Stainable hepatic iron in 341 African American adults at coroner/medical examiner autopsy

Background  

Results of previous autopsy studies indicate that increased hepatic iron stores or hepatic iron overload is common in African Americans dying in hospitals, but there are no reports of hepatic iron content in other cohorts of African Americans.     

Thromboembolic diseases in neonates and children

Acquired and inherited prothrombotic risk factors increase the risk of thrombosis in neonates, infants and children. After suffering thrombosis white paediatric patients should be screened for common gene mutations, i.e. the factor V G1691A, factor II G20210A and MTHFR C677T genotypes, rare inherited prothromboticrisk factors, i.e. deficiencies of protein C,protein S, and antithrombin, plasminogen, probably inherited risk factors, i.e. fibrinogen, factor VIIIC, factor XII, new candidates, i.e. elevation of lipoprotein (a),and fasting homocysteine concentrations (3-6 months after thrombotic onset). Data interpretation is based on age-dependent reference ranges or the identification of causative gene mutations/polymorphisms with respect to individual ethnic backgrounds.     

Clonality of Endocrine Proliferative Lesions: A Critical Reappraisal

The distinction between nodular hyperplasia and benign tumors of the endocrine system is problematical. Although numerous parameters including lesional size, multicentricity and histological features have been suggested as distinguishing criteria, none of these is absolute. Analyses based on X-chromosome inactivation have provided conflicting results with respect to the clonal origins of these lesions, and at least some lesions conventionally classified as hyperplastic nodules appear to be monoclonal, Although clonality has been generally equated with neoplasia, it is likely that clonal expansion of genetically normal cells can occur in the endocrine system as a result of a variety of growth of promoting stimuli. Multiparametric studies employing markers for X-chromosome inactivation together with methods for identification of unique non-X-linked genetic alterations will be required to resolve the many questions relating to the pathogenesis of endocrine proliferative lesions.     

Effect of HFA-flunisolide on peripheral lung inflammation in asthma

BACKGROUND: New hydrofluoroalkane (HFA) formulations of glucocorticoids have been shown to effectively control asthma. HFA glucocorticoids are deposited across all sizes of airways, including the small ones. However, it is not clear whether they can suppress peripheral airway inflammation. OBJECTIVE: We sought to determine whether HFA-flunisolide could suppress peripheral inflammation in asthma. METHODS: Twelve patients with mild to moderate asthma received HFA-flunisolide for 6 weeks. Transbronchial and endobronchial biopsy specimens were obtained before and after treatment, and spirometry was performed. Changes in inflammatory cells (eosinophils, neutrophils, lymphocytes, macrophages, basophils) and IL-5 and eotaxin were measured by using immunocytochemistry and in situ hybridization. RESULTS: Lung function significantly improved after treatment (P <.05). HFA-flunisolide significantly reduced eosinophils, IL-5, and eotaxin in both peripheral and central airways (P <.01). Neutrophils significantly increased after treatment in peripheral and central airways (P <.05). The numbers of lymphocytes remained unchanged. CONCLUSIONS: These results show that HFA-flunisolide effectively suppressed eosinophilic inflammation in peripheral and central airways. These changes were accompanied by improvement in lung function.     

Effects of cGMP-dependent phosphorylation on rat and human connexin43 gap junction channels

The effects of 8-bromoguanosine 3:5-cyclic monophosphate (8Br-cGMP), a membrane-permeant activator of protein kinase G (PKG), were studied on rat and human connexin43 (Cx43), the most abundant gap junction protein in mammalian heart, which were exogenously expressed in SKHep1 cells. Under dual whole-cell voltage-clamp conditions, 8Br-cGMP decreased gap junctional conductance (g_j) in rat Cx43-transfected cells by 24.0±3.7% (mean±SEM, n=5), whereas g_j was not affected in human Cx43-transfected cells by the same treatment. The relaxation of g_j in response to steps in transjunctional voltage observed in rat Cx43 transfectants was best fitted with three exponentials. Time constants and amplitudes of the decay phases changed in the presence of 8Br-cGMP. Single rat and human Cx43 gap junction channels were resolved in the presence of halothane. Under control conditions, three single-channel conductance states (_j) of about 20, 40–45 and 70 pS were detected, the events of the intermediate size being most frequently observed. In the presence of 8Br-cGMP, the _j distribution shifted to the lower size in rat Cx43 but not in human Cx43 transfectants. Immunoblot analyses of Cx43 in subconfluent cultures of rat Cx43 or human Cx43 transfectants showed that 8Br-cGMP did not induce changes in the electrophoretic mobility of Cx43 in either species. However, the basal incorporation of [³²P] into rat Cx43 was significantly altered by 8Br-cGMP, whereas this incorporation of [³²P] into human Cx43 was not affected. We conclude that 8Br-cGMP modulates phosphorylation of rat Cx43 in SKHep1 cells, but not of human Cx43. This cGMP-dependent phosphorylation of rat Cx43 is associated with a decreased g_j, which results from both an increase in the relative frequency of the lowest conductance state and a change in the kinetics of these channels.     

The Effects of Discrimination Training on Voluntary Control of Cephalic Vasomotor Activity

The present study was conducted to test Brener's calibration theory of visceral learning. It was hypothesized that training in discrimination of cephalic vasomotor responses would enhance acquisition of voluntary and biofeedback control of cephalic vasomotor response. Four groups were given discrimination training to detect either constriction, dilation, both constriction and dilation, or given false feedback. All groups were then given biofeedback training in constriction. All groups were assessed on discrimination accuracy, acquisition of biofeedback control of constriction, and voluntary control of dilation and constriction. The results indicated that discrimination of cephalic vasomotor responses can be learned and that this skill facilitates the acquisition of biofeedback and voluntary control of vasomotor responses. This facilitation occurs only if discrimination training is given for the specific response to be learned. The data suggest that discrimination of the relevant response is a necessary but not sufficient condition for acquisition of voluntary control in biofeedback learning.     

Changes in the cytoskeleton of 3T3 fibroblasts induced by the phosphatase inhibitor,calyculin-A

Summary Addition of the protein phosphatase inhibitor, calyculin-A, to 3T3 fibroblasts causes a marked change in cell morphology. Initially the cells become rounded, develop surface blebs and then detach from the substratum. In the detached cells an unusual ball-like structure is observed. This study focuses on the cytoskeleton during these calyculin-A-induced morphological changes. Stress fibres disappear as the cells begin to round and aggregates of actin are formed towards the apical surface of the cell. These aggregates condense, in the detached cells, to form the ball structure of approximately 3 m diameter. Between the ball and the nucleus are cables of intermediate filaments that appear to be attached to the surface of the ball and to the nuclear lamina. Using a procedure designed for the isolation of nuclei the nucleus-ball complex can be obtained. Analysis of the nucleus-ball preparation by immunofluorescence and electron microscopy demonstrate that the ball contains actin and that intermediate filaments are located between the ball and the nucleus. In this preparation, the intermediate filaments also appear to attach to the surfaces of the ball and the nucleus. Electrophoretic analysis of the nucleus-ball preparation indicates that, in addition to actin, a major component of the ball is myosin. It is suggested that the formation of the ball is caused by an actin-myosin-based contractile process, initiated by the phosphorylation of myosin. The aggregation of the actomyosin draws together the intermediate filaments into the area between the ball and nucleus. This hypothesis requires that vimentin binds both to the nucleus and to some component of the ball.     

Construction of peptoliposomes for the incorporation of nutrient lipid supplements in insect cell culture media

Summary Nutrient liposomes that incorporate peptones instead of serum proteins can be used for the lipid supplementation of insect cells in lieu of or in addition to vertebrate serum to enhance the growth or differentiation of specific insect cell types in culture. The technique described here for the preparation of nutrient peptoliposomes involves the combination of both natural and synthetic phosphatidyl cholines (containing essential polyunsaturated fatty acids) with appropriate sterols. These are protected against premature oxidation by antioxidants (glutathione, alanine, protein hydrolysates) and antioxidant synergists (citrate, ascorbate, plus other amino acids) in the basal tissue culture medium as well as in the liposomal preparation itself (alphatocopherol acetate and protein hydrolysates). The lipid components are filter sterilized in chloroform and then dried before aqueous sonication, allowing the subsequent formation of a random array of unsized uni- and multilamellar liposomes, which are suitable as direct suppliers of lipid nutrients as well as nutrient carriers for lipid-soluble supplements.