bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Synthetic Peptides Derived from Human Apo(a) on Cell Proliferation, VEGF Production, and Angiogenesis in Cancer Cells and Vascular Endothelial Cells.
Authors: Bao Bin , Prasad Ananda S. , Dou Dex , Jin Steve , Bao Ginny W. 
Published: April 2020

Abstract
Angiogenesis, the formation of new blood vessels from the existing vascular bed, has been described as one of the hallmarks of cancer, and plays an essential role in tumor growth, invasion, and metastasis. The development of specific anti-angiogenic agents is an attractive therapeutic approach for the treatment of cancer. Apolipoprotein, Apo(a), is a large glycoprotein with multiple kringle structures, which play an important role in regulating the intermolecular reaction in the body. The evidence shows that Apo(a) has anti-angiogenic activity on vascular endothelial cells and inhibits tumor growth in mice. The 38th kringle on Apo(a) has been found to be homologous to the kringle 5 of plasminogen, a known endogenous anti-angiogenic kringle structure. According to our preliminary study, the 38th kringle of Apo(a) had an inhibitory effect on bovine capillary endothelial (BCE) cells. Seven peptides of the 38th kringle on Apo(a) were synthesized for screening of anti-angiogenic activity. Two synthetic peptides (P4 and P5) based on the 38th kringle structure sequence of Apo(a) were found to inhibit the proliferation of BCE cells. In the current study, we examined the effects of P4 and P5 synthetic peptides on cell proliferation by MTT assay, and VEGF production by ELIAS assay in human prostate cancer cells (C4-2B, LNCap, and PC3), and/or vascular endothelial cells such as human aortic endothelial cells (HAEC), human umbilical vein endothelial cell (HUVEC), and mouse microvascular endothelial cells (MVEC) after 2 days of incubation. The results are shown in the Table 1 and 2 below.
Table 1. Effect of synthetic peptides on cell proliferation in cancer and vascular endothelial cells (%) P4 P5 Cell proliferation assay was conducted by MTT methos. The % of cell proliferation in peptide treatment groups was compared to the cells without peptide treatment HAEC 64.7±16.4 62.4±12.0 HUVEC 59.4±3.7 71.7±1.2 MVEC 76.9±6.1 75.8±5.6 C4-2B 64.1±5.1 60.9±4.3 LNCap 77.9±2.9 51.8±1.6 PC3 75.8±3.4 75.4±3.6 Table 2. Effect of synthetic peptides on VEGF production in cancer cells (pg/mL) Control P4 P5 C4-2B 905.0±87.7 694.1±99.1 720.1±106.2 LNCap 1116.5±191.6 717.9±100.1 794.3±119.7 PC3 902.6±52.0 743.2±123.7 721.3±92.7
Our data indicate that these synthetic peptides inhibited the cell proliferation and VEGF production. We also examined the effect of P4 and P5 peptides on angiogenesis in HAEC and MVEC cells after 10h of incubation by Matrigel tube formation assay. The data indicate that angiogenesis declined by 40–50% when P4 or P5 was added to the cell culture. All these data suggest that P4 and P5, synthetic peptides derived from the 38th Kringle of Apo(a) have anti-proliferative and anti-angiogenic effects, which may potentially be applicable for cancer treatment. Further studies are in progress in order to define the mechanisms action of these peptides.
TNF-α-Mediated Tumor Promotion Is Characterized by Enhanced Vasculogenesis and Generation of Myeloid/Endothelial Vascular Leukoctyes.
Authors: Li Bin , Pagni Matthew , Cates Justin , Polk D. Brent , Young Pampee P. 
Published: April 2020

Abstract
Whereas in many contexts myeloid cells are cytotoxic, it is well-established that as yet unknown microenvironment cues instruct the infiltrating tumor associated myeloid cells (TAMs) to drive malignant progression and dissemination. Recently, we and others have characterized a significant subpopulation of tumor associated myeloid cells that co-express endothelial and myeloid markers designated “vascular leukocytes”. Studies suggest that vascular leukocytes play an important role in tumor progression and also demonstrate modest contribution to functional vessels, i.e. vasculogenesis, suggesting that they represent a critical tumor-promoting TAM subpopulation. We have identified TNFα as a key regulator of the vascular transdifferentiation of myeloid progenitors in vitro and within the tumor milieu. TNFα at 40ng/ml significantly increased the numbers of flk-1/VE-cadherin dual positive, early outgrowth EPCs from human CD14+ cells by day 7 (about five fold of the control), starting with increased spindle-shaped population appeared as early as day 3. Consistent with this, we observed increased flk-1 expression by ∼9-fold (p&lt;0.05) in cells treated with 40ng/ml TNFα by real time RT-PCR. Transcripts for VE-cadherin and tie2, both endothelial-enriched, were detected by day 3 in cells exposed to 40ng/ml TNFa but not in its absence (control). TNFα-directed upregulation of endothelial markers in mouse monocytes in vitro was dependent on TNFα receptors as monocytes isolated from mice lacking both TNF receptors displayed significantly delayed endothelial marker upregulation. These data suggested that TNF was a component of the molecular pathway that accelerated, but was not required for, endothelial transdifferentiation of murine and human myeloid cells. Enhanced TNFα expression in both B16 murine melanoma and PyV-mT tumor showed local TNFα significantly promoted tumor growth versus control (&gt;5-fold increase for B16 tumor, p=0.04; &gt;8-fold increase for PyV-mT tumor, p&lt;0.01). Both tumor models indicated that overexpressing TNFα caused higher vascular density over control, while tumor necrosis was significantly reduced. Additionally, we observed increased bone marrow-derived vessels (vasculogenesis) in mouse TNFα-overexpressing tumors, which can be specifically inhibited by an anti-TNFα blocking antibody. A significant increase in association of vascular leukoctyes was detected in tumors overexpressing TNFα by FACs, which was abrogated in the mice lacking TNF receptors. Interestingly, TNF-overexpressing tumors did not recruit greater overall numbers of tumor-associated (myeloid or lymphoid) leukocytes, suggesting a specific role in myeloid to endothelial transdifferentiation in vivo. Our studies suggest that TNFα constitutes part of the microenvironment repertoire that biases recruited myeloid cells towards a proangiogenic/provasculogenic phenotype.
Piperacillin Induced Thrombocytopenia in Critical Care Patients as Compared to Non Critical Patients.
Authors: Naik Seema , Sangal Ashish , Kodali Srinivas , Dumlao Theresa , Kalavar Madhumati , Steier William , He Zili 
Published: April 2020

Abstract
Introduction: Drug-induced thrombocytopenia in the critically ill is documented in the literature with limited frequency. Implicated agents are antiepileptics, anticoagulants, antiarrhythmics, histamine receptor antagonists, and antimicrobials .Piperacillin has only rarely been implicated as a cause of thrombocytopenia, and there is only limited evidence that this complication is caused by immune mechanisms.
Methods: We conducted a retrospective chart review of patients admitted during a 6-month period to determine the frequency of and potential risk factors associated with thrombocytopenia, and the association of acquired thrombocytopenia with the use of piperacillin ICU versus non ICU patients.
Results: Data were collected for 154 patients (M:71, F:83),), admitted to the ICU and Non-ICU setting. 55% of the patients were more than 65 years of age. Platelet drop occurred in 123 patients. Thrombocytopenic patients had a longer ICU stay (11.2 vs 5.6 days) and greater mortality (9% vs 3%) than nonthrombocytopenic patients .The patients developed thrombocytopenia as follows:Mild(100–150k): 22 pts-(15%) ; Moderate(50–100k): 7 pts-(5%) ;and Severe(&lt;50k): 4 pts- (3%). The other drugs during hospitalization were heparin (30%), ceftazidime(11%), famotidine(9%), bactrim(0.3%),esomeprazole (11%), aspirin(18%). Patients received piperacillin for mean duration of 9 days. In patients with thrombocytopenia, the platelet levels dropped by a mean of 15.15% on Day 2 from pretreatment values (range, 2% to 61%) while they were receiving piperacillin. On average, the nadir platelet count was reached 7 days after treatment with piperacillin was initiated (range, 2 to14days). The median time required for platelet recovery was 8.4 days (range 5.6 in ICU to 11.2 in Non-ICU pts).Bleeding was unusual in patients with thrombocytopenia. Platelet transfusions failed to elevate platelet counts.
Discussion: Thrombocytopenia occurs in 23–63% of patients in the intensive care unit (ICU). Factors associated with the disorder in these patients include sepsis, disseminated intravascular coagulation (DIC), blood transfusions, central catheters, and drugs, some of which may have a significant effect on morbidity and mortality. The major mechanisms of drug-induced thrombocytopenia are immune-mediated platelet destruction and concentration-dependent bone marrow suppression. Bone marrow toxicity, mainly neutropenia, has been described as an uncommon secondary effect of most beta-lactams, and it is usually related to large cumulative doses.
Conclusion: Thrombocytopenia is associated with an increased ICU stay and increased mortality. Thrombocytopenic events associated with antimicrobial agents in the ICU may warrant further investigation because of the increased administration of these drugs to combat more virulent bacterial strains.
Salmonella Arizonae Bacteremia Associated with Septic Arthritis Following Consumption of Rattlesnake Capsules in a Patient with Idiopathic Thrombocytopenic Purpura (ITP) on Chronic Steroid Therapy.
Authors: Herrada Juan , Antony Suresh J. 
Published: April 2020

Abstract
Background: Folk medicine plays an important role in some populations in the United States. In particular, the use of rattle snake powder is becoming increasingly popular among the Mexican-American population along the US-Mexico border. Infections associated with the ingestion of this preparation have increasingly been reported in this country. We present a patient who presented with Salmonella Arizonae bacteremia and septic arthritis with underlying ITP on chronic treatment with steroids and surreptitious use of rattle snake powder.
Case Report: A 53 year-old Mexican -American male with a past history of ITP on chronic oral prednisone with intact spleen was admitted with fever, chills, and an acute onset of pain, swelling and tenderness of his left knee. On admission to the hospital, his temperature was 101.5 F, blood pressure was 124/68, and pulse 102/min. The physical findings were significant for swelling and tenderness to the left knee with evidence of synovial effusion and restricted range of motion. The white blood cell count was 18,000cu/mm. Culture of the patient’s left knee synovial fluid aspirate grew Salmonella Arizonae, as did his blood cultures. The pathogen was sensitive to 3rd generation cephalosporins and quinolones, and he was treated with intravenous ceftriaxone for 2 weeks with resolution of the bacteremia and improvement of the septic knee. He subsequently underwent a total knee arthroplasty, and follow up 1 year later revealed no evidence of persistent infection. After the pathogen identification, a careful alternative medicine history revealed the consumption of rattle snake powder preparation intended for treatment of his arthritis and ITP.
Conclusion: Physicians should be aware of Salmonella Arizonae associated illnesses in both immunocompetent as well as immunosuppressed patients. Because the surge of interest in complementary and alternative medicine, a careful history should be elucidated, especially in immunocompromised patients who present with this syndrome.
Heparin-Induced Thrombocytopenia (HIT): A Rural Community Based Experience.
Authors: Mullai N. , Brock Amanda , Harper Shona 
Published: April 2020

Abstract
Background: Heparin-induced thrombocytopenia (HIT) is a known complication of heparin therapy. This study was planned to assess the experience of a community based medical practice with HIT in a rural setting.
Method: A retrospective study was done from medical records of patients suspected clinically of HIT from January 2006 to January 2007. The data were analyzed with regard to test results of patients, especially those who were positive for the HIT antibody and correlated with national statistics.
Result: Fifty-two (52) patients were suspected clinically of having HIT during the study period. All 52 patients received heparin and most of them had cardiac surgery before the onset of thrombocytopenia. Six out of fifty-two (6/52) patients were found to have positive HIT antibody. Two out of six (2/6) also had positive serotonin release assay. Two out of six (2/6) developed heparin-induced thrombocytopenia with thrombosis (HITT). One of the two patients with HITT died of complications. The range of time to obtain test results was 5–7 days. Four out of fifty-two (4/52) patients received thrombin inhibitor lepirudin (Refludan) as alternate anticoagulation.
Conclusion: The overall incidences, time of onset, relation to heparin treatment were similar to that of national averages. The time to obtain diagnostic test results ranged 5–7 days and heparin was withheld in all of them, and more expensive anticoagulation was used for some of them while waiting for the test results. This dilemma in diagnosis and treatment could be avoided if a rapid test that can help to assess the risk early in about 12–24 hrs, is possible. Such a test would be very beneficial especially in small, rural community settings where the availability of expensive testing and medications for HIT are limited.
The Correlation Analysis of Venous Thromboembolism and Acute Myocardial Infarction with the Levels and Polymorphisms of Coagulation and Anticoagulation Factors.
Authors: Yang Linhua , Han Xuanmao , Qiao Zhenhua , Ren Jinfang , Liu Xiue , Hou Lihong , Wang Xuefeng , Ding Qiulan 
Published: April 2020

Abstract
To evaluate levels of coagulation /anticoagulation factors and distribution of their gene polymorphisms in patients with venous thromboembolism(VTE) and acute myocardial infarction(AMI). Of 95 VTE, 95 AMI patients and 95 normal controls were be studied. The results showed that the levels of fibrinogen and D-Dimer, the activies of FII, FV and FVIII were remarkably higher in patient with VTE than those in healthy group, and the activities of FIX, PC and AT were of no significant difference between VTE group and healthy group. The mean levels of fibrinogen, D-Dimer, FV:C and FVIII:C were significantly higher in AMI group than that in controls; while, no significant difference of FII:C, FIX:C, PC:A and AT:A between AMI patients and the controls. In controls, -148CT + -148TT was associated with higher fibrinogen concentrations, the genotypes of other gene polymorphisms were not associated with levels of coagulation /anticoagulation factors. Clear difference were observed for the T allele frequencies of -148C/T and distribution frequencies of FII A19911G were found between VTE group and normal group. there was significant difference of -1476TT genotype distributions and T allele frequencies in -1476A/T between VTE and control subjects. There was significant difference of AC+CC genotype distribution in 1298 A/C polymorphisms between AMI and control, and it was so with the GA genotype in 1793 G/A polymorphisms. But neither genotype frequencies nor allele frequencies of other polymorphisms were found to be no of significant difference between VTE /AMI group and control group. This study proved the importance of combined functions of several coagulant factors in causing VTE and AMI. The carriage of the C148T mutation, FII 20210G/A and -1476A/T polymorphism might be associated with an increased risk of VTE, while the MTHFR 1298A/C and 1793G/A polymorphisms may be related to the development of AMI. Only some of joint occurrence of above polymorphisms might increase the occurrence rate of VTE or AMI.
A Highly Accurate and Linear Clauss Fibrinogen Assay Provides Increased Clinical Value for Patient Reporting throughout the 30 – 1000 mg/dL Medical Decision-Making Range.
Authors: Callahan Janet , Laurant Nathalie , Arcidiacono Sam , Polgar Janos , Mary Doyle , Triscott Mark 
Published: April 2020

Abstract
The availability of accurate and precise Fibrinogen concentration measurements throughout low, normal and elevated ranges are of significant utility in clinical practice. The assessment of elevated fibrinogen levels is valuable as a known marker of coronary heart disease, cerebrovascular disease, cancer, diabetes, hypertension, acute phase reactions, pregnancy, etc. Likewise, the decreased fibrinogen levels associated with liver disease, DIC, thrombolytic therapy, miscarriage, poor wound healing and intracranial hemorrhage support the premise that accurate quantification of very low levels of fibrinogen is needed. The Hemosil TM Fibrinogen-C XC Clauss Fibrinogen (FibC) assay measurement range for Instrumentation Laboratory (IL) ACL TOP family (ACL TOP/CTS) analyzers has been expanded to 30–1000 mg/dL. This assay has the capability of accurately measuring plasma fibrinogen in three mode segments: Near Normal for the 100–500mg/dL range, High Fib for samples 500 to 1000mg/dL and Low Fib for samples less than 100mg/dL. The accuracy of the expanded Fibrinogen assay was assured by calibration with the 2nd International Standard for Fibrinogen calibrator, plasma 98/612 and verification with the SCC/ISTH Secondary Coagulation Standard Lot # 3 as well as a 100 donor normal pool. Precision is consistent across the entire range. Normal, low and high samples demonstrated Total CVs of &lt; 7%. The linearity of values across the expanded Fib C measurement range was established using a statistical evaluation based on CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures. Overlapping linearity of the 3 mode segments was demonstrated for Low Fib from 30–150 mg/dL, for Fib C from 85–500 mg/dL, for High Fib from 200 –1000 mg/dL as well as for the overall range of 30–1000 mg/dL. As noted, recovered values from Low Fib to Fib C and from Fib C to High Fib overlap when the tests are evaluated individually, but in practice, this Fib C assay will reflex seamlessly to the appropriate low or high test range. Deviation from Linearity, a statistical measure of goodness of fit, was low, less than 7% for 9 equidistant points between 30 and 1100 mg/dL. Linearity and accuracy were further confirmed in an extensive and statistically rigorous CLSI EP9 method comparison study of 200 samples representing a wide variety of clinical disorders Additional studies investigated interferences and other sample specific conditions. Measurements using reflexive modes to extend the Fibrinogen measurable range deliver timely, precise and accurate information to the practicing clinician over the wide diagnostic range of 30–1000 mg/dL.
Global Analysis of Age-Related Expression Profiles of Mouse Liver Genes: Toward Understanding Age-Related Homeostasis.
Authors: Kurachi Sumiko , Suenaga Emi , Kurachi Kotoku 
Published: April 2020

Abstract
For understanding aging as well as various age-related diseases, it is critical to establish the basic regulatory mechanisms underlying age-related homeostatsis. Through systematic analyses of transgenic mice carrying factor IX and protein C genes, we recently discovered the first molecular mechanism of age-related homeostasis, ASE/AIE-mediated age-related regulatory mechanism of gene expression (Kurachi et. al., Science 1999; Zhang et. al., J. Biol. Chem. 2002; J. Thromb. Haemost. 2005). This laid the foundation for further studies toward an integrated understanding of age-related homeostasis. Here we report global analyses of age-related expression profiles of mouse liver genes. For quantification of expression levels of liver genes of mice at 1, 3, 6, 12, 18 and 24 month of age, Affymetrix GeneChip® Mouse Expression Array 430A (MOE430A with 23,643 probes) were used. These microarray analyses detected 9148 probes as qualified meaningful and the data were subjected to extensive analyses by GeneSpring and IPA network analysis softwares. Real time PCR analyses of representative genes were performed for verifying excellent reproducibility of age-related expression profiles determined by microarray analyses. Age-related stages, particularly of puberty and aging, were identified as the major phases for age-related changes in gene expression. Strong relationships between expression level and ontology, indicating that the highest expression gene group, next highest expression group and lowest level expression gene group are of secreted proteins, mitochondoreal proteins and nuclear regulatory protein, respectively. Most importantly, we successfully identified about a dozen unique and fundamental age-related gene expression patterns including those of age-related stable, gradual increase or decrease, and aging-related dramatic increase or decrease types of expression. These findings led us to a new hypothesis that complex and dynamic age-related regulations of genes are produced by a relatively small number of fundamental regulatory mechanisms. These mechanisms may function independently or in various combinations, thus explaining an essential feature of age-related homeostasis.
Deletion of Pro1648-Leu1650 in VWF73, the Conservative Substrate for ADAMTS13, Causes von Willebrand Disease.
Authors: Su Jian , Bai Xia , Yu Ziqiang , Wang Zhaoyue , Ruan Changgeng 
Published: April 2020

Abstract
The multimer distribution of Von Willebrand factor (VWF) in plasma is regulated by the specific VWF cleaving protease ADAMTS13, which cleaves at the Y1605-M1606 bond in the A2 domain of VWF under the shear stress, plays paramount roles in mediating platelet adhesion to the subendothelium during vascular damage. Quantitative deficiency or qualitative abnormity in VWF caused by the mutations in the VWF gene leads to von Willebrand disease (vWD). There exist three types of vWD. Type 1 vWD is characterized by the partial quantitative deficiency of VWF and normal multimers. Type 3 refers to complete deficiency of VWF. Type 2 vWD refers to the qualitative deficiency of VWF and is subdivided into types of 2A, 2B, 2M, 2N. Meanwhile, the subtype of 2A vWD is also subdivided into two groups regarding ADAMTS13-dependent proteolysis of VWF. Group I includes the mutations G1505R, S1506L, L1540P, V1607D, which hinder the multimer assembly and diminish the secretion of VWF while group II includes R1597W, R1597Q, G1505E, I1628T, E1628K, which make VWF more susceptible to ADAMTS13 -dependent proteolysis. All these published point mutations cluster in the A2 domain of VWF and the corresponding mutation mechanism upon VWF has been elucidated. We have identified a patient with bleeding symptoms and reduced plasma VWF antigen, factor VIII and ristocetin cofactor activity, compatible with clinical von Willebrand disease. Analysis of proband’s plasma VWF multimers in low resolution agarose gels demonstrated similar results compared to the healthy. The patient carried a heterozygous deletion mutation from position 1648 to 1650 resulting in loss of three consecutive amino acids (ProIleLeu) in the pre-pro-VWF. It has been demonstrated that the minimal substrate for ADAMTS13 is intact VWF73, a region from Asp1596 to Arg1668 of von Willebrand factor. The novel deletion mutation in this patient occurred in the intact VWF73 and its mutated effect upon cleavage by ADAMTS13 could be clarified by further experiments such as in vitro recombinant expression of mutated VWF and might strengthen our understanding of the interaction between VWF and ADAMTS13.