Methodological and chemical factors affecting amyloid beta peptide amyloidogenicity.
Explore the source record for details and available documents.
Alzheimer Disease↗
Biomedical subjects
K Ma
Publications and source records attributed to K Ma.
A hyperactive NAD(P)H:Rubredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus.
NAD(P)H:rubredoxin oxidoreductase (NROR) has been purified from the hyperthermophilic archaeon Pyrococcus furiosus. The enzyme is exceedingly active in catalyzing the NADPH-dependent reduction of rubredoxin, a small (5.3-kDa) iron-containing redox protein that had previously been purified from this organism. The apparent Vmax at 80 degrees C is 20,000 micromol/min/mg, which corresponds to a kcat/Km value of 300,000 mM(-1) s(-1). The apparent Km values measured at 80 degrees C and pH 8.0 for rubredoxin, NADPH, and NADH were 50, 5, and 34 microM, respectively. The enzyme did not reduce P. furiosus ferredoxin. NROR is a monomer with a molecular mass of 45 kDa and contains one flavin adenine dinucleotide molecule per mole but lacks metals and inorganic sulfide. The possible physiological role of this hyperactive enzyme is discussed.
Amino Acid Sequence↗
An unusual oxygen-sensitive, iron- and zinc-containing alcohol dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus.
Pyrococcus furiosus is a hyperthermophilic archaeon that grows optimally at 100 degreesC by the fermentation of peptides and carbohydrates to produce acetate, CO2, and H2, together with minor amounts of ethanol. The organism also generates H2S in the presence of elemental sulfur (S0). Cell extracts contained NADP-dependent alcohol dehydrogenase activity (0.2 to 0.5 U/mg) with ethanol as the substrate, the specific activity of which was comparable in cells grown with and without S0. The enzyme was purified by multistep column chromatography. It has a subunit molecular weight of 48,000 +/- 1,000, appears to be a homohexamer, and contains iron ( approximately 1.0 g-atom/subunit) and zinc ( approximately 1.0 g-atom/subunit) as determined by chemical analysis and plasma emission spectroscopy. Neither other metals nor acid-labile sulfur was detected. Analysis using electron paramagnetic resonance spectroscopy indicated that the iron was present as low-spin Fe(II). The enzyme is oxygen sensitive and has a half-life in air of about 1 h at 23 degreesC. It is stable under anaerobic conditions even at high temperature, with half-lives at 85 and 95 degreesC of 160 and 7 h, respectively. The optimum pH for ethanol oxidation was between 9. 4 and 10.2 (at 80 degreesC), and the apparent Kms (at 80 degreesC) for ethanol, acetaldehyde, NADP, and NAD were 29.4, 0.17, 0.071, and 20 mM, respectively. P. furiosus alcohol dehydrogenase utilizes a range of alcohols and aldehydes, including ethanol, 2-phenylethanol, tryptophol, 1,3-propanediol, acetaldehyde, phenylacetaldehyde, and methyl glyoxal. Kinetic analyses indicated a marked preference for catalyzing aldehyde reduction with NADPH as the electron donor. Accordingly, the proposed physiological role of this unusual alcohol dehydrogenase is in the production of alcohols. This reaction simultaneously disposes of excess reducing equivalents and removes toxic aldehydes, both of which are products of fermentation.
Alcohol Dehydrogenase↗
Protein adsorption and osteoblast responses to heat-treated titanium surfaces.
The clinical success of dental implants is governed in part by surface properties of implants and their interactions with the surrounding tissues. The objective of this study was to investigate the effect of heat-treated titanium (Ti) surfaces on protein adsorption and osteoblast responses in vitro. The passivated Ti samples used in this study were either nonheat-treated or heat-treated at 750 degrees C for 90 minutes. Using x-ray diffraction analyses, no oxide peaks were observed on the nonheat-treated surfaces, suggesting an amorphous oxide. Crystalline rutile TiO2 peaks were observed on the heat-treated Ti surfaces. The contact angles of water on heat-treated Ti surfaces (32.0 +/- 2.5 degrees) were statistically lower compared with the nonheat-treated Ti surfaces (47.7 +/- 2.3 degrees). In addition, the mean albumin concentration on the nonheat-treated Ti surfaces (3.57 +/- 0.33 micrograms/mL) was observed to be significantly different from the mean albumin concentration on heat-treated Ti surfaces (2.25 +/- 0.26 micrograms/mL). In the presence of an osteoblast precursor cell line, significantly different hexosaminidase activity, protein production, and alkaline phosphatase activity were observed for cells grown on heat-treated Ti surfaces compared with nonheat-treated Ti surfaces.
Adsorption↗
[Clinical studies on the effects of burn trauma on pituitary-testis axis].
OBJECTIVE: To investigate the effects of burn trauma on pituitary-testis axis. METHODS: The changes in serum estradiol(E2), testosterone(T), luteinizing hormone(LH), and follicle stimulating hormone(FSH) levels were dynamically investigated by RIA in 30 days after thermal injury in 28 burnt men. RESULTS: The serum FSH, LH, and T levels significantly decreased after injury, and there was some increase from PBD(postburn day) 14 to 30. In patients in group II and III (BSA > 30% TBSA), not all of their FSH, LH, and T levels reached the normal control on the PBD 30. Serum E2 levels were elevated after injury, then returned gradually to normal. In three patients who died, their mean T levels were significantly lower than patients who survived, but mean E2 levels were significantly higher than that of survivors. CONCLUSION: The activity of pituitary might be depressed after burn trauma. The imbalance between E2 and T might play a role in the processes of immuno-depression after injury. The changed extent of E2 and T levels was correlated to burn size. They could be sensitive indicators of burn stress.
Adolescent↗
Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting.
Myostatin, a member of the transforming growth factor-beta superfamily, is a genetic determinant of skeletal muscle growth. Mice and cattle with inactivating mutations of myostatin have marked muscle hypertrophy. However, it is not known whether myostatin regulates skeletal muscle growth in adult men and whether increased myostatin expression contributes to wasting in chronic illness. We examined the hypothesis that myostatin expression correlates inversely with fat-free mass in humans and that increased expression of the myostatin gene is associated with weight loss in men with AIDS wasting syndrome. We therefore cloned the human myostatin gene and cDNA and examined the gene's expression in the skeletal muscle and serum of healthy and HIV-infected men. The myostatin gene comprises three exons and two introns, maps to chromosomal region 2q33.2, has three putative transcription initiation sites, and is transcribed as a 3.1-kb mRNA species that encodes a 375-aa precursor protein. Myostatin is expressed uniquely in the human skeletal muscle as a 26-kDa mature glycoprotein (myostatin-immunoreactive protein) and secreted into the plasma. Myostatin immunoreactivity is detectable in human skeletal muscle in both type 1 and 2 fibers. The serum and intramuscular concentrations of myostatin-immunoreactive protein are increased in HIV-infected men with weight loss compared with healthy men and correlate inversely with fat-free mass index. These data support the hypothesis that myostatin is an attenuator of skeletal muscle growth in adult men and contributes to muscle wasting in HIV-infected men.
Adult↗
Synthesis of C3 heteroatom-substituted azetidinones that display potent cholesterol absorption inhibitory activity.
The C3 phenylpropyl side chain of N-phenylazetidinones related to SCH 56524 was modified by replacing the hydroxymethylene with various isoelectronic or isosteric groups. Modifications at the 3' position led to less-active compounds; however, modifications at the 1' position provided compounds with improved cholesterol absorption inhibitory activity. An enantioselective route for the synthesis of C3 1'-sulfur-substituted azetidinones and the development of structure-activity relationships for this series of compounds are presented.
Animals↗
Evolution of mammalian HNRPG and its relationship with the putative azoospermia factor RBM.
Explore the source record for details and available documents.
Animals↗
The genetic basis of male infertility.
Defective spermatogenesis can be the end result of a multitude of causes, such as systemic disease, malnutrition, endocrinologic disorder, genetic defects, anatomic obstruction of the passage of spermatozoa, infections, and environmental toxins. A genetic basis of infertility is thought to exist in a majority of infertile men currently classified as having idiopathic infertility. Despite advances in molecular technology, the pathophysiology of spermatogenic failure in a majority of infertile men remains unknown. Although a large number of genes and loci in experimental animals are associated with sterility, the human homologues of most of these genes have not been cloned yet. Infertility is a heterogeneous syndrome in men; therefore, it is likely that a multitude of genes and loci will be implicated in different infertility subsets.
Animals↗
Changes in neutrophil surface phenotype during hemodialysis.
The initiation of hemodialysis using cuprophane membranes is followed by a rapid fall in the circulating neutrophil count. This neutropenia is caused by a transient sequestration of neutrophils in the lung due to homotypic aggregation, largely in response to generation of C5a by contact of plasma with the dialyzer. The transient nature of hemodialysis neutropenia is due to desensitization of neutrophils to stimulation by C5a, thus demonstrating desensitization in vivo. To examine the in vivo effects on surface phenotype of continuous exposure of neutrophils to C5a over 3 h, the surface expression of 22 antigens was examined by flow cytometry in patients undergoing dialysis. Neutropenia was prominent at 15 min and absent at 60 and 180 min of dialysis. CD10, CD11b, CD11c, CD13, CD18, CD35, CD45, CD66acde, and CD66b were upregulated at 15 min and remained upregulated at 180 min. CD61 and CD63 increased slightly at 15 min and returned to baseline by 180 min. CD16 and CD62L were down regulated at 15 min and normalized by 180 min. CD15s, CDw17, CD32, and CD44 were slightly down regulated at 15 min and then returned to baseline by 180 min. CD11a, CD15, CD24, CD31, and CDw65 did not change during dialysis. This study demonstrates the changes in surface phenotype of neutrophils during prolonged in vivo exposure to C5a over 3 h, during which time neutrophils become desensitized to subsequent stimulation by similar concentrations of C5a but maintain responsiveness to other chemotactic stimuli.
Adult↗
A randomized, prospective, comparative study of manual and automated renal biopsies.
A percutaneous renal biopsy can be performed in several ways, including using a spring-loaded biopsy gun. As this form of renal biopsy has become more popular, a controversy has developed regarding tissue adequacy and the incidence of complications. To compare these two aspects in an automated biopsy and a manual biopsy, we studied 166 patients assigned to one of the two renal biopsy methods. In a randomized, prospective manner from June 1994 until February 1997, group 1 (67 patients) received a 14 G Tru-cut needle (Baxter, Deerfield, IL) manual biopsy while group 2 (99 patients) received an 18 G automated gun biopsy. There was no difference in sex, age, hemoglobin level, prothrombin time, partial thromboplastin time, or diastolic and systolic blood pressure prebiopsy in groups I and II. Indications for biopsy were proteinuria (38%), proteinuria accompanied by hematuria (31.3%), acute renal failure (9.6%), lupus nephropathy (9.6%), chronic renal failure (6%), and hematuria only (5.4%). In group I, the number of cores was 1.88 +/- 0.56, the glomeruli obtained were 27.3 +/- 13.8, and the number of glomeruli per core were 15.3 +/- 8.4. In group II, the values were 2.37 +/- 0.88, 20.7 +/- 11.1, and 9.95 +/- 6.9, respectively. These results showed a statistically significant difference (P < 0.05). In all cases, pathological diagnosis was possible. The histology showed IgA nephropathy in 25.9%, minimal change disease in 16.3%, lupus nephritis in 11.4%, membranous glomerulonephropathy in 9.3%, membranoproliferative glomerulonephritis in 5.4%, and others. The incidence of postbiopsy hematoma was marginally greater in group I (22.3% v 11.1%) and the area of perirenal hematoma shown on ultrasound 24 hours postbiopsy was larger in group I, as well (848 +/- 623 mm2 v 338 +/- 260 mm2). Hematocrit levels before and after biopsy showed a significant difference (34.9% +/- 7.9% and 34.0% +/- 7.6%, respectively; P < 0.05) in group I, but no significant difference was observed in group II (35.1% +/- 7.0% and 34.7% +/- 6.9%). Both techniques rendered adequate tissue sampling, but the extent of bleeding was more severe with the manual 14 G Tru-cut needle biopsy.
Acute Kidney Injury↗
Genetic disorders and spermatogenesis.
Male infertility affects one man in twenty and a genetic basis seems likely in at least 30% of those men. Genetic regulation of fertility involves the inter-related processes of testicular development, spermatogenesis (involving germ cell mitosis, meiosis and spermatid maturation), and their endocrine and paracrine regulation. In regard to spermatogenesis, particular attention has been given to the Yq11 region, where some spermatogenesis genes ('azoospermia factors') appear to be located. Several candidate genes have been identified but have not been shown to have a defined or essential role in spermatogenesis. Microdeletions of Yq11 are found in approximately 15% of azoospermic or severely oligospermic men. The complexity of the genetic control of male fertility is demonstrated by the evidence for genes involved in spermatogenesis and sexual differentiation on the X chromosome and autosomes. Better understanding of the genetic regulation of normal spermatogenesis will provide new probes for clinical studies; however, at present the majority of spermatogenic failure remains without an identified genetic linkage. The advent of intracytoplasmic sperm injection permits fertility in many previously sterile men and presents the possibility of their transmission of infertility; appropriate counselling is required.
Aneuploidy↗
[Pharmacognostic identification of Chinese drug luxiancao].
In this pper, the crude drugs of Balanophora involucrata and B. harlandii are identified on character, microproperties, UV spectra and TLC. Result of the identification may provide a basis for its diferentication, exploitage and utilization.
Balanophoraceae↗
Pyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon, Pyrococcus furiosus, functions as a CoA-dependent pyruvate decarboxylase.
Pyruvate ferredoxin oxidoreductase (POR) has been previously purified from the hyperthermophilic archaeon, Pyrococcus furiosus, an organism that grows optimally at 100 degrees C by fermenting carbohydrates and peptides. The enzyme contains thiamine pyrophosphate and catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2 and reduces P. furiosus ferredoxin. Here we show that this enzyme also catalyzes the formation of acetaldehyde from pyruvate in a CoA-dependent reaction. Desulfocoenzyme A substituted for CoA showing that the cofactor plays a structural rather than a catalytic role. Ferredoxin was not necessary for the pyruvate decarboxylase activity of POR, nor did it inhibit acetaldehyde production. The apparent Km values for CoA and pyruvate were 0.11 mM and 1.1 mM, respectively, and the optimal temperature for acetaldehyde formation was above 90 degrees C. These data are comparable to those previously determined for the pyruvate oxidation reaction of POR. At 80 degrees C (pH 8.0), the apparent Vm value for pyruvate decarboxylation was about 40% of the apparent Vm value for pyruvate oxidation rate (using P. furiosus ferredoxin as the electron acceptor). Tentative catalytic mechanisms for these two reactions are presented. In addition to POR, three other 2-keto acid ferredoxin oxidoreductases are involved in peptide fermentation by hyperthermophilic archaea. It is proposed that the various aldehydes produced by these oxidoreductases in vivo are used by two aldehyde-utilizing enzymes, alcohol dehydrogenase and aldehyde ferredoxin oxidoreductase, the physiological roles of which were previously unknown.
Aldehyde Oxidoreductases↗
Potent tetracyclic guanine inhibitors of PDE1 and PDE5 cyclic guanosine monophosphate phosphodiesterases with oral antihypertensive activity.
Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).
3',5'-Cyclic-AMP Phosphodiesterases↗
Novel saponins hainaneosides A and B isolated from Marsdenia hainanensis.
Novel saponins possessing fertility-regulating activity, hainaneosides A (1) and B (2), have been isolated from the twigs and stems of Marsdenia hainanensis, and their structures have been elucidated unambiguously as 12-nicotinoyl sarcostin-3-O-beta-D-glucopyranosyl-(1-->4)-3-O-methyl-6-deoxy-bet a-D- allopyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D- cymaropyranosyl-(1-->4)-beta-D-cymaropyranoside and 12-nicotinoyl-20-cinnamoyl sarcostin-3-O-beta-D-glucopyranosyl-(1-->4)-3-O-methyl-6-deoxy-bet a-D- allopyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D-c ymaropyranoside using NMR spectroscopic techniques and chemical transformations.
Abortifacient Agents, Nonsteroidal↗
A human candidate spermatogenesis gene, RBM1, is conserved and amplified on the marsupial Y chromosome.
Three genes, RBM1, DAZ and TSPY, map to a small region of the long arm of the human Y chromosome which is deleted in azoospermic men. RBM1, but not DAZ or TSPY, has a Y-linked homologue in marsupials which is transcribed in the testis. This suggests that RBM1 has been retained on the Y chromosome because of a critical male-specific function. Marsupial RBM1 is closely related to human RBM1, but, like the related autosomal gene hnRNPG, lacks the amplification of an exon. This suggests that RBM1 evolved from hnRNPG at least 130 million years ago and has undergone internal amplification in primates, as well as independent amplification in several therian [corrected] lineages.
Amino Acid Sequence↗
Y-chromosome microdeletions and male infertility.
A genetic basis of infertility may exist in many men currently classified as having idiopathic infertility. Approximately 7% of infertile men harbour submicroscopic deletions of the Y chromosome that are not detectable on routine karyotype. Two candidate gene families, namely the RNA-binding motif-containing gene family, and the deleted-in-azoospermia gene family, have been cloned by deletion mapping of infertile men with Y microdeletions and proposed as candidates for the putative azoospermia factor. The precise function of these two gene families remains unclear. It is likely that additional Y-specific and autosomal genes will be implicated in other subsets of male infertility. Recognition of the association of Y deletions and other genetic defects with male infertility has implications for the diagnosis, treatment, and genetic counselling of infertile men, particularly those who are being considered for intracytoplasmic sperm injection.
Chromosome Deletion↗