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J Klemm

Publications and source records attributed to J Klemm.

At least 19 recordsLinked to original sources
PubMed2001

Phorbol ester up-regulates capacities for nuclear translocation and phosphorylation of 5-lipoxygenase in Mono Mac 6 cells and human polymorphonuclear leukocytes.

The leukotrienes are inflammatory mediators derived from arachidonic acid. It was demonstrated that the priming of leukocytes with phorbol-12-myristate-13-acetate (PMA) leads to the increased formation of 5-lipoxygenase (5-LO) products in parallel with the increased association of 5-LO with the nucleus and the activation of kinases that can phosphorylate 5-LO in vitro. Stimulation of the monocytic cell line Mono Mac 6 with calcium ionophore gave low 5-LO product formation and no detectable redistribution of 5-LO. However, after priming of Mono Mac 6 cells with phorbol esters, ionophore led to the association of 45% to 75% of cellular 5-LO with the nuclear membrane, to 5-LO kinase activation, to enhanced release of arachidonate, and to substantial leukotriene synthesis. Similar results were obtained for human polymorphonuclear leukocytes stimulated with low-dose ionophore. In addition, for each cell type, PMA priming up-regulated leukotriene biosynthesis in the presence of exogenous arachidonic acid. A protein kinase inhibitor, calphostin C, reduced the association of 5-LO with the nucleus and 5-LO kinase activity, and the formation of 5-LO products was inhibited. These results suggest that PMA up-regulates leukotriene biosynthesis not only by increasing the release of endogenous arachidonate, but also by increasing the capacity for 5-LO phosphorylation and for the translocation of 5-LO to the nucleus in leukocytes.

Active Transport, Cell Nucleus↗
PubMed2001

p38 MAP kinase mediates stress-induced leukotriene synthesis in a human B-lymphocyte cell line.

5-Lipoxygenase (5-LO), which catalyzes the first two steps in leukotriene biosynthesis, is a target for pharmacological treatment of inflammatory disorders. Previous studies have shown that B-lymphocytes express 5-LO. Here we demonstrate that several stimuli of cell stress such as osmotic shock (sorbitol, NaCl), oxidative stress (hydrogen peroxide, diamide), chemical stress sodium arsenite, and inflammatory cytokines enhanced cellular 5-LO activity in a B cell line (BL41-E95-A), when added simultaneously with ionophore plus arachidonate. It is interesting that sorbitol alone was sufficient for 5-LO product formation in the presence of exogenous arachidonic acid. These stimuli also activated p38 mitogen-activated protein (MAP) kinase and downstream MAP kinase-activated protein kinases in BL41-E95-A cells, which could phosphorylate 5-LO or heat shock protein 27 in vitro. The p38 MAP kinase inhibitor SB203580 abolished stress-induced leukotriene synthesis in B cells, without inhibition of 5-LO catalytic activity in cell-free systems. Our results indicate that p38 MAP kinase activation by cell stress is required for efficient leukotriene synthesis in B-lymphocytes.

Arachidonate 5-Lipoxygenase↗
PubMed2000

5-lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases.

5-lipoxygenase (5-LO) catalyzes the initial steps in the formation of leukotrienes, a group of inflammatory mediators derived from arachidonic acid (AA). Here we describe that activation of p38 mitogen-activated protein kinase in human polymorphonuclear leukocytes and in Mono Mac 6 cells leads to activation of downstream kinases, which can subsequently phosphorylate 5-LO in vitro. Different agents activated the 5-LO kinase activities, including stimuli for cellular leukotriene biosynthesis (A23187, thapsigargin, N-formyl-leucyl-phenylalanine), compounds that up-regulate the capacity for leukotriene biosynthesis (phorbol 12-myristate 13-acetate, tumor necrosis factor alpha, granulocyte/macrophage colony-stimulating factor), and well known p38 stimuli as sodium arsenite and sorbitol. For all stimuli, 5-LO kinase activation was counteracted by SB203580 (3 microM or less), an inhibitor of p38 kinase. At least two p38-dependent 5-LO kinase activities were found. Based on migration properties in in-gel kinase assays and immunoreactivity, one of these was identified as mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP kinase 2). The other appeared to be MAPKAP kinase 3; however, it could not be excluded that also other p38-dependent kinases contributed. When polymorphonuclear leukocytes were incubated with sodium arsenite (strong activator of 5-LO kinases), platelet-activating factor and exogenous AA, there was a 4-fold increase in 5-LO activity as compared with incubations with only platelet-activating factor and AA. This indicates that 5-LO phosphorylation can be one factor determining cellular 5-LO activity.

Amino Acid Sequence↗
PubMed1998

CD49d expression and function on allergen-stimulated T cells from blood and airway.

The alpha4 chain (CD49d), which constitutes one of the chains of alpha4beta1 (very late activating antigen-4 [VLA-4]) and alpha4beta7 integrins, mediates migration of T cells to extravascular spaces. The interaction between VLA-4 and vascular cell adhesion molecule-1 (VCAM-1) has been shown to be the critical pathway for the selective accumulation of eosinophils and basophils at sites of allergic inflammation. T lymphocytes are also specifically recruited into allergic sites, including the allergic asthmatic airway. Increased numbers of activated CD4+ cells expressing the DR antigen subset of the human leukocyte antigens (HLA-DR) appear in the allergic lung 48 h after allergen inhalation. The mechanisms by which these cells localize into the lung are still unknown. We report that stimulation of allergen-specific T cells with allergen in vitro resulted in enhanced expression of alpha4 chain (CD49d) as measured by receptor density on allergen-specific T-cell lines and T-cell clones. Kinetic studies showed that CD49d density was enhanced over a 24- to 48-h period in a time-dependent fashion, and was coordinately upregulated with HLA-DR expression. We also demonstrated that increased expression of CD49d on T-cell lines 24 h and 48 h after stimulation correlated with increased adhesion to the CS-1 fragment of fibronectin. In contrast, lymphocyte function-associated antigen-1b (LFA-1b) (CD11b), LFA-3 (CD58), and intercellular adhesion molecule-1 (ICAM-1) (CD54) expression did not change with allergen stimulation. We also showed that CD49d receptor density on T cells obtained by bronchoalveolar lavage (BAL) of allergic patients before and 48 h after allergen challenge was significantly higher than that on T cells taken from BAL of normal subjects and from controls with other inflammatory lung diseases. Taken together, these findings indicate that allergen stimulation activates allergen-specific T cells and coordinately induces increased CD49d receptor expression and binding to counterligands. We postulate that allergen-driven upregulation of CD49d, which together with the beta1 chain constitutes VLA-4 integrin, may be responsible for the selective accumulation of T cells in the allergic asthmatic lung.

Adult↗
PubMed1992

Recent trends in Medicaid expenditures.

Total net Medicaid expenditures exceeded $94 billion in FY 1991, with 5 states accounting for more than 40 percent--New York, California, Massachusetts, Pennsylvania, and Texas. Nationally, inpatient and institutional long-term care payments each comprise about one-third of Medicaid spending. Medicaid expenditures have grown rapidly. From 1987 to 1991 they nearly doubled, greatly exceeding the expenditure growth for Medicare and private health insurance. This growth has been unevenly distributed. Expenditures increased by 125 percent or more in 12 States during this period, but an equal number of States had increases below 75 percent. Although expenditures grew the most slowly in institutional long-term care, this still comprises the largest payment category. Spending for inpatient services, community long-term care, insurance payments, and services not otherwise classified had the fastest rate of growth. By 1995, projected Federal expenditures for Medicaid will exceed $100 billion, approximately equal to those for Medicare in 1991. Health care inflation, State program decisions, and Federal mandates all affect the growth in Medicaid expenditures. Legislative changes have expanded coverage of pregnant women, infants, and children, and also have increased Medicaid payments of Medicare premiums and cost sharing for the elderly and disabled. Other Federal mandates raised nursing home standards and expanded EPSDT services. Legislative requirements and court challenges caused some States to increase provider payment rates. Some States developed alternative financing arrangements to accommodate the fiscal demands of higher expenditure growth. Requirements for DSH payments allowed States to use Medicaid to offset State support of public hospitals. Provider taxes and donations permitted States to increase Medicaid payments without having to raise other revenues or place an economic burden on providers. These arrangements were significantly curtailed by legislation passed in 1991.

Cost Sharing↗
PubMed1990

Deciphering Medicaid data: issues and needs.

The wide range of data bases that can be used for Medicaid analyses and research are reviewed in this article. The Health Care Financing Administration, State Medicaid agencies, and other groups have developed useful data bases and made them available to the public. Efforts could be made to obtain better quality national data, including annual reports on State participation, expenditures and program characteristics, and person-based data bases about medicaid clients and services. State-level analyses and research could be enhanced and disseminated more widely. More complex data collection and analysis efforts are an inevitable tradeoff for the flexibility of the Federal-State structure of Medicaid.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1984

[Treatment of cerebral circulatory insufficiency. Double-blind study of the efficacy of a quinine-papaverine combination].

Four weeks of oral therapy with a combination of quinine and papaverine at a dose of 3 X 1 coated tablet per day cause a marked and--as compared with placebo--statistically highly significant increase (p less than 0.01) in cerebral blood flow of patients with a moderate impairment of the terminal vascular system of the brain. The combination of substances brings about a more pronounced improvement (p less than 0.05) in the cerebral blood flow than papaverine alone which itself is superior to placebo (p less than 0.05). The quinine contained in the combination evidently increases its efficacy. The results of platelet aggregation tests, performed simultaneously, suggest that rheological factors in the sense of an improvement of the flow properties of the blood might play a part in causing these effects. Clinical and neurological findings indicate a clear parallel with the results of the measurements of the cerebral blood flow, even though this was not statistically significant.

Cerebrovascular Circulation↗
PubMed1980

Microbiological quality of Queensland stockfeeds with special reference to salmonella.

One hundred Queensland stockfeeds were examined for their counts of total aerobic bacteria, coliforms, fungi and salmonellas. The total aerobic bacteria, coliform and fungal counts were significantly higher (P < 0.005) for mashes than for crumbles and pellets and salmonellas were isolated from significantly more (P < 0.005) mashes (64%) than pellets and crumbles (8%). Counts of less than 1 salmonella per 100 g were found in 36.4% of the 44 positive feeds. The remainder of the counts ranged from 1.2 per 100 g to greater than 147 salmonellas per 100 g feed.

Aerobiosis↗
PubMed1980

Tc-99m-labeled red blood cells for the measurement of red cell mass in newborn infants: concise communication.

In vitro and in vivo investigations were performed to examine the binding of Tc-99m to neonatal red blood cells (RBC). Labeling efficiency was about 90%, and unbound Tc-99m less than 3% after one washing, in premature and full-term newborns and in children. Thus presence of high percentages of fetal hemoglobin (Hb F) did not influence the labeling of RBCs with Tc-99m. RBCs of 11 newborns were hemolysed and the distribution of Tc-99m on RBC components was analyzed. Although Hb F percentage averaged (60.0 +/- 8.1)% (s.d.), only (11.9 +/- 3.7)% of Tc-99m was bound by Hb F, whereas (45.0 +/- 6.1)% was associated with Hb A. RBC membranes bound (13.7 +/- 4.3)% and (29.3 +/- 4.0)% were found unbound in hemolysates. These results indicate that Tc-99m preferentially binds to beta chains. In vivo equilibration of Tc-99m RBCs and of albumin labeled with Evans blue was investigated in five newborn infants. Tc-99m RBCs were stable in each case during the first hour after injection. Elution of Tc-99m from RBCs was (3.4 +/- 1.5)% per hour. Body-to-venous hematocrit ratio averaged 0.86 +/- 0.03.

Child↗
PubMed1977

[Adrevil improves the peripheral blood flow. Results of a study using the 133-Xe muscle clearance method on lower limbs].

The efficacy of Adrevil has been investigated in 35 patients suffering from arterial blood flow disorders in the lower limb. The patients were given a daily dose of 3 X 2 tablets over a period of 30 days. Changes in muscle perfusion were determined by means of the 133 Xenon muscle clearance. The perfusion volume was found to be increased by 8--12% depending on the severity of the clinical state before treatment. The effect of the drug was more pronounced in cases with severe pathological changes prior to treatment. No adverse reactions were observed.

Arterial Occlusive Diseases↗