Crossmatch difficulties following the prophylactic use of Rh immune globulin.

With increasing demand for platelet transfusion the need to use platelets from Rh-positive persons for Rh-negative individuals often arises. The administration of Rho(D) immune globulin (human) in this situation has been recommended, but may cause serologic difficulties owing to the recipient''s passive acquisition of antibodies other than anti-D.     

Improved Movat Pentachrome Stain

Movat in 1955 developed a staining method which demonstrates collagen fibers, mucin, muscle fibers, elastic fibers, fibrin and fibrinoid changes in a single section. His procedure was considered excellent by Lynch et al. (1969)     

Purification and characterization of the bifunctional thymidylate synthetase-dihydrofolate reductase from methotrexate-resistant Leishmania tropica

Thymidylate synthetase (TS) and dihydrofolate reductase (DHFR) in Leishmania tropica exist as a bifunctional protein. By use of a methotrexate-resistant strain, which overproduces the bifunctional enzyme, the protein was purified 80-fold to apparent homogeneity in two steps. The native protein has an apparent molecular weight of 110 000 and consists of two subunits with identical size and charge. Available data indicate that each of the subunits possesses TS and DHFR. The TS of the bifunctional protein forms a covalent 5-fluoro-2'-deoxyuridylate (FdUMP)-(+/-)-5,10-methylenetetrahydrofolate-enzyme complex in which 2 mol of FdUMP is bound per mole of enzyme. In contrast, titration of DHFR with methotrexate indicated that only 1 mol of the inhibitor is bound per mole of dimeric enzyme. Both TS and DHFR activities of the bifunctional enzyme were inactivated by the sulfhydryl reagent N-ethylmaleimide. Substrates of the individual enzymes afforded protection against inactivation, indicating that each enzyme requires at least one cysteine for catalytic activity. Kinetic evidence indicates that most, if not all, of the 7,8-dihydrofolate produced by TS is channeled to DHFR faster than it is released into the medium. Although the mechanism of channeling is unknown, the possibility that the two enzymes share a common folate binding site has been ruled out.     

Naphthyridinone (NTD) integrase inhibitors: N1 Protio and methyl combination substituent effects with C3 amide groups

Substituent effects of a series of N1 protio and methyl naphthyridinone HIV-1 integrase strand-transfer inhibitors has been explored. The effects of combinations of the N1 substituent and C3 amide groups was extensively studied to compare enzyme inhibition, antiviral activity and protein binding effects on potency. The impact of substitution on ligand efficiency was considered and several compounds were advanced into in vivo pharmacokinetic studies ultimately leading to the clinical candidate GSK364735.     

American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD)

ObjectiveTo provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders.MethodsThe American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development.Recommendation SummaryThis guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base.ConclusionNAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.     

Genes and biochemical pathways in human skeletal muscle affecting resting energy expenditure and fuel partitioning

Genes influencing resting energy expenditure (REE) and respiratory quotient (RQ) represent candidate genes for obesity and the metabolic syndrome because of the involvement of these traits in energy balance and substrate oxidation. We aim to explore the molecular basis for individual variation in REE and fuel partitioning as reflected by RQ. We performed microarray studies in human vastus lateralis muscle biopsies from 40 healthy subjects with measured REE and RQ values. We identified 2,392 and 1,115 genes significantly correlated with REE and RQ, respectively. Genes correlated with REE and RQ encompass a broad array of functions, including carbohydrate and lipid metabolism, gene expression, mitochondrial processes, and membrane transport. Microarray pathway analysis revealed that REE was positively correlated with upregulation of G protein-coupled receptor signaling (meet criteria/total genes: 65 of 283) involved in autonomic nervous system functions, including those receptors mediating adrenergic, dopamine, γ-aminobutyric acid (GABA), neuropeptide Y (NPY), and serotonin action (meet criteria/total genes: 46 of 176). Reduced REE was associated with an increase in genes participating in ubiquitin-proteasome-dependent proteolytic pathways (58 of 232). Serine-type peptidase activity (9 of 76) was positively correlated with RQ, while genes involved in the protein phosphatase type 2A complex (4 of 9), mitochondrial function and cellular respiration (38 of 315), and unfolded protein binding (19 of 97) were associated with reduced RQ values and a preference for lipid fuel metabolism. Individual variations in whole body REE and RQ are regulated by differential expressions of specific genes and pathways intrinsic to skeletal muscle.