Test and teach. Number eighty seven: hepatic angiomyolipoma.
Explore the source record for details and available documents.
Actins↗
Biomedical subjects
T Wilson
Publications and source records attributed to T Wilson.
Examination of the two-dimensional pupil function in coherent scanning microscopes using spherical particles.
The determination of the modulus of the pupil function in reflection acoustic and optical microscopy with the help of spherical particles is demonstrated. The theoretical examination shows that this method can give good results if the pupil function drops smoothly towards the edge. For a pupil with a sharp edge this technique can give the accurate pupil function only by imaging large spheres. The dependence of the accuracy of the method on the size of the spherical particle is analyzed. Numerical and experimental results obtained for the confocal scanning optical microscope and the scanning acoustic microscope are examined.
Acoustics↗
Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer.
Mutations in the human mismatch repair protein hMSH2 have been found to cosegregate with hereditary nonpolyposis colorectal cancer (HNPCC). Previous biochemical and physical studies have shown that hMSH2 forms specific mispair binding complexes with hMSH3 and hMSH6. We have further characterized these protein interactions by mapping the contact regions within the hMSH2-hMSH3 and the hMSH2-hMSH6 heterodimers. We demonstrate that there are at least two distinct interaction regions of hMSH2 with hMSH3 and hMSH2 with hMSH6. Interestingly, the interaction regions of hMSH2 with either hMSH3 or hMSH6 are identical and there is a coordinated linear orientation of these regions. We examined several missense alterations of hMSH2 found in HNPCC kindreds that are contained within the consensus interaction regions. None of these missense mutations displayed a defect in protein-protein interaction. These data support the notion that these HNPCC-associated mutations may affect some other function of the heterodimeric complexes than simply the static interaction of hMSH2 with hMSH3 or hMSH2 with hMSH6.
Binding Sites↗
Bioluminescence.
Bioluminescence has evolved independently many times; thus the responsible genes are unrelated in bacteria, unicellular algae, coelenterates, beetles, fishes, and others. Chemically, all involve exergonic reactions of molecular oxygen with different substrates (luciferins) and enzymes (luciferases), resulting in photons of visible light (approximately 50 kcal). In addition to the structure of luciferan, several factors determine the color of the emissions, such as the amino acid sequence of the luciferase (as in beetles, for example) or the presence of accessory proteins, notably GFP, discovered in coelenterates and now used as a reporter of gene expression and a cellular marker. The mechanisms used to control the intensity and kinetics of luminescence, often emitted as flashes, also vary. Bioluminescence is credited with the discovery of how some bacteria, luminous or not, sense their density and regulate specific genes by chemical communication, as in the fascinating example of symbiosis between luminous bacteria and squid.
Animals↗
[Role of gravidin, a phospholipase A2 inhibitor, in uterine contraction].
OBJECTIVE: What is the significance of gravidine, a phospholipase A2 inhibitor, in parturition? METHODS: Gravidine concentrations were measured in amniotic fluid obtained by transabdominal amniocentesis from women in labor at term and not in labor using a sensitive and specific ELISA. RESULTS: (1) Amniotic fluid gravidine concentrations were lower in the presence than in the absence of labor. (2) Gravidine concentrations in the amniotic fluid of the forebag were higher than in the amniotic fluid of the upper compartment. (3) There was a positive correlation between gestational age and amniotic fluid gravidine concentrations. (4) No such correlation could be demonstrated between cervical dilatation and amniotic fluid gravidine concentrations. CONCLUSION: These results suggest that gravidine may play a permissive role in the interplay with prostanoids in the mechanism of parturition.
Amniotic Fluid↗
Short-term reciprocal international academic exchange program.
Explore the source record for details and available documents.
Cultural Diversity↗
The pharmacological evaluations of some N-[pyridyl-(phenyl)carbonylamino]hydroxypropyl-1,2,3,6-tetrahy dropyridi nes as potential antiinflammatory agents.
A few novel tetrahydropyridines like benzoylamino-4-hydroxypropyl-1,2,3,6-tetrahydropyridine (THP), 7a (Fig. 1) which had been previously synthesized in our laboratory were tested for their antiinflammatory and hypo/hyperglycemic activities. The tetrahydropyridines contained a hydroxypropyl group in either the 4 or 5 position of the THP ring. Antiinflammatory activities using the Buxco paw edema assay on the male Sprague-Dawley rat model were carried out to investigate if a change in the position of the substituent would produce a corresponding change in the antiinflammatory activities. The two most active analogs that showed significant antiinflammatory activities were N-2-(pyridylcarbonylamino)-4-hydroxypropyl-1,2,3,6-tetrahydropyrid ine, 7b and N-2-(pyridyl-carbonlyamino)-5-hydroxypropyl-1,2,3,6-tetrahydropyri dine, 7f. The other six analogs 7a, 7c, 7d, 7e, 7g and 7h also exhibited antiinflammatory effects in a dose-dependent manner. Compounds 7f and 7h also showed significant hyperglycemic activities when compared with the control.
Animals↗
A comparison of the efficacies and duration of action of the angiotensin II receptor blockers telmisartan and amlodipine.
OBJECTIVES: To compare the antihypertensive effects and duration of action of the angiotensin II receptor antagonist, telmisartan, amlodipine, and placebo in patients with mild-to-moderate hypertension using both conventional clinic blood pressures and ambulatory blood pressure monitoring (ABPM). METHODS: After a 4-week single-blind, placebo run-in period, qualifying patients were randomly allocated in double-blind manner to be administered 40 mg telmisartan (n = 73; increased to 80 and 120 mg as necessary for patients whose diastolic blood pressure (DBP) remained > 90 mmHg); 5 mg amlodipine (n = 78; titrated to 5 mg and titrated to 10 mg for patients whose DBP remained > 90 mmHg); or placebo (n = 81). ABPM was performed at the end of the baseline period and again at the end of 12 weeks of double-blind treatment. RESULTS: Telmisartan and amlodipine treatments significantly decreased trough supine systolic blood pressure and DBP (P < 0.001, measured conventionally) to a similar extent (by 13.1/7.1 and 14.0/7.1 mmHg, respectively, at the end of 12 weeks' treatment) compared with placebo. Both drugs also significantly reduced 24 h mean systolic blood pressures and DBP compared with placebo (P < 0.0001), measured using ABPM, maintaining control of blood pressure throughout the dosing period. Reductions in DBP with telmisartan were greater (P < 0.05) than those with amlodipine during the night-time interval and the last 4 h of the dosing period. Twenty-four-hour mean ABPM DBP < 85 mmHg were observed in 71% of telmisartan patients and in 55% of patients administered amlodipine. In addition, heart rates in patients treated with telmisartan were lower than heart rates in those treated with amlodipine during the final 4 h of the dosing period (P = 0.0003) and during the morning interval (P = 0.005). Generally, both telmisartan and amlodipine were well tolerated, however, drug-related edema occurred significantly more commonly (P < 0.05) among the patients administered amlodipine than it did among patients administered either telmisartan or placebo. CONCLUSIONS: Clinic blood pressure measurements detected no difference between the antihypertensive effects and durations of action of telmisartan and amlodipine, both agents producing statistically significant reductions compared with placebo. ABPM measurements, however, revealed differences between the efficacies at specific time points within the dosing periods. These findings highlight the potential importance of the use of ABPM for evaluating and comparing efficacies of antihypertensive agents.
Journal Article↗
Felodipine extended release versus conventional diuretic therapy for the treatment of systolic hypertension in elderly patients. The National Trial Group.
OBJECTIVE: To compare 8 weeks of monotherapy using either felodipine extended release (ER) or a conventional diuretic therapy, triamterene/hydrochlorothiazide (HCTZ), in elderly patients with systolic hypertension. DESIGN: Prospective, randomized, single-blind screening, double-blind treatment, parallel group comparison. SETTING: Twenty-nine general and family practice sites across Canada. PARTICIPANTS: Men and post-menopausal women aged 60 to 85 years, with mild to moderate primary systolic hypertension (systolic blood pressure > 160 mm Hg or blood pressure > 140/ > 90 mm Hg). INTERVENTIONS: Daily doses of either felodipine ER (2.5 mg) or triamterene/HCTZ (25/12.5 mg) for 8 weeks. After the first 4 weeks, the patients who responded to the initial dosage (a reduction in systolic blood pressure of at least 15 mm Hg) or whose blood pressure was controlled on the dosage (systolic blood pressure < 140 mm Hg) continued to take the low dose. Among the others, the daily doses were doubled for the final 4 weeks. OUTCOME MEASURES: Systolic blood pressure before beginning treatment and at the end of the study, as well as adverse events and results of heart rate measurement, clinical chemistry tests, electrocardiograms and physical examinations before and after therapy. RESULTS: Sufficient data for analysis were obtained from 216 patients (86 men and 130 women). Mean seated blood pressure was reduced significantly in both the felodipine group (from 168/91 to 151/84 mm Hg) and the diuretic group (from 168/92 to 147/84 mm Hg). The difference in mean reductions in systolic blood pressure between the groups was 2.2 mm Hg (with a 95% confidence interval of-1.7 to 6.0 mm Hg), which was not significant. Clinical chemistry measurements taken before treatment and at the end of the study showed that more patients in the diuretic group developed abnormal values for blood urea nitrogen, uric acid and creatinine. Other changes were unremarkable. The incidence of adverse events was similar in both groups, but more patients in the felodipine group (9) than in the diuretic group (3) discontinued treatment owing to an adverse event. CONCLUSIONS: Felodipine ER (2.5 to 5 mg daily) is as effective in reducing systolic blood pressure as triamterene/HCTZ (25/12.5 mg to 50/25 mg daily). More patients discontinued felodipine treatment than triamterene/HCTZ treatment owing to adverse events. However, patients receiving triamterene/HCTZ tended to have abnormal levels in clinical chemistry tests; these should be monitored.
Aged↗
Mutator phenotype in Msh2-deficient murine embryonic fibroblasts.
Embryonic fibroblast cell lines were established from mice deficient, heterozygous, or proficient for Msh2, one of the three known DNA mismatch repair genes involved in hereditary nonpolyposis colon cancer (HNPCC). Cell lines were established by transfection of primary mouse embryo fibroblasts with E7 and Ras oncogenes or mutant p53. Spontaneously immortalized cells derived from the primary cultures were also studied. To determine whether these cells developed a mutator phenotype similar to that found in colon cancer cells deficient in mismatch repair, we measured mutation rates, microsatellite instability, and sensitivities to a range of DNA-damaging agents. The mutator phenotype detected in the E7 and Ras or mutant p53-immortalized Msh2-/- mouse cells was similar to that found in human mismatch repair-deficient colorectal carcinoma cell lines. Mutation rates to ouabain resistance were increased 8-12-fold relative to lines from Msh2+/+ mice, and microsatellite instability was detectable in 12-18% of subclones derived from the Msh2-/- line but was undetectable in subclones developed from the Msh2+/+ line. Furthermore, E7 and Ras or spontaneously immortalized Msh2-/- cells were significantly more resistant to the cytotoxic effects of 6-thioguanine relative to Msh2+/+ cells. In contrast, these lines showed various responses to UV light and cis-platinum, suggesting that mismatch repair deficiency was not the sole determinant for sensitivity to these DNA-damaging agents. Particular attention was paid to the properties of cells heterozygous for the Msh2 mutant gene, which would mimic the situation of an HNPCC carrier. However, our studies failed to reveal any properties of these cells that might provide a growth advantage or predispose them for the acquisition of further mutations. This observation is consistent with the model that inactivation of the wild-type Msh2 allele is a critical step for tumorigenesis in HNPCC patients.
Animals↗
Cell cycle regulation of the human DNA mismatch repair genes hMSH2, hMLH1, and hPMS2.
Hereditary nonpolyposis colorectal cancer is a cancer susceptibility syndrome that has been found to be caused by mutations in any of several genes involved in DNA mismatch repair, including hMSH2, hMLH1, or hPMS2. Recent reports have suggested that hMSH2 and hMLH1 have a role in the regulation of the cell cycle. To determine if these genes are cell cycle regulated, we examined their mRNA and protein levels throughout the cell cycle in IMR-90 normal human lung fibroblasts. We demonstrate that the levels of hMSH2 mRNA and protein do not change appreciably throughout the cell cycle. Although hMLH1 mRNA levels remained constant, there was a modest (approximately 50%) increase in its protein levels during late G1 and S phase. The levels of hPMS2 mRNA fluctuated (decreasing 50% in G1 and increasing 50% in S phase), whereas hPMS2 protein levels increased 50% in late G1 and S phase. Our data indicate that, at least in normal cells, the machinery responsible for the detection and repair of mismatched DNA bases is present throughout the cell cycle.
Adenosine Triphosphatases↗
MutS homologs in mammalian cells.
Alterations of the human mismatch repair genes have been linked to hereditary non-polyposis colon cancer (HNPCC) as well as to sporadic cancers that exhibit microsatellite instability. The human mismatch repair genes are highly conserved homologs of the Escherichia coli MutHLS system. Six MutS homologs have been identified in Saccharomyces cerevisiae and four MutS homologs have been identified in human cells. At least three of these eukaryotic MutS homologs are involved in the recognition/binding of mispaired nucleotides and nucleotide lesions. MSH2 plays a fundamental role in mispair recognition whereas MSH3 and MSH6 appear to modify the specificity of this recognition. The redundant functions of MSH3 and MSH6 explain the greater prevalence of hmsh2 mutations in HNPCC families.
Adenosine Triphosphatases↗
Production of avirulent Mycobacterium bovis strains by illegitimate recombination with deoxyribonucleic acid fragments containing an interrupted ahpC gene.
SETTING: Molecular genetic techniques have been used to elucidate virulence determinants and to produce vaccines for many bacterial pathogens but reliable techniques for slow-growing mycobacteria have not been available. OBJECTIVE: Oxidative defence genes including ahpC are involved in isoniazid resistance of strains of the Mycobacterium tuberculosis complex. The aim of this study was to inactivate ahpC by allelic exchange and to screen the expected background of illegitimate recombinants for their inability to grow in minimal medium (auxotrophy). DESIGN: M. bovis ATCC35723 was electroporated with linear fragments of deoxyribonucleic acid (DNA) containing an ahpC gene interrupted by a kanamycin resistance gene. Kanamycin-resistant colonies were screened for allelic exchange and auxotrophy. RESULTS: Southern blotting of DNA from kanamycin-resistant colonies revealed that no allelic exchange had occurred. Four of these recombinants were auxotrophs and subsequently were found to be avirulent in guinea pigs. The fragment insertion sites in the chromosome of each auxotroph were determined by DNA sequencing. In three cases, large chromosomal deletions had occurred. CONCLUSION: The M. bovis ahpC gene was not inactivated by this linear fragment approach but illegitimate insertion of such a fragment can be successfully used to produce avirulent auxotrophs which have potential for vaccine development.
Alleles↗
Female embryonic lethality in mice nullizygous for both Msh2 and p53.
The mutator hypothesis of tumorigenesis suggests that loss of chromosomal stability or maintenance functions results in elevated mutation rates, leading to the accumulation of the numerous mutations required for multistep carcinogenesis. The human DNA mismatch repair (MMR) genes are highly conserved homologues of the Escherichia coli MutHLS system, which contribute to genomic stability by surveillance and repair of replication misincorporation errors and exogenous DNA damage. Mutations in one of these MMR genes, hMSH2, account for about half of all cases of genetically linked hereditary non-polyposis colorectal cancer. Loss of function of p53 has also been proposed to increase cellular hypermutability, thereby accelerating carcinogenesis, although a clear role for p53 in genomic instability remains controversial. p53 is mutated frequently in a wide range of human cancers, including colonic tumours. Both Msh2- and p53-targeted knockout mice are viable and susceptible to cancer. Here we demonstrate that combined Msh2 and p53 ablation (Msh2-/-p53-/-) results in developmental arrest of all female embryos at 9.5 days. In contrast, male Msh2-/-p53-/- mice are viable, but succumb to tumours significantly earlier (t1-2 is 73 days) than either Msh2-/- or p53-/- littermates. Furthermore, the frequency of microsatellite instability (MSI) in tumours from Msh2-/-p53-/- mice is not significantly different than in Msh2-/- mice. Synergism in tumorigenesis and independent segregation of the MSI phenotype suggest that Msh2 and p53 are not genetically epistatic.
Animals↗
STDs, HIV, and crack cocaine: a review.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
RU486 inhibits synthesis of an endogenous inhibitor of cell arachidonate release from choriodecidua tissue.
Gravidin is a potent phospholipase A2 inhibitor that may contribute to the maintenance of human pregnancy. The aims of this study were to determine firstly, the site of gravidin synthesis within placental membranes and secondly, whether the antiprogestin compound, RU486, regulates synthesis. Membrane explants were taken from placentae, dissected and cultured in the presence of RU486, progesterone or inhibitors of DNA or protein synthesis and gravidin production was measured by a specific enzyme-linked immunosorbent assay. Production of gravidin was consistently greatest from choriodecidua compared with amnion and decidua. The antibiotics, cycloheximide and actinomycin D inhibited production of gravidin. The progesterone receptor antagonist RU486 at 10(-8) and 10(-7) M reduced gravidin production to 55 and 39% of the control value in membranes cultured after and before the onset of labour respectively. Progesterone at 10(-6) M stimulated gravidin production by 47% after the onset of labour. The increase in gravidin production was correlated with progesterone concentration (r = 0.47, F = 6.38, P = 0.019) in labour tissue. We conclude that the data are consistent with the hypothesis that gravidin production may be partially regulated by progesterone.
Adult↗
Capsular chondroid metaplasia following total hip arthroplasty.
Explore the source record for details and available documents.
Cartilage↗
Aerosol delivery of liposome-encapsulated ciprofloxacin: aerosol characterization and efficacy against Francisella tularensis infection in mice.
The aerosol delivery of liposome-encapsulated ciprofloxacin by using 12 commercially available jet nebulizers was evaluated in this study. Aerosol particles containing liposome-encapsulated ciprofloxacin generated by the nebulizers were analyzed with a laser aerodynamic particle sizer. Mean mass aerodynamic diameters (MMADs) and geometric standard deviations (GSDs) were determined, and the drug contents of the sampling filters from each run onto which aerosolized liposome-encapsulated ciprofloxacin had been deposited were analyzed spectrophotometrically. The aerosol particles of liposome-encapsulated ciprofloxacin generated by these nebulizers ranged from 1.94 to 3.5 microm, with GSDs ranging from 1.51 to 1.84 microm. The drug contents of the sampling filters exposed for 1 min to aerosolized liposome-encapsulated ciprofloxacin range from 12.7 to 40.5 microg/ml (0.06 to 0.2 mg/filter). By using the nebulizer selected on the basis of most desirable MMADs, particle counts, and drug deposition, aerosolized liposome-encapsulated ciprofloxacin was used for the treatment of mice infected with 10 times the 50% lethal dose of Francisella tularensis. All mice treated with aerosolized liposome-encapsulated ciprofloxacin survived the infection, while all ciprofloxacin-treated or untreated control mice succumbed to the infection (P < 0.001). These results suggest that aerosol delivery of liposome-encapsulated ciprofloxacin to the lower respiratory tract is feasible and that it may provide an effective therapy for the treatment of respiratory tract infections.
Administration, Inhalation↗