Concerns about the safety of intravenous immunoglobulin in acute ischaemic stroke.
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Brain Ischemia↗
Biomedical subjects
L A Wilson
Publications and source records attributed to L A Wilson.
Different regional effects of voluntary exercise on the mechanical and electrical properties of rat ventricular myocytes.
Short-term (6 weeks) voluntary wheel running exercise in young female rats that were in an active growth phase resulted in whole-heart hypertrophy and myocyte concentric hypertrophy, when compared to sedentary controls. The cross-sectional area of ventricular myocytes from trained rats was significantly greater than for those isolated from sedentary rats, with the greatest change in morphology seen in sub-endocardial cells. There was no statistically significant effect of training on cell shortening in the absence of external mechanical loading, in [Ca2+](i) transients, or in myofilament Ca2+ sensitivity (assessed during re-lengthening following tetanic stimulation). Under the external mechanical load of carbon fibres, absolute force developed in myocytes from trained rats was significantly greater than in those from sedentary rats. This suggests that increased myocyte cross-sectional area is a major contractile adaptation to exercise in this model. Training did not alter the passive mechanical properties of myocytes or the relative distribution of titin isomers, which was exclusively of the short, N2B form. However, training did increase the steepness of the active tension-sarcomere length relationship, suggesting an exercise-induced modulation of the Frank-Starling mechanism. This effect would be expected to enhance cardiac contractility. Training lengthened the action potential duration of sub-epicardial myocytes, reducing the transmural gradient in action potential duration. This observation may be important in understanding the cellular causes of T-wave abnormalities found in the electrocardiograms of some athletes. Our study shows that voluntary exercise modulates the morphological, mechanical and electrical properties of cardiac myocytes, and that this modulation is dependent upon the regional origin of the myocytes.
Actin Cytoskeleton↗
Acute demyelinating encephalomyelitis (ADEM) in a patient with HIV infection.
A case of acute demyelinating encephalomyelitis (ADEM) in a patient with HIV infection is reported. Although the diagnosis of ADEM is based on clinical and radiological findings, the potential for full recovery, with appropriate treatment, is highlighted by this case. A concise review of the subject is given in the discussion.
Acute Disease↗
Mouse models for the Wolf-Hirschhorn deletion syndrome.
Wolf-Hirschhorn syndrome (WHS) is a deletion syndrome caused by segmental haploidy of chromosome 4p16.3. Its hallmark features include a 'Greek warrior helmet' facial appearance, mental retardation, various midline defects and seizures. The WHS critical region (WHSCR) lies between the Huntington's disease gene, HD, and FGFR3. In mice, the homologs of these genes map to chromosome 5 in a region of conserved synteny with human 4p16.3. To derive mouse models of WHS and map genes responsible for subphenotypes of the syndrome, five mouse lines bearing radiation-induced deletions spanning the WHSCR syntenic region were generated and characterized. Similar to WHS patients, these animals were growth-retarded, were susceptible to seizures and showed midline (palate closure, tail kinks), craniofacial and ocular anomalies (colobomas, corneal opacities). Other phenotypes included cerebellar hypoplasia and a shortened cerebral cortex. Expression of WHS-like traits was variable and influenced by strain background and deletion size. These mice represent the first animal models for WHS. This collection of nested chromosomal deletions will be useful for mapping and identifying loci responsible for the various subphenotypes of WHS, and provides a paradigm for the dissection of other deletion syndromes using the mouse.
Abnormalities, Multiple↗
Urinary biomarkers for assessing dietary exposure to caffeine.
The feasibility of using metabolites specific to caffeine as urinary biomarkers to be employed in the estimation of dietary caffeine intake is reported. The influence of inter-individual differences in the metabolism of caffeine and the effect of volunteer phenotype on the interpretation of potential biomarkers has been investigated using urinary caffeine metabolite data. This method of phenotype determination accurately reflected the rate constant for the cytochrome P4501A2 (CYP1A2)-catalysed 3-demethylation of caffeine in vivo. Three studies with up to 20 human volunteers demonstrated that a 24-h urine collection after a caffeine dose allows quantification of the metabolites excreted; that the ratios of selected metabolites used to classify the volunteers into fast, intermediate or slow caffeine metabolizers by CYP1A2 phenotype gave a similar result (2:7:3, slow:intermediate:fast) to that found in the general population (1:7:2); and that three metabolites, 1,7-dimethylxanthine, 1,7-dimethyluric acid and 1-methylxanthine, could be studied further as potential biomarkers for caffeine dietary intake.
Adult↗
CT colonography without cathartic preparation: feasibility study.
PURPOSE: To evaluate methods for contrast material labeling of stool in the unprepared colon for computed tomographic (CT) colonography and to determine their sensitivity for polyp detection. MATERIALS AND METHODS: Fifty-six patients with suspected or known polyps were assigned to five groups. Two to seven doses of 225 mL of dilute contrast material were orally administered during 24 or 48 hours. Transverse CT images were assessed for effectiveness of stool labeling. Colonoscopy was performed in all patients and was the standard. Two radiologists blinded to prior imaging and colonoscopic results assessed polyp detection. RESULTS: For each group, average stool labeling scores and ranges were as follows: 24 hour two dose, 16% and 8%-21%; 24 hour five dose, 53% and 27%-66%; 48 hour four dose, 38% and 22%-48%; 48 hour six dose, 68% and 54%-77%; and 48 hour seven dose, 88% and 75%-98%. Sensitivity for the two radiologists for the identification of patients with polyps 1 cm or larger for each group was as follows: 24 hour two dose, 50% and 67%; 24 hour five dose, 100% and 100%; 48 hour four dose, 58% and 75%; 48 hour six dose, 56% and 67%; and 48 hour seven dose, 100% and 80%. CONCLUSION: Ingestion of contrast material adequately labels stool for lesion identification; a 48-hour lead time and multiple doses of contrast material are required. Sensitivity for polyp detection in patients with adequate stool labeling approaches the sensitivity for polyp detection in prepared colons.
Barium Sulfate↗
IL-2Ralpha-Directed monoclonal antibodies provide effective therapy in a murine model of adult T-cell leukemia by a mechanism other than blockade of IL-2/IL-2Ralpha interaction.
Adult T-cell leukemia (ATL) develops in a small proportion of human T-cell lymphotrophic virus-I infected individuals. The leukemia consists of an overabundance of activated T cells, which are characterized by the expression of CD25, or IL-2Ralpha, on their cell surface. Presently, there is not an accepted curative therapy for ATL. We developed an in vivo model of ATL in non-obese diabetic/severe combined immunodeficient (NOD/ SCID) mice by introducing cells from an ATL patient (MET-1) into the mice. The leukemic cells proliferated in these mice that lack functional T, B, and natural killer (NK) cells. The MET-1 leukemic cells could be monitored by measurements of both serum soluble Tac (IL-2Ralpha) and soluble human beta2-microglobulin (beta2mu) by ELISA. The disease progressed to death in the mice after approximately 4-6 weeks. The mice developed grossly enlarged spleens and a leukemia involving ATL cells that retained the phenotype and the T-cell receptor rearrangement and human T-cell lymphotrophic virus-I integration pattern of the patient's ATL leukemia cells. This model is of value for testing the efficacy of novel therapeutic agents for ATL. The administration of humanized anti-Tac (HAT), murine anti-Tac (MAT), and 7G7/B6, all of which target IL-2Ralpha, significantly delayed the progression of the leukemia and prolonged the survival of the tumor-bearing mice. In particular, HAT induced complete remissions in 4 of 19 mice and partial remissions in the remainder. It appears that the antibodies act by a mechanism that had not been anticipated. The prevailing view is that antibodies to the IL-2Ralpha receptor have their effective action by blocking the interaction of IL-2 with its growth factor receptor, thereby inducing cytokine deprivation apoptosis. However, although both HAT and MAT block the binding of IL-2 to IL-2Ralpha of the high affinity receptor, the 7G7/B6 monoclonal antibody binds to a different epitope on the IL-2Ralpha receptor, one that is not involved in IL-2 binding. This suggested that the antibodies provide an effective therapy by a mechanism other than induction of cytokine deprivation. In accord with this view, the MET-1 cells obtained from the spleens of leukemic mice did not produce IL-2, nor did they express IL-2 mRNA as assessed by reverse transcription-PCR. Another possible conventional mechanism of action involves complement-mediated killing. However, although MAT and 7G7/B6 fix rabbit complement, HAT does not do so. Furthermore, in the presence of NOD/SCID mouse serum, there was no complement-mediated lysis of MET-1 cells. In addition, the antibodies did not manifest antibody-dependent cellular cytotoxicity with NOD/SCID splenocytes that virtually lack NK cells as the effector cells as assessed in an in vitro chromium-release assay. However, in contrast to the efficacy of intact HAT, the F(ab')2 version of this antibody was not effective in prolonging the survival of mice injected with MET-1 ATL cells. In conclusion, in our murine model of ATL, monoclonal antibodies, HAT, MAT, and 7G7/B6, appear to delay progression of the leukemia by a mechanism of action that is different from the accepted mechanism of IL-2 deprivation leading to cell death. We consider two alternatives: the first, antibody-dependent cellular cytotoxicity mediated by FcRI- or FcRIII-expressing cells other than NK cells, such as monocytes or polymorphonuclear leukocytes. The second alternative we consider involves direct induction of apoptosis by the anti-IL-2R antibodies in vivo. It has been shown that the IL-2R is a critical element in the peripheral self-tolerance T-cell suicide mechanism involved in the phenomenon of activation-induced cell death.
Animals↗
Analysis of annatto (Bixa orellana) food coloring formulations. 2. Determination of aromatic hydrocarbon thermal degradation products by gas chromatography.
Twenty samples of commercial annatto formulations have been analyzed for m-xylene and toluene using ambient alkaline hydrolysis, followed by solvent extraction and capillary gas chromatography. Fifteen of the samples contained <5 mg/kg toluene, four samples contained between 5 and 10 mg/kg toluene, and one sample contained 12 mg/kg toluene. The amounts found of m-xylene were 200 mg/kg (one sample), 160 mg/kg (one sample), between 30 and 88 mg/kg (four samples), between 7 and 25 mg/kg (seven samples), and <5 mg/kg (seven samples). Bixin-in-oil formulations contained the highest m-xylene concentrations and also gave the largest increase in headspace m-xylene concentration when heated in closed systems. The results are evidence for the thermal degradation of annatto during source extraction and processing, resulting in contamination by internal generation of both bixin and norbixin types with aromatic hydrocarbons. Two samples of norbixin of known production history (i. e., thermal versus nonthermal processes) were analyzed specifically to identify possible differences in their degradation component profiles. They were found to differ significantly in m-xylene content, which is consistent with their respective production histories.
Bixaceae↗
Identification of SIV env-specific CTL in the jejunal mucosa in vaginally exposed, seronegative rhesus macaques (Macaca mulatta).
We previously reported major histocompatibility complex Class I-restricted cytotoxic T lymphocytes (CTL) in jejunal lamina propria (LP) of monkeys following colonic exposure to subinfectious SIV doses. Those monkeys with strong mucosal CTL responses specific for simian immunodeficiency virus (SIV) envelope (env) were protected from later colonic challenge with a heterologous pathogenic virus dose. Here, env-specific CTL were similarly induced in jejunal LP in five of eight non-progesterone treated macaques that were vaginally exposed to SIV, but not infected. Subsequent vaginal challenge following progesterone treatment produced systemic infection. The only two monkeys that had jejunal env-specific CTL detectable post-challenge developed significantly lower plasma virus loads, and had delayed disease progression. Either vaginal or colonic exposure to subinfectious SIV doses can induce CTL detectable in jejunal LP. The association of such CTL with protection or delayed disease upon challenge suggests that successful vaccine protection against SIV/HIV may require CTL responses in the mucosa.
Animals↗
Interdigitated deletion complexes on mouse chromosome 5 induced by irradiation of embryonic stem cells.
Chromosome deletions have several applications in the genetic analysis of complex organisms. They can be used as reagents in region-directed mutagenesis, for mapping of simple or complex traits, or to identify biological consequences of segmental haploidy, the latter being relevant to human contiguous gene syndromes and imprinting. We have generated three deletion complexes in ES (Embryonic Stem) cells that collectively span approximately 40 cM of proximal mouse chromosome 5. The deletion complexes were produced by irradiation of F(1) hybrid ES cells containing herpes simplex virus thymidine kinase genes (tk) integrated at the Dpp6, Hdh (Huntington disease locus), or Gabrb1 loci, followed by selection for tk-deficient clones. Deletions centered at the adjacent Hdh and Dpp6 loci ranged up to approximately 20 cM or more in length and overlapped in an interdigitated fashion. However, the interval between Hdh and Gabrb1 appeared to contain a locus haploinsufficient for ES cell viability, thereby preventing deletions of either complex from overlapping. In some cases, the deletions resolved the order of markers that were previously genetically inseparable. A subset of the ES cell-bearing deletions was injected into blastocysts to generate germline chimeras and establish lines of mice segregating the deletion chromosomes. At least 11 of the 26 lines injected were capable of producing germline chimeras. In general, those that failed to undergo germline transmission bore deletions larger than the germline-competent clones, suggesting that certain regions of chromosome 5 contain haploinsufficient developmental genes, and/or that overall embryonic viability is cumulatively decreased as more genes are rendered hemizygous. Mice bearing deletions presumably spanning the semidominant hammertoe locus (Hm) had no phenotype, suggesting that the classic allele is a dominant, gain-of-function mutation. Overlapping deletion complexes generated in the fashion described in this report will be useful as multipurpose genetic tools and in systematic functional mapping of the mouse genome.
Animals↗
Optimization of CT colonography technique: prospective trial in 180 patients.
PURPOSE: To assess the added benefits of prone positioning in addition to supine positioning and oral iodinated contrast medium for help in the detection of colonic polyps at computed tomographic (CT) colonography. MATERIALS AND METHODS: CT colonography was performed in prone and supine positions in 180 patients with polyps or risk factors for colonic neoplasia. Patients were randomly assigned to receive a standard bowel preparation or a standard preparation plus oral iodinated contrast medium. One radiologist interpreted supine images alone, and another analyzed supine and prone images. All patients subsequently underwent colonoscopy. RESULTS: At colonoscopy, 121 large (> or =1-cm-diameter) polyps and 142 smaller (0.5-0.9-cm) polyps were identified. Prone positioning resulted in increased sensitivity for identification of patients with large (> or =1-cm) polyps (increase from 70% to 85%, P: =.004) and of patients with polyps 0.5 cm or larger (increase from 75% to 88%, P: <.005), with no change in specificity. Use of oral contrast medium did not significantly improve polyp detection even in the subset of patients in whom colonic fluid attenuation was markedly increased. CONCLUSION: Acquisition and review of supine and prone CT colonographic images significantly improves the ability to identify patients with polyps 0.5 cm in diameter or larger. Administration of oral iodinated contrast medium does not significantly improve polyp detection.
Colon↗
Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa.
The identification of mucosal immune responses required for protection against sexual transmission of HIV is essential for the development of an efficacious vaccine. To gain a better understanding of these responses, we have characterized the immune responses in the lamina propria (LP) and epithelium of the jejunum, the mesenteric lymph nodes, and peripheral blood (PBMC) of 11 rhesus monkeys following colonic exposure to two molecular clones of SIV. Two monkeys had no signs of infection. Three monkeys became persistently infected. Transient infections, characterized by the sporadic detection of virus in the periphery and/or detection of SIV-specific immune responses in either the gut-associated tissues or PBMC, were induced in six of the monkeys. One persistently infected and three transiently infected monkeys had high levels of SIV env-specific MHC class I restricted CTL in the jejunal LP. Another transiently infected monkey had SIV-specific IgA secreting B cells in the LP. Three or six months postexposure, these animals and four naive controls were challenged intracolonically with the heterologous primary isolate, SIV/DeltaB670. All four monkeys with strong SIV env-specific MHC-restricted CTL in the LP were protected, whereas none of the naive controls or the remaining seven monkeys with little or no CTL in the LP were protected. These experiments provide the first direct evidence that transient mucosal infection can induce SIV-specific immunity that remains localized to the gut-associated tissues. Furthermore, a strong correlation between SIV env-specific MHC-restricted CTL in the LP and protection against colonic mucosal challenge was observed.
Animals↗
Mild tactile disturbance and a lhermitte phenomenon in a middle-aged man.
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Adult↗
Urinary monitoring of saccharin and acesulfame-K as biomarkers of exposure to these additives.
A method was developed to determine the levels of two intense sweeteners, saccharin and acesulfame-K, in human urine. Measurement of these two analytes in urine allowed an assessment to be made of dietary exposure to the sweeteners using intake/excretion curves. This paper describes an intake/excretion study in which 22 volunteers consumed known amounts of saccharin and acesulfame-K at five different levels ranging between 1.4 and 70 mg of saccharin (0.7-30% of the ADI for a 60 kg person) and 2.2-102 mg of acesulfame-K (0.4-19% of the ADI for a 60 kg person). Urine collections were then carried out by the volunteers for 24 h after each dose. The data obtained from this study were used to construct intake/excretion curves for both sweeteners. To test the methodology developed, 188 volunteers aged between 3 and 74 years were asked to carry out a 24-h urine collection whilst keeping a 48-h food diary. Comparison of the intake data obtained using the biomarker approach with the questionnaire-based results was generally good, although discrepancies due to the format and assessment of the questionnaire data were noticed.
Adolescent↗
Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog.
DMC1 is a meiosis-specific gene first discovered in yeast that encodes a protein with homology to RecA and may be component of recombination nodules. Yeast dmc1 mutants are defective in crossing over and synaptonemal complex (SC) formation, and arrest in late prophase of meiosis I. We have generated a null mutation in the Dmc1 gene in mice and show that homozygous mutant males and females are sterile with arrest of gametogenesis in the first meiotic prophase. Chromosomes in mutant spermatocytes fail to synapse, despite the formation of axial elements that are the precursor to the SC. The strong similarity of phenotypes in Dmc1-deficient mice and yeast suggests that meiotic mechanisms have been highly conserved through evolution.
Adenosine Triphosphatases↗
Quality of commercial shelf-stable soymilk products.
Four brands of shelf-stable soymilks (three lots each) were evaluated for their quality. All samples were tested for trypsin inhibitor activity, microbial load (coliforms, aerobic mesophiles, and psychrotrophs), solids content, pH, color, and viscosity. Storage stability at 5 degrees C of the opened original containers was evaluated by microbiological analyses. Physical properties were consistent among three lots of the same brand, but varied among brands. Trypsin inhibitor activity ranged from 3.43 to 10.35 mg/g dried soymilk. The pH values of the soymilks varied between 6.41 and 7.34. Viscosity was measured between 16.5 and 26.4 mPa. Solids content varied considerably among soymilks, from 6.88 to 12.37% (wt/vol). Freshly opened commercial soymilk contained fewer than one microorganism per ml in all microbial counts. During storage at 5 degrees C, microbial counts increased sharply after 2 to 3 weeks. A single microorganism predominated in each stored sample. Shelf life (defined as the time during which aerobic mesophile counts remained below 10(6) CFU/ml) varied from 3 to 4 weeks. The appearance and pH of soymilks remained unchanged even after 4 weeks of storage. Five types of microorganisms were found in stored soymilk samples; none of them produced acid.
Bacteria↗
The source of coagulase-negative staphylococci in the Endophthalmitis Vitrectomy Study. A comparison of eyelid and intraocular isolates using pulsed-field gel electrophoresis.
OBJECTIVE: To determine the species distribution of coagulase-negative staphylococci (CoNS) in patients with endophthalmitis and to ascertain whether the patient's own flora was a major source of postoperative endophthalmitis following cataract extraction. METHODS: In a 4-year multicenter prospective study, 524 bacterial isolates were submitted from 225 Endophthalmitis Vitrectomy Study patients. From the 524 isolates, 250 represented CoNS cultured from the anterior chamber, the vitreous, or both of the 225 patients. Where possible, paired isolates from an individual patient's eyelid and intraocular compartment(s) were studied by pulsed-field gel electrophoresis, an established molecular strain-typing technique. RESULTS: From all sites the most frequently isolated CoNS were Staphylococcus epidermidis (81.9%) and Staphylococcus lugdunensis (5.9%). Where analysis was possible, eyelid isolates were indistinguishable from intraocular isolates in 71 (67.7%) of 105 comparisons. Non-S epidermidis CoNS caused postoperative endophthalmitis in 5 patients. Four of the 5 had postoperative endophthalmitis caused by S lugdunensis and 1 by Staphylococcus haemolyticus. CONCLUSIONS: Coagulase-negative staphylococci from the patient's periocular skin flora play a significant role in causing intraocular infections, and non-S epidermidis CoNS play a small but significant role. These results reinforce the necessity to follow stringent surgical site preparation prior to eye surgery.
Anterior Chamber↗
Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study.
OBJECTIVE: To analyze the data for cultures and Gram stains prospectively collected by protocol in the Endophthalmitis Vitrectomy Study. DESIGN: Cultures of aqueous, undiluted vitreous, and (for patients who underwent vitrectomy) vitrectomy cassette fluid obtained from 420 patients were prepared on chocolate agar, in thioglycolate broth, and on Sabouraud dextrose agar; Gram stains of the aqueous and undiluted vitreous were made. Criteria were devised to distinguish true pathogens (confirmed positive cultures) from contaminants. SETTING: Private and university-based retina-vitreous practices and corresponding microbiology laboratories. RESULTS: Compared with the aqueous, undiluted vitreous produced a higher percentage of confirmed positive cultures and higher colony counts on chocolate agar and was more frequently the only source of a positive culture from the eye. Nevertheless, the aqueous and vitrectomy cassette fluid were the only source of a positive culture from the eye in 4.2% and 8.9% of eyes, respectively. The overall yields of chocolate agar and thioglycolate broth were similar. A positive Gram stain from the aqueous or undiluted vitreous was highly predictive of a positive culture from the eye, but a negative Gram stain had little predictive value for the culture result. The overall rate of laboratory-confirmed infection was not statistically significantly higher in the vitrectomy group than in the tap or biopsy group. CONCLUSIONS: The vitreous was a richer source of positive cultures and high colony counts than was the aqueous, either because it is more supportive of bacterial growth or because a somewhat larger inoculum of the vitreous than of aqueous could be obtained. The result of Gram stain should not determine the choice of antibiotic drugs in the treatment of endophthalmitis. Vitrectomy, with culture of the vitrectomy cassette fluid, did not produce significantly more positive cultures than tap or biopsy material, and the procedure should not be performed to improve the microbiological yield.
Aqueous Humor↗