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Reduction in Platelet Reactivity With Prasugrel 5 mg in Low-Body-Weight Patients Is Noninferior to Prasugrel 10 mg in Higher-Body-Weight Patients: Results From the FEATHER Trial.

OBJECTIVES: The aim of this study was to confirm prior modeling data suggesting that prasugrel 5 mg in low-body-weight (LBW) patients would be noninferior to prasugrel 10 mg in higher-body-weight (HBW) patients as assessed by maximal platelet aggregation (MPA). BACKGROUND: Prasugrel 10 mg reduced ischemic events compared with clopidogrel 75 mg but increased bleeding, particularly in LBW patients.

Rat dihydroorotate dehydrogenase : isolation of the recombinant enzyme from mitochondria of insect cells

Mammalian dihydroorotate dehydrogenase (EC 1.3.99.11), the fourth enzyme of pyrimidine de novo synthesis is located in the mitochondrial inner membrane with functional connection to the respiratory chain. From the cDNA of rat liver dihydroorotate dehydrogenase cloned in our laboratory the first complete sequence of a mammalian enzyme was deduced. Two hydrophobic stretches centered around residues

Association between COLIA1 Sp1 alleles and femoral neck geometry

Genetic factors play an important role in the pathogenesis of osteoporosis by affecting bone mineral density and other predictors of osteoporotic fracture risk such as ultrasound properties of bone and skeletal geometry. We previously identified a polymorphism of a Sp1 binding site in the Collagen Type 1 Alpha 1 gene (COLIA1) that has been associated with reduced BMD and an increased risk of osteo

Structure-functional characterization of Lactococcus AbiA phage defense system

Bacterial reverse transcriptases (RTs) are a large and diverse enzyme family. AbiA, AbiK and Abi-P2 are abortive infection system (Abi) RTs that mediate defense against bacteriophages. What sets Abi RTs apart from other RT enzymes is their ability to synthesize long DNA products of random sequences in a template- and primer-independent manner. Structures of AbiK and Abi-P2 representatives have rec

Identification of the TRM2 gene encoding the tRNA(m5U54)methyltransferase of Saccharomyces cerevisiae

The presence of 5-methyluridine (m5U) at position 54 is a ubiquitous feature of most bacterial and eukaryotic elongator tRNAs. In this study, we have identified and characterized the TRM2 gene that encodes the tRNA(m5U54)methyltransferase, responsible for the formation of this modified nucleoside in Saccharomyces cerevisiae. Transfer RNA isolated from TRM2-disrupted yeast strains does not contain

A primordial tRNA modification required for the evolution of life?

The evolution of reading frame maintenance must have been an early event, and presumably preceded the emergence of the three domains Archaea, Bacteria and Eukarya. Features evolved early in reading frame maintenance may still exist in present-day organisms. We show that one such feature may be the modified nucleoside 1-methylguanosine (m(1)G37), which prevents frameshifting and is present adjacent

Immune functions in melanoma patients during treatment with interferon [HuIFN-alpha (Le)] alone or in combination with cimetidine

While leukocyte interferon was found therapeutically ineffective in a series of 20 patients with metastatic malignant melanoma, subsequent combination treatment with interferon and cimetidine induced 5 complete and 1 partial tumour remissions. Prior to interferon therapy initiation, regressor patients demonstrated a significantly greater ability to mediate antibody-dependent cellular cytotoxicity

Quality of life in patients with metastatic breast cancer receiving either docetaxel or sequential methotrexate and 5-fluorouracil. A multicentre randomised phase III trial by the Scandinavian breast group

The purpose of this study was to evaluate the effects of two alternative chemotherapy regimes on the quality of life (QoL) of patients with advanced breast cancer. In a multicentre trial, 283 patients were randomised to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research

Childhood socioeconomic status and childhood maltreatment : Distinct associations with brain structure

The present study examined the relationship between childhood socioeconomic status (SES), childhood maltreatment, and the volumes of the hippocampus and amygdala between the ages of 25 and 36 years. Previous work has linked both low SES and maltreatment with reduced hippocampal volume in childhood, an effect attributed to childhood stress. In 46 adult subjects, only childhood maltreatment, and not

The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two disti

Acute respiratory distress syndrome due to Cryptococcus albidus pneumonia : case report and review of the literature

Although cryptococcal infections due to Cryptococcus neoformans are frequently reported in the immunosuppressed patients, infections related to other Cryptococcus spp. are rarely reported. We are reporting a case of pulmonary infection and ARDS due to C. albidus in a patient receiving immunosuppressive therapy because of Still's disease. The diagnosis was made by tissue biopsy and culture. The pat

Vertical drift chambers for the Hall A high-resolution spectrometers at Jefferson Lab

The High-Resolution Spectrometers in Hall A at Jefferson Laboratory have been instrumented with state-of-the-art Vertical Drift Chambers designed and constructed by the Nuclear Interactions Group at MITLNS in conjunction with the Physics Division at Jefferson Lab. These chambers rely on a unique, high cell-density design made possible by the absence of field-shaping wires. Each chamber has an inhe

Distal respiratory tract viral infections in young children trigger a marked increase in alveolar mast cells

Viral infections predispose to the development of childhood asthma, a disease associated with increased lung mast cells (MCs). This study investigated whether viral lower respiratory tract infections (LRTIs) can already evoke a MC response during childhood. Lung tissue from young children who died following LRTIs were processed for immunohistochemical identification of MCs. Children who died from

Prediction of local fixed charge density loss in cartilage following ACL injury and reconstruction : A computational proof-of-concept study with MRI follow-up

The purpose of this proof-of-concept study was to develop three-dimensional patient-specific mechanobiological knee joint models to simulate alterations in the fixed charged density (FCD) around cartilage lesions during the stance phase of the walking gait. Two patients with anterior cruciate ligament (ACL) reconstructed knees were imaged at 1 and 3 years after surgery. The magnetic resonance imag

Human genes for the alpha and beta chains of complement C4b-binding protein are closely linked in a head-to-tail arrangement

C4b-binding protein (C4BP) is an important component in the regulation of the complement system and also binds the anticoagulant vitamin K-dependent protein S. These activities are performed by distinct, although structurally related, polypeptides of 70 kDa (alpha chain) and 45 kDa (beta chain), respectively. In this report we have investigated the genetic relationships between these polypeptides.

Novel subunit in C4b-binding protein required for protein S binding

C4b-binding protein (C4BP) is a multimeric protein with regulatory functions in the complement system. It also interacts with vitamin K-dependent protein S, which is involved in the regulation of the coagulation system. It has been demonstrated that C4BP consists of seven disulfide-linked, identical 70-kDa subunits, which are arranged to give the molecule a spider-like structure. We now have evide

Predicting the survival of patients with peritoneal carcinomatosis of colorectal origin treated by aggressive cytoreduction and hyperthermic intraperitoneal chemotherapy

BACKGROUND: Peritoneal carcinomatosis in the absence of distant metastasis occurs in approximately 8 per cent of patients with colorectal cancer. Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a new treatment option. Patient selection is crucial to outcome.METHODS: Cytoreduction followed by HIPEC was performed in 102 patients with peritoneal carcinomatosis. The foll

Ion channels and electrical activity in vascular smooth muscle: Effects of calcium store depletion, cholesterol and cholesterol-lowering drugs.

Popular Abstract in Swedish Ateroskleros är en sjukdomsprocess vars grundläggande utveckling i blodkärlens väggar sannolikt börjar flera decennier innan insjuknandet i infarkt eller slaganfall inträffar. Som svar på endotelskada, inflammatoriska mediatorer eller tillväxtfaktorer i kärlet kommer glatta muskelceller att dela sig, migrera in mot blodbanan och börja syntetisera en helt ny uppsättning Smooth muscle cells (SMCs) in the vessel wall contract to regulate blood flow and pressure, a function essential for normal circulation through tissues. On the other hand, migration and proliferation of SMCs are important factors in vascular disease, such as atherosclerosis and restenosis following surgical dilatation. The conversion of the SMC to this role is marked by a modulation from contracti

Confidence in COVID-19 vaccine effectiveness and safety and its effect on vaccine uptake in Tanzania : A community-based cross-sectional study

COVID-19 is a major public health threat associated with increased disease burden, mortality, and economic loss to countries and communities. Safe and efficacious COVID-19 vaccines are key in halting and reversing the pandemic. Low confidence in vaccines has been one of the factors leading to hesitancy. We aimed to assess the COVID-19 vaccine confidence (safety and effectiveness), associated facto

Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring : A prospective nested case-control study

Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic