Clinical characteristics of patients with metastatic castration-resistant prostate cancer after treatment with combined androgen blockade.

Background: Although the second-generation androgen receptor inhibitors and taxanes have recently been recommended for the initial treatment of metastatic prostate cancer, bicalutamide and flutamide are still used in a large number of cases. Therefore, it is important to elucidate the clinical characteristics of these treated CRPC cases and their sensitivity to the currently used therapeutic agents. We aimed to examine the outcomes of metastatic castration-resistant prostate cancer following combined androgen blockade as initial therapy at our institution.

Federated learning for predicting clinical outcomes in patients with COVID-19.

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.

Federated Learning used for predicting outcomes in SARS-COV-2 patients.

'Federated Learning' (FL) is a method to train Artificial Intelligence (AI) models with data from multiple sources while maintaining anonymity of the data thus removing many barriers to data sharing. During the SARS-COV-2 pandemic, 20 institutes collaborated on a healthcare FL study to predict future oxygen requirements of infected patients using inputs of vital signs, laboratory data, and chest x-rays, constituting the "EXAM" (EMR CXR AI Model) model. EXAM achieved an average Area Under the Curve (AUC) of over 0.

Artificial intelligence for the detection of COVID-19 pneumonia on chest CT using multinational datasets.

Chest CT is emerging as a valuable diagnostic tool for clinical management of COVID-19 associated lung disease. Artificial intelligence (AI) has the potential to aid in rapid evaluation of CT scans for differentiation of COVID-19 findings from other clinical entities. Here we show that a series of deep learning algorithms, trained in a diverse multinational cohort of 1280 patients to localize parietal pleura/lung parenchyma followed by classification of COVID-19 pneumonia, can achieve up to 90.

Light Stress-Induced Increase of Sphingosine 1-Phosphate in Photoreceptors and Its Relevance to Retinal Degeneration.

Sphingosine 1-phosphate (S1P) is a potent lipid mediator that modulates inflammation and angiogenesis. In this study, we investigated the possible involvement of S1P in the pathology of light-induced retinal degeneration in vivo and in vitro. The intracellular S1P and sphingosine kinase (SphK) activity in a photoreceptor cell line (661W cells) was significantly increased by exposure to light.

Enzymatic characterization of recombinant rat DDHD2: a soluble diacylglycerol lipase.

DDHD2 has been reported to exhibit phospholipase A, triacylglycerol (TG) lipase and diacylglycerol (DG) lipase activities. However, the detailed enzymatic properties of DDHD2 have not yet been elucidated. In the current study, the substrate specificity of DDHD2 towards DG, TG and phosphatidic acid (PA) has been examined using highly purified recombinant rat DDHD2 (rDDHD2) with a liquid chromatography mass spectrometer.

Individual variation of human S1P₁ coding sequence leads to heterogeneity in receptor function and drug interactions.

Sphingosine 1-phosphate receptor 1 (S1P₁), an abundantly-expressed G protein-coupled receptor which regulates key vascular and immune responses, is a therapeutic target in autoimmune diseases. Fingolimod/Gilenya (FTY720), an oral medication for relapsing-remitting multiple sclerosis, targets S1P₁ receptors on immune and neural cells to suppress neuroinflammation. However, suppression of endothelial S1P₁ receptors is associated with cardiac and vascular adverse effects.

BDNF protects human vascular endothelial cells from TNFα-induced apoptosis.

Brain-derived neurotrophic factor (BDNF) enhances periodontal tissue regeneration. Tissue regeneration is characterized by inflammation that directs the quality of tissue repair. In this study, we investigated the anti-apoptotic effect of BDNF against the toxicity of tumor necrosis factor α (TNFα), which is known for its pro-apoptotic action in human microvascular endothelial cells (HMVECs).

Cofilin is required for organization of sarcomeric actin filaments in chicken skeletal muscle cells.

Cofilin is an actin regulatory protein that plays a critical role in actin filament dynamics in a variety of cells. We have previously demonstrated that excess cofilin in skeletal muscle cells leads to disruption of actin filaments, followed by actin-cofilin rod formation in the cytoplasm. In this study, to further clarify the role of cofilin in actin assembly during myofibrillogenesis, cofilin expression was suppressed in cultured chicken skeletal muscle cells.

Sphingosine 1-phosphate in coagulation and inflammation.

Sphingosine 1-phosphate (S1P) is a lipid mediator produced from sphingomyelin by the sequential enzymatic actions of sphingomyelinase, ceramidase, and sphingosine kinase. Five subtypes of cell surface G-protein-coupled receptors, S1P(1-5), mediate the actions of S1P in various organs systems, most notably cardiovascular, immune, and central nervous systems. S1P is enriched in blood and lymph but is present at much lower concentrations in interstitial fluids of tissues.

Preoperative management of Cushing's syndrome with metyrapone for severe psychiatric disturbances.

A 56-year-old woman suffered from severe depression due to Cushing's syndrome with right adrenal adenoma. She had a normal mental state before developing Cushing's syndrome. Because of her depressive state, informed consent for the treatment could not be obtained, and oral administration of 1.

p51/p63 Inhibits ultraviolet B-induced apoptosis via Akt activation.

The epidermis must be protected against excess apoptotic cell death in response to ultraviolet-B (UV-B) irradiation. p53 is known to be critical for this protection. Although the p53 family member DeltaNp51B/DeltaNp63alpha (an N terminal-deleted form of p51/p63) is abundantly expressed in keratinocytes, its contribution to UV-B-dependent apoptosis is largely unknown.

5-Oxo-eicosatetraenoic acid-induced chemotaxis: identification of a responsible receptor hGPCR48 and negative regulation by G protein G(12/13).

While screening genes encoding G protein-coupled receptors (GPCRs) in the human genome, we and other groups have identified a GPCR named hGPCR48 as a high affinity receptor for 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is arachidonic acid metabolite and an endogenous chemoattractant for granulocytes. Using Chinese hamster ovary (CHO) cells stably expressing hGPCR48, we show here that activation of the receptor causes the chemotaxis of the cells toward 5-oxo-ETE. We also show that the chemotaxis of human granulocytes toward 5-oxo-ETE is inhibited by pretreatment with anti-hGPCR48 antibodies, indicating that hGPCR48 is an endogenous receptor responsible for chemotaxis of granulocytes toward 5-oxo-ETE.

Inhibition of protein kinases A and C demonstrates dual modes of response in human eosinophils stimulated with platelet-activating factor.

Background: Platelet-activating factor (PAF) is a potent stimulator of human eosinophils involved in the pathogenesis of allergic diseases. However, intracellular signaling mechanisms in eosinophils involving the PAF receptor are incompletely understood.

Objective: We sought to determine the roles of protein kinase C (PKC) and cyclic AMP-dependent protein kinase (protein kinase A [PKA]) in signaling pathways of human eosinophils stimulated with PAF.

Possible oncogenic potential of DeltaNp73: a newly identified isoform of human p73.

p73, a recently identified gene highly homologous to p53, can transactivate p53 target genes and induce apoptosis. Here we report the identification of an NH(2)-terminal truncated isoform of human p73, DeltaNp73, which is capable of suppressing p53- and p73-dependent transactivation. We speculate that this suppression is achieved by competing for the DNA binding site in the case of p53 and by direct association in the case of TAp73.

MIDA1, an Id-associating protein, has two distinct DNA binding activities that are converted by the association with Id1: a novel function of Id protein.

Id proteins not only regulate cell differentiation negatively, but they also promote growth, immortalization, and apoptosis. To know the mechanism of how Id regulates cell fate, we previously isolated an Id-associating protein, MIDA1, which positively regulates cell growth (1). Its predicted amino acid sequence consists of a Zuotin (a Z-DNA binding protein in yeast) homology region and tryptophan-mediated repeats (Tryp-med repeats).

Organization of connectin/titin filaments in sarcomeres of differentiating chicken skeletal muscle cells.

Very long, elastic connectin/titin molecules position the myosin filaments at the center of a sarcomere by linking them to the Z line. The behavior of the connectin filaments during sarcomere formation in differentiating chicken skeletal muscle cells was observed under a fluorescent microscope using the antibodies to the N terminal (located in the Z line), C terminal (M line), and C zone (myosin filament) regions ofconnectin and was compared to the incorporation of alpha-actinin and myosin into forming sarcomeres. In early stages of differentiating muscle cells, the N terminal region of connectin was incorporated into a stress fiber-like structure (SFLS) together with alpha-actinin to form dots, whereas the C terminal region was diffusely distributed in the cytoplasm.

BDM (2,3-butanedione monoxime), an inhibitor of myosin-actin interaction, suppresses myofibrillogenesis in skeletal muscle cells in culture.

During the initial phase of myofibrillogenesis in developing muscle cells, the majority of thin filaments lie parallel to, and exhibit correct polarity and spatial position with thick filaments, as in mature myofibrils. Since myosin is known to function as an accelerator of actin polymerization in vitro, it has been postulated that myosin-actin interaction is important in the initial phase of myofibrillogenesis. To clarify further the role of actin-myosin interaction in myofibril formation during development, BDM (2, 3-butanedione 2-monoxime), an inhibitor of myosin ATPase, was applied to primary cultures of skeletal muscle to inhibit myosin activity during myofibrillogenesis, and myofibril formation was examined.

Suppression of morphological transformation by radicicol is accompanied by enhanced gelsolin expression.

Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines and human carcinoma cell lines and to revert their cell morphology to be flat. In the radicicol-treated flat cells, actin stress fiber bundles were reorganized.

Dephosphorylation of cofilin in polymorphonuclear leukocytes derived from peripheral blood.

We show that human and porcine polymorphonuclear leukocytes express significant amounts of cofilin, a low-molecular-weight actin regulatory protein, as well as profilin. Fifty percent of the cofilin in the resting state was phosphorylated and dephosphorylation occurred after activation by fMLP or TPA. The time course of the dephosphorylation induced by fMLP was very rapid, ending within 1 min, while TPA induced relatively gradual dephosphorylation over a period of 10 min.

Inhibition by tunicamycin of mucin synthesis, not morphological changes, in epidermis during retinol-induced mucous metaplasia of chick embryonic cultured skin.

Background: Our previous studies have shown that epidermal mucous metaplasia of chick embryonic skin can be induced by culture in medium containing 20 microM retinol for only 8 hr and then in a chemically defined medium without retinol for 2 days and that retinol primarily affects the dermal cells, which then transform the epithelial cells into mucus-secreting cells.

Methods: Tarsometatarsal skin of 13-day-old chick embryo was cultured with 20 microM retinol for 1 day and then without the vitamin but with 0.1 microgram/ml tunicamycin for 5 days.

Dephosphorylation of cofilin in parotid acinar cells.

Cofilin is an actin-depolymerizing protein, whose depolymerizing activity is supposed to be regulated in part by phosphorylation and dephosphorylation. Thus, we studied the phosphorylation states of cofilin in rat parotid acinar cells during stimulation for amylase exocytosis. Isoproterenol and carbachol induced rapid and extensive dephosphorylation of cofilin; 60-70% dephosphorylation was clearly detectable within 1 min.

Bone marrow stromal cells induce myeloid and lymphoid development of the sorted hematopoietic stem cells in vitro.

Regulation of development of hematopoietic stem cells was examined by culturing Lin- c-Kit+ Sca1+ stem cells sorted from bone marrow (BM) cells by fluorescence-activated cell sorting on a layer of TBR59, a BM stromal cell line established from simian virus 40 T-antigen gene transgenic mice. The sorted stem cells did not show self-renewal, but two waves (at 7 and 13 days) of a cobblestone formation were induced by the stromal cell layer. The cobblestones were formed by finite cell division (eight divisions on average) of sorted Lin- c-Kit+ Sca1+ stem cells, and divided cells were still immature.

Stimulation by Bt2cAMP of epidermal mucous metaplasia in retinol-pretreated chick embryonic cultured skin, and its inhibition by herbimycin A, an inhibitor for protein-tyrosine kinase.

Epidermal mucous metaplasia of cultured 13-day-old chick embryonic tarsometatarsal skin can be induced by culture in medium containing retinol (20 microM) for only 8-24 h and then in a chemically defined medium without vitamins or serum for 6 days. In the induction of mucous metaplasia, retinol primarily affects the dermal cells and a signal(s) induced in the dermis by excess retinol alters epidermal differentiation toward secretory epithelium. In this work we found that Bt2cAMP (2 mM) stimulated mucous metaplasia severalfold when added to retinol-pretreated skin but inhibited epidermal mucous metaplasia when added together with retinol.