Hydroxyoctadecadienoic Acids Regulate Apoptosis in Human THP‐1 Cells in a PPARγ‐Dependent Manner

Macrophage apoptosis, a key process in atherogenesis, is regulated by oxidation products, including hydroxyoctadecadienoic acids (HODEs). These stable oxidation products of linoleic acid (LA) are abundant in atherosclerotic plaque and activate PPARγ and GPR132. We investigated the mechanisms through which HODEs regulate apoptosis. The effect of HODEs on THP‐1 monocytes and adherent THP‐1 cells were compared with other C18 fatty acids, LA and α‐linolenic acid (ALA). The number of cells was reduced within 24 hours following treatment with 9‐HODE (p < 0.01, 30 μM) and 13 HODE (p < 0.01, 30 μM), and the equivalent cell viability was also decreased (p < 0.001). Both 9‐HODE and 13‐HODE (but not LA or ALA) markedly increased caspase‐3/7 activity (p < 0.001) in both monocytes and adherent THP‐1 cells, with 9‐HODE the more potent. In addition, 9‐HODE and 13‐HODE both increased Annexin‐V labelling of cells (p < 0.001). There was no effect of LA, ALA, or the PPARγ agonist rosiglitazone (1μM), but the effect of HODEs was replicated with apoptosis‐inducer camptothecin (10μM). Only 9‐HODE increased DNA fragmentation. The pro‐apoptotic effect of HODEs was blocked by the caspase inhibitor DEVD‐CHO. The PPARγ antagonist T0070907 further increased apoptosis, suggestive of the PPARγ‐regulated apoptotic effects induced by 9‐HODE. The use of siRNA for GPR132 showed no evidence that the effect of HODEs was mediated through this receptor. 9‐HODE and 13‐HODE are potent—and specific—regulators of apoptosis in THP‐1 cells. Their action is PPARγ‐dependent and independent of GPR132. Further studies to identify the signalling pathways through which HODEs increase apoptosis in macrophages may reveal novel therapeutic targets for atherosclerosis.     

Climatic effects on occurrence of clinical mastitis

Clinical mastitis records for 6.5 yr from a large north Florida dairy and corresponding daily weather data were analyzed. Monthly incidence of clinical mastitis was expressed as percent of cow-days in milk and graphed against monthly average daily maximum temperature humidity index values and monthly total rainfall. No trends were evident with rainfall. In 3 of 6 yr, monthly incidence of clinical mastitis increased more than 50% above annual incidence, and this followed high monthly temperature-humidity values. Least squares was used to estimate regression coefficients of temperature-humidity index categories based on 999,969 Holstein records. A temperature humidity index category represented the number of days used to calculate average daily maximum temperature-humidity index value. Sources of variation in observed occurrence of clinical mastitis were cow, parity, month, year, interaction of parity by month, and continuous effects of temperature-humidity index categories 2, 6, 15, 30, 60, each to third order and 60 by parity interaction. In all temperature-humidity index categories as the temperature-humidity index value increased, occurrence of clinical mastitis increased. When values rose from 55 to 80, twice as many for 2 d cows showed signs of clinical mastitis.     

Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues

We have built a fiber-optic confocal reflectance microscope capable of imaging human tissues in near real time. Miniaturization of the objective lens and the mechanical components for positioning and axially scanning the objective enables the device to be used in inner organs of the human body. The lateral resolution is 2 micrometers and axial resolution is 10 micrometers. Confocal images of fixed tissue biopsies and the human lip in vivo have been obtained at 15 frames/s without any fluorescent stains. Both cell morphology and tissue architecture can be appreciated from images obtained with this microscope.     

On segmenting the three-dimensional scan data of a human body

Software for categorizing a cloud of more than 300,000 three-dimensional (3-D) surface data points, captured from a human subject, is presented. The software is part of an incremental approach that progressively refines the identification of human anthropometric landmarks. The first phase of identification is to orient and segment the human body data points. A step-by-step method for these tasks is presented. One of the algorithms, a discrete point cusp detector, plays a fundamental role in separating the data cloud. The theory and operation of the algorithm is explained. The discrete cusp detector can be used to separate any two cylindrical objects, in (3-D) data, whose boundaries touch. The software has been tested on over a hundred different body scan data sets and shown to be robust.     

Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis

Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis.     

"Milk makes me sick but my body needs it": conflict and contradiction in the establishment of authoritative knowledge

This article takes lactose intolerance as a topic for exploring clashes of power, authority, and knowledge in clinical interactions and interpretations of laywomen. In clinics providing maternal and child care, staff and clients jointly produced authoritative knowledge, most often a version of biomedicine. The Euroamerican staff tended to give advice that was biologically appropriate for them but not for many of their patients, a process reflecting what we refer to as biocentrism. Resulting information given to pregnant and lactating women and diagnoses of children's growth patterns were inappropriate in some cases, with potentially serious legal and health implications. Clinic staff often unwittingly ignored the efforts of their clients to begin a discussion of discrepancies between their bodily knowledge and clinic advice. Some women created their own syntheses, which supported the ascendancy of biomedical knowledge but were not in the interests of their own health.     

Plasma corticosterone fluctuations in an infant-learning paradigm.

Plasma corticosterone fluctuations of infant rats were examined in a learning task. A blood sample for analysis of plasma corticosterone was collected from groups of 10- and 15-day-old pups following either no disturbance, standard maternal deprivation only, or deprivation and training in an established approach-mother, avoid-shock conflict task. In the latter condition, pups remained in the goalbox either alone or with an anesthetized dam for either 15 or 60 min before blood sample collection. Plasma corticosterone levels were elevated following deprivation plus training in pups of both ages and following deprivation only in the 15-day-old pups. Further, the presence of the dam in the goalbox reduced plasma corticosterone elevations, particularly among 15-day-old pups and at 60 min. These findings suggest that the mother's capacity to moderate the pup's plasma corticosterone response may contribute to her reinforcement value in infant-learning paradigms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)