Receptor-mediated increase in cytosolic calcium in LLC-PK1 cells by platelet activating factor and thromboxane A2

Receptor-mediated increase in cytosolic calcium in LLC-PK1 cells by platelet activating factor and thromboxane A2. Several studies indicate an important role of platelet activating factor (PAF) and thromboxane A2 (TXA2) in glomerular pathophysiology. However, the potential role of PAF or TXA2 in renal tubular pathophysiology has received little attention, and the presence of functional receptors for these autacoids in renal tubular epithelium has not been previously studied. We examined the effects of PAF and the TXA2 analogue, ONO11113, on the cytosolic free calcium concentration ([Ca2+]i) in cultured LLC-PK1, cell line using a fluorescent probe, fura-2. In these cells, the addition of PAF or ONO11113 caused a significant increment in [Ca2+]i in a dose-dependent manner: both agonists (10-7 M) increased [Ca2+]i from 148 ± 16 to 288 ± 39 nM and from 130 ± 8 to 240 ± 18 nM, with the values of EC50 for PAF and ONO11113 being 17 ± 4 and 17 ± 2 nM, respectively. These effects were both rapid and transient, returning to baseline in two minutes. The effect of PAF was selectively blocked by PAF receptor antagonist BN50730, but not by TXA2 receptor antagonist L657925. Similarly ONO1113 response was abolished by L657925, but not by BN50730. PAF- or ONO11113-challenged cells did not respond to a second addition of the same agent and showed heterologous desensitization to the other agonist. The initial peaks of [Ca2+]i as well as the sustained elevations in [Ca2+]i induced by PAF or ONO11113 were reduced following the chelation of extracellular Ca2+ by 10 mM ethylene glycol-bis(β-aminomethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA). In the absence of extracellular Ca2+ 8-(N,N-dimethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) (which has extensively been used to study the contribution of Ca2+ released from intracellular storage sites in the increase in [Ca2+]i), blocked the increment in [Ca2+]i induced by PAF or ONO1113. These results indicate that LLC-PKi cells express discrete receptors for PAF and TXA2 that are coupled to an increase in [Ca2+]i through mobilization of calcium from both intracellular storage sites and extracellular milieu, and suggest the possible importance of PAF and TXA2 in tubular pathophysiology

Evaluation of Beef Cattle Operations Utilizing Different Seasons of Calving, Weaning Strategies, Postweaning Management, and Retained Ownership

Data from a 3-yr study in Montana were utilized to evaluate impacts of season of calving, weaning strategy, and retained ownership of steer calves on enterprise profitability. Calving seasons were late winter (LW), early spring (ES), or late spring (LS). Each season had 2 weaning times: 190 (LW190, ES190) or 240 (LW240, ES240) d for LW and ES, and 140 (LS140) or 190 (LS190) d for LS. Backgrounding options included shipping steers to Oklahoma (OK1), or backgrounding in Montana to a constant age (MT2) or weight (MT3). Steers from OK1 and MT2 were finished in Oklahoma in confinement or via self-feeders on pasture and harvested in Texas. Steers in MT3 were finished in Montana in confinement and harvested in Colorado. Performance of each system was modeled based on actual animal performance, market prices, and variable input costs. When calves were sold at weaning, gross margins per cow were greatest for LS190 (P \u3c 0.05) and lowest for LW240. During backgrounding, costs of gain were similar among cow-calf systems, and gross margins per steer were greatest for LS140 (P \u3c 0.05), but not different among backgrounding systems. During finishing, costs of gain were greatest for steers from MT2 due to transportation costs to Oklahoma (P \u3c 0.05), and gross margin per steer favored MT3 (P \u3c 0.05). Gross margin for a ranch with a fixed land base did not differ among systems if calves were sold at weaning, but was greatest for LS systems after backgrounding or finishing (P \u3c 0.05)

Regional Cerebral Blood Flow in Mood Disorders. II. Comparison of Major Depression and Alzheimer's Disease

We contrasted regional cerebral blood flow in matched groups of 30 patients with major depression,30 patients with Alzheimer's disease and 30 normal controls using the 133Xe inhalation technique. Whereas both the depressed and AIzheimer's disease groups had markedly reduced global cortical blood flow, the Scaled Subproflle Model,developed to identify abnormalities in regional networks, indicated that they had distinct topographic profiles. Previous findings of an abnormal regional network in major depression were unaltered by the inclusion of Alzheimer's disease patients in the analysis. Alzheimer's disease was associated with a distinct parietotemporal deficit and the degree of this abnormality strongly covaried with cognitive impairment. Alzheimer's disease patients also had abnormal manifestation of three other regional networks. We illustrate a method for distinguishing when a disease imposes a new pattern of interactions among brain regions and when a disease alters the expression of regional patterns characteristic of normal functioning

Synergistic effects of traumatic head injury and apolipoprotein 4 in patients with Alzheimer’s disease

The apolipoprotein 4 allele increases the risk of Alzheimer’s disease (AD), but cerebral deposition of B-amyloid with age, a genetic mutation, or head injury may contribute to the pathogenesis of this disease. We examined the risks of AD associated with traumatic head injury and apolipoprotein 4 in 236 community-dwelling elderly persons. A 10-fold increase in the risk of AD was associated with both apolipoprotein 4a nd a history of traumatic head injury, compared with a two-fold increase in risk with apolipoprotein 4 alone. Head injury in the absence of an apolipoprotein 4 allele did not increase risk. These data imply that the biological effects of head injury may increase the risk of AD, but only through a synergistic relationship with apolipoprotein 4

A Preliminary Study of Apolipoprotein E Genotype and Psychiatric Manifestations of Alzheimer's Disease

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations

Conservation, Evaluation and Dissemination of Groundnut Germplasm and Foundation Seed Production and Distribution for the West African Region Proceedings of the final workshop 22-25 April 2002 Bamako, Mali

The Gr o u n d n u t Germplasm Project (GGP) was ini t iated in 1996 wi t h the pr incipal aim of restor ing the genetic diversi t y of groundnut in West Af r ica and supplying seed of improved varieties t o Nat ional Agr icul tural Research Systems (NARS) and other benef iciar ies. ICRISAT, as Project Execut ing Agency and, in col laborat ion wi t h its par tners ISRA and CIRAD, organized an end-of -project workshop f r o m 22 to 25 Ap r i l 2002 at Bamako, Ma l i . The object ive of thi s wor k shop was to present the remarkable achievements of the project to a wide range of stakeholders and ident i f y fol low-up act ion for a sustainable seed produc t ion and del iver y scheme in West Af r ica. Par t icipants at the workshop were f r o m various spheres, including research and development ( R & D ) , nongovernmental organizations (NGOs ) , the pr ivate sector, and groundnut producers. Project results were presented dur ing the di f ferent sessions, one of wh i c h focused on presentat ions by NARS about groundnut seed suppl y systems in selected count r ies. Parallel group discussions focused on conservat ion of genet ic resources and thei r opt imal ut i l izat ion, st rengthening of seed mul t ipl i cat ion and di s t r ibut ion, and the role of the publ i c and pr ivate sector in the groundnut sector. These produced impor tant conclusions that wi l l help guide the future development of sustainable seed systems in West Af r ica. The opinions in this publ icat ion are those of authors and not necessarily those of ICRISAT. The designations employed and the presentat ions of the mater ial in this publ icat ion do not imp l y the expression of any opinion whatsoever on the par t of ICRISAT concerning the legal status of any count ry, ter r i tory, city, or area, or of i ts author i t ies, or concerning the del imi tat ion of its f ront ier s or boundar ies. Wh e r e t rade names are used this does not const i tute endorsement of or discr iminat ion against any product by the Inst i tute

The apolipoprotein ϵ4 allele in Parkinson\u27s disease with and without dementia

The ϵ4 isoform of apolipoprotein E (Apo-E) may confer genetic susceptibility for familial and sporadic Alzheimer\u27s disease (AD). Because dementia in AD and Parkinson\u27s disease (PD) share many biologic and clinical features, we determined the Apo-E genotypes for 79 patients with PD, 22 of whom were demented, and for 44 age-matched healthy elderly controls from the same community. We hypothesized that if the dementia was similar to AD, there would be a higher allele frequency of apolipoprotein ϵ4 (Apoϵ4) in demented PD patients compared with nondemented PD patients and controls. The ϵ4 allele frequency for PD without dementia was 0.132, for PD with dementia, 0.068, and for controls, 0.102. There was no association between Apoϵ4 and dementia in the PD patients. We conclude that the biologic basis for dementia in PD may differ from that of AD

Strengthening conservation and utilization of ground-nut (Arachis hypogaea L.) genetic resources in West Africa

This paper describes the status of ground-nut (Arachis hypogaea L.) genetic resources conservation and utilization in West Africa. A proportion of ground-nut accessions conserved in the ICRISAT gene bank in Patancheru, India, were duplicated at ICRISAT, Niamey, Niger, to provide ready access to a greater range of diversity for crop improvement scientists. With support from the Common Fund for Commodities (CFC), 6000 accessions from 73 countries were assembled, representing the major botanic types and maturity groups. These accessions were characterized and evaluated for desirable traits at selected locations in West Africa, India and Malawi. The accessions were screened for their reaction to important diseases, including rust, early and late leaf spots, ground-nut rosette virus and aflatoxin contamination. In the collection, 166 accessions show resistance to rust, 80 to late leaf spot, 30 to early leaf spot, 150 to ground-nut rosette disease and 74 to Aspergillus flavus invasion and aflatoxin contamination. The germplasm has been documented in printed catalogues, digitally on CD-ROMs and posted on the Web. Procedures for the distribution and exchange of germplasm were developed and 6371 samples were distributed to users. With support from the World Bank, an additional room was constructed at the gene bank at Niamey to accommodate 13 deep freezers to conserve the entire global ground-nut germplasm and other species, especially pearl millet

Effect of Age, Ethnicity, and Head Injury on the Association between APOE Genotypes and Alzheimer's Disease

The apolipoprotein E (APOE)-e4 allele is neither necessary nor sufficient to cause Alzheimer's disease (AD) because it develops in the absence of APOE e4, and some persons escape the disease despite having an APOE €4 allele. Although the presence of the €4 allele of the APOE gene has been consistently associated with an increased risk of it is apparent that the degree of risk may be modified by age, gender, ethnic group, certain risk factors, and possibly other genes. Roses et al. proposed that APOE genotypes have a direct influence on the age at onset of disease. In both familial and sporadic AD, an earlier age at onset among APOE €4 homozygous and APOE €4 heterozygous cases than among those cases with other APOE genotypes. Thus, it is possible that APOE genotypes strongly influence age at onset and that certain factors, both genetic and nongenetic, modify this effect by shifting the distribution curves. In this review we will discuss demographic and putative risk factors that may modify (enhance or diminish) the association between APOE genotypes and AD