TKI treatment. [Display omitted] Disclosures:Off Label Use: The drug is currently in development and has an NDA submitted for use in TKI resistant CML. Cram: ChemGenex: Employment, Equity Ownership. Humphriss: ChemGenex: Employment, Equity Ownership. Benichou: ChemGenex: Consultancy, Equity Ownership. Craig: ChemGenex: Employment, Equity Ownership, Executive Management Level.

Indirect Pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in Polymicrobial Otitis Media Occurs via Interspecies Quorum Signaling

Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis promotes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrhalis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. catarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm.

Effect of Long-Term Fertilization on Organic Carbon and Nitrogen in a Subtropical Paddy Soil

A long-term experiment beginning in 1981 in Jinxian County of Jiangxi Province, subtropical China, was conducted in a paddy field under a double rice cropping system with four different fertilization regimes, including 1) no fertilizer as control (CK), 2) balanced chemical N, P, and K fertilizers (NPK), 3) organic manure using milk vetch and pig manure in the early and late rice growing season, respectively (OM), and 4) balanced chemical fertilizers combined with organic manure (NPKM). Samples (0–17 cm) of the paddy field soil, which was derived from Quaternary red clay, were collected after the late rice harvest in November 2003 for determination of total organic carbon (TOC) and total nitrogen (TN) and fractions of organic C and N. Results showed that TOC and TN in the NPKM and OM treatments were significantly higher than those in other two treatments (CK and NPK). Application of organic manure with or without chemical fertilizers significantly increased the contents of all fractions of organic C and N, whereas chemical fertilizer application only increased the contents of occluded particulate organic C (oPOC) and amino acid N. In addition, application of organic manure significantly enhanced the proportions of free particulate organic carbon (fPOC) and oPOC in total C, and those of amino sugar N and amino acid N ( P < 0.01) in total N. In contrast, chemical fertilizer application only increased the proportions of oPOC and amino acid N ( P < 0.05). There were no significant differences in either contents or proportions of soil organic C and organic N fractions between the NPKM and OM treatments. These indicated that organic manure application with or without chemical fertilizers played the most significant role in enhancing soil organic C and N quantity and quality in the paddy field studied.

Long-term manure and fertilizer effects on soil organic matter fractions and microbes under a wheat–maize cropping system in northern China

As an essential indicator of soil quality, soil organic carbon (SOC) and its different labile fractions have an important role in determining soil chemical, physical, and biological properties. The objective of this study was to evaluate the soil carbon (C) and nitrogen (N) contents in different soil organic matter (SOM) pools (light and heavy fractions), the role of light- and heavy-fraction C in SOC sequestration, and culturable microbial counts in the surface (0–20 cm) of a fluvo-aquic soil after 18 years of fertilization treatments under a wheat–maize cropping system in the North China Plain. The experiment included seven treatments: (1) OM, organic manure; (2) 1/2OMN, half organic manure with mineral fertilizer NPK; (3) NPK, mineral fertilizer NPK; (4) NP, mineral fertilizer NP; (5) PK, mineral fertilizer PK; (6) NK, mineral fertilizer NK; and (7) CK, unfertilized control. Carbon and N contents of the light and heavy fractions were highest in the OM treatment, while the CK treatment showed the lowest value. Application of half organic manure with mineral fertilizer NPK (treatment 2) significantly increased C and N contents of the light and heavy fractions in soil in comparison with application of mineral fertilizer alone (treatments 3, 4, 5, and 6). For the mineral fertilizer treatments, a balanced application of NPK (treatment 3) showed higher C and N contents of the light and heavy fractions than an unbalanced use of fertilizers (treatments 4, 5, and 6). Heavy-fraction C dominated total SOC storage in all treatments. The total SOC increase under fertilization treatments is attributed to an increase in C content of both the light and the heavy fraction. However, the SOC increase for the manure treatments was mainly due to an increase in the C content of the heavy fraction, whereas that for mineral fertilizer treatments was mainly due to an increase in the C content of the light fraction. The total soil culturable microbial counts (including bacteria, fungi, and actinomycetes) was observed to be highest for the OM treatment, while the control plot showed the lowest value. Application of half organic manure with mineral fertilizer NPK was found to produce a higher culturable microbial counts than application of mineral fertilizers alone, and the NPK treatment gave a higher culturable microbial counts than other mineral fertilizer treatments (NP, PK or NK). Light-fraction C is probably the better predictor of microbial abundance, as it correlated more strongly with culturable microbial counts than total SOC did.

Long-term manuring and fertilization effects on soil organic carbon pools under a wheat–maize cropping system in North China Plain

The effects of organic manure and chemical fertilizer on total soil organic carbon (CT), water-soluble organic C (CWS), microbial biomass C (CMB), labile C (CL), C mineralization, C storage and sequestration, and the role of carbon management index (CMI) in soil quality evaluation were studied under a wheat–maize cropping system in a long-term experiment, which was established in 1989 in the North China Plain. The experiment included seven treatments: (1) OM: application of organic manure; (2) 1/2OMN: application of half organic manure plus chemical fertilizer NPK; (3) NPK: balanced application of chemical fertilizer NPK; (4) NP: application of chemical fertilizer NP; (5) PK: application of chemical fertilizer PK; (6) NK: application of chemical fertilizer NK; and (7) CK: unfertilized control. Application of organic manure (OM and 1/2OMN) was more effective for increasing CT, CWS, CMB, CL, C mineralization, and CMI, as compared with application of chemical fertilizer alone. For the chemical fertilizer treatments, balanced application of NPK (treatment 3) showed higher CT, CWS, CMB, CL, C mineralization, and CMI than the unbalanced use of fertilizers (treatments 4, 5, and 6). The C storage in the OM and 1/2OMN treatments were increased by 58.0% and 26.6%, respectively, over the NPK treatment, which had 5.9–25.4% more C storage than unbalanced use of fertilizers. The contents of CWS, CMB, and CL in organic manure treatments (treatments 1 and 2) were increased by 139.7–260.5%, 136.7–225.7%, and 150.0–240.5%, respectively, as compared to the CK treatment. The CMI was found to be a useful index to assess the changes of soil quality induced by soil management practices due to its significant correlation with soil bulk density and C fractions. The OM and 1/2OMN treatments were not a feasible option for farmers, but a feasible option for sequestering soil carbon, especially for the OM treatment. The NPK treatment was important for increasing crop yields, organic material inputs, and soil C fractions, so it could increase the sustainability of cropping system in the North China Plain.

Physiological responses of the seagrass Posidonia oceanica to elevated organic matter content in sediments: An experimental assessment

Here we studied the effects of adding organic carbon and nutrients to sediment on the physiology and survival of the seagrass Posidonia oceanica in a field experiment in the Medes Islands (NE Spain). Nine randomly selected plots were established at a depth of 10 m; three were enriched with organic carbon (OM treatment), three with organic carbon and nutrients (OMN treatment), and three were kept as controls (CON). The experiment was performed over 5 months and sampling of plants and sediments was done in March, May and July 2002. Sediment sulfide pools and pore water ammonium concentrations increased significantly in OM and OMN plots, both treatments showing increased reducing conditions in the sediment. Plants in these two treatments showed higher mortality and lower biomass compared to plants from CON plots. The greatest effects on seagrass occurred in the OMN plots, indicating a synergistic effect of organic carbon and nutrient additions. Treatments had significant effects on plant nitrogen (N) and phosphorous (P) metabolism, shown by an increase in free amino acid (FAA) content, a change in FAA composition and a lack of increase in N and P tissue content. Treated plants showed higher g-aminobutyric acid (GABA) and malate concentrations and lower concentrations of non-structural carbohydrates compared to CON, indicating that anaerobic respiration in below-ground tissues occurred. Several of the physiological changes shown by P. oceanica can be interpreted as adaptations to anoxia exposure. However, the increased mortality in treated plots demonstrates that this seagrass does not tolerate highly reduced sediments.

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Interaction of lime, organic matter and fertilizer on growth and uptake of arsenic and mercury by Zorro fescue (Vulpia myuros L.)

The Sulphur Bank Mercury Mine (SBMM) is an abandoned open pit mine located on the eastern shores of Clear Lake, California. Revegetation efforts have been difficult because the mine-soils at SBMM have low pH, low fertility and elevated As and Hg concentrations. In a greenhouse study, we examined the interactions of lime, N, P and OM additions with respect to plant growth, and As and Hg uptake. Three selected acidic mine-soils from the site containing high (164 mg/kg) (S-H), medium (123 mg/kg) (S-M) and low (31 mg/kg) (S-L) total As content were planted to the Eurasian annual grass, Zorro fescue (Vulpia myuros L.). The Hg concentrations for these soils varied between 1700 and 3000 mg/kg with S-L > S-H ≅ S-M. A factorial design used 3 soils, 2 lime, 2 N, 2 P and 2 OM treatments with treatments replicated three times. Multiple regression analyses indicated a strong relationship between As plant uptake, root length density (RLD) and soluble As. A highly significant linear relationship between Hg uptake and RLD for plants growing on the three soils illustrated the importance of plant root characteristics in influencing Hg uptake. Soluble As decreased in the order S-H > S-M > S-L in positive correlation with P and DOC but in inverse relationship to oxalate extractable Fe. Lime and OM additions correlated negatively with soluble Hg and Hg tissue concentration due to either Hg adsorption to OM or to inorganic surfaces. Addition of lime increased dry matter yield and Hg uptake in all three soils.

Regulation of Inflammatory Responses by Oncostatin M

Oncostatin M (OM) is a pleiotropic cytokine produced late in the activation cycle of T cells and macrophages. In vitro it shares properties with related proteins of the IL-6 family of cytokines; however, its in vivo properties and physiological function are as yet ill defined. We show that administration of OM inhibited bacterial LPS-induced production of TNF-alpha and lethality in a dose-dependent manner. Consistent with these findings, OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and Ab production were not impaired by OM treatment. Taken together these data indicate the activities of this cytokine in vivo are antiinflammatory without concordant immunosuppression.

Effects of Organic Matter and Nitrogen Fertilizer Applications on Fruit Quality of Satsuma Mandarin in a High Density Planting.

A differential nitrogen (N) fertilization trial for a high density planting of satsuma mandarin was conducted for 11 years starting in 1982 on 13-year-old trees. Satsuma mandarin (Citrus unshiu Marc. cv. Sugiyama) trees, which had been grown in a 0.4 ha field with little or no fertilizer, were administered a combination of 2 levels of organic matter application and 3 levels of N triplicated in a factorial arrangement. Levels of organic matter were +OM (rice straw application of 20 t·ha-1·year-1) and -OM (sod culture system). Levels of N fertilizers were N-1 : 100, N-2 : 200, and N-3 : 300 kg·ha-1·year-1. The total soluble solids-titratable acidity (TSS-TA) ratio of the juice, the 'a' index of peel color, percentage of mesocarp, and specific gravity of fruit in the -OM treatment were slightly higher than those in the +OM treatment. In contrast, TA content in the juice and mean fruit weight were slightly increased by organic matter application. TSS-TA ratio, the color indices of 'L', 'a' and 'b', % of mesocarp, and specific gravity of fruit decreased with increased N application, whereas TA content in the juice increased. The N and K contents in the leaves and leaf color index in the +OM treatment were slightly higher than those in the -OM treatment. Leaf N content and the leaf color index increased, but leaf P and K contents decreased with increased N application. TSS, TSS-TA ratio, the 'L', 'a' and 'b' color indices, % of mesocarp, and specific gravity of fruit were negatively correlated to leaf N content, wherease TA content correlated positively with leaf N.

Optimizing Nitrogen Fertilizer Application for a High Density Planting of Satsuma Mandarin

A differencial nitrogen fertilization trial for a high density planting of satsuma mandarin was conducted for 11 years. Starting in 1981, 12-year-old satsuma 'Sugiyama Unshiu' trees, which had been grown in a 0.4 ha field with little or no fertilizer were administered a combination of 2 levels of organic matter application and 3 levels of N replicated 3 times as a factorial design. Levels of organic matter were-OM (no organic matter application) and +OM (rice straw application of 20 t•ha-1•year-1).Levels of nitrogen fertilization were N-1 : 100, N-2 : 200, and N-3 : 300 kg-ha-lyear-1.The trees were spaced 2.2 m × 2.2 m, a quarter of the trees being designated as the permanent, another quarter of trees as the semipermanent, and the rest as fillers.1. The yield per hectare in all treatments increased significantly in the second year but then decreased slightly on account for bacterial canker attack ; the trees recovered and the yield increased rapidly but eventually leveled off with some yearly fluctuations.2. In the + OM treatment, the yield per hectare in the N-1 treatment was less than 10% of the N-2 and N-3 treatments, whereas in the OM treatment, the N-2 and N-3 treatments, the yields were 8% and 14% larger, respectively, than in the N-1 treatment. These results led to the conclusion that the amount of nitrogen fertilizer in a high density planting of satsuma mandarin can be reduced to 100 kg•ha-1•year-1 when 20 t•-1•year-1 of rice straw was annually applied or 200 kg•ha-1•year-1 when no organic matter was applied, without substantial crop reduction.

Omeprazole decreases H(+)-K(+)-ATPase protein and increases permeability of oxyntic secretory membranes in rabbits.

Amounts and fractional distributions of gastric H(+)-K(+)-adenosinetriphosphatase (ATPase) activity and H(+)-K(+)-ATPase protein as well as properties of H(+)-K(+)-ATPase-containing membranes were studied in rabbits injected with omeprazole (OM; 1 mg/kg sc twice daily for 5 days). Total H(+)-K(+)-ATPase activity decreased to 22 +/- 2% of control (n = 4). Densitometry of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots showed H(+)-K(+)-ATPase protein was decreased to 60-70% of control. In vitro reduction of the enzyme-OM disulfide bond with 0.1 M 2-mercaptoethanol increased microsomal H(+)-K(+)-ATPase activity to 56 +/- 7% of control (n = 3), consistent with a substantial decrease in enzyme protein. Incorporation of 35S-labeled methionine for 30 min before death resulted in 2.2-fold more label per unit of microsomal alpha-subunit protein (5 days OM vs. control). Thus the decrease in enzyme protein resulted from increased breakdown rather than decreased synthesis. A striking shift in distribution of H(+)-K(+)-ATPase-containing microsomes (tubulovesicles) on sucrose gradients reflected slow equilibration of most control vesicles with the gradient medium and faster equilibration after 5 days OM, indicating increased permeability. After 5 days OM, microsomal vesicle acidification (by acridine orange uptake assay) was negligible, even with 2-mercaptoethanol treatment, and H+ leakage on sudden delta pH was faster than control. We conclude that extended OM treatment not only inhibits H(+)-K(+)-ATPase but accelerates its breakdown and renders H(+)-K(+)-ATPase-containing membranes more permeable. It is thus possible that increased backward H+ flux contributes to profound inhibition of acid secretion during extended omeprazole treatment. In parallel experiments, H(+)-K(+)-ATPase activity and density gradient sedimentation of tubulovesicles returned to near normal 3 days after OM withdrawal.

Regulation of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Expression by Oncostatin M

AbstractOncostatin M (OM) is structurally and functionally related to a subclass of hematopoietic cytokines including leukemia-inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), granulocyte colony-stimulating factor (G-CSF), and interleukin-6 (IL-6). Using human endothelial cells (HEC) as a model for cytokine regulation of hematopoietic growth factor expression, we tested OM as an inducer of colony-stimulating activity. Colony-forming cell assays supplemented with culture supernatants from OM-treated HEC contained a threefold increase in colony-forming unit granulocyte-macrophage colonies. Specific immunoassay (enzyme-linked immunosorbent assay) of culture supernatants indicated that OM treatment of HEC resulted in a dose- and time-dependent increase in the accumulation of G-CSF and granulocyte-macrophage CSF (GM-CSF) (> 28-fold). The ED50 for OM induction of G-CSF and GM-CSF protein expression was 17 and 7 pmol/L, respectively. Increased protein expression was associated with a similar increase in steady-state expression of G-CSF and GM-CSF mRNA. Furthermore, a period of 12 to 24 hours elapsed before there were measurable increases in CSF expression, suggesting that OM may stimulate CSF production through a mechanism requiring the synthesis or activation of a secondary mediating factor or pathway. These findings provide the first evidence that OM may regulate myelopoiesis by inducing the cellular expression of hematopoietic growth factors.

Improved protection of swine from pleuropneumonia by vaccination with proteinase K-treated outer membrane of Actinobacillus (Haemophilus) pleuropneumoniae

The immunogenic and protective potentials of an outer membrane-enriched fraction (OM) from a serotype 5 strain of Actinobacillus (Haemophilus) pleuropneumoniae (APP) and the same OM degraded with proteinase K or periodate were evaluated in swine. Groups of pigs were vaccinated with two doses of OM, proteinase K-treated OM (P-OM), periodate-treated OM (PI-OM), or placebo vaccine and challenged intranasally with the homologous strain of APP. Results from triplicate experiments indicated that proteinase K treatment of OM resulted in an improved efficacy. This improved efficacy of P-OM vaccine over untreated OM vaccine was evidenced not only by less severe lung lesions in P-OM vaccinated pigs but also by significant reduction ( P<0.05) in the number of P-OM vaccinated pigs which developed lung lesions upon challenge with APP. Assessment of sera from vaccinated animals by immunoblotting, complement fixation test, or ELISA indicated that the immunogenicity of some but not all protein or carbohydrate components were reduced (or eliminated) by proteinase K and periodate treatments respectively.

Phosphorus Behavior in Flooded‐Drained Soils. III. Phosphorus Desorption and Availability

AbstractFour California soils that showed wide variability in soil properties and P sorptivity under flooded‐drained (FD) conditions were selected for this study. The soils were flooded for 0 to 90 d at two levels of organic matter (OM, 0 and 10 g kg−1) and two temperatures (23 and 35 °C). They were subsequently drained and used for P‐sorption studies at 0.3, 1.2, and 2.0 mM initial P concentrations. The P desorption from P‐sorbed soils were carried out in three consecutive extractions with 0.1 M NaCl. The effect of FD conditions on P availability to corn (Zea mays L.), was studied at three levels of P (0, 5, and 20 mg P kg−1 soil). Without OM treatment, FD conditions decreased P desorption in three of four soils examined. Added OM and higher temperature further decreased P desorption and the period of flooding (FP) required to reach the minimum P desorption. Organic matter markedly decreased P desorption even in Soil 3, which was unaffected by FD conditions. Under FD conditions, plant‐tissue P concentration of corn was decreased to a variable extent depending on soil type. The desorption of added fertilizer P in a given FD soil correlated well with changes in the amorphous FeA fraction under comparable conditions. Phosphorus sorption and desorption were controlled by the changes in amorphous FeA and, in some cases, amorphous FeB fractions.