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Posterior capsule opacification (PCO) is the most common complication of cataract surgery, and intraocular lens (IOL) implantation is the standard of care for cataract patients. Induction of postoperative epithelial‐mesenchymal transition (EMT) in residual lens epithelial cells (LEC) is the main mechanism by which PCO forms. Previous studies have shown that IOLs made with different materials have varying incidence of PCO. The aim of this paper was to study the interactions between human (h)LEC and polymer substrates. Polymers and copolymers of 2‐hydroxyethyl methacrylate (HEMA) and 3‐methacryloxypropyl tris(trimethylsiloxy)silane (TRIS) were synthesized and evaluated due to the clinical use of these materials as ocular biomaterials and implants. The chemical properties of the polymer surfaces were evaluated by contact angle, and polymer stiffness and roughness were measured using atomic force microscopy. In vitro studies showed the effect of polymer mechanical properties on the behavior of hLECs. Stiffer polymers increased α‐smooth muscle actin expression and induced cell elongation. Hydrophobic and rough polymer surfaces increased cell attachment. These results demonstrate that attachment of hLECs on different surfaces is affected by surface properties in vitro, and evaluating these properties may be useful for investigating prevention of PCO.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem-cell disorder in which the affected cells are deficient in glycosylphosphatidylinositol (GPI)-anchored proteins. Paroxysmal nocturnal hemoglobinuria is frequently associated with aplastic anemia, although the basis of this relation is unknown. Objective: To assess the PNH status of patients with diverse marrow failure syndromes. Design: Correlation of cytofluorometric data with clinical features. Setting: Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland. Patients: 115 patients with aplastic anemia, 39 patients with myelodysplasia, 28 patients who had recently undergone bone marrow transplantation, 18 patients with cancer that was treated with chemotherapy, 13 patients with large granular lymphocytosis, 20 controls who had received renal allografts, and 21 healthy participants. Intervention: Patients with aplastic anemia, myelodysplasia, or renal allografts received antithymocyte globulin. Measurements: Flow cytometry was used to assess expression of GPI-anchored proteins on granulocytes. Results: Evidence of PNH was found in 25 of 115 (22%) patients with aplastic anemia. No patient with normal GPI-anchored protein expression at presentation developed PNH after therapy (n = 16). Nine of 39 (23%) patients with myelodysplasia had GPI-anchored protein-deficient cells. Abnormal cells were not detected in patients with constitutional or other forms of bone marrow failure or in renal allograft recipients who had received antithymocyte globulin. Aplastic anemia is known to respond to immunosuppressive therapy; in myelodysplasia, the presence of a PNH population was strongly correlated with hematologic improvement after administration of antithymocyte globulin (P = 0.0015). Conclusions: Flow cytometric analysis is superior to the Ham test and permits concomitant diagnosis of PNH in about 20% of patients with myelodysplasia (a rate similar to that seen in patients with aplastic anemia). The presence of GPI-anchored protein-deficient cells in myelodysplasia predicts responsiveness to immunosuppressive therapy. Early emergence of GPI-anchored protein-deficient hematopoiesis in a patient with marrow failure may point to an underlying immune pathogenesis., Paroxysmal nocturnal hemoglobinuria (PNH) is better diagnosed by flow cytometric analysis than by the Ham test, especially in patients with myelodysplasia, a condition of minor defects in the spinal cord. PNH is an acquired hematopoietic stem-cell disorder in which blood cells which are deficient in certain components appear intermittently in the urine, usually at night and usually for several days at a time. Of 115 patients with aplastic anemia, 22% showed signs of PNH. A similar percentage (23%) was found in patients with myelodysplasia. These results suggest that these patients might respond well to immunosuppressive therapy.

The article discusses about the control of Democrats both its chambers for the first time in almost 25 years after swearing of legislators in to the Virginia General Assembly in January, 2020 and this change may herald a national progressive victory: the passage of the Equal Rights Amendment.

The article offers U.S. demographic information on aging, service costs for older people and home care services.

The article discusses the California legislative bill Assembly Bill 5 (AB5) on the classification of independent contractors by businesses, including the transportation network company Uber's plan to contest this bill in court.

The article informs that 2014, France's channel TF1 produced a documentary that imagined a weather report in the year 2050 featuring temperatures in the low 40s Celsius, and mentions that just five years later, a European heat wave has made those scary projections seem optimistic.

Perforin is a cytolytic protein expressed mainly in activated cytotoxic lymphocytes and natural killer cells. Inherited perforin mutations account for 20% to 40% of familial hemophagocytic lymphohistiocytosis, a fatal disease of early childhood characterized by the absence of functional perforin. Aplastic anemia, the paradigm of immune-mediated bone marrow failure syndromes, is characterized by hematopoietic stem cell destruction by activated T cells and Th1 cytokines. We examined whether mutations in the perforin gene occurred in acquired aplastic anemia. Three nonsynonymous PRF1mutations among 5 unrelated patients were observed. Four of 5 patients with the mutations showed some hemophagocytosis in the bone marrow at diagnosis. Perforin protein levels in these patients were very low or absent, and perforin granules were completely absent. Natural killer (NK) cell cytotoxicity from these patients was significantly decreased. Our data suggest that PRF1genetic alterations help explain the aberrant proliferation and activation of cytotoxic T cells and may represent genetic risk factors for bone marrow failure.

The article discusses how television show "Get Smart" got started and made its way into television comedy history. On September 18, 1965, NBC introduced the comedy show about the exploits of Maxwell Smart, the world's greatest, sharpest, most physically graceful secret agent. The show is a parody of James Bond and the whole spy craze, which pitted Smart and the good guys of CONTROL against the insidious forces of KAOS. "Get Smart" ran five seasons, won seven Emmy awards, and launched a slew of catchphrases.

We have previously reported the identification of a novel simian parvovirus in cynomolgus monkeys, which causes severe anemia in immunosuppressed cynomolgus monkeys and is currently being studied as an animal model for human B19 infection. We now report two similar outbreaks of anemia in rhesus and pig-tailed macaques associated with two distinct but similar simian parvoviruses (pig-tailed macaque and rhesus parvovirus). Both viruses have been cloned and over 5000 nucleotides sequenced from each virus. The viruses show marked similarities to other members of the Erythrovirus genus in the Parvoviridaefamily.

We recently reported the identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. We now describe the cloning and sequencing of 4986 nucleotides of the viral DNA. Like the human parvovirus B19, simian parvovirus encapsidates both positive and negative single-stranded DNA. The positive strand contains two large open reading frames, with the left open reading frame encoding the nonstructural protein(s) and the right reading frame encoding the two capsid proteins. Simian parvovirus has little homology with the autonomous parvoviruses or the dependovirus AAV-2 but 50% overall homology with parvovirus B19 DNA. At the amino acid level there was 70% homology with B19 capsid proteins and 50% homology with B19 nonstructural protein. Based on this genetic similarity and with the known tropism of the virus for cynomolgus erythroid precursors, we suggest that this new virus should be classified as a new member of the Erythrovirus genus of the Parvoviridae.

Cell number, protein, and phorbol myristate acetate (PMA)-induced H202production were measured in cultured human peripheral blood monocytes for six days after exposure to varying doses of γ-radiation. Both the number of adherent cells and the protein per dish decreased with increasing radiation doses. The dose of radiation decreasing the number of adherent cells by 37% on days 4 and 6 postirradiation was 29 Gy. Four hours postirradiation there was a small decrease in PMA-induced H202production for doses of 7.5 Gy or greater; levels returned to normal by eight hours and increased at 24 hours postirradiation. By day 4 postirradiation significant increases in PMA-induced H202production were noted at all radiation doses (2.5 to 50 Gy). This increase was not due to a shift in the PMA dose-response curve, a change in the time course of the PMA response, or an effect of decreased cell density on the assay system. Superoxide levels were not significantly changed in cells exposed to 20 Gy. Catalase, glutathione peroxidase, and superoxide dismutase levels also were unchanged. Culturing irradiated cells with γ-interferon increased PMA-induced H202 release, which indicated that irradiated cells retained their capacity to respond to γ-interferon. These data demonstrate that irradiation affects the PMA-induced H202 production of human monocytes in a time- and dose-dependent manner. An increase in the release of reactive oxygen intermediates by the macrophage may play a role in enhancing the deleterious effects of radiation in vivo.PMA response, or an effect of decreased cell density on the assay system. Superoxide levels were not significantly changed in cells exposed to 20 Gy. Catalase, glutathione peroxidase, and superoxide dismutase levels also were unchanged. Culturing irradiated cells with γ-interferon increased PMA-induced H202release, which indicated that irradiated cells retained their capacity to respond to γ-interferon. These data demonstrate that irradiation affects the PMA-induced H202production of human monocytes in a time- and dose-dependent manner. An increase in the release of reactive oxygen intermediates by the macrophage may play a role in enhancing the deleterious effects of radiation in vivo.This is a US government work. There are no restrictions on its use. 0006-4971/87/7003-0013$0.00/0

Goose parvovirus is the etiological agent of Derzsy's disease, a fatal hepatitis of young geese. The virus infects geese and Muscovy ducks and can be propagated in the laboratory in primary embryonic goose fibroblasts. To date the virus has only been classified by morphological, biochemical, and culture characteristics as an autonomous parvovirus. We now report the cloning and partial sequencing of 3434 nucleotides of the vital genome. Three overlapping clones were obtained, encoding regions in the nonstructural and capsid coding region. The nucleotide sequence show little homology to other autonomous parvoviruses but 55% homology to the dependovirus AAV2. This homology to AAV2 was also confirmed at the amino acid level (nonstructural protein 55%, capsid coding region 51%). DNA cross hybridization studies indicate an even closer similarity of goose parvovirus to the yet unsequenced human dependoviruses AAV1 and AAV3 than to AAV2. These findings suggest that goose parvovirus may be genetically related to the dependovirus genus rather than to the other autonomous parvoviruses.

Exposure of the macrophage‐like cell line J774.1 to 20 gray of cobalt‐60 gamma radiation resulted in a block of tritiated thymidine incorporation, along with an increase in cell “activation,” as assessed by increases in lysosomal enzyme and ectoenzyme content, PMA‐induced H2O2production, and NBT staining, ingestion of E(IgG), spreading, and membrane ruffling. These changes are evident within 1 day postradiation and peak at 4 days postradiation.

The political journalist on the timidity of liberal foundations, the peril of ignoring local reporting, and whether organizers have succeeded where party politics has failed. [ABSTRACT FROM AUTHOR]

No relevant conflicts of interest to declare.

Perforin is a cytolytic protein expressed mainly in activated cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. In T and NK cells perforin is stored in cytoplasmic granules and is essential for killing via non-Fas-mediated mechanisms. Perforin regulates the translocation of granzyme B from cytotoxic cells into target cells; after entering the target-cell granzyme B migrates to the target cell nucleus to participate in triggering apoptosis. Functional perforin is essential for normal CTL and NK cell function; without perforin CTL and NK cells show reduced or no cytolytic effect. Inherited perforin mutations account for 20–40% of familial hemophagocytic lymphohistiocytosis, an autosomal recessive fatal disease of early childhood characterized by uncontrolled accumulation of activated T cells and macrophages in many organs, increased Th1 cytokines and absent functional perforin. Acquired aplastic anemia (AA), the paradigm of immune mediated bone marrow failure syndromes, is characterized by hematopoietic stem cell destruction by activated T cells and Th1 cytokines. We examined whether mutations in Prf1 occur in AA; peripheral blood DNA samples from 75 patients and 302 controls were analyzed. Three novel nonsynonymous Prf1 mutations among five unrelated patients (ages: 21, 31, 33, 75, and 77 years old), not present in controls, were discovered; two polymorphisms were also identified (H300H, A274A). The mutations were in the coding region of Prf1 gene. In exon 2, arginine was replaced by histidine in one patient (CGT/CAT, R4H) and in 3 patients the same A91V mutation was identified (GCG/GTG, alanine to valine substitution). In exon 3, serine was replaced by isoleucine (S388I; AGC/ATC) in one patient. Germ-line origin of the Prf1 mutations was established by their presence also in DNA from buccal mucosa obtained from affected AA patients. Four of five patients with mutations showed some hemophagocytosis in the bone marrow examination when first diagnosed, but there were no other typical features of hemophagocytic syndrome such as hepatosplenomegaly or altered liver function tests. None of the patients with Prf1 mutations experienced hematologic recovery with immunosuppressive treatment. Perforin protein levels in all patients carrying mutations were very low or absent. By confocal microscopy, CD8 cells from patients with Prf1 mutations had complete absence of perforin granules (perforin and cathepsin D showed the expected pattern of co-localization in controls’ cytotoxic granules). NK cell killing efficiency from patients carrying mutations in a standard Cr51-release cytolytic assay was significantly decreased compared to controls. Prf1 gene mutations may be related to a more severe phenotype of AA associated with marrow hemophagocytosis and failure to respond to immunosuppression. Mutations in the immune regulatory mechanisms identified in young children can manifest in adults without typically associated clinical findings or a suggestive family history. Mechanistically, Prf1 gene mutations help explain the aberrant proliferation and activation of cytotoxic T cells that are destructive of hematopoietic stem cells in AA and may be useful as predictive factors for responses to immunosuppressive treatments and the decision to rapidly undertake stem cell replacement. Prf1 gene mutations are genetic risk factors for bone marrow failure syndromes.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder characterized by intravascular hemolysis, thrombosis, and bone marrow failure; in PNH, mutations in the PIG-A gene prevent synthesis of glycosylphosphoinositol (GPI) anchors and therefore cell membrane expression of GPI-anchored proteins. PNH cell clonal expansion occurs in the setting of immune-mediated hematopoietic cell destruction. The mechanism responsible for PNH clonal expansion is uncertain, but there is experimental evidence for relative resistance of GPI-anchored protein negative cells to NK-cell mediated cytotoxicity. Signaling lymphocyte activation molecule (SLAM; CD150; SLAMF1) is a glycosylated type-I transmembrane protein of relative molecular mass 70 Kd; the protein has a cytoplasmic domain bearing a paired immunoreceptor tyrosine-based switch motif. SLAM is constitutively expressed on the surface of activated T-, B- lymphocytes, dendritic cells and macrophages with a high-affinity self ligand. SLAM functions include co-stimulation of T and B cells, augmentation of T-cell cytotoxicity, and regulation of proliferation and differentiation of B cells. The recruitment of SLAM or SLAM-associated proteins is important in modulating innate and adaptive immune responses. Engagement of CD244 (2B4), another SLAM family member, by CD48--a GPI-anchored protein--results in CD244 activation, leading to NK cell stimulation and NK cell mediated cytotoxicity. We examined SLAM and CD244 expression in peripheral blood mononuclear cells from patients with PNH and healthy controls to establish their involvement in PNH. We first analyzed SLAM expression by flow cytometry on CD56+ and CD3+ cells from 11 PNH patients (5 females, 6 males) and 10 healthy controls. In CD56+ cells membrane SLAM (mSLAM) was up-regulated in 10 of 11 patients compared to controls (p=0.04). mSLAM was more modestly elevated in CD3+ cells from patients (p=0.04). Expression of CD244 also showed increased expression in PNH patients’ CD56+ cells (p=0.0008) and in CD3+ (p= 0.05). mRNA levels, measured by RT-PCR, of mSLAM in patients (n=4) and controls (n=4) were consistent with flow cytometric data, PNH patients having increased mSLAM mRNA levels (p=0.18). In a single PNH patient who showed up-regulation by flow and RT-PCR we also detected increased mSLAM protein levels by immunoblot. RT-PCR was also employed to quantitate mRNA levels of soluble or cytoplasmic SLAM (sSLAM): sSLAM expression was decreased in patients (n=4) compared to controls (n=3) (p< 0.0001). All differences between groups were evaluated using the F test to compare variances. In summary, NK cells from PNH patients have increased levels of mSLAM and 2B4; up-regulation suggests involvement of SLAM family members in immunologically mediated selection of PNH clones in immune-mediated marrow failure syndromes and is consistent with a role for NK cells in PNH clonal expansion.

Aplastic anemia is a bone-marrow-failure syndrome characterized by low blood-cell counts and a fatty bone marrow. In most cases, no obvious etiological factor can be identified, but clinical responses to immunosuppressive treatment (IST) strongly suggest an immune pathophysiology. Our previous study of T-cell receptor (TCR) Vβ (variable region of β-chain) repertoire usage by flow cytometry suggested that aplastic anemia results from antigen-specific lymphocyte attack on hematopoietic progenitors (Risitano et al. Lancet2004; 364:355). In the current work, 7 patients were investigated for Vβ pattern expression before first immunosuppresive treatment, at the remission, and again on relapse. The TCR Vβ repertoire was analyzed for CD4+ and CD8+ subsets, separately, by flow cytometry, using a monoclonal antibody set of 22 different Vβ chains. Most patients had very different patterns of Vβ usage from healthy individuals, and all but one showed expansion of at least one Vβ family before immunosuppressive treatment (Vβ family expansions were defined as 2 standard deviations (SD) from the means in controls). The median number of expanded Vβ families was 4 per patient among CD8CD28dim effector cells. At remission, almost all the initially expanded Vβ subfamilies decreased to less than 2SD of controls. At relapse, most of the expanded Vβ subsets were increased again. However, 5/7 patients showed new expanded Vβ subsets at recurrence of cytopenias, suggesting antigenic spread of new epitopes recognized by immune systems. Although no common pattern of specific expanded Vβ subsets could be identified among different patients, some Vβ subfamilies appeared to be more frequently involved (Vβ 5.1 and Vβ 5.2 were expanded in 4 of 7 patients both at initial presentation and relapse ). These data suggest that monitoring Vβ subsets in aplastic anemia, and potentially in other immune-mediated human diseases of a similar pathophysiology could be used to guide individual therapeutic decisions and in the development of new treatments.

Parvovirus B19 (B19) DNAwas detected by dot blot hybridization in sera from 5 (17%) of 30 human immunodeficiency virus (HIV)-infected patients with hematocrits (HCT) of 24 and 4 (31%) of 13 HIV-infected patients with HCT of 20, suggesting that B19 is a reasonably common cause of severe anemia in HIVinfection. The anemia promptly remitted after immunoglobulin therapy in 3 of 4 treated patients. The presence of IgM to B19, the clinical circumstance in which anemia developed, and the marrow morphology were poor predictors of chronic B19 infection. DNA hybridization studies of sera from 191 HIV-infected and 117 HIV-seronegative homosexual males attending a clinic in the Seattle area revealed that 1 (0.5%) and 2 (2%) samples, respectively, from the 2 groups contained B19. However, when assayed by polymerase chain reaction (PCR), 5% of the serum samples from HIVinfected persons and 9% from uninfected persons contained B19, although each had an HCT of 40. The data argue that anemia results from chronic high-titer B19 infection. Although a negative PCR assay excludes this diagnosis, DNA hybridization may be the more specific serum test.