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Biomedical subjects

G Marshall

Publications and source records attributed to G Marshall.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prevalence of the APC E1317Q variant in colorectal cancer patients.

The notion that some common variants of APC might confer an increased colorectal tumour risk is supported by studies of the I1307K polymorphism. Recently it has been proposed that the E1317Q variant is also associated with an increased risk. We have studied the prevalence of E1317Q in 364 colorectal cancer patients and in 290 controls. Two patients were shown to possess E1317Q. Neither had a family history of colorectal cancer or co-existent adenomatous polyps. Two controls also carried E1317Q. This finding suggests that E1317Q is unlikely to be associated with anything more than a moderate increase in risk of colorectal cancer.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype.

Inhibitory neurotransmission in the brain is largely mediated by GABA(A) receptors. Potentiation of GABA receptor activation through an allosteric benzodiazepine (BZ) site produces the sedative, anxiolytic, muscle relaxant, anticonvulsant and cognition-impairing effects of clinically used BZs such as diazepam. We created genetically modified mice (alpha1 H101R) with a diazepam-insensitive alpha1 subtype and a selective BZ site ligand, L-838,417, to explore GABA(A) receptor subtypes mediating specific physiological effects. These two complimentary approaches revealed that the alpha1 subtype mediated the sedative, but not the anxiolytic effects of benzodiazepines. This finding suggests ways to improve anxiolytics and to develop drugs for other neurological disorders based on their specificity for GABA(A) receptor subtypes in distinct neuronal circuits.

Allosteric Site↗
PubMed2000

A clinical comparison of pain perception to the Wand and a traditional syringe.

OBJECTIVES: This study compared the pain response of a group of 40 volunteers to the Wand with the response to syringe injections. STUDY DESIGN: Of 240 total injections given, 120 were with the Wand system, and 120 were with the traditional aspirating syringe. Three injections were evaluated: injections to the middle superior alveolar (MSA) of the maxillary right first premolar and the maxillary left first premolar; palatal injections of the maxillary right first premolar and the maxillary left first premolar; and inferior alveolar nerve injection (IAN) of both the right and the left sides. Each volunteer received 6 injections, 3 on one side with the Wand and 3 on the opposite side with the syringe (control). All injections were given by the primary investigator without the use of a topical anesthetic. Pain perception levels were recorded with a 4-point visual analog scale: no pain, mild pain, moderate pain, and severe pain. The results were evaluated statistically by using an unpaired t test. RESULTS: The results showed injections with the syringe were statistically more painful than injections with the Wand in 4 of 18 evaluations: MSA of the maxillary left first premolar, female volunteers responses to MSA of the maxillary left first premolar, IAN left side injections, and male responses to IAN left injections (P =.01, P =.05, P =.05 and P =.05, respectively). CONCLUSIONS: The Wand generally seemed to provide less painful injections; however, the mean ratings of pain were mostly mild pain for both injections. Therefore, the clinical significance of the results should be interpreted with caution. The operator technique and tactile skill in syringe injections and site of injection (right or left) could be important factors that were not evaluated in this study.

Adult↗
PubMed2000

Lung cancer and arsenic concentrations in drinking water in Chile.

Cities in northern Chile had arsenic concentrations of 860 microg/liter in drinking water in the period 1958-1970. Concentrations have since been reduced to 40 microg/liter. We investigated the relation between lung cancer and arsenic in drinking water in northern Chile in a case-control study involving patients diagnosed with lung cancer between 1994 and 1996 and frequency-matched hospital controls. The study identified 152 lung cancer cases and 419 controls. Participants were interviewed regarding drinking water sources, cigarette smoking, and other variables. Logistic regression analysis revealed a clear trend in lung cancer odds ratios and 95% confidence intervals (CIs) with increasing concentration of arsenic in drinking water, as follows: 1, 1.6 (95% CI = 0.5-5.3), 3.9 (95% CI = 1.2-12.3), 5.2 (95% CI = 2.3-11.7), and 8.9 (95% CI = 4.0-19.6), for arsenic concentrations ranging from less than 10 microg/liter to a 65-year average concentration of 200-400 microg/liter. There was evidence of synergy between cigarette smoking and ingestion of arsenic in drinking water; the odds ratio for lung cancer was 32.0 (95% CI = 7.2-198.0) among smokers exposed to more than 200 microg/liter of arsenic in drinking water (lifetime average) compared with nonsmokers exposed to less than 50 microg/liter. This study provides strong evidence that ingestion of inorganic arsenic is associated with human lung cancer.

Adult↗
PubMed2000

In vitro activities of methylenecyclopropane analogues of nucleosides and their phosphoralaninate prodrugs against cytomegalovirus and other herpesvirus infections.

Human cytomegalovirus (HCMV) infection does not generally cause problems in the immunocompetent adult but can result in severe clinical disease in the fetus, neonate, and immunocompromised host. Ganciclovir (GCV), the agent currently used to treat most HCMV infections, has resulted in much therapeutic success; however, efficacy remains suboptimal. Therefore, there is still a need to develop new compounds for use against HCMV infections. In the present study, several Z- and E-series methylenecyclopropane analogues and their phosphoroalaninate prodrugs were tested initially for activity against HCMV, strain AD169, and murine cytomegalovirus (MCMV) in vitro. Many were found to exhibit efficacy comparable to that of GCV against HCMV in plaque assays and were active against MCMV as well. The compounds were also tested for efficacy against herpes simplex virus types 1 and 2, varicella-zoster virus, and Epstein-Barr virus, and some had levels of activity that were comparable to that of acyclovir. In addition, the compounds synguanol (QYL-438) and 2-amino-6-cyclopropylamino analogue (QYL-769) were chosen for further evaluation and were found to be effective against additional laboratory and clinical isolates of HCMV and GCV-resistant isolates. QYL-438 and QYL-769 were found to be nontoxic in human and mouse fibroblasts and were considerably less toxic than GCV in granulocyte macrophage CFUs and erythroid burst-forming units. These results provide evidence for the high activity of some of these methylenecyclopropane analogues against various herpesviruses, particularly HCMV, in tissue culture and suggest that further evaluation is warranted to determine their potential for use in future clinical studies.

Adult↗
PubMed2000

Sub-ice foraging behavior of emperor penguins.

Emperor penguins (Aptenodytes forsteri) were equipped with a remote underwater video camera, the Crittercam, to evaluate sub-ice foraging behavior while the birds dived from an isolated dive hole. Three birds dived and foraged successfully for 1 h periods after being trained to wear and to dive with a harness for camera attachment. Video and depth profile recordings revealed that emperor penguins travel at shallow depths (<50 m), ascend to the undersurface of the ice to feed on fish, and descend back to depth to return to the exit hole. Although the mean durations of dives of individual birds with the Crittercam were 21-35 % shorter than the diving durations of these same birds without the camera, the dive profiles in both situations were similar, thus demonstrating a similar foraging strategy in birds diving without the camera. Despite shorter diving durations with the camera, the penguins were still successful at prey capture in 80 % of 91 dives greater than 1 min in duration. Prey included the sub-ice fish Pagothenia borchgrevinki. Hunting ascents (from depth to within 5 m of the surface) occurred in 85 % of dives, ranged from zero to three per dive, and were associated with successful prey capture in 77 % of 128 ascents. Occasionally, several fish were captured during a single ascent. These observations and this application of video technology create a model for further physiological and behavioral studies of foraging, and also emphasize the potential importance of shallow dives as sources of food intake for emperor penguins during foraging trips to sea.

Animals↗
PubMed2000

Ancient atomists.

Explore the source record for details and available documents.

Chemistry, Physical↗
PubMed2000

[Academic performance of medical students: a predictable result?].

BACKGROUND: Traditionally, medical schools demand their students a high dedication in time, responsibility and integrity. AIM: To assess the predictive capacity of several specific variables, on the academic performance of medical students. MATERIAL AND METHODS: All students who entered during 1984-1995 period were studied. The academic performance was assessed using two indices: an overall evaluation of successfulness as determined by the approval rate in different courses and grade-point average obtained during the first three years at the Medical School. The variables used to predict academic performance were year of enrollment, high school grades, university admission test scores, biomedical and demographic characteristics. All these were measured at the time when the student was enrolled. RESULTS: Eight hundred and eight students were studied at the end of the third year. The most important predictive variables selected for both performance indices were: high school grades, admission biology test scores, place were high school studies were done, and previous university studies. In addition verbal and mathematics admission academic performance tests scores were selected for grade-point average index. Although, the overall admission score and high school academic performance were significantly associated with the two outcomes, they were not selected in the final models. CONCLUSIONS: The best predictors of an optimal academic performance in these medical students were high school grades, admission biology test scores, residing in Metropolitan Santiago and previous university studies.

Adolescent↗
PubMed2000

[Number of physicians in Chile: current and prospective estimate, and an international comparison].

BACKGROUND: In the last decades, the number of Universities with medical schools has increased dramatically in our country. AIM: To introduce a conceptual model to estimate the number of physicians that are incorporated to the profession in Chile every year as well as the cumulative number of active physicians in specific time frame. To provide information about the number of available physicians in the country and compare it with the international context. MATERIAL AND METHODS: This model includes information about the number of students that are admitted in all medical schools of the country, the dropout rate, the number of immigrant physicians from other countries, and the cumulative number of active physicians in the previous period. RESULTS: There is an increased number of new medical students starting in 1994 that will produce, starting in 2001, a significant increased in the number of new physicians graduated from Chilean Universities. Meanwhile the increased number of new physicians in recent years is mainly explained by a significant increase in immigrant physicians. The number of active physicians estimated by the year 2000 is 18,549 and this number will be 25,704 by the year 2007. With these estimated numbers, we introduce a qualitative model that allowed us to compare the current number of active physicians in Chile with other countries, especially those with a comparable degree of development. This model uses first The Human Development Index and later the per capita income of different countries adjusted by purchasing power in USA. According to these calculations, Chile has a lower number of physicians than similar countries, and this difference will persist, even after the significant increase in the new physicians expected for the new future. CONCLUSIONS: Chile continues to have a lower number of physicians than countries with similar human development indices (Rev Méd Chile 2000; 128: 1167-76).

Chile↗
PubMed1999

An analysis of canal centering using mechanical instrumentation techniques.

The purpose of this study was to compare canal transportation in moderately curved canals using mechanical instrumentation systems. Mesial roots of mandibular first or second molars were mounted in resin using a modified Bramante muffle system and divided into four groups. The roots were cross-sectioned 2 mm from the working length and at the height of root curvature. Tracings of the canal were made from preinstrumentation slides of the cross-sections. The canals were prepared using ProFile Series 29 rotary instruments, Quantec 2000 rotary instruments, Flex-R files in the Endo Gripper contra-angle handpiece, and Shaping Hedstrom files in the M4 contra-angle handpiece. Tracings of the prepared canals were made onto the originals from postinstrumentation slides. A canal centering ratio was calculated along the line of maximum transportation. Quantec 2000 rotary instruments yielded significantly greater transportation at the apical level when compared with the Profile Series 29 system. There were no other significant differences in transportation at either level. There were no differences in the direction of canal transportation between instrument systems, and the direction of canal transportation was not related to the direction of canal curvature. Canal preparation time was shortest with Profile Series 29 system followed by Flex-R files in the Endo Gripper, Quantec 2000, and Shaping Hedstrom files in the M4.

Dental High-Speed Equipment↗
PubMed1999

Alterations in HIV expression in AIDS patients with psoriasis or pruritus treated with phototherapy.

BACKGROUND: Ultraviolet light (UVL) upregulates HIV transcription in vitro and in transgenic mice. AIDS-associated psoriasis and pruritus respond to phototherapy. OBJECTIVE: Our goal was to determine the effect of phototherapy on viral load and immunologic parameters in HIV-positive patients. METHODS: T cell subsets, p24, plasma cytokines, serum or plasma HIV-RNA, dosage, and antivirals were assessed in HIV-positive patients and negative controls receiving 6 weeks of phototherapy with UVB and in untreated controls. RESULTS: Phototherapy improved skin conditions without significantly affecting T cell numbers. Plasma p24 increased 2-fold (P = .055) and HIV-RNA levels 4-fold (P = .022) 6 weeks from baseline in patients who entered the trial before March 1995. Later patients who were mostly receiving combination antiviral therapy showed a 4-fold reduction in serum HIV-RNA (P = .012) at 2 weeks. The effect of UVB on viral load at 6 weeks was dependent on the baseline level (P = .006). IL-10 increased and was inversely related to HIV-RNA levels (P = .0267). CONCLUSION: Phototherapy is associated with HIV load alterations, depending on patients' initial HIV-RNA, antiviral therapy, skin type, and UVL dosage.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Genetic characterization of heather (Calluna vulgaris (L.) hull) subject to different management regimes across great britain

Heather plants were collected from 34 populations in Great Britain, which differed according to their geographical location and associated management histories. Comparisons of differential grazing regimes were made across 10 sites in the first year of study, whereas the influence of differential burning regimes was considered at four sites during the second year. The extent of genetic variation, both within and between the selected heather populations, was examined using polymerase chain reaction (PCR)-based DNA fingerprinting methodologies. Initially, high genetic variation within populations obscured differences between populations. Heather stands that were geographically close proved to be genetically similar. Site latitude and longitude were strongly associated with genetic differences between heather populations; however, a range of grazing and burning management treatments had no consistent effect upon genetic diversity. The results represent the first national survey of genetic variation at the DNA level within UK populations of this important heathland species. They provided insights into the genetic structure of heather-dominated heathlands, revealing a lack of clonal dominance within populations, but rather a much more varied genetic makeup than might have been expected given the species' ability to propagate vegetatively. The processes that influence genetic diversity in heather populations are discussed, and the potential role of molecular techniques in heathland conservation is considered.

Journal Article↗
PubMed1999

Social mobility and personal satisfaction: evidence from ten countries.

This paper examines survey data relating class mobility to satisfaction and dissatisfaction with seven different domains of everyday life among nationally representative samples of men and women living in ten industrialized nations. The evidence is set against competing pessimistic and optimistic accounts of the mobility experience found in earlier literature. Results show that individuals who move from working-class origins to middle-class destinations are no more likely to be systematically satisfied or dissatisfied with life than are the socially immobile or even those downwardly mobile from advantaged backgrounds into the working class. Indeed, in all nations, the overall association between class experience and satisfaction with life is both weak and uneven across the different life-domains. The study also serves to illustrate an important principle of research methodology more generally.

Analysis of Variance↗
PubMed1999

Residues in transmembrane domains I and II determine gamma-aminobutyric acid type AA receptor subtype-selective antagonism by furosemide.

GABAA receptors in cerebellar granule cells are unique in expressing a subtype containing the alpha6 subunit. This receptor subtype has high affinity for GABA and produces a degree of tonic inhibition on cerebellar granule cells, modulating the firing of these cells via spillover of GABA from GABAergic synapses. This receptor subtype also has selective affinity for the diuretic furosemide over receptors containing other alpha-subunits. Furosemide exhibits approximately 100-fold selectivity for alpha6-containing receptors over alpha1-containing receptors. By making alpha1/alpha6 chimeras we have identified a transmembrane region (209-279) responsible for the high furosemide sensitivity of alpha6beta3gamma2s receptors. Within the alpha1 transmembrane region, a single amino acid was identified that when mutated from threonine to isoleucine, increased furosemide sensitivity by 20-fold. We demonstrate the beta-subunit selectivity of furosemide to be due to asparagine 265 in the beta2 and beta3 transmembrane-domain II similar to that observed with potentiation by the anticonvulsant loreclezole. We also show that Ile in transmembrane-domain I accounts for the increased GABA sensitivity observed at alpha6beta3gamma2s compared with alpha1beta3gamma2s receptors, but did not affect direct activation by pentobarbital or potentiation by the benzodiazepine flunitrazepam. Location of these residues within transmembrane domains leads to speculation that they may be involved in the channel-gating mechanism conferring increased receptor activation by GABA, in addition to conferring furosemide sensitivity.

Amino Acid Sequence↗
PubMed1999

Pharmacokinetics and inflammatory-fluid penetration of moxifloxacin following oral or intravenous administration.

A single 400-mg oral or intravenous (i.v.) dose of moxifloxacin was given to each of eight healthy male volunteers, and 6 weeks later the dose was administered by the other route. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured over the subsequent 24 h. The mean maximum concentrations observed in plasma were 4.98 microg/ml after oral dosing and 5.09 microg/ml after i.v. dosing. The mean maximum concentrations attained in the inflammatory fluid were 2.62 and 3.23 microg/ml, respectively. The mean elimination half-lives from plasma were 8.32 and 8.17 h, respectively. The overall penetration into the inflammatory fluid was 103.4 and 104.2%. Over 24 h 15% of the drug was recovered in the urine when administered by either route.

Administration, Oral↗
PubMed1999

Tear lipocalins: potential lipid scavengers for the corneal surface.

PURPOSE: To investigate the dynamic effect of tear lipocalins (TLs), the major lipid-binding protein in tears, at aqueous-cornea and lipid-aqueous interfaces, and their potential contribution to surface tension in the tear film. METHODS: Human apo- and holo-TLs were applied to the aqueous subphase in a Langmuir trough, and changes in surface pressure were measured. Changes in the contact angle of tear components were observed on Teflon and ferric-stearate-treated surfaces. A nitroxide-labeled derivative of lauric acid and a fluorescence-labeled derivative of palmitic acid were used to monitor the dynamic interaction of lipid removed from a hydrophobic surface by the major tear components in solution. RESULTS: TLs increase the surface pressure at the aqueous-air interface by penetrating, spreading, and rearranging on the surface. Apo-TLs show a longer diffusion-dependent induction time than holo-TLs due to more extensive oligomerization of the apoprotein. Kinetic analysis of relaxation time suggests that apo-TLs have more rapid surface penetration and rearrangement than holo-TLs, indicative of a more flexible structure in apo-TLs. TLs reduce the contact angle of solutions on lipid films, a property that is greater with TLs than other tear proteins. TLs, unlike lysozyme and lactoferrin, remove labeled lipids from hydrophobic surfaces and deliver them into solution. CONCLUSIONS: TLs are potent lipid-binding proteins that increase the surface pressure of aqueous solutions while scavenging lipids from hydrophobic surfaces and delivering them to the aqueous phase of tears. These data suggest important functional roles for TLs in maintaining the integrity of the tear film.

Carrier Proteins↗
PubMed1998

Genetic epidemiology of cholesterol cholelithiasis among Chilean Hispanics, Amerindians, and Maoris.

BACKGROUND & AIMS: The etiology of cholesterol gallstones is multifactorial, with interactions of genes and the environment. The hypothesis that aborigine cholesterol lithogenic genes are widely spread among Chileans, a population with a high prevalence of gallstones, was tested. METHODS: Medical history and anthropometric measurements were obtained and abdominal ultrasonography was performed in 182 Mapuche Indians, 225 Maoris of Easter Island, and 1584 Hispanics. Blood groups, DNA, lipids, and glucose were analyzed. The Amerindian Admixture Index and mitochondrial DNA (mtDNA) assessed the ethnicity and degree of racial admixture. RESULTS: Amerindian Admixture Index was 0.8 in Mapuches and 0.4 in Hispanics. All Mapuches, 88% of Hispanics, but none of Maoris had Amerindian mtDNA haplotypes. Age- and sex-adjusted global prevalence of gallstone disease was higher in Mapuches (35%) than in Hispanics (27%) and Maoris (21%). Compared with Hispanics, the youngest group of Mapuches had the greatest corrected risk of gallstones: odds ratios of 6.0 in women and 2.3 in men. In contrast, the gallstone risk in Maoris was lower compared with Hispanics: odds ratios of 0.6 for women and 0.5 for men. CONCLUSIONS: Cholesterol lithogenic genes appear widely spread among Chilean Indians and Hispanics. They could determine the early formation of gallstones and explain the high prevalence of gallbladder diseases among some South American populations.

Adult↗