Tilt susceptibility at an antiferroelectric smectic-CA*-smectic-A phase transition.
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Journal Article↗
Biomedical subjects
Z Li
Publications and source records attributed to Z Li.
Inhibitory action of metabolites of Pseudomonas aeruginosa against gram-negative bacteria.
Fifty clinical isolates of Pseudomonas aeruginosa were tested for inhibition of growth of clinical isolates of Escherichia coli, Salmonella infantis, Klebsiella pneumoniae and other Gram-negative bacteria in the authors' laboratory. Pseudomonas aeruginosa was strongly active against both E. coli and Enterobacter cloacae, with 89.4% and 94.7% inhibition respectively, but weakly active against S. infantis, K. pneumoniae and Proteus mirabilis with 56.3%, 48.8% and 23.8% inhibition, respectively. The pigmented strains were found to have stronger antimicrobial activity than the unpigmented strains. Pyocyanin, the major metabolite of Pseudomonas aeruginosa, has been shown to inhibit Escherichia coli, Proteus spp. and other Gram-negative bacteria, by research with a few strains of P. aeruginosa and a single inhibited strain. However, little attempt has been made to determine the inhibitory action of many strains of P. aeruginosa against a large number of clinical isolates such as Escherichia spp., Klebsiella spp., and Salmonella spp., up to now. For this reason, in this study we examined 50 randomly selected clinical isolates of P. aeruginosa for inhibition of growth of a wide range of Gram-negative bacteria, including 30 strains of E. coli, 30 of K. pneumoniae, 30 of S. infantis, 6 of Enterobacter cloacae and 9 of Proteus mirabilis.
Antibiosis↗
Minimization of target positioning error in accelerator-based radiosurgery.
The stereotactic radiosurgery system used at the Mallinckrodt Institute of Radiology is patterned after that developed at the Joint Center for Radiation Therapy (Brigham & Women's Hospital, Boston, MA) and uses the Brown-Roberts-Wells computed tomography (CT) stereotactic system. The patient's head is attached to a stand that rotates with the treatment couch. The irradiation is conducted using a set of converging arcs of irradiation. Because of mechanical limitations, no accelerator or treatment couch is capable of placing the center of the radiation beam at precisely the same point for all gantry and couch angles and a compromise must be made when locating the nominal isocenter. The stand settings are checked by placing a radiopaque QA sphere at the desired target location. The QA sphere is imaged using a series of eight films exposed at a set of couch and gantry angles that encompass the treatment angles. The distances between the QA sphere image and the center of the radiation field indicate if the correct coordinates were set on the stand and if the radiation beam converges to a sufficiently small region (< 0.1-cm diameter) for treatment. A mathematical procedure has been developed to use the film-measured position errors to determine a stand offset that will minimize the distance between the accelerator isocenter and the target. The technique is capable of reducing the average placement error, as measured by imaging the QA sphere, to 0.035 cm with a maximum deviation of 0.07 cm.
Humans↗
Monte Carlo aided dosimetry of the microselectron pulsed and high dose-rate 192Ir sources.
Despite the large number of single-stepping source pulsed and high dose-rate (HDR) remote after-loading devices in clinical use, the published literature contain little data characterizing dose-rate distributions around the high-intensity (4 x 10(3)-4 x 10(4) microGy m2h-1) 192Ir sources currently used in these devices. We have used the Monte Carlo method to calculate complete two-dimensional dose-rate distributions about the most widely used high dose-rate source design, as well as the Nucletron pulsed dose-rate (PDR) 192Ir source. A Monte Carlo photon transport code, incorporating the detailed internal geometry of the source, was used to calculate the dose rate per unit air-kerma strength in water medium on the transverse bisecting axis over the 0.15-12 cm distance range. In addition, polar dose profiles were calculated at distances ranging from 0.25 to 5 cm. The PDR and HDR dose-rate distributions are tabulated using the formalism endorsed by the Interstitial Collaborative Working Group and the AAPM Task Group 43, and includes dose-rate constant, radial dose function, anisotropy function, geometry function, and anisotropy factors. The dose-rate constants, lambda, of the MicroSelectron/HDR and PDR sources were found to be 1.115 and 1.128 cGy h-1 per unit air-kerma strength, respectively, in good agreement with previously published data for low dose-rate interstitial 192Ir sources. Oblique filtration by the high-density iridium metal core resulted in deviations from anisotropy as large as 35%-55% near the longitudinal axis of the source. Dose-rate distributions are also presented in Cartesian ("away" and "along") coordinates.
Brachytherapy↗
Characterization of the katG and inhA genes of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis.
Resistance to isoniazid in Mycobacterium tuberculosis has been associated with mutations in genes encoding the mycobacterial catalase-peroxidase (katG) and the InhA protein (inhA). Among the 26 isoniazid-resistant clinical isolates evaluated in this study, mutations in putative inhA regulatory sequences were identified in 2 catalase-positive isolates, katG gene alterations were detected in 20 strains, and 4 isolates had wild-type katG and inhA genes. Mutations in the katG gene were detected in all 11 catalase-negative isolates: one frameshift insertion, two partial gene deletions, and nine different missense mutations were identified. An arginine-to-leucine substitution at position 463 was detected in nine catalase-positive isolates. However, site-directed mutagenesis experiments demonstrated that the presence of a leucine at codon 463 did not alter the activity of the M. tuberculosis catalase-peroxidase and did not affect the capacity of this enzyme to restore isoniazid susceptibility to isoniazid-resistant, KatG-defective Mycobacterium smegmatis BH1 cells. These studies further support the association between katG and inhA gene mutations and isoniazid resistance in M. tuberculosis, while also suggesting that other undefined mechanisms of isoniazid resistance exist.
Antitubercular Agents↗
Identification of a Bordetella pertussis bvg-regulated porin-like protein.
Bordetella pertussis 18323 produces a bvg-regulated 39.1-kDa porin-like protein, OmpQ. OmpQ had 61% similarity to the major porin of B. pertussis and contains conserved regions common to both the neisserial and enteric porin families. The results of Southern blot analysis indicate that strains of Bordetella parapertussis and Bordetella bronchiseptica but not Bordetella avium contain this gene.
Amino Acid Sequence↗
Activation of multiple antibiotic resistance and binding of stress-inducible promoters by Escherichia coli Rob protein.
Multiple antibiotic resistance in Escherichia coli can be mediated by induction of the SoxS or MarA protein, triggered by oxygen radicals (in the soxRS regulon) or certain antibiotics (in the marRAB regulon), respectively. These small proteins (SoxS, 107 residues; MarA, 127 residues) are homologous to the C terminus of the XylS-AraC family of proteins and are more closely related to a approximately 100-residue segment in the N terminus of Rob protein, which binds the right arm of the replication origin, oriC. We investigated whether the SoxS-MarA homology in Rob might extend to the regulation of some of the same inducible genes. Overexpression of Rob indeed conferred multiple antibiotic resistance similar to that known for SoxS and MarA (against chloramphenicol, tetracycline, nalidixic acid, and puromycin), as well as resistance to the superoxide-generating compound phenazine methosulfate. The Rob-induced antibiotic resistance depended only partially on the micF antisense RNA that down-regulates the OmpF outer membrane porin to limit antibiotic uptake. Similar antibiotic resistance was conferred by expression of a Rob fragment containing only the N-terminal 123 residues that constitute the SoxS-MarA homology. Both intact Rob and the N-terminal fragment activated expression of stress genes (inaA, fumC, sodA) but with a pattern distinct from that found for SoxS and MarA. Purified Rob protein bound a DNA fragment containing the micF promoter (50% bound at approximately 10(-9) M Rob) as strongly as it did oriC, and it bound more weakly to DNA containing the sodA, nfo, or zwf promoter (50% bound at 10(-8) to 10(-7) M). Rob formed multiple DNA-protein complexes with these fragments, as seen previously for SoxS. These data point to a DNA-binding gene activator module used in different protein contexts.
Bacterial Proteins↗
Geographical clustering of human T-cell lymphotropic virus type 1 infection in Honduras.
Geographical clustering of human T-cell lymphotropic virus type 1 (HTLV-1) infection has been identified in the nonmestizo communities in several cities along the Atlantic coast of Honduras. Of the 2,651 serum samples tested, 122 samples were repeatedly reactive for HTLV-1 antibodies in two different enzyme immunoassays and 3 were indeterminate. These sera did not react in the HTLV-2-specific antibody tests. The presence of HTLV-1 antibodies was confirmed by HTLV-1 immunoblots or Western blots (immunoblots), and the infection was verified by the detection of HTLV-1-specific genetic sequences in the cellular DNA by PCR. Genomic DNA from the peripheral blood mononuclear cells was first tested with generic primers and probes that identified both HTLV-1 and HTLV-2. Next, all DNA samples that showed HTLV reactivity were tested by PCR with specific primers and probes that distinguished HTLV-1 sequences from those of HTLV-2. Our results indicate that only HTLV-1 infection was present in the blood of both mestizo and nonmestizo residents of 15 cities in the Republic of Honduras. The overall prevalence of HTLV-1 infection in the nonmestizo population was 8.1% (95% confidence limit, 6.6 to 9.7%). The mestizo population residing in the same geographical vicinities showed a HTLV-1 antibodies in 0.5% of serum samples tested (95% confidence limit, 0.6 to 1.7%), indicating a significantly greater prevalence of HTLV-1 infection in the nonmestizo population than in the mestizo ethnic groups living in Honduras (P = 0.0001). Since no HTLV-2 antibody reactivity or HTLV-2-specific genetic sequences were detected by PCR with different primers and probes, it was concluded that HTLV-2 infection was not present in the Honduran population groups we tested. Our study also suggested an endemic nature for this virus because there was no difference in the prevalence rate of HTLV-1 antibodies in the nonmestizo community living in the coastal towns of Honduras between 1989 and 1993. This is the first report of HTLV-1 cluster identification in Honduras, Central America.
Adolescent↗
Simian immunodeficiency virus SIVmac chimeric virus whose env gene was derived from SIV-encephalitic brain is macrophage-tropic but not neurovirulent.
We inoculated four rhesus macaques with molecularly cloned simian immunodeficiency virus SIVmac239/17E env, a chimeric virus whose env gene was derived from the brain of an SIV-encephalitic macaque. Blood and lymphoid tissues had high frequencies of infected cells. The virus was neuroinvasive, but productive virus replication did not occur in the brain, and animals did not develop encephalitis.
Animals↗
Adenovirus type 12-induced fragility of the human RNU2 locus requires U2 small nuclear RNA transcriptional regulatory elements.
Infection of human cells with oncogenic adenovirus type 12 (Ad12) induces four specific chromosome fragile sites. Remarkably, three of these sites appear to colocalize with tandem arrays of genes encoding small, abundant, ubiquitously expressed structural RNAs--the RNU1 locus encoding U1 small nuclear RNA (snRNA), the RNU2 locus encoding U2 snRNA, and the RN5S locus encoding 5S rRNA. Recently, an artificial tandem array of the natural 5.8-kb U2 repeat unit has been shown to generate a new Ad12-inducible fragile site (Y.-P. Li, R. Tomanin, J. R. Smiley, and S. Bacchetti, Mol. Cell. Biol. 13:6064-6070, 1993), demonstrating that the U2 repeat unit alone is sufficient for virally induced fragility. To identify elements within the U2 repeat unit that are required for virally induced fragility, we generated cell lines containing artificial tandem arrays of the entire 5.8-kb repeat unit, an 834-bp fragment spanning the U2 gene alone, or the same 834-bp fragment from which key U2 transcriptional regulatory elements had been deleted. The U2 snRNA coding regions within each artificial array were marked by an innocuous single base change (U to C at position 87) so that the relative expression of supernumerary and endogenous U2 genes could be monitored by a primer extension assay. We find that artificial arrays of both the 5.8- and the 0.8-kb U2 repeat units are fragile but that arrays lacking either the distal sequence element or both the distal and the proximal sequence elements of the promoter are not. Surprisingly, variations in repeat copy number and/or transcriptional activity of the artificial arrays do not appear to correlate with the degree of Ad12-inducible fragility. We conclude that U2 transcriptional regulatory elements are required for virally induced fragility but not necessarily U2 snRNA transcription per se.
Adenovirus Infections, Human↗
Feedback inhibition of the yeast ribosomal protein gene CRY2 is mediated by the nucleotide sequence and secondary structure of CRY2 pre-mRNA.
The Saccharomyces cerevisiae CRY1 and CRY2 genes, which encode ribosomal protein rp59, are expressed at a 10:1 ratio in wild-type cells. Deletion or inactivation of CRY1 leads to 5- to 10-fold-increased levels of CRY2 mRNA. Ribosomal protein 59, expressed from either CRY1 or CRY2, represses expression of CRY2 but not CRY1. cis-Acting elements involved in repression of CRY2 were identified by assaying the expression of CRY2-lacZ gene fusions and promoter fusions in CRY1 CRY2 and cry1-delta CRY2 strains. Sequences necessary and sufficient for regulation lie within the transcribed region of CRY2, including the 5' exon and the first 62 nucleotides of the intron. Analysis of CRY2 point mutations corroborates these results and indicates that both the secondary structure and sequence of the regulatory region of CRY2 pre-mRNA are necessary for repression. The regulatory sequence of CRY2 is phylogenetically conserved; a very similar sequence is present in the 5' end of the RP59 gene of the yeast Kluyveromyces lactis. Wild-type cells contain very low levels of both CRY2 pre-mRNA and CRY2 mRNA. Increased levels of CRY2 pre-mRNA are present in mtr mutants, defective in mRNA transport, and in upf1 mutants, defective in degradation of cytoplasmic RNA, suggesting that in wild-type repressed cells, unspliced CRY2 pre-mRNA is degraded in the cytoplasm. Taken together, these results suggest that feedback regulation of CRY2 occurs posttranscriptionally. A model for coupling ribosome assembly and regulation of ribosomal protein gene expression is proposed.
Base Sequence↗
A time to pregnancy questionnaire designed for long term recall: validity in Oxford, England.
STUDY OBJECTIVE: To establish the degree of validity of data on time to pregnancy, derived retrospectively using a short questionnaire. DESIGN: Information from the questionnaire was compared with data that had been collected concurrently from the same individuals. SETTING AND PARTICIPANTS: Questionnaires were mailed to 1647 women who continue to be followed up by the Oxford Family Planning Association contraceptive study, and a further 424 were approached for personal interview. Response rates were 91% and 79% respectively. MAIN RESULTS: Matching was successful in 91% of pregnancies. Median recall time was 14 years (interquartile range, 11-16 years). At the group level, remarkably good agreement was found between the two sources of information, presented as cumulative percentage distributions of live births. The findings were at least as good with longer recall (> 14 years) as with shorter recall. Digit performance was present to a limited degree. At the individual level, some misclassification was evident, which has implications for statistical power. For detection of clinical infertility (no conception within 12 months), the sensitivity was in the range 67%-91%, and the specificity was 92%-96%. Variations with format, duration of recall, age at delivery, year of birth, parity, social class, smoking habit, last contraceptive method, and outcome (live birth or not) were generally small, and were not statistically significant. CONCLUSIONS: Time to pregnancy is a sensitive way of assessing reproductive function in either sex. Valid data at a group level can be derived retrospectively, with a long duration of recall, using a short questionnaire.
Adult↗
Role of cyclooxygenase metabolites in mediating platelet-induced baroreceptor dysfunction.
The goal of the study was to determine the role of cyclooxygenase metabolites in mediating platelet-induced suppression of baroreceptor activity. Exposure of the isolated carotid sinus of rabbits to thrombin-activated rabbit platelets (3 x 10(8) cells/ml Krebs buffer) decreased baroreceptor activity (P < 0.05) without significantly altering the slope of the pressure-activity relation (gain). The platelet-induced suppression of activity was not blocked but instead was even more pronounced after inhibition of cyclooxygenase with indomethacin; both maximum baroreceptor activity and gain were decreased markedly. The exacerbation of platelet-induced baroreceptor dysfunction contrasted with equivalent carotid vasoconstrictor responses to platelets before and after indomethacin. Furthermore, the stable thromboxane (TxA2) mimetic U-46619 caused similar vasoconstriction as platelets but did not influence baroreceptor gain or maximum activity. In contrast to indomethacin, the selective TxA2 synthesis inhibitor and receptor blocker CGS-22652 failed to influence platelet-induced suppression of activity. In summary, 1) rabbit platelet aggregating in carotid sinus suppress baroreceptor activity, which cannot be explained by the vasoconstriction, and 2) the suppression of activity is not mediated by TxA2 from platelets and is opposed by prostacyclin (PGI2) or other prostanoids produced in carotid sinus. The combination of impaired formation of PGI2 and platelet activation in atherosclerotic and thrombotic states may lead to profound baroreceptor dysfunction.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Vasopressin actions on area postrema neurons in vitro.
The area postrema (AP) is a circumventricular organ located on the dorsal surface of the medulla. Substantial evidence suggests that the AP is an important site involved in cardiovascular regulation. Arginine vasopressin (AVP) is thought to act at the AP to increase the sensitivity of the baroreceptor reflex. We have therefore examined the effects of AVP on AP neurons with the use of extracellular single unit recordings in vitro. Coronal medullary brain slices (thickness = 400 microns) were obtained from male Sprague-Dawley rats and maintained in oxygenated artificial cerebrospinal fluid (aCSF). The slices were perfused with AVP (10(-8) to 10(-6) M), and the effect on single AP neurons was recorded. A total of 79 AP neurons was tested of which 50 (63.3%) were excited by AVP and 5 (6.3%) were inhibited, whereas the remaining 24 (30.3%) cells were unaffected. The excitatory effects of AVP were dose dependent: firing rate increased 92.6 +/- 25.8% at 10(-8) M, 289.4 +/- 53.9% at 10(-7) M, and 456.8 +/- 113.1% at 10(-6) M, respectively. We also examined whether these effects of AVP resulted from direct actions of this peptide on AP cells by testing if responses were retained during blockade of synaptic transmission (achieved by perfusion with a low Ca(2+)-high Mg2+ aCSF) in 11 cells excited by AVP. Nine of these cells were excited by AVP during such synaptic blockade. Finally, we demonstrated that the excitatory responses of five AP cells to AVP were all totally abolished by perfusion of slices with aCSF containing the V1 antagonist ([1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid,2-(O-methyl)tyrosine]-Arg8-vasopressin; Peninsula Laboratories, 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Time-varying pulmonary arterial input impedance via wavelet decomposition.
Wavelet decomposition is proposed as a novel approach for determining pulmonary arterial input impedance throughout the breathing cycle. The canine pulmonary arterial input impedance was evaluated throughout the ventilatory cycle at 5, 10, and 15 cmH2O of positive end-expiratory pressure. The impedance spectrum was obtained by Fourier transformation of wavelets generated by decomposing the pulmonary arterial pressure and flow waveforms. With wavelet decomposition, each heart beat is viewed individually as a transient pulse rather than as an interval within a continuous function of pressure and flow. The advantage of using this approach is the ability to obtain stable estimates of input impedance spectra with high-frequency resolution over the entire frequency range with only a limited data set of pressure and flow decomposed to wavelets as short as singular extrapolated cardiac cycles. This method was used to define the changes of input impedance that occur during the ventilatory cycle. Results show that the impedance spectrum undergoes notable changes during the breathing cycle and demonstrate the utility of the proposed method.
Animals↗
Effects of alcohol consumption on lipoproteins of premenopausal women. A controlled diet study.
A substantial portion of American women consume alcohol, but controlled studies of alcohol-induced changes in lipoproteins of women are rare. In this study, the effects of alcohol consumption (equivalent to two drinks per day) on the lipoprotein profiles of 34 premenopausal women were measured while controlling subjects' diet and various other potentially confounding variables including phase of the menstrual cycle. Alcohol and no-alcohol treatments were administered in a crossover design, and blood samples were obtained during the early follicular phase of the third month of treatment. With alcohol, HDL cholesterol levels increased 10%, LDL levels decreased 8%, and levels of lipoprotein(a) were unchanged. The increase in HDL cholesterol was due to an increase in both HDL2 and HDL3, and the overall size of HDL particles was increased. HDL particles containing apolipoprotein (apo) A-I and apoA-II as well as those containing apoA-I but no apoA-II were elevated in response to alcohol. Although these observations are limited to a single phase of the menstrual cycle, the alcohol-induced changes in lipoproteins are consistent with changes that are thought to confer protection against coronary heart disease.
Adult↗
Efficacy of a National Cholesterol Education Program Step 2 diet in normolipidemic and hypercholesterolemic middle-aged and elderly men and women.
We tested the effects of a National Cholesterol Education Program (NCEP) Step 2 diet (30% of calories or less as total fat, less than 7% saturated fat, and less than 200 mg cholesterol per day) on plasma lipid levels in normocholesterolemic and hypercholesterolemic middle-aged and elderly men and women. Thirty-two subjects were studied. Eight normolipidemic subjects (6 men and 2 women, mean age 56 +/- 13 years) with LDL cholesterol levels of less than 4.14 mmol/L (160 mg/dL) were given a baseline diet similar in composition to the diet currently consumed in the United States (35% of calories as total fat and 14% as saturated fat, with 147 mg cholesterol per 1000 kcal) for 6 weeks. Subjects were then placed on an NCEP Step 2 diet (26% total fat, 4% saturated fat, 45 mg cholesterol per 1000 kcal) for 24 weeks. In addition, 24 subjects (12 men and 12 women, mean age 62 +/- 12 years) with moderate hypercholesterolemia (LDL cholesterol levels of 4.14 mmol/L or above) were given a baseline diet for 6 weeks and then the NCEP Step 2 diet for 6 weeks. Energy intakes were adjusted to keep body weight constant throughout the study. In both normolipidemic and hypercholesterolemic subjects, consumption of the NCEP Step 2 diet was associated with significant changes in levels of total cholesterol (-20% and -16%, respectively), LDL cholesterol (-21% and -18%, respectively), and HDL cholesterol (-16% and -15%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Tumor necrosis factor-alpha modulates monocyte/macrophage apoprotein E gene expression.
apo E has been shown to modulate cholesterol balance in arterial wall cells. Production of apo E by macrophages in atherosclerotic plaques could thereby influence the development of the plaque lesion. Cytokines, including TNF alpha, have been identified in human lesions, therefore, we undertook a series of studies to evaluate the effect of TNF alpha on monocyte/macrophage apo E production. The addition of TNF alpha to freshly isolated human monocytes led to a four- to fivefold increase of apo E mRNA abundance. The addition of TNF alpha to fully differentiated macrophages either had no effect or modestly inhibited apo E mRNA expression. THP1 human monocytic cells also responded to TNF alpha in a phenotype-specific manner. Treatment of these cells with TNF alpha produced a dose- and time-dependent increase in apo E mRNA. This increase was reflected in apo E synthesis and was associated with inhibition of DNA synthesis, and with induction of c-fos and ICAM-1 gene expression. Cell-permanent analogues of ceramide did not reproduce TNF alpha effect on apo E, but antagonists of protein kinase C did inhibit its effect. TNF alpha induction of apo E mRNA abundance was associated with stimulation of apo E promoter-dependent gene transcription. In summary, TNF alpha stimulates apo E gene transcription, mRNA abundance, and protein synthesis in the monocyte/macrophage in a phenotype-specific manner. Such regulation could significantly modify the amount of apo E present in vessel wall lesions.
Apolipoproteins E↗