Observation of an anomalous quasi-one-dimensional behavior in Na2Ru4O9- delta single crystals.
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Biomedical subjects
Publications and source records attributed to G Cao.
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OBJECTIVES: This study sought to examine the relation between body height and incidence of myocardial infarction, coronary heart disease, overall mortality and mortality from cardiovascular disease. BACKGROUND: An association between short stature and increased risk of fatal and nonfatal cardiovascular disease has been observed in several studies, attracting considerable attention. METHODS: We used data from the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-Up Study, a prospective study of a large random sample of the U.S. population, to examine the association between height and risk of four end points. RESULTS: Baseline data were collected from 1971 to 1975 for 13,031 respondents (5,296 men, 7,735 women), and the average follow-up period was 13 years, through 1987. Height was inversely associated with risk of all four of the end points studied in both men and women. However, after adjustment for age and years of education in Cox proportional hazards analyses, the relation no longer existed. Using the same adjustment procedures, persons in the lowest height quintile had no increase in risk compared with those in the highest category. The findings were consistent for men and women, blacks and whites and different age groups. CONCLUSIONS: Data from this study in a national sample do not support the hypothesis of an inverse height-heart disease relation.
Previous in vitro studies provide evidence that RF electromagnetic radiation modulates proliferation of human glioma, lymphocytes, and other cell types. The mechanism of RF radiation cell proliferation modulation, as well as mechanisms for effects on other cell physiologic endpoints, are not well understood. To obtain insight regarding interaction mechanisms, we investigated effects of RF radiation exposure on interleukin 2 (IL-2) -dependent proliferation of cytolytic T lymphocytes (CTLL-2). After exposure to RF radiation in the presence or absence of IL-2 cells were cultured at various physiological concentrations of IL-2. Treatment effects on CTLL-2 proliferation were determined by tritiated thymidine incorporation immediately or 24 h after exposure. Exposure to 2450 MHz RIF radiation at specific absorption rates (SARs) of greater than 25 W/kg (induced E-field strength 98.4 V/m) induced a consistent, statistically significant reduction in CTLL-2 proliferation, especially at low IL-2 concentrations. At lower SARs, 2450 MHz exposure increased CTLL-2 proliferation immediately after exposure but reduced 24 h postexposure proliferation. RF radiation effects depended on the mitotic state of the cells at the time of exposure. Comparison of the effects of temperature elevation and RF radiation indicated significant qualitative and quantitative differences.
Continuing advances in molecular biology have provided tools for a promising approach to the treatment of cancer. Among the various strategies of gene therapy for cancer, many are aimed at killing tumour cells indirectly by the induction or reinforcement of a host immune response by gene transduction of various cytokines, major histocompatibility complex or immune accessory molecules. In the present study, we selected the tumour necrosis factor-alpha, interleukin-2 and interleukin-3 genes as potential cytokine genes to induce antitumour effects. We constructed retroviral vectors carrying these cytokine genes under the control of the murine albumin enhancer and promoter and retrovirally transduced these genes into hepatoma and non-hepatoma cell lines. Strong expression of the cytokine genes was induced in transduced hepatoma cells, while no evident expression was detected in transduced non-hepatoma cells. These results demonstrate the hepatoma-specific expression of cytokine genes and imply the feasibility of in vivo gene transfer into hepatomas without affecting any other tissues. Furthermore, these cytokine genes were expressed much more intensively when they were derived from the albumin enhancer and promoter than when derived from the simian virus 40 early region promoter. These results indicate that transcriptional regulatory sequences specific for the target tissues could be preferable to viral promoters for the gene therapy of cancer.
The antioxidant capacity in heart, liver, lung, and kidney was studied in young (6 months) and old (22 months) male Fischer 344 rats, using the oxygen radical absorbance capacity (ORAC) assay system with two different reactive oxygen species (ROS) generators. The results indicated that liver in old rats had significantly lower peroxyl radical absorbance capacity (ORACROO), units/g wet wt), but higher hydroxyl radical absorbance capacity (ORACOH), units/mg protein) than in young rats. The decreased liver ORACROO in the old rats was mainly due to the loss of cytosol protein, while the increased liver ORACOH in the old rats was a result of an increased resistance of cytosol proteins to the attack of ROS. This conclusion was further supported by the finding that the contribution of nonprotein fraction of liver cytosol to the ORACOH of the cytosol decreased with age. No effect of age was found on either ORACROO or ORACOH in other tissues. The antioxidant capacity for both ORACROO and ORACOH, was usually high in liver and kidney but low in lung and heart.
Discrete mixtures of normal distributions are widely used in modeling amplitude fluctuations of electrical potentials at synapses of human and other animal nervous systems. The usual framework has independent data values yj arising as yj = mu j + xn0 + j, where the means mu j come from some discrete prior G(mu) and the unknown xno + j's and observed xj, j = 1,...,n0, are Gaussian noise terms. A practically important development of the associated statistical methods is the issue of nonnormality of the noise terms, often the norm rather than the exception in the neurological context. We have recently developed models, based on convolutions of Dirichlet process mixtures, for such problems. Explicitly, we model the noise data values xj as arising from a Dirichlet process mixture of normals, in addition to modeling the location prior G(mu) as a Dirichlet process itself. This induces a Dirichlet mixture of mixtures of normals, whose analysis may be developed using Gibbs sampling techniques. We discuss these models and their analysis, and illustrate them in the context of neurological response analysis.
The authors' initial experience of angioscopic in-situ arterial bypass of 37 extremities reveals that angioscopy can be used to assist complete valvular ablation and precise location and ligation of tributaries of saphenous vein grafts, avoiding postoperative arterial-venous fistula and warm ischemic injury to grafts. Angioscopy is also used to perform intraoperative completion inspection of the grafts and anastomoses. The designed biocomposite graft and common ostium technique promotes the usage rate of the limited autogenous vein grafts and enlarges the diameter of grafts and blood flow through the distal anastomosis. Because of the above new series of procedures, the extremity salvage rate in this study was 34/37 limbs. During the follow-up period of 2-18 months, all anastomoses were patent. The preoperative ankle and toe pressure of 3.5 +/- 0.2 kPa and 2.0 +/- 0.1 kPa respectively rose to 5.4 +/- 0.1 kPa and 3.8 +/- 0.2 kPa postoperatively. We conclude that angioscopic in-situ arterial bypass surgery is of practical value and specially advantageous in lower extremity revascularization.
Based on pharmacological studies in files, mice and rats, the powder of sea pearl (Pteria martensii), mother-of-pearl and freshwater pearl has been proved to have tonic, anti-aging and anti-radiative actions. The effect of the sea pearl and mother-of-pearl powder is higher than that of freshwater pearl powder.
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A current hypothesis explaining the aging process implicates the accumulation of oxidized protein in animal tissues. This hypothesis is based on a series of reports showing an age-dependent increase in protein carbonyl content and an age-dependent loss of enzyme function. This hypothesis is also supported by the report of a novel effect of N-tert-butyl-alpha-phenylnitrone (PBN) in reversing these age-dependent changes. Here we specifically study the method that was used to measure reactive protein carbonyls in tissues. This method uses 2,4-dinitrophenylhydrazine (DNPH) and includes a washing procedure. Our results indicate that reactive protein carbonyls in normal crude tissue extracts cannot be reliably measured by this method, although it does reliably measure reactive carbonyls in purified proteins which have been oxidatively modified in vitro. The nucleic acids in tissues could be a major problem encountered in the assay. Using the streptomycin sulfate treatment combined with a dialysis step, we were successful in removing most nucleic acids from a crude tissue extract, but then the reactive carbonyl level in the crude tissue extract was too low to be reliably measured. This streptomycin sulfate treatment procedure, however, had no effect on the reactive carbonyl measurement of an oxidized protein sample. The unwashed free DNPH was another major problem in the assay because of its very strong absorption around 370 nm, where reactive carbonyls were quantitated. Nevertheless, on using the procedure described in the literature to measure total "reactive carbonyls" in rat liver and gerbil brain cortex, no change with age or PBN treatment was found. Then, we investigated a HPLC procedure which uses sodium dodecyl sulfate in the mobile phase but this was also found to be unsuitable for the reactive protein carbonyl assay in tissues.
A current hypothesis explaining the aging process implicates the accumulation of oxidized protein in animal tissues. This is primarily based on a series of reports showing an age-dependent increase in protein carbonyl content and an age-dependent decrease in the activities of enzymes, especially of alkaline proteases, which preferentially degrade oxidatively modified protein. Recently, this hypothesis was strongly supported by the report of a novel effect of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) in reversing these age-dependent changes. However, we found that the reactive protein carbonyls could not be reliably measured in tissues by using the 2,4-dinitrophenylhydrazine procedure described in the PBN study. We now focus on the alkaline protease activity assay and show that alkaline protease activity cannot be reliably measured in crude tissue extracts by using the fluorescamine procedure also described in the PBN study. We were, however, able to reliably measure a protease activity in crude tissue extracts at alkaline pH by using a synthetic fluorogenic peptide substrate, but no effect of aging or PBN treatment was found on the protease activity in rat brain cortexes. Thus, the reported age-dependent changes in protein carbonyl formation and alkaline protease activity remain to be confirmed.
Leader peptidase is a novel serine protease in Escherichia coli, which functions to cleave leader sequences from exported proteins. Its catalytic domain extends into the periplasmic space and is anchored to the membrane by two transmembrane segments located at the N-terminal end of the protein. At present, there is no information on the structure of the catalytic domain. Here, we report on the properties of a soluble form of leader peptidase (delta 2-75), and we compare its properties to those of the wild-type enzyme. We find that the truncated leader peptidase has a kcat of 3.0 S-1 and a Km of 32 microM with a pro-OmpA nuclease A substrate. In contrast to the wild-type enzyme (pI of 6.8), delta 2-75 is water-soluble and has an acidic isoelectric point of 5.6. We also show with delta 2-75 that the replacement of serine 90 and lysine 145 with alanine residues results in a 500-fold reduction in activity, providing further evidence that leader peptidase employs a catalytic serine/lysine dyad. Finally, we find that the catalysis of delta 2-75 is accelerated by the presence of the detergent Triton X-100, regardless if the substrate is pro-OmpA nuclease A or a peptide substrate. Triton X-100 is required for optimal activity of delta 2-75 at a level far below the critical micelle concentration. Moreover, we find that E. coli phospholipids stimulate the activity of delta 2-75, suggesting that phospholipids may play an important physiological role in the catalytic mechanism of leader peptidase.
The role of the membrane electrochemical potential in the translocation of acidic and basic residues across the membrane was investigated with the M13 procoat protein, which has a short periplasmic loop, and leader peptidase, which has an extended periplasmically located N-terminal tail. For both proteins we find that the membrane potential promotes membrane transfer only when negatively charged residues are present within the translocated domain. When these residues are substituted by uncharged amino acids, the proteins insert into the membrane independently of the potential. In contrast, when a positively charged residue is present within the N-terminal tail of leader peptidase, the potential impedes translocation of the tail domain. However, an impediment was not observed in the case of the procoat protein, where positively charged residues in the central loop are translocated even in the presence of the membrane potential. Intriguingly, several of the negatively charged procoat proteins required the SecA and SecY proteins for optimal translocation. The studies reported here provide insights into the role of the potential in membrane protein assembly and suggest that electrophoresis can play an important role in controlling membrane topology.
Previous research has indicated that age-related reductions in muscarinic (m) (e.g. oxotremorine, Oxo) agonist enhancement of striatal K(+)-evoked dopamine release (K(+)-ERDA) and decreased IP3 release upon m receptor (mAChR) agonist stimulation are partially the result of deficits in signal transduction (ST). The present experiments were carried out to test the hypothesis that these age-related ST deficits occur as a result of free radical-induced alterations in membranes containing receptor-G protein complexes. To test this hypothesis, the effects of in vivo and in vitro administration of the nitrone trapping agent, n-tert-butyl-alpha-phenylnitrone (PBN), on the Oxo-enhancement of K(+)-ERDA were examined. Results showed that: both in vivo (10 mg/kg/2 x day PBN i.p./14 days) in vitro (incubation of striatal slices 0-100 microM PBN/30 min) applications of PBN were effective in ameliorating age-related deficits in Oxo-enhanced K(+)-ERDA. The results of the in vivo administration of PBN indicate that the loss of mAChR sensitivity in aging may be the result of oxidative stress that can be restored by this nitrone trapping agent. These findings show that reductions of endogenous or exogenous free radicals may alter one important biomarker of aging, i.e. the loss of sensitivity in mAChR systems. However, these results, when considered along with those obtained with in vitro administration indicate that in addition, PBN may have acute effects (e.g. perhaps membrane structural alterations) which can also improve mAChR responsiveness.
To achieve correct spatial location of blood vessels, first order gradient moment nulling applied to the phase encoding axes can be used. However, gradient moment nulling prolongs echo time (TE), which may degrade the flow image in regions of complex flow. The fact that abbreviated moment compensated phase-encoding (AMCPE) can be used to apply partial flow compensation to the phase-encoding axes to prevent spatial misregistration of vessels without requiring the use of long echo times or using arbitrary chosen TE is demonstrated. AMCPE defines two cutoff lines in k-space. The flow-induced phase is completely compensated for values between the cutoff lines and partially compensated beyond the cutoff lines. The AMCPE technique has been tested on both a flow phantom and a human volunteer. The AMCPE images from both the in vivo and the in vitro study demonstrate correctly imaged flow. Computer simulations have been performed to analyze the penalty caused by the incomplete flow compensation. The result shows that the ripple artifacts due to the incomplete flow compensation are unobservable when 60%-70% of k-space is completely flow compensated.
Leader peptidase, a novel serine protease in Escherichia coli, catalyzes the cleavage of the amino-terminal leader sequences from exported proteins. It is an integral membrane protein containing two transmembrane segments with its carboxy-terminal catalytic domain residing in the periplasmic space. Here, we report a procedure for the purification and the crystallization of a soluble non-membrane-bound form of leader peptidase (delta 2-75). Crystals were obtained by the sitting-drop vapor diffusion technique using ammonium dihydrogen phosphate as the precipitant. Interestingly, we have found that the presence of the detergent Triton X-100 is required to obtain crystals sufficiently large for X-ray analysis. The crystals belong to the tetragonal space group P4(2)2(1)2, with unit cell dimensions of a = b = 115 A and c = 100 A, and contain 2 molecules per asymmetric unit. This is the first report of the crystallization of a leader (or signal) peptidase.
To determine the accuracy of self-reported weights and heights and of relative weight status in a sample of American Indian adolescents, a survey was conducted in middle and high schools on or near three Indian reservations-Navajo, Choctaw, and Blackfeet. Self-reported weights and heights were compared with measured weights and heights. Participants were 12 through 19 years old. (N = 806, 47.4% male). Overall, both boys and girls underreported weight (mean difference = self-reported - measured mean values)(-3.4 +/- 13.1 and -4.6 +/- 13.0 lb, respectively) and overreported height (0.6 +/- 2.1 and 0.2 +/- 2.6 in, respectively) However, underweight boys and girls overreported weight (normal: -1.6 +/- 7.9 and -1.4 +/- 6.3; overweight: -7.5 +/- 17.9 and -11.6 +/- 19.0 lb, respectively). Although correlations between measured and reported weight, height, and body mass index (BMI) were high, the sensitivity of relative weight categories based on BMI using self-reported weight and height compared with measured weight and height was poor: 66.7% for underweight (BMI < 15th percentile, based on a national reference population), 88.9% for normal weight, and 73.6% for overweight (> 85th percentile). These results call into question the accuracy of self-reported weight and height measurements among American Indian youth and are similar to findings among non-American Indian adolescents. Therefore, their use in prevalence studies should be avoided, and they should be used cautiously in other types of epidemiologic studies.
A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.