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Biomedical subjects

J Ma

Publications and source records attributed to J Ma.

At least 487 records · Page 27Linked to original sources

Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study.

The objective of this study was to examine the relationships of serum and dietary magnesium (Mg) with prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus, fasting insulin, and average carotid intimal-medial wall thickness measured by B-mode ultrasound. A cross-sectional design was used. The setting was the Atherosclerosis Risk in Communities (ARIC) Study in four US communities. A total of 15,248 participants took part, male and female, black and white, aged 45-64 years. Fasting serum Mg, lipids, fasting glucose and insulin were measured; as was usual dietary intake by food frequency questionnaire and carotid intima-media thickness by standardized B-mode ultrasound methods. The results showed that serum Mg levels and dietary Mg intake were both lower in blacks than whites. Mean serum Mg levels were significantly lower in participants with prevalent CVD, hypertension, and diabetes than in those free of these diseases. In participants without CVD, serum Mg levels were also inversely associated with fasting serum insulin, glucose, systolic blood pressure and smoking. Dietary Mg intake was inversely associated with fasting serum insulin, plasma high density lipoprotein-cholesterol, systolic and diastolic blood pressure. Adjusted for age, race, body mass index, smoking, hypertension, Low density lipoprotein-cholesterol, and field center, mean carotid wall thickness increased in women by 0.0118 mm (p = 0.006) in diuretic users and 0.0048 mm (p = 0.017) in nonusers for each 0.1 mmol/l decrease in serum Mg level; the multivariate association in men was not significant. In conclusion, low serum and dietary Mg may be related to the etiologies of CVD, hypertension, diabetes, and atherosclerosis.

Black People↗

Low serum albumin. Association with diabetes mellitus and other cardiovascular risk factors but not with prevalent cardiovascular disease or carotid artery intima-media thickness. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

We examined the association of serum albumin concentration with diabetes mellitus and other cardiovascular risk factors, prevalent cardiovascular disease, and ultrasonographically assessed carotid artery intima-media thickness using data from 45- to 64-year-old adults in the Atherosclerosis Risk in Communities (ARIC) Study. The mean albumin concentration was 0.04 to 0.12 g/L lower in participants with diabetes and 0.02 to 0.06 g/L lower in those with cardiovascular disease, compared to participants without these conditions. However, lower serum albumin level was also correlated with most traditional risk factors and hemostatic variables. On adjustment for these, there was essentially no association between serum albumin and prevalent cardiovascular disease. Likewise, there was no association between albumin and carotid intima-media thickness (a marker of atherosclerosis). While hypoalbuminemia may be a marker for chronic disease and perhaps renal loss of albumin, it seems unlikely that it is an important cause of atherosclerosis.

Arteriosclerosis↗

Rectification of skeletal muscle ryanodine receptor mediated by FK506 binding protein.

The cytosolic receptor for immunosuppressant drugs, FK506 binding protein (FKBP12), maintains a tight association with ryanodine receptors of sarcoplasmic reticulum (SR) membrane in skeletal muscle. The interaction between FKBP12 and ryanodine receptors resulted in distinct rectification of the Ca release channel. The endogenous FKBP-bound Ca release channel conducted current unidirectionally from SR lumen to myoplasm; in the opposite direction, the channel deactivated with fast kinetics. The binding of FKBP12 is likely to alter subunit interactions within the ryanodine receptor complex, as revealed by changes in conductance states of the channel. Both on- and off-rates of FKBP12 binding to the ryanodine receptor showed clear dependence on the membrane potential, suggesting that the binding sites of FKBP12 reside in or near the conduction pore of the Ca release channel. Rectification of the Ca release channel would prevent counter-current flow during the rapid release of Ca from SR membrane, and thus may serve as a negative feedback mechanism that participates in the process of muscle excitation-contraction coupling.

Animals↗

Desensitization of the skeletal muscle ryanodine receptor: evidence for heterogeneity of calcium release channels.

Ca release channels from the junctional sarcoplasmic reticulum (SR) membranes of rabbit skeletal muscle were incorporated into the lipid bilayer membrane, and the inactivation kinetics of the channel were studied at large membrane potentials. The channels conducting Cs currents exhibited a characteristic desensitization that is both ligand and voltage dependent: 1) with a test pulse to -100 mV (myoplasmic minus luminal SR), the channel inactivated with a time constant of 3.9 s; 2) the inactivation had an asymmetric voltage dependence; it was only observed at voltages more negative than -80 mV; and 3) repetitive tests to -100 mV usually led to immobilization of the channel, which could be recovered by a conditioning pulse to positive voltages. The apparent desensitization was seen in approximately 50% of the experiments, with both the native Ca release channel (in the absence of ryanodine) and the ryanodine-activated channel (1 microM ryanodine). The native Ca release channels revealed heterogeneous gating with regard to activation by ATP and binding to ryanodine. Most channels had high affinity to ATP activation (average open probability (po) = 0.55, 2 mM ATP, 100 microM Ca), whereas a small portion of channels had low affinity to ATP activation (po = 0.11, 2 mM ATP, 100 microM Ca), and some channels bound ryanodine faster (< 2 min), whereas others bound much slower (> 20 min). The faster ryanodine-binding channels always desensitized at large negative voltages, whereas those that bound slowly did not show apparent desensitization. The heterogeneity of the reconstituted Ca release channels is likely due to the regulatory roles of other junctional SR membrane proteins on the Ca release channel.

Adenosine Triphosphate↗

Current sample handling methods for measurement of platinum-DNA adducts in leucocytes in man lead to discrepant results in DNA adduct levels and DNA repair.

DNA adduct levels were measured with atomic spectroscopy in white blood cells (WBCs) from patients with solid tumours who were treated with six weekly courses of cisplatin. In 21 patients (I) the WBCs were collected after thawing frozen whole-blood samples according to a previously described method. In 32 other patients (II) WBCs were collected immediately after blood sample collection. The two methods for WBC collection were also compared in vitro. The maximal DNA adduct levels in vivo after the first course were in I 2.48 +/- 1.14 and in II 1.28 +/- 0.40 pg of platinum per microgram of DNA (P < 0.0001). The DNA 'repair' in the first course (DNA adduct level at the end of the infusion minus the level 15 h post infusion) was in I 40% +/- 29% and in II 18% +/- 29% (P = 0.009). These differences were consistent in all measured courses. In vitro, the DNA adduct levels in the freshly prepared WBCs were significantly lower at 0, 1 and 4, but not 24 h, after start of the incubation with cisplatin than in the WBCs collected after freezing and thawing the blood sample. The same experiment with carboplatin in vitro also resulted in significantly lower adducts in freshly isolated WBCs. The higher DNA adduct levels and DNA 'repair' in I are caused by remaining unbound cisplatin in the sample tubes, which can form DNA adducts ex vivo. The same results in vivo can be anticipated when carboplatin is used.

Antineoplastic Combined Chemotherapy Protocols↗

Plasma fatty acid composition as an indicator of habitual dietary fat intake in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

We compared the plasma fatty acid (FA) composition of the habitual diet, measured by a 66-item semiquantitative food-frequency questionnaire (FFQ), with the corresponding plasma phospholipid and cholesterol ester (CE) FA composition measured by gas chromatography in 3570 free-living, middle-aged adults. Pearson correlations between dietary and plasma FA (expressed as % of total FAs) for phospholipid and CE, respectively, were as follows: saturated FA (r = 0.15 and 0.23), monounsaturated FA (r = 0.05 and 0.01), polyunsaturated FA (r = 0.25, 0.31), linoleic acid (r = 0.22 and 0.28), linolenic acid (r = 0.15 and 0.21), eicosapentaenoic acid (r = 0.20 and 0.23), and docosahexaenoic acid (r = 0.42 and 0.42). The correlations between diet and plasma FAs held relatively constant regardless of whether participants were overweight, had chronic diseases, were alcohol drinkers, or were cigarette smokers. However, at similar reported dietary intakes, the plasma lipid concentration of saturated FAs was higher and/or that of linoleic acid was lower in people with these characteristics compared with those without these characteristics.

Alcohol Drinking↗

Short- and long-term repeatability of fatty acid composition of human plasma phospholipids and cholesterol esters. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

We examined short-term and long-term repeatability (reliability) of the fatty acid (FA) composition of plasma phospholipids and cholesterol esters (CEs). For short-term reliability, fasting blood samples of 34 subjects were collected three times, 2 wk apart, and in 24 subjects duplicate samples were collected during each visit. For long-term reliability, two fasting samples were collected in 50 subjects approximately 3 y apart. In both phospholipids and CEs, short-term and long-term reliability coefficients were > 0.65 for the major plasma FAs (16:0, 18:0, 18:2n-6, and 20:4n-6), with the exception of 18:1n-9, but were generally lower for FAs that compose < 1% of total FAs. Reliability tended to be better for CEs than for phospholipids. Method variability was small (< 5% of total variability for most FAs), indicating that biological and dietary variability contribute most to total variability. Plasma FA measurement warrants consideration as a biochemical marker of diet in epidemiologic studies.

Cholesterol Esters↗

A handy database for culture collections worldwide: CCINFO-PC.

Culture collections are reservoirs of cultivable microbes, cell lines and gene libraries. Their role and duty are to supply biological resources to biomedical communities; nevertheless, their visibility from the public is low because most culture collections still have poor accesses via the Internet. Therefore the WFCC World Data Center on Micro-organisms (WDCM) developed a database that runs on IBM PCs and compatibles, which are the most popular computer and will be as powerful as workstations. The database includes various information: activities of 484 culture collections from 58 countries; an integrated list of their holdings of bacteria, fungi and yeast; and data entry system for culture collections.

Bacteria↗

Radiation-sensitive mutants of Arabidopsis thaliana.

Five Arabidopsis mutants have been isolated on the basis of hypersensitivity of leaf tissue to UV light. For each mutant, the UV-hypersensitive phenotype (uvh) was inherited as a single recessive Mendelian trait. In addition, each uvh mutant represented a separate complementation group. Three of the mutations producing the UV hypersensitive phenotype have been mapped relative to either genetic markers or physical microsatellite polymorphisms. Locus UVH1 is linked to nga76 on chromosome 5, UVH3 to GL1 on chromosome three, and UVH6 to nga59 on chromosome 1. Each uvh mutant has a characteristic pattern of sensitivity based on UV sensitivity of leaf tissue, UV sensitivity of root tissue, and ionizing radiation sensitivity of seeds. On the basis of these patterns, possible molecular defects in these mutants are discussed.

Arabidopsis↗

Protection of dogs from Lyme disease with a vaccine containing outer surface protein (Osp) A, OspB, and the saponin adjuvant QS21.

A vaccine consisting of purified Escherichia coli-expressed recombinant full-length outer surface proteins A (OspA) and B (OspB) and the saponin adjuvant QS21 was evaluated for protection against Borrelia burgdorferi infection. Eleven beagles were vaccinated twice and then challenged with 10 field-collected adult female Ixodes scapularis. Xenodiagnosis revealed that all 11 nonvaccinated control dogs and 2 of 10 vaccinated dogs were infected with B. burgdorferi. Six of 11 control dogs also developed fever (0.75 +/- 0.38 degrees C) and were lethargic. One of the control dogs also developed a limp. Both of the infected vaccinated dogs were asymptomatic. Thus, the vaccine prevented tick-vectored infection and associated symptoms of Lyme disease.

Adjuvants, Immunologic↗

Characterization of canine humoral immune responses to outer surface protein subunit vaccines and to natural infection by Lyme disease spirochetes.

Canine antibody responses to Lyme disease subunit vaccines and to natural borrelial infection were investigated. Vaccines were formulated with QS21 and outer surface proteins A (OspA) and B (OspB) derived from Borrelia burgdorferi B31. Vaccines containing QS21 and the lipoproteins gave 4-fold higher IgG1 and 8-fold higher IgG2 antibody responses than without QS21. Antisera to lipidated OspA or OspB vaccines containing QS21 had high antiborrelial activity against isolates B31 and CA-2-87, similar to those with a vaccine containing both OspA and OspB. Only the combination vaccine induced antiborrelial activity against heterologous isolates 24008 Fr and Borrelia garinii G25. Nonlipidated OspA- and OspB-based vaccines with QS21 elicited lower antibody and antiborrelial activity than did lipidated OspA and OspB vaccines; 49% of naturally exposed dogs had low titers to OspA or OspB. Thus, vaccines using lipidated OspA, OspB, and QS21 could induce higher antiborrelial activity than did natural exposure.

Adjuvants, Immunologic↗

Molecular analysis of neutralizing epitopes on outer surface proteins A and B of Borrelia burgdorferi.

The neutralizing epitopes of the major outer surface proteins A and B (OspA and OspB) of Borrelia burgdorferi B31 were investigated by epitope mapping using overlapping synthetic peptides, encompassing full-length OspA and OspB, and antiborrelial monoclonal antibodies (MAbs). OspA MAb N4B12 and OspB MAbs N5G5, W7C2, and P4D1 displayed a complement-independent antiborrelial activity, and complement failed to enhance the antiborrelial activity, as measured by a sensitive colorimetric assay. A combination of N4B12 with N5G5 displayed a higher antiborrelial activity than did the MAbs individually. OspA MAbs B3G11 and L3B5, however, exhibited a significant antiborrelial activity only in the presence of complement. Epitope mapping showed that B3G11 bound to one OspA synthetic peptide with the sequence of amino acids 247 to 256 (QYDSNGTKLE) and produced more than sixfold-higher reactivity than with other sequences, as measured by an enzyme-linked immunosorbent assay. OspB MAb N5G5 bound to an OspB peptide with the sequence of amino acids 211 to 220 (TLKREIEKDG), yielding at least threefold-higher reactivity than with other sequences. These two peptide sequences were found to contain neutralizing epitopes. Other MAbs had weak binding activities with the synthetic peptides, and their specific epitopes remain to be further analyzed. Thus, this study demonstrated both complement-independent and complement-dependent antiborrelial MAbs and identified the linear epitopes on OspA and OspB capable of inducing neutralizing antibody responses.

Amino Acid Sequence↗

Central actions of parathyroid hormone on blood calcium and hypothalamic neuronal activity in the rat.

The central actions of parathyroid hormone (PTH) on the blood ionized calcium level in anesthetized rats and the neuronal activity of the ventromedial nucleus of the hypothalamus (VMH) in vitro were investigated. An intracerebroventricular injection of PTH (0.01, 0.1, and 1 microgram) prevented urethan-induced hypocalcemia in a dose-dependent manner, whereas either an intravenous or an intracisternal injection of PTH (1 microgram) was ineffective. Eighty-three of 177 VMH neurons responded to a bath application of PTH (10(-7) or 3 x 10(-7) M): a majority (72, 83%) of the responsive cells decreased, whereas 11 increased their activity. This inhibitory effect of PTH on neuronal activity still persisted after synaptic blocking in a Ca(2+)-free/high-Mg2+ medium. A PTH receptor antagonist, [Tyr34]bPTH-(7-34)-NH2, suppressed the effect of PTH on the neuronal activity. These findings thus suggest that brain PTH has a calciotropic function and that one of the possible target sites is the VMH, where PTH inhibits its neuronal activity through a postsynaptic mechanism mediated by PTH receptors.

Analysis of Variance↗

The endolymphatic sac: microsurgical topographic anatomy.

The endolymphatic sac is part of the membranous labyrinth; it plays an important role in the hearing mechanism. Injury to the endolymphatic sac may, over time, severely compromise hearing. The endolymphatic sac is located in a duplication of the dura of the posterior aspect of the petrous pyramid and is, therefore, in the surgical field of many neurosurgical operations performed on the posterolateral cranial base. The endolymphatic sac was exposed bilaterally in 10 anatomic specimens; the distance from the center of the sac to the posterior lip of the internal auditory meatus and to the XIth nerve in the jugular foramen was measured with a caliper. Also measured was the distance between the center of the sac and the closest point on the petrous ridge and the distance between that point and the petro-sigmoid intersection. The petro-sigmoid intersection was defined as the point at which the medial aspect of the sigmoid sinus intersects the lateral aspect of the petrous ridge. The dimensions of the sac were also recorded. On the average, the sac was found to be 15.7 mm posterosuperior (superolateral) to the XIth nerve in the jugular foramen (range, 11.0-18.5 mm) and 13.3 mm posterior (lateral) to the internal auditory meatus (range, 10.0-18.0 mm). The center of the sac was 24.1 mm (mean value) (range, 20.0-28.0 mm) in front of the petro-sigmoid intersection at a point 11.5 mm (mean value) (range, 8-17 mm) below the petrous ridge. The mean width and height of the sac were 3.83 (range, 2-6 mm) and 3.80 mm (range, 2.5-8 mm), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomy, Artistic↗

Agrin: toward a molecular understanding of synapse regeneration.

One of the foremost challenges to repairing damage after stroke, trauma, or disease is the regeneration of synaptic connections between neurons. Here, we consider recent strides in our understanding of the molecular basis of synapse formation and regeneration. We will focus on the protein agrin, a key player in synaptogenesis at neuromuscular junctions and perhaps at central nervous system synapses as well. Insights into agrin and its receptor could guide the development of rational therapies to combat neuronal degeneration. We will also consider recent surprising and provocative data linking the mechanisms of synapse formation and the cellular pathology in Duchenne muscular dystrophy.

Agrin↗

Expression of major histocompatibility complex in mouse peritoneal macrophages increasingly depends on plasma corticosterone levels: stimulation by aconitine.

Influence of aconite extract and a main component of aconite, aconitine were investigated on the plasma corticosterone level for the expression of major histocompatibility complex class II (Ia antigen) of macrophage. In peritoneal macrophage exposed to corticosterone (2.9-87 microns) in vitro the interferon (IFN)-gamma (0.1 unit/ml)-induced Ia antigen expression was inhibited in a dose-dependent manner. Ia antigen expression in macrophages harvested from the corticosterone (1.25mg/mouse/d, i.m., 4d)-excessive mice and aconitine (3 micrograms/kg, i.p., 7d)-treated mice was significantly stimulated, whereas that of adrenalectomized (7d) mice was inhibited. In macrophage exposed to aconitine up to 46.5 microns in culture Ia antigen expressed was not affected. Administration of aconite extract (3 mg/kg, i.p., 7d) and aconitine (3 micrograms/kg, i.p., 7d) increased plasma corticosterone levels. These result demonstrate that high levels of corticosterone increases the macrophage response to ifn-gamma on Ia antigen expression and that low levels of corticosterone decrease it. Aconite extract and aconitine stimulate the response to IFN-gamma-activated expression of Ia antigen by macrophages which is caused by increasing the plasma corticosterone level.

Aconitine↗