bluuebunny/crossref_metadata_2025 huggingface dataset:
Termination of Pregnancy due to Fetal Abnormalities Performed after 23 Weeks’ Gestation: Analysis of Indications in 144 Cases from a Single Medical Center
Authors: Vaknin Zvi , Lahat Yael , Barel Oshri , Ben-Ami Ido , Reish Orit , Herman Arie , Maymon Ron
Published: July 2009

Background/Aims: To assess the indications for late termination (≥23 weeks’ gestation) of pregnancy (LTOP), and to evaluate the rate of cases potentially diagnosable earlier. Methods: Cases of singleton pregnancy ending in LTOP due to fetal abnormalities in our institute between 1/1998 and 12/2005 were retrospectively reviewed. The women were divided into two groups according to the sequence of events that led to LTOP: Group 1 – the first test indicating an abnormal finding was performed ≤23 weeks’ gestation, but LTOP was performed >23 weeks; Group 2 – the first test indicating an abnormal finding was performed ≥23 weeks of gestation, or the fetal prognosis was not certain at the time of diagnosis and there was a medical recommendation to continue investigation. Results: There were 144 cases of LTOP (average gestational age 26.2 ± 3.4 weeks). More than 70% of the cases were aborted because of chromosomal/genetic indication in Group 1; many of them could have been detected earlier in pregnancy, while about 80% of the cases were aborted because of structural abnormalities in Group 2 (p < 0.001). The structural anomaly could have been diagnosed earlier in 56 cases (∼74%) if the pregnant woman had undergone an earlier anomaly scan. In another 13 cases (9%), fetal prognosis was not certain and continuing prenatal investigation was required. Conclusions: The most common indications for LTOP were structural abnormalities (91 cases, 70%) which included the central nervous system (26 cases, 29%), cardiac abnormalities (24 cases, 26%), and multiple malformations (18 cases, 20%). The diagnosis of fetal anomaly could have been made earlier in more than half of the pregnant women undergoing LTOP.
Narrative Exposure Therapy versus Interpersonal Psychotherapy
Authors: Schaal Susanne , Elbert Thomas , Neuner Frank
Published: July 2009

Background: The aim of the present study was to evaluate the efficacy of treatment modules for trauma spectrum disorders in a sample of Rwandan genocide orphans. Methods: Twenty-six orphans (originally 27) who presented with posttraumatic stress disorder (PTSD) at first assessment continued to meet a PTSD DSM-IV diagnosis 6 months after their initial assessment. They were offered participation in a controlled treatment trial. A group adaptation of interpersonal psychotherapy (IPT, n = 14) was compared to individual narrative exposure therapy (NET, n = 12). The last NET session involved guided mourning. Each treatment program consisted of 4 weekly sessions. Main outcome measures were diagnostic status and symptoms of PTSD and depression assessed before treatment, at 3 months post-test and at 6 months follow-up using the Clinician-Administered PTSD Scale, Mini-International Neuropsychiatric Interview, and Hamilton Rating Scale. Results: At post-test, there were no significant group differences between NET and IPT on any of the examined outcome measures. At 6-month follow-up, only 25% of NET, but 71% of IPT participants still fulfilled PTSD criteria. There was a significant time × treatment interaction in the severity of PTSD [Wilks’ Λ = 0.75, F(2,23) = 3.93; p < 0.05] and depression symptoms [Wilks’ Λ = 0.23, F(2,23) = 3.40; p = 0.05]. At follow-up, NET participants were significantly more improved than IPT participants with respect to both the severity of symptoms of PTSD and depression. Conclusions: Individual NET in combination with group-based mourning comprises an effective treatment for traumatized survivors who have to bear the loss of loved ones and have been suffering from symptoms of PTSD and depression.
Allergen Binding to Human Peripheral Leukocytes
Authors: Hubscher T. , Eisen A.H.
Published: July 2009

Washed human leukocytes isolated from ragweed allergic and normal donors were incubated with 125 labelled ragweed antigen E, in the presence of EDTA. Autoradiographs of peripheral white blood cells from ragweed allergic donors were incubated with 125 labelled ragweed antigen E, in the presence phils and only rarely on the neutrophils. By immunofluorescence γE immunoglobulin localized on the eosinophils and basophils in both ragweed allergic and normal donors. The results indicate that these eosinophilic leukocytes bind ragweed antigen E and that the eosinophils and basophils both are coated with γE immunoglubulin.
Cryoglobulins. II. The Biological and Chemical Properties of Cryoproteins in Acute Post-Streptococcal Glomerulonephritis
Authors: McIntosh R.M. , Kulvinskas C. , Kaufman D.B.
Published: July 2009

Cryoglobulins isolated from patients with acute post-streptococcal glomerulonephritis, fixed complement in vitro and were associated with inflammatory changes following intradermal administration to unsensitized guinea pigs. Intravenous administration to laboratory animals was followed by clinical and morphologic changes resembling anaphylactic shock or by glomerulitis with the deposition of human IgG but no host IgC on the glomerular basement membrane and in the mesangium. Gel filtration using Sephadex G200 of cryoglobulin solution dissolved in, and eluted with, barbital buffer yielded a single component in the macroglobulin fraction. Gel filtration chromatography using dilute acid yielded 2 components; a large molecular weight component which was not identified by chemical or immunologic methods and another fraction which had the same chemical composition as normal human IgG except for a lower sialic acid content. Streptococcal antibody was not detected in either fraction and streptococcal antigens were not localized in the glomeruli of animals that developed glomerulitis. These studies show that mixed cryoglobulins isolated from patients with acute post-streptococcal glomerulonephritis exhibit properties similar to those of antigen-antibody complexes and suggest that they may have a primary or secondary role in the production of glomerular injury.
Mixed Agglutination with Platelets
Authors: Juji T. , Kano K. , Milgrom F.
Published: July 2009

Platelet layers firmly adhering to the glass surface were obtained by allowing human platelets to sediment onto the wall of test tubes or onto glass slides and ‘fixing’ them by means of a 2% formaldehyde solution. Mixed agglutination tests with these platelet preparations were performed in following the procedure used for studies on monolayer cell cultures. It was shown that platelets contain human species-specific antigens similar to those present on all human nucleated cells. Reactions with human sera containing antibodies to alloantigens were also studied. Mixed agglutination tests with platelets gave antiserum titers 100 times higher than those obtained in the corresponding lymphocytotoxicity tests. In some instances, mixed agglutination tests with platelets detected HL-A antigens which were not demonstrable by means of lymphocytotoxicity tests.
Immune Responses to the Hemocyanin from Limulus polyphemus in Allergic and Normal Individuals
Authors: Hansen R.L. , Gleich G.J.
Published: July 2009

Atopic and normal individuals were immunized with the hemocyanin from the horseshoe crab (LPH) by subcutaneous or nasal routes. Subjects were divided into 3 groups: (1) atopic, (2) normal, and (3) ‘indeterminant’. The ‘indeterminant’ group was comprised of subjects who did not fit the criteria for designation as either atopic or normal. Antibody production in serum and saliva was characterized by hemagglutination, radioimmunodiffusion, radioimmunoprecipitation, and direct skin testing. Ten of 11 subjects immunized subcutaneously produced detectable antibody activity in one or more immunoglobulin classes. Only two subjects developed positive wheal-and-flare skin reactions. Salivary IgA antibody was not detected in any subjects in spite of high levels of serum IgA antibody. Seven of 11 subjects immunized by the nasal route produced serum antibody limited to a single class. Skin tests in all these subjects were negative. Also, salivary antibodies were not detected in these individuals.
Specific Inhibition of Allergic Reactions to Penicillin in Man by a Monovalent Hapten
Authors: de Weck A.L. , Girard J.P.
Published: July 2009

The monovalent hapten BPO-FLYS has been shown experimentally to inhibit specifically immunological reactions to penicillin in vitro and in vivo. In order to evaluate its potential under clinical conditions, it was administered parenterally to 15 patients having presented acute allergic reactions to penicillin and requesting further penicillin therapy. The parenteral administration of BPO-FLYS (100–400 mg/day) was well tolerated in all cases. An objective demonstration of the inhibiting activity of the hapten, namely, the suppression of previously positive skin tests and a marked diminution of the titer of hemagglutinating antibodies was obtained in most cases. 12 out of 13 patients where it was attempted were able to pursue penicillin therapy without allergic symptoms under cover of the hapten. The demonstration that a monovalent hapten is capable of inhibition specifically clinical allergic reactions to penicillin in man could represent a significant advance in the prevention of penicillin allergy.
The Immune Response to Multichain Poly-dl-Alanine-Poly-l-Lysine in Guinea Pigs and its Relation to the PLL Gene
Authors: Ben-Efraim S. , Raveh Lilly , Spirer Z. , Liacopoulos P.
Published: July 2009

A multichain polypeptide poly-dl-alanyl-poly-l-lysine (A--L) was immunogenic in guinea pigs randomly bred and of inbred strain 2 and non-immunogenic for guinea pigs of inbred strain 13. The immune response to A--L in randomly bred guinea pigs was not related to the ability to respond to a DNP-p(Lys) conjugate.
Lysis of Antibody-Treated Human Erythrocytes by Human Leukocytes and Macrophages in Tissue Culture
Authors: Holm G.
Published: July 2009

The 51Cr-chromate method was used for quantitation of lysis of antibody-treated human RBC which had been labilized by pretreatment with 1% trypsin. RBC treated with heat-inactivated isoantiserum to A, B or Rh antigens were lysed within 3–6 h by blood leukocytes or peritoneal macrophages. Macrophages or suspensions containing mainly granulocytes and monocytes were cytotoxic at the leukocyte-RBC ratio 1:5 while an excess of purified lymphocytes ( > 99%) had no hemolytic effect. Erythrophagocytosis by monocytes and some granulocytes was frequently seen and is assumed to be the main mechanism of hemolysis. There was no evidence of hemolytic factors released by leukocyte suspensions. This method may be useful for studies of cell mediated hemolysis in human immune hemolytic diseases.
Antibody-Inhibiting Activity of Bone Marrow Cells in vitro
Authors: Singhal S.K. , King S. , Drury P.J.
Published: July 2009

Mouse bone marrow and thymus cells have been studied according to their immunological reactivity. The test system involved measurement of the levels of IgM plaque-forming cells following the immunization of spleen cells in vitro in the presence of graded numbers of syngeneic bone marrow and/or thymus cells. All experimental evidence showed the existence of a radiosensitive subpopulation of cells in the bone marrow, capable of inhibiting both the primary and secondary IgM-antibody production irrespective of the dose of antigen used in the system. That this inhibition of antibody production may represent a central control mechanism was indicated by a small change in reactivity of antibody-inhibiting cells derived from the bone marrow of tolerant or normal animals. Furthermore, the inability of supernatants from bone marrow cells, premaintamed in vitro with or without antigen, to suppress the immune response suggested the absence of a released humoral factor responsible for their antibody-inhibiting activity. An enhancement of the immune response with all doses of thymus cells and their inability to overcome the inhibiting activity of bone marrow cells suggested that these immunological events are operating independently of each other.
Leucocyte Migration Inhibition in Thyroid Disease
Authors: Wartenberg Janina , Doniach Deborah , Brostoff J. , Roitt I.M.
Published: July 2009

Leucocyte migration inhibition tests (LMT) were carried out in 49 patients with thyroid disease and 47 healthy controls using purified human thyroid microsomes and thyroglobulin as the antigens. Patients with autoimmune thyroiditis or thyrotoxicosis gave positive LMT with thyroid microsomes, while the leucocytes of healthy subjects and patients with non-toxic-colloid goitre were inactive. Control tests with liver microsomes gave negative results in all groups. In Hashimoto’s goitrous thyroiditis, it was further possible to show that the most intense cell-mediated hypersensitivity was present in patients who had the ‘hypercellular’ histological variant of the disease, which has a mild clinical course and is characterized serologically by low or absent thyroglobulin antibodies and moderate titres of thyroid microsomal antibodies. Slow regression of the goitre despite thyroxine treatment was associated with marked migration inhibition in the presence of thyroid microsomes. Thyroglobulin proved inactive in LMT in both patients and controls in concentrations varying from 50 to 5,000 μg/ml. The reason for this is not clear in view of positive results occasionally reported by other workers.
The Role of Soft Connective Tissue in the Breakdown of Pig Articular Cartilage Cultivated in the Presence of Complement-Sufficient Antiserum to Pig Erythrocytes
Authors: Poole A.R. , Barratt M.E.J. , Fell H.B.
Published: July 2009

1. The penetration and interaction of IgG of normal heat-inactivated rabbit serum (NRS), and of rabbit antiserum to pig erythrocytes (A-S) without (A-S + NRS) and with complement (A-S + C′), have been studied in organ cultures of pig articular cartilage by immunohistochemical methods. 2. In explants of metacarpal condylar cartilage cut above the level of the invading marrow (invasion zone), IgG of NRS, A-S + NRS and A-S + C′ did not penetrate beyond the most superficial layers of the articular chondrocytes; the reaction was more intense after treatment with A-S, especially in the presence of C′. 3. In similar explants cut at a deeper level to include part of the invasion zone, IgG of NRS entered the invasion cavities in the cartilage and penetrated a short distance into the overlying matrix. After exposure to A-S + C′, the invading marrow reacted intensely, and IgG often penetrated far into the cartilage where the matrix was depleted (see Part I); cellular staining was restricted to the surfaces of viable chondrocytes but was intense throughout dead cells. 4. Fibrous cartilage from the junction between the condylar cartilage and the periosteum and periosteal bone, was very permeable to IgG of NRS, A-S + NRS and A-S + C′. In explants treated with A-S, many cells reacted for IgG; the intensity of the response was increased by the presence of C′. 5. When condylar cartilage without the invasion zone was grown in contact with fragments of joint capsule (affronted explants), IgG of NRS and A-S entered the area of depleted matrix near the capsular explant (see Part I) and reacted with the chondrocytes; penetration and cellular reaction were greater after exposure to both A-S and C′.
Studies in Immunodermatology
Authors: Holubar K. , Chorzelski T.P. , Gauto Maria , Beutner E.H.
Published: July 2009

Intraepithelial lesions comparable to those which characterize pemphigus vulgaris developed following repeated intramucosal injections of monkey lip with pemphigus antibodies. Transfer experiments were performed, injecting samples of patients’ sera or their IgG fractions, once, twice, or three times into mucosal locations. At sites injected with pemphigus antibodies, immunofluorescence studies almost invariably revealed their binding to the intercellular region of the mucosal epithelium. Suprabasal clefts could be detected in 6 of 16 sites which had received three injections; five of these occurred 21–25 h after the first of three injections. Controls utilizing sera of patients with bullous pemphigoid, systemic lupus erythematosus, normal human serum and normal human IgG were all negative.
Mechanism of Histamine Release from Rat Mast Cells by Compound 48/80. Comparison with the Release Induced by Cationic Protein
Authors: Ranadive N.S. , Ruben D.H.
Published: July 2009

Rat peritoneal mast cells incubated with compound 48/80 at temperatures below 10 °C and washed released histamine upon warming to 37 °C. Evidence has been put forward to show that this release of histamine was due to the activation of mast cells at low temperatures. The active state reached at low temperature decayed at 10 °C without establishment of unresponsiveness in mast cells to a second challenge. Mast cells, however, could be desensitized to compound 48/80 in presence of theophylline and 2,4-dinitrophenol. The presence of theophylline during the activation of cells at low temperature had no effect on the subsequent release of histamine in a second incubation. The cells activated at low temperature, however, showed inhibition of histamine release when theophylline was added to the medium in the second incubation. The cells desensitized to compound 48/80 were found to be unresponsive to the stimulation by a cationic protein from neutrophil lysosome (band 2 protein). These findings have been discussed in view of the earlier studies on the mechanism of histamine release.
Antigen Dose Dependence of Reagin Formation in Rabbits
Authors: Strannegård Ö.
Published: July 2009

The effect of antigen dosage on the formation of reagins in rabbits was studied using various routes of immunization. Upon immunization with adjuvant-incorporated haemocyanin, very high and very low antigen doses failed to induce a detectable reagin response although other antibodies were produced. Similar dose-response curves were obtained after intravenous injection of bovine y-globulin. Intravenous injection of a low dose of haemocyanin resulted in a reagin response, initially in the absence of demonstrable IgG or IgM antibodies. Upon stimulation with polymerized bovine γ-globulin it was again found that high or low doses of antigen induced reagin formation poorly. Polymerization of the antigen appeared to enhance its ability to induce reagin production at high antigen dosage, but to diminish this ability at low antigen dosage. Development of immediate hypersensitivity was observed after intranasal administration of low doses of birch pollen. The results explain previous contradictory reports as to dose dependence in reagin formation. They suggest that some reagin-forming cell precursors have high affinity for antigen and that the apparent unresponsiveness to high antigen doses may be due to consumption of circulating reagins by antigens. Although polymerization of an antigen may make it more immunogenic, the allergenicity of a substance is probably not markedly enhanced if it occurs in particulate rather than soluble form.
IgE and IgG Antibodies against Aspergillus fumigatus in Sera of Patients with Bronchopulmonary Allergic Aspergillosis
Authors: Patterson Roy , Roberts Mary
Published: July 2009

Studies of sera from patients with bronchopulmonary allergic aspergillosis (BPAA) confirm a previous report that serum IgE concentrations are elevated. Both IgE and IgG antibodies against Aspergillus fumigatus antigen (AF Ag) can be detected in vitro using a solid phase radioimmunoadsorbent technique. Sera were studied by several techniques to determine if the elevated serum IgE concentrations in BPAA were composed primarily of IgE antibodies directed against AF Ag. The results indicated that the opposite is more likely: that most of the IgE in the sera obtained from patients with BPAA and used in these studies is not directed against AE Ag.
Expulsion of Nippostrongylus brasiliensis from the Small Intestine of the Rat by Prostaglandin-Like Factors from Ram Semen
Authors: Dineen J.K. , Kelly J.D. , Goodrich B.S. , Smith I.D.
Published: July 2009

The widespread distribution of prostaglandins in tissues and fluids, their association with inflammatory responses of immunological origin and their biological properties suggest that they may play a role in expulsion of parasites from the gastro-intestinal tract. The present studies showed that intraduodenal injection of chloroform extracts of ram semen (containing prostaglandin-like factors) and fractions of these extracts obtained by preparative thin-layer chromatography caused the expulsion of Nippostrongylus brasiliensis adult worms from the small intestine in the rat. Administration of aspirin and d-propoxyphene, which are potent inhibitors of prostaglandins, prevented the expulsion of parasites which normally occurs in rats between days 10 and 16 of a primary infection with N. brasiliensis. Cell transfer studies showed that these analgesics did not affect production of immune lymphocytes and provided additional evidence that they prevented worm expulsion by interfering with the activity of non-specific mediators.
Presence and Kinetics of Sensitized Cells in Different Tissue Compartments
Authors: Bröcker Eva-Bettina , Müller-Ruchholtz W.
Published: July 2009

The question was studied as to whether lymph nodes (LN), spleen (SP) and bone marrow (BM) contain different amounts of sensitized cells at various times after one or repeated immunizations. The following model was used: C57 mice were injected i.p. once, twice or three times with C3H cells. Between 3 and 20 days after the last immunization, LN, SP and BM cell suspensions were tested in vivo for their local cutaneous lymphocyte transfer reactivity in C3H mice and in vitro for their lymphocytotoxicity (partially after preincubation with anti-theta serum). In both test systems similar observations were made: after one sensitization, reactive cells were demonstrated first in the LN and then in the SP, but only during the next few days; BM cell reactivity appeared later. In the first few days after two sensitizations SP cells reacted strongly whereas LN and BM cells reacted weakly; later BM cell reactivity increased while the others decreased. After three sensitizations reactivity of the SP cells predominated during the entire period of observations; the BM cells showed less, the LN cells no reactivity. These findings suggest dependance of T cell-mediated reactivity on (1) the origin of the cells from LN, SP or BM, (2) the time of the harvesting from these tissues, and (3) the degree of sensitization.
A Radioisotopic Method to Measure Delayed Type Hypersensitivity in the Mouse
Authors: Miller J.F.A.P. , Vadas M.A. , Whitelaw Alison , Gamble Jennifer
Published: July 2009

Sensitized lymphoid cells could transfer to normal non-sensitized (naive) mice by 24-48 h after antigen challenge in the ear, the capacity to incorporate, at the site of antigen deposition, 5-iodo-2′deoxyuridine-125I in amounts significantly above those obtained in control mice. This was associated with a mononuclear cell infiltration in the pinna. In contrast to lymphoid cells, serum antibodies were unable to transfer a 24- or 48 hour ear reaction. The cells responsible were T lymphocytes as demonstrated by successful transfer following enrichment for T lymphocytes, and abrogation of transfer following treatment with anti-Θ serum and complement. Transfer was achieved whether the naive recipients were normal, T-cell deprived, pretreated with cyclophosphamide, or lightly irradiated but not when they were heavily irradiated. Adoptive transfer of the 24-hour ear response was demonstrated with three different antigenic systems. The time-response curves were different with each system although peak reactions were obtained 5 days after sensitization of the donors in all cases. The specificity patterns of the 24-hour ear reactions on transfer were similar to those obtained in the sensitized donors. The results of these studies indicate that the radioisotopic ear method can, under defined conditions, demonstrate the existence of a state of delayed type hypersensitivity in the donors.
Leukocyte Migration Inhibition in Nickel Dermatitis
Authors: Mirza A.M. , Perera M.G. , Maccia C.A. , Dziubynskyj O.G. , Bernstein I.L.
Published: July 2009

Leukocyte migration inhibitory factor assay was employed as an in vitro diagnostic aid in nickel dermatitis, the second most common contact dermatitis in North America. 15 patch test-positive and 5 patch test-negative patients, all giving a past history suggestive of nickel dermatitis, were investigated. Significant inhibition of leukocyte migration in both groups of patients was obtained only with nickel sulfate-albumin conjugate and not with unconjugated nickel sulfate. Specificity of this system was tested by utilizing an unrelated metallic albumin complex, and no inhibition was found. When patch testing is equivocal or contraindicated, this in vitro technique may be a practical alternative.
Impaired Recovery of Blood Flow After Hind-Limb Ischemia in Mice Lacking Guanylyl Cyclase-A, a Receptor for Atrial and Brain Natriuretic Peptides
Authors: Tokudome Takeshi , Kishimoto Ichiro , Yamahara Kenichi , Osaki Tsukasa , Minamino Naoto , Horio Takeshi , Sawai Kazutomo , Kawano Yuhei , Miyazato Mikiya , Sata Masataka , Kohno Masakazu , Nakao Kazuwa , Kangawa Kenji
Published: July 2009

Objective—

Atrial and brain natriuretic peptides (ANP and BNP, respectively) function via guanylyl cyclase (GC)-A, resulting in diuresis, natriuresis, and blood vessel dilation. Here, we investigated the role of endogenous ANP/BNP-GC-A signaling on reparative vascular remodeling using a hind-limb ischemia model.

Methods and Results—

In GC-A–deficient mice (GC-A-KO), hind-limb ischemia resulted in autoamputation or severe ulcers in 60% of mice (6/10) during the 28-day observation period. In wild-type (WT) mice, partial amputation or mild ulcers were detected in only 20% of mice (2/10). Laser Doppler perfusion imaging revealed that the recovery of blood flow in the ischemic limb was significantly inhibited in GC-A-KO mice compared with WT mice. Immunostainings with anti–PECAM-1 antibody demonstrated that, in GC-A-KO, the capillary density of the ischemic tissue was significantly diminished compared to WT. Furthermore, bone marrow transplantation showed the predominant role of GC-A on local ischemic tissue rather than on vascular progenitor cells mobilized from bone marrow during vascular remodeling. In cultured human endothelial cells, ANP treatment significantly stimulated mRNA expressions of vascular endothelial growth factor and endothelial nitric oxide synthase via Erk1/2-dependent mechanism.

Conclusion—

These results suggest that endogenous ANP and BNP play important roles in reparative vascular remodeling in ischemic tissue.
Monocyte Chemoattractant Proteins Mediate Myocardial Microvascular Dysfunction in Swine Renovascular Hypertension
Authors: Lin Jing , Zhu Xiangyang , Chade Alejandro R. , Jordan Kyra L. , Lavi Ronit , Daghini Elena , Gibson Matthew E. , Guglielmotti Angelo , Lerman Amir , Lerman Lilach O.
Published: July 2009

Background—

Monocyte chemoattractant proteins (MCPs) play an important role in mediating inflammatory processes. Hypertension (HTN) is associated with inflammation as well as impaired cardiac microcirculatory function and structure, but the contribution of MCPs to these alterations remained unclear. This study tested the hypothesis that MCPs regulate cardiac microvascular function and structure in experimental HTN.

Methods and Results—

Pigs (n=6 per group) were studied after 10 weeks of normal, renovascular HTN, or renovascular HTN+ bindarit (MCPs inhibitor, 50 mg/kg/d PO). Left ventricular (LV) function, myocardial microvascular permeability, and fractional vascular volume were assessed by fast computed tomography before and after adenosine infusion (400 μg/kg/min). Myocardial fibrosis, inflammation, and microvascular remodeling were determined ex vivo. Hypertension was not altered by bindarit, but LV hypertrophy and diastolic function were improved. In response to adenosine, myocardial microvascular permeability increased in HTN (from 0.0083±0.0009 to 0.0103±0.0011 AU,
P
=0.038 versus baseline) and fractional vascular volume decreased, whereas both remained unchanged in normal and HTN+bindarit pigs. HTN upregulated endothelin-1 expression, myocardial inflammation, and microvascular wall thickening, which were inhibited by bindarit.

Conclusions—

MCPs partly mediate myocardial inflammation, fibrosis, vascular remodeling, and impaired vascular integrity induced by hypertension. Inhibition of MCPs could potentially be a therapeutic target in hypertensive cardiomyopathy.
Shear Stress Induces Synthetic-to-Contractile Phenotypic Modulation in Smooth Muscle Cells via Peroxisome Proliferator-Activated Receptor α/δ Activations by Prostacyclin Released by Sheared Endothelial Cells
Authors: Tsai Min-Chien , Chen Lihong , Zhou Jing , Tang Zhihui , Hsu Tzu-Fang , Wang Ying , Shih Yu-Tsung , Peng Hsin-Hsin , Wang Nanping , Guan Youfei , Chien Shu , Chiu Jeng-Jiann
Published: July 2009

Rationale
:

Phenotypic modulation of smooth muscle cells (SMCs), which are located in close proximity to endothelial cells (ECs), is critical in regulating vascular function. The role of flow-induced shear stress in the modulation of SMC phenotype has not been well defined.

Objective
:

The objective was to elucidate the role of shear stress on ECs in modulating SMC phenotype and its underlying mechanism.

Methods and Results
:

Application of shear stress (12 dyn/cm
2
) to ECs cocultured with SMCs modulated SMC phenotype from synthetic to contractile state, with upregulation of contractile markers, downregulation of proinflammatory genes, and decreased percentage of cells in the synthetic phase. Treating SMCs with media from sheared ECs induced peroxisome proliferator-activated receptor (PPAR)-α, -δ, and -γ ligand binding activities; transfecting SMCs with specific small interfering (si)RNAs of PPAR-α and -δ, but not -γ, inhibited shear induction of contractile markers. ECs exposed to shear stress released prostacyclin (PGI
2
). Transfecting ECs with PGI
2
synthase-specific siRNA inhibited shear-induced activation of PPAR-α/δ, upregulation of contractile markers, downregulation of proinflammatory genes, and decrease in percentage of SMCs in synthetic phase. Mice with PPAR-α deficiency (compared with control littermates) showed altered SMC phenotype toward a synthetic state, with increased arterial contractility in response to angiotensin II.

Conclusions
:

These results indicate that laminar shear stress induces synthetic-to-contractile phenotypic modulation in SMCs through the activation of PPAR-α/δ by the EC-released PGI
2
. Our findings provide insights into the mechanisms underlying the EC-SMC interplays and the protective homeostatic function of laminar shear stress in modulating SMC phenotype.
Dynamical Mechanism for Subcellular Alternans in Cardiac Myocytes
Authors: Gaeta Stephen A. , Bub Gil , Abbott Geoffrey W. , Christini David J.
Published: July 2009

Rationale:

Cardiac repolarization alternans is an arrhythmogenic rhythm disturbance, manifested in individual myocytes as a beat-to-beat alternation of action potential durations and intracellular calcium transient magnitudes. Recent experimental studies have reported “subcellular alternans,” in which distinct regions of an individual cell are seen to have counterphase calcium alternations, but the mechanism by which this occurs is not well understood. Although previous theoretical work has proposed a possible dynamical mechanism for subcellular alternans formation, no direct evidence for this mechanism has been reported in vitro. Rather, experimental studies have generally invoked fixed subcellular heterogeneities in calcium-cycling characteristics as the mechanism of subcellular alternans formation.

Objective:

In this study, we have generalized the previously proposed dynamical mechanism to predict a simple pacing algorithm by which subcellular alternans can be induced in isolated cardiac myocytes in the presence or absence of fixed subcellular heterogeneity. We aimed to verify this hypothesis using computational modeling and to confirm it experimentally in isolated cardiac myocytes. Furthermore, we hypothesized that this dynamical mechanism may account for previous reports of subcellular alternans seen in statically paced, intact tissue.

Methods and Results:

Using a physiologically realistic computational model of a cardiac myocyte, we show that our predicted pacing algorithm induces subcellular alternans in a manner consistent with theoretical predictions. We then use a combination of real-time electrophysiology and fluorescent calcium imaging to implement this protocol experimentally and show that it robustly induces subcellular alternans in isolated guinea pig ventricular myocytes. Finally, we use computational modeling to demonstrate that subcellular alternans can indeed be dynamically induced during static pacing of 1D fibers of myocytes during tissue-level spatially discordant alternans.

Conclusion:

Here we provide the first direct experimental evidence that subcellular alternans can be dynamically induced in cardiac myocytes. This proposed mechanism may contribute to subcellular alternans formation in the intact heart.
Epicardium and Myocardium Separate From a Common Precursor Pool by Crosstalk Between Bone Morphogenetic Protein– and Fibroblast Growth Factor–Signaling Pathways
Authors: van Wijk Bram , van den Berg Gert , Abu-Issa Radwan , Barnett Phil , van der Velden Saskia , Schmidt Martina , Ruijter Jan M. , Kirby Margaret L. , Moorman Antoon F.M. , van den Hoff Maurice J.B.
Published: July 2009

Rationale
:

The epicardium contributes to the majority of nonmyocardial cells in the adult heart. Recent studies have reported that the epicardium is derived from Nkx2.5-positive progenitors and can differentiate into cardiomyocytes. Not much is known about the relation between the myocardial and epicardial lineage during development, whereas insights into these embryonic mechanisms could facilitate the design of future regenerative strategies.

Objective
:

Acquiring insight into the signaling pathways involved in the lineage separation leading to the differentiation of myocardial and (pro)epicardial cells at the inflow of the developing heart.

Methods and Results
:

We made 3D reconstructions of Tbx18 gene expression patterns to give insight into the developing epicardium in relation to the developing myocardium. Next, using DiI tracing, we show that the (pro)epicardium separates from the same precursor pool as the inflow myocardium. In vitro, we show that this lineage separation is regulated by a crosstalk between bone morphogenetic protein (BMP) signaling and fibroblast growth factor (FGF) signaling. BMP signaling via Smad drives differentiation toward the myocardial lineage, which is inhibited by FGF signaling via mitogen-activated protein kinase kinase (Mek)1/2. Embryos exposed to recombinant FGF2 in vivo show enhanced epicardium formation, whereas a misbalance between FGF and BMP by Mek1/2 inhibition and BMP stimulation causes a developmental arrest of the epicardium and enhances myocardium formation at the inflow of the heart.

Conclusion
:

Our data show that FGF signaling via Mek1/2 is dominant over BMP signaling via Smad and is required to separate the epicardial lineage from precardiac mesoderm. Consequently, myocardial differentiation requires BMP signaling via Smad and inhibition of FGF signaling at the level of Mek1/2. These findings are of clinical interest for the development of regeneration-based therapies for heart disease.
Reducing Attention Deficits After Stroke Using Attention Process Training
Authors: Barker-Collo Suzanne L. , Feigin Valery L. , Lawes Carlene M.M. , Parag Varsha , Senior Hugh , Rodgers Anthony
Published: July 2009

Background and Purpose—

Impaired attention contributes to poor stroke outcomes. Attention process training (APT) reduces attention deficits after traumatic brain injury. There was no evidence for effectiveness of APT in stroke patients. This trial evaluated effectiveness of APT in improving attention and broader outcomes in stroke survivors 6 months after stroke.

Methods—

Participants in this prospective, single-blinded, randomized, clinical trial were 78 incident stroke survivors admitted over 18 months and identified via neuropsychological assessment as having attention deficit. Participants were randomly allocated to standard care plus up to 30 hours of APT or standard care alone. Both groups were impaired (z≤−2.0) across measures of attention at baseline, with the exception of Paced Auditory Serial Addition Test, which was below average (z≤−1.0). Outcome assessment occurred at 5 weeks and 6 months after randomization. The primary outcome was Integrated Visual Auditory Continuous Performance Test Full-Scale Attention Quotient.

Results—

APT resulted in a significantly greater (
P
<0.01) improvement on the primary outcome than standard care. Difference in change on the Cognitive Failures Questionnaire approached significance (
P
=0.07). Differences on other measures of attention and broader outcomes were not significant.

Conclusion—

APT is a viable and effective means of improving attention deficits after incident stroke.
Alternate Pathways Preserve Tumor Necrosis Factor-α Production After Nuclear Factor-κB Inhibition in Neonatal Cerebral Hypoxia–Ischemia
Authors: Nijboer Cora H. , Heijnen Cobi J. , Groenendaal Floris , van Bel Frank , Kavelaars Annemieke
Published: July 2009

Background and Purpose—

Nuclear factor-κB (NF-κB) is an important regulator of inflammation and apoptosis. We showed previously that NF-κB inhibition by intraperitoneal TAT-NBD treatment strongly reduced neonatal hypoxic–ischemic (HI) brain damage. Neuroprotection by TAT-NBD was not associated with inhibition of cerebral cytokine production. We investigated how tumor necrosis factor-α (TNF-α) production is maintained after NF-κB inhibition and whether TNF-α contributes to brain damage.

Methods—

Postnatal Day 7 rats were subjected to unilateral carotid artery occlusion and hypoxia. Rats were treated immediately after HI with TAT-NBD, the JNK inhibitor TAT-JBD, and/or the TNF-α inhibitor etanercept. We determined brain damage, NF-κB and AP-1 activity, Gadd45β, XIAP, (P-)TAK1, TNF-α, and TNF receptor expression.

Results—

Our data confirm that TAT-NBD treatment reduces brain damage without inhibiting TNF-α production. We now show that TAT-NBD treatment increased HI-induced AP-1 activation concomitantly with reduced Gadd45β, XIAP, and increased (P)-TAK1 expression. Combined inhibition of NF-κB and JNK/AP-1 abrogated HI-induced TNF-α production. However, this treatment reduced the neuroprotective effect of NF-κB inhibition alone. We show that etanercept was detectable in the HI brain after intraperitoneal administration and that etanercept treatment also reduced the neuroprotective effect of NF-κB inhibition. Finally, NF-κB inhibition decreased HI-induced upregulation of TNF-R1 and increased TNF-R2 expression.

Conclusions—

When NF-κB was inhibited after neonatal cerebral HI, JNK/AP-1 activity was increased and required for increased TNF-α expression. Our data indicate that the switch to JNK/AP-1 activation preserves HI-induced TNF-α expression and thereby might contribute to the neuroprotective effect of TAT-NBD possibly through a TNF-R2 dependent mechanism.
Interrater Reliability of Posture Observations
Authors: Bao Stephen , Howard Ninica , Spielholz Peregrin , Silverstein Barbara , Polissar Nayak
Published: July 2009

Objective: The aims of this research were (a) to study the interrater reliability of a posture observation method, (b) to test the impact of different posture categorization systems on interrater reliability, and (c) to provide guidelines for improving interrater reliability. Background: Estimation of posture through observation is challenging. Previous studies have shown varying degrees of validity and reliability, providing little information about conditions necessary to achieve acceptable reliability. Method: Seven raters estimated posture angles from video recordings. Different measures of interrater reliability, including percentage agreement, precision, expression as interrater standard deviation, and intraclass correlation coefficients (ICC), were computed. Results: Some posture parameters, such as the upper arm flexion and extension, had ICCs ≥ 0.50. Most posture parameters had a precision around the 10° range. The predefined categorization and 30° posture categorization strategies showed substantially better agreement among the raters than did the 10° strategy. Conclusions: Different interrater reliability measures described different aspects of agreement for the posture observation tool. The level of agreement differed substantially between the agreement measures used. Observation of large body parts generally resulted in better reliability. Wider width angle intervals resulted in better percentage agreement compared with narrower intervals. For most postures, 30°angle intervals are appropriate. Training aimed at using a properly designed data entry system, and clear posture definitions with relevant examples, including definitions of the neutral positions of the various body parts, will help improve interrater reliability. Application: The results provide ergonomics practitioners with information about the interrater reliability of a postural observation method and guidelines for improving interrater reliability for video-recorded field data.
Gender Differences in Needs and Care of Severely Mentally Ill Persons: Findings From a Swedish Cross-Sectional and Longitudinal Study
Authors: Arvidsson Hans
Published: July 2009

Background: A great amount of research has been done in the area of gender and severe mental illness. However, there is an apparent lack of studies on gender differences concerning needs and care.

Aim: To analyze differences in needs and care between men and women considered to be severely mentally ill (SMI) after the 1995 Swedish mental health care reform.

Method: In one area of Sweden, surveys were made in 1995/96 and 2006 of persons considered to be SMI. These persons were interviewed and their needs assessed. In a cross-sectional study in 2006, the needs and care of men and women were compared. In a longitudinal study, men and women interviewed in both 1995/96 and 2006 were compared concerning the development of needs and care.

Results: The structure of needs differed between men and women. Men had more needs concerning functional disability and those needs seemed possible to meet in the existing service structure. Women’s needs concerning physical health, information about health and own security, seemed to be more difficult to meet. Only a few gender differences were found in satisfaction with services and service utilization.

Conclusion: It seems urgent to have a gender perspective in a needs-led mental healthcare service.
Steady‐State Pharmacokinetics Following Application of a Novel Transdermal Estradiol Spray in Healthy Postmenopausal Women
Authors: Morton Terri L. , Gattermeir David J. , Petersen Craig A. , Day Wesley W. , Schumacher Robert J.
Published: July 2009

This study was designed to evaluate the steady‐state pharmacokinetics (PK) of estradiol and its metabolites, estrone and estrone sulfate, following application of a novel estradiol transdermal spray to healthy postmenopausal women. Participants were randomly assigned in parallel to receive 1‐, 2‐, or 3‐spray doses (24 participants/dose level) of a 1.7% estradiol metered‐dose transdermal spray (1.53 mg/spray) once daily for 14 days. Blood was collected predose on days 1 to 14 and over 7 days after the last dose. Serum concentrations for all 3 analytes reached steady state by day 7 or 8 and were still slightly above baseline on day 21. Estradiol, estrone, and estrone sulfate serum concentrations generally increased with increasing dose. Mean estradiol and estrone maximum serum concentration (Cmax) following 1, 2, or 3 sprays for 14 days were 36 and 50, 57 and 60, and 54 and 71 pg/mL, respectively. Estradiol time when maximum concentration occurred (tmax) was 18 to 20 hours. The area under the serum concentration‐time curve over 24 hours following the last dose of study drug (AUC0–24 h) on day 14 for the 1‐, 2‐, and 3‐spray groups, respectively, was 471, 736, and 742 pg·h/mL for estradiol; 886, 1208, and 1367 pg·h/mL for estrone; and 16 501, 26 515, and 27 971 pg·h/mL for estrone sulfate. The metered‐dose estradiol transdermal spray delivers estradiol at therapeutic levels and produces low serum estrone concentrations.
Admicellar Polymerization of Polystyrene on Natural Rubber Particles
Authors: Magaraphan Rathanawan , Srinarang Vijitra
Published: July 2009

Admicellar polymerization is a reaction for coating a thin-film of polymer on a surface. The process consists of the polymerization of the adsolubilized monomer in the hydrophobic regions of the surfactant bilayers that adsorbed on the substrate surface. In this research, the admicellar polymerization of polystyrene was carried out using micron to submicron size natural rubber particles as substrates. Cetyl trimethyl ammonium bromide (CTAB) was used to form the surfactant template. The adsorption isotherm of CTAB was determined in the absence and presence of salt. Styrene adsolubilization was found to increase with initial styrene concentration and in the presence of salt. The synthesized polystyrene in the molecular bilayer of micelles surrounding the natural rubber particles was characterized by optical microscope, Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The observed morphology of the rubber particles after reaction was clearly two phases, a core-shell structure having the natural rubber core covered by the polystyrene shell. These core-shell particles were spheres and aggregated strongly in the emulsion. Effect of initiator type was investigated. The synthesized products showed core-shell morphology, which was still obtained after heating but after cooling phase inversion occurred and showed polystyrene-rich core and natural rubber-rich shell. Thin lamellar of both components was found in both polystyrene-rich core and natural rubber-rich shell making unique morphology and extended single transition of thermal decomposition. FTIR results show characteristic peaks of natural rubber and polystyrene and the absorbance of styrene increases with increasing styrene content. The TGA result showed that the decomposition temperatures of the products were altered by the amount of polystyrene.
Perspectives for Practice
Authors: Rentfro Anne Rath , McEwen Marylyn , Ritter Leslie
Published: July 2009

Purpose

The purpose of this article is to facilitate translation of the Consensus Statement to practice for diabetes educators and other professionals who contribute to the care of individuals with diabetes.

Methods

The 2007 Consensus Statement from the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), and International Diabetes Federation (IDF) called for the standardization of glycated hemoglobin measurement in reporting and use of average glucose values in clinical practice.

Results

Conversion of glycated hemoglobin percentage to average blood glucose was anchored historically in early laboratory techniques linked to disease outcomes rather than to definitive laboratory standardization. Recently, the A1C-Derived Average Glucose (ADAG) study demonstrated that A1C values can be accurately expressed as estimated average glucose (eAG) and endorsed eAG as the best way to standardize the expression of laboratory values of glycated hemoglobin.

Conclusions

Adoption of the 2007 Consensus Statement will influence clinical practice and decision making and subsequently influence self-management for individuals with diabetes.