Acute toxicity profile of 1-butyl-3-methylimidazolium chloride.
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Administration, Cutaneous↗
Biomedical subjects
K Brooks
Publications and source records attributed to K Brooks.
Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors.
The bacterial family Enterobacteriaceae is notable for its well studied human pathogens, including Salmonella, Yersinia, Shigella, and Escherichia spp. However, it also contains several plant pathogens. We report the genome sequence of a plant pathogenic enterobacterium, Erwinia carotovora subsp. atroseptica (Eca) strain SCRI1043, the causative agent of soft rot and blackleg potato diseases. Approximately 33% of Eca genes are not shared with sequenced enterobacterial human pathogens, including some predicted to facilitate unexpected metabolic traits, such as nitrogen fixation and opine catabolism. This proportion of genes also contains an overrepresentation of pathogenicity determinants, including possible horizontally acquired gene clusters for putative type IV secretion and polyketide phytotoxin synthesis. To investigate whether these gene clusters play a role in the disease process, an arrayed set of insertional mutants was generated, and mutations were identified. Plant bioassays showed that these mutants were significantly reduced in virulence, demonstrating both the presence of novel pathogenicity determinants in Eca, and the impact of functional genomics in expanding our understanding of phytopathogenicity in the Enterobacteriaceae.
Base Sequence↗
Large changes in Pluto's atmosphere as revealed by recent stellar occultations.
Pluto's tenuous nitrogen atmosphere was first detected by the imprint left on the light curve of a star that was occulted by the planet in 1985 (ref. 1), and studied more extensively during a second occultation event in 1988 (refs 2-6). These events are, however, quite rare and Pluto's atmosphere remains poorly understood, as in particular the planet has not yet been visited by a spacecraft. Here we report data from the first occultations by Pluto since 1988. We find that, during the intervening 14 years, there seems to have been a doubling of the atmospheric pressure, a probable seasonal effect on Pluto.
Journal Article↗
Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.
Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.
Animals↗
The genome sequence of Schizosaccharomyces pombe.
We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.
Base Sequence↗
Observation of radiation-specific damage in human cells exposed to depleted uranium: dicentric frequency and neoplastic transformation as endpoints.
Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalised human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. DU possesses both a radiological (alpha-particle) and chemical (metal) component. Since DU has a low specific activity in comparison to natural uranium, it is not considered to be a significant radiological hazard. The potential contribution of radiation to DU-induced biological effects is unknown and the involvement of radiation in DU-induced biological effects could have significant implications for current risk estimates for internalised DU exposure. Two approaches were used to address this question. The frequency of dicentrics was measured in HOS cells following DU exposure in vitro. Data demonstrated that DU exposure (50 microM, 24 h) induced a significant elevation in dicentric frequency in vitro in contrast to incubation with the heavy metals, nickel and tungsten which did not increase dicentric frequency above background levels. Using the same concentration (50 microM) of three uranyl nitrate compounds that have different uranium isotopic concentrations and therefore, different specific activities, the effect on neoplastic transformation in vitro was examined. HOS cells were exposed to one of three-uranyl nitrate compounds (238U-uranyl nitrate, specific activity 0.33 microCi.g-1; DU-uranyl nitrate, specific activity 0.44 microCi.g-1; and 235U-uranyl nitrate, specific activity 2.2 microCi.g-1) delivered at a concentration of 50 microM for 24 h. Results showed, at equal uranium concentration, there was a specific activity dependent increase in neoplastic transformation frequency. Taken together these data suggest that radiation can play a role in DU-induced biological effects in vitro.
Cell Transformation, Neoplastic↗
Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.
Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.
Chromosome Mapping↗
Genome sequence of Yersinia pestis, the causative agent of plague.
The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.
Animals↗
Improved flow cytometric detection of HLA alloantibodies using pronase: potential implications in renal transplantation.
BACKGROUND: Flow cytomeric crossmatch (FCXM) has grown in popularity and has become the "standard of practice" in many programs. Although FCXM is the most sensitive method for detecting alloantibody, the B cell FCXM has been problematic. Difficulties with the B cell FCXMs have been centered around high nonspecific fluorescence background owing to Fc-receptors present on the B cells and autoantibodies. To improve the specificity and sensitivity of the B cell FCXM, we utilized the proteolytic enzyme pronase to remove Fc receptors from lymphocytes before their use in FCXM. METHODS: Lymphocytes isolated from peripheral blood, spleen, or lymph nodes were treated with pronase and then used in a three-color FCXM. A total of 167 T- and B cell FCXMs using pronase-treated and untreated cells were performed. Testing used serial dilutions of HLA allosera (22 class I and 6 class II), with the titer of each antibody at one dilution past the titer at which the complement-mediated cytotoxicity anti-human globulin crossmatch became negative. RESULTS: After pronase treatment, the actual channel values of the negative control in both T cell and B cell FCXMs declined from 78+/-10 to 57+/-4 (P<0.05) and 107+/-11 to 49+/-3 (P<0.00001), respectively. Pronase treatment resulted in improved sensitivity of the T and B cell FCXM in detecting class I antibody by 20% and 80%, respectively. In no instance was a false-positive reaction observed. In this study, pronase treatment improved the specificity of B cell FCXM for detecting class II antibodies from 75% to 100% (P=0.03). In no instance was a false-negative reaction recorded. Lastly, on the basis of these observations we re-evaluated three primary transplant recipients who lost their allografts because of accelerated rejection. One of the patients was transplanted across negative T and B cell FCXM, whereas the other two patients were transplanted across a positive T cell, but negative B cell, FCXM. After pronase treatment, T and B cell FCXMs of each patient became strongly positive, and donor-specific anti-HLA class I antibody was identi. fied in each case. CONCLUSION: Utilization of pronase-treated lymphocytes improves both the sensitivity and specificity of the FCXM.
False Negative Reactions↗
Sociocultural issues in clinical research.
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Black or African American↗
Stereomotion speed perception is contrast dependent.
The effect of contrast on the perception of stimulus speed for stereomotion and monocular lateral motion was investigated for successive matches in random-dot stimuli. The familiar 'Thompson effect'--that a reduction in contrast leads to a reduction in perceived speed--was found in similar proportions for both binocular images moving in depth, and for monocular images translating laterally. This result is consistent with the idea that the monocular motion system has a significant input to the stereomotion system, and dominates the speed percept for approaching motion.
Adult↗
Perceived speed of motion in depth is reduced in the periphery.
The perceived speed of motion in depth (MID) for a monocularly visible target was measured in central and peripheral vision using a 2AFC speed discrimination task. Only binocular cues to MID were available: changing disparity and interocular velocity difference (IOVD). Perceived speed for monocular lateral motion and perceived depth for static disparity were also assessed, again in both central and peripheral vision. The purpose of the experiment was to assess the relative contributions of changing disparity and IOVD cues to the perceived speed of stereomotion. Although peripheral stimuli appeared to lie at approximately the same depth as their central counterparts, their apparent speed was reduced. Monocular/lateral and binocular/MID speeds were reduced to a similar extent. It seems that reduced apparent monocular speed leads to reduced perceived MID speed, despite the fact that the disparity system appears to be unaffected. These results suggest that the IOVD cue makes a significant contribution to MID speed perception.
Adult↗
Human T cell lymphotropic virus type I-associated infective dermatitis in Jamaica: a case report of clinical and biologic correlates.
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CD4-CD8 Ratio↗
Systemic lupus erythematosus in three ethnic groups. V. Acculturation, health-related attitudes and behaviors, and disease activity in Hispanic patients from the LUMINA cohort. LUMINA Study Group. Lupus in Minority Populations, Nature versus Nurture.
OBJECTIVE: To assess the relationship between acculturation and clinical, socioeconomic-demographic, and behavioral/psychosocial features in Hispanic patients with systemic lupus erythematosus (SLE) from the LUMINA (Lupus in Minority Populations, Nature versus Nurture) cohort. METHODS: An empirically derived questionnaire was administered to 67 Mexican American SLE patients participating in a longitudinal study of outcome. This questionnaire inquired about place of birth, upbringing and length of stay in the United States, language (proficiency, usage, and preferences; English/bilingual versus Spanish), type of neighborhood, self-identity, and social interactions. Responses to this questionnaire and an informal interaction with a single bilingual, bicultural Mexican American research assistant were used to generate a score on a 10-cm anchored visual analog scale (VAS) (0 = no acculturation and 10 = maximum acculturation). The responses to the questionnaire were then quantified and scored by a physician who was unaware of the VAS. A composite score was then obtained utilizing 4 of the 6 components of the instrument. The VAS was found to have adequate sensitivity (91%), specificity (88%), and overall predictive value (89%) when the composite score was used as the validity criterion. Therefore, the VAS was used in all subsequent analyses; the median in this VAS separated patients into high and low acculturation groups. The relationship between acculturation and sociodemographic, behavioral/psychosocial (social support, abnormal illness-related behaviors, and helplessness) and clinical variables (disease duration, onset type, number of American College of Rheumatology criteria met, disease activity, and damage) at study entry was then explored. RESULTS: Patients in the low acculturation group had fewer years of education, were less likely to have private health insurance, and had less social support as compared with those in the high acculturation group; they also exhibited less disease activity as determined by the overall physician and patient global assessments of the Systemic Lupus Activity Measure. Abnormal illness-related behaviors and helplessness were not increased in the low acculturation group. CONCLUSIONS: Low levels of acculturation were associated with indicators of low socioeconomic status, but also with less disease activity at enrollment into LUMINA; they were, however, not associated with more abnormal illness-related behaviors or with helplessness, as measured in this study. The possible impact of acculturation and of its mediators in the course and outcome of SLE among Hispanic patients needs to be determined longitudinally.
Acculturation↗
Temporal trends in pharmacotherapy for congestive heart failure at an academic medical center: 1990-1995.
The objectives of this study were to assess current practice patterns in pharmacotherapy for congestive heart failure at an academic medical center and to analyze temporal trends in management of congestive heart failure from 1990 to 1995. Records of all patients discharged from the hospital in 1990 or 1995 with a primary diagnosis of congestive heart failure who also underwent echocardiography were found by a search of the hospital's medical records database. All charts were reviewed, and relevant clinical data, including all discharge medications, were recorded. On the basis of echocardiograms, patients were classified as having preserved or impaired left ventricular systolic function (estimated ejection fraction > or =45% versus <45%). The use of digoxin, diuretics, angiotensin-converting enzyme (ACE) inhibitors, calcium and beta-blockers, nitrates, and hydralazine in 1990 and 1995 were compared in subgroups according to left ventricular function. A total of 297 patients were identified who fulfilled study criteria and for whom all pertinent data were available (1990, n = 109; 1995, n = 188). The median age was 74 years; 37.3% of the patients were men, and 45.1% were white. Among patients with impaired systolic function, the proportion receiving either an ACE inhibitor or the combination of nitrates and hydralazine increased from 80.9% in 1990 to 95.4% in 1995 (p = 0.009). In addition, among patients treated with an ACE inhibitor, the proportion receiving an optimal dose increased from 24.3% in 1990 to 61.5% in 1995 (p < 0.001). The use of beta-blockers also increased significantly during this time period (2.1% versus 15.7%; p = 0.031 ). Among patients with preserved ventricular function, the use of ACE inhibitors and beta-blockers increased from 1990 to 1995 (both p < 0.05). The use of other medications did not change for either subgroup. Current use of appropriate vasodilator therapy at an academic medical center is very high and is in accordance with published guidelines for the management of congestive heart failure. The use of vasodilators and beta-blockers has increased significantly since 1990 among patients with congestive heart failure with either impaired or preserved left ventricular contractility.
Academic Medical Centers↗
Modulation of IL-1beta, IL-6 and TNF-alpha secretion and mRNA expression by the trichothecene vomitoxin in the RAW 264.7 murine macrophage cell line.
Oral exposure of mice to vomitoxin (VT) has been previously shown to enhance gene expression of several cytokines associated with macrophage activation. Here, the effects of exposure to VT in vitro on cytokine secretion and mRNA expression were determined in the murine macrophage cell line RAW 264.7. Enzyme-linked immunosorbent assay (ELISA) of supernatants revealed that significant increases in secreted tumour necrosis factor alpha (TNF-alpha) were observed 2 days after exposure to VT at 100 ng/ml and 250 ng/ml, both with and without lipopolysaccharide (LPS) activation. While VT did not affect IL-6 secretion in the absence of LPS, significantly increased IL-6 production was observed in culture supernatants after 1, 2 and 5 days of exposure to VT at 250 ng/ml in the presence of LPS. Soluble IL-1beta was not detected in control or VT-treated cell cultures with or without LPS activation. Immunochemical staining of intracellular cytokines in conjunction with flow cytometric analysis was used to detect the effects of VT on the percentage of positive cells and output per cell. The percentage of cells that produced intracellular TNF-alpha were significantly increased at 100 and 250 ng/ml VT with and without LPS whereas increased IL-6 output per cell was observed at 100 and 250 ng/ml VT with LPS. To assess the effects of VT on cytokine mRNA expression, RAW 264.7 cells were analysed semi-quantitatively using reverse transcription-polymerase chain reaction(RT-PCR) in conjunction with Southern hybridization analysis. Elevated TNF-alpha mRNA was observed at 100 and 250 ng VT/ml at 6 and 24 hr in the absence of LPS. With the addition of LPS, superinduction of TNF-alpha was not observed in the presence of VT. Increased IL-1beta and IL-6 mRNAs were observed at 100 and 250 ng VT/ml at 24 hr in the presence of LPS. These results demonstrated that VT could superinduce both cytokine secretion and mRNA levels in macrophage cultures.
Animals↗
A randomized, prospective comparison of pain after gasless laparoscopy and traditional laparoscopy.
STUDY OBJECTIVE: To compare pain after laparoscopic tubal ligation by gasless laparoscopy versus carbon dioxide (CO2) pneumoperitoneum. DESIGN: Prospective, randomized, single-blind comparison (Canadian Task Force classification I). SETTING: Private obstetric-gynecology hospital associated with a university resident teaching program. PATIENTS: Women age 21 to 42. INTERVENTION: Single-puncture laparoscopic tubal ligation was performed with a silicone elastomer band. Gasless laparoscopy was performed with a Laprolift and traditional laparoscopy with CO2 pneumoperitoneum. Postoperative pain in the shoulder and periumbilical and lower pelvic regions was measured by visual analog scale on the day of surgery and postoperative days 1, 2, 3, 7, and 14. MEASUREMENTS AND MAIN RESULTS: Of the 67 patients, 54 provided visual analog scales for analysis, 30 in the gasless group and 24 in the traditional group. No statistical difference was seen in scores for shoulder, periumbilical, and pelvic pain between techniques. CONCLUSION: Patients undergoing gasless laparoscopy and traditional laparoscopy experience similar postoperative pain.
Adult↗
Comparison of the anticoagulant action of sulfated and phosphorylated polysaccharides.
Oat spelts xylan (OSX), fucoidan, kappa carrageenan and chondroitin sulfates A and C were sulfated using chlorosulfonic acid-pyridine complex while the first three were phosphorylated using methane sulfonic acid-phosphorous pentoxide mixture. The compounds were isolated as the sodium salts and their in vitro anticoagulant properties were determined by measuring the concentration of each compound required to double prothrombin time of pooled normal human plasma. The results of 31P-nmr spectroscopy showed that phosphorylation significantly increased the molecular weights of the polysaccharides by forming phosphodiester and diphosphodiester bonds. In general the anticoagulant properties of the sulfated polysaccharides were related to the % sulfate while the phosphorylated polysaccharides showed increases in anticoagulant properties which were related to the increase in the molecular weight and inversely related to the % phosphate. The mechanism of action of oat spelts xylan phosphate (OSXP) was studied using 125I-thrombin and normal human plasma. The results showed that at lower concentration of the OSXP, the complexation of 125I-thrombin with heparin cofactor-II(HC-II) was enhanced, while at higher concentration of the compound, the complexation with both antithrombin-III(AT-III) and HC-II was enhanced.
Anticoagulants↗