Cover slip sizes for routine cervical screening.
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Female↗
Biomedical subjects
J Sutton
Publications and source records attributed to J Sutton.
How collaboration = quality in maintaining POCT (point-of-care testing) and phlebotomy programs.
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Clinical Competence↗
The role of cytotoxic T-cells in HIV infection.
HIV-specific cytotoxic T lymphocytes (CTL) are believed to play a major role in controlling virus levels through the asymptomatic period of HIV infection. For the rational design of an HIV vaccine, we need to know whether protective immunity can ever develop following HIV exposure in people who remain uninfected. We have detected HIV-specific CTL in 5/6 repeatedly exposed, persistently seronegative female sex-workers in The Gambia. Their CTL, repeatedly detected over two years, recognise epitopes presented by HLA-B35 which are cross-reactive between HIV-1 & HIV-2, suggesting they could have been primed first by HIV-2 exposure and subsequently boosted by exposure to HIV-1. Using previously identified clade B HIV-1 epitope peptides, we have now detected HIV-specific CTL in 6/15 highly exposed and apparently HIV-resistant Kenyan prostitutes, predominantly towards epitopes highly conserved between B and the Kenyan A & D clades of HIV-1. This CTL activity towards conserved virus epitopes may represent protective immunity to HIV generated in response to repeated exposure, and prophylactic HIV vaccines should aim to generate similar CTL responses.
Cells, Cultured↗
Bladder calculi in dogs and cats.
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Animals↗
PLAB, a novel placental bone morphogenetic protein.
Bone morphogenetic proteins (BMP) constitute a sub-group of the large transforming growth factor-beta (TGF-beta) family. They play important roles in the embryonic development of multiple structures and in adult bone modeling. We have recently isolated a novel member of the BMP family from placenta, termed PLAB. PLAB is expressed highly in placenta, but can be found upon stringent analysis in low levels in most other tissues. At the amino acid level, PLAB is most closely related to BMP-8/OP-2, another member of the BMP family. Like TGF-beta, PLAB inhibits the proliferation of primitive hematopoietic progenitors. The high expression of PLAB by placenta raises the possibility that it may be a mediator of placental control of embryonic development.
3T3 Cells↗
Comparison of right ventricular outflow tract and apical lead permanent pacing on cardiac output.
Cardiac output was measured in 89 patients using transthoracic continuous-wave echo Doppler comparing right ventricular outflow tract pacing with the right ventricular apex at the time of permanent pacemaker implantation. Overall, cardiac output improved 18.8% (p <0.0001) and cardiac index 21.0% (p <0.0001) with outflow tract placement; patients with a lower baseline cardiac index had a greater percent improvement with outflow tract placement.
Adult↗
Blood metabolite and catecholamine responses to prolonged exercise following either acute plasma volume expansion or short-term training.
To determine the effect of acute plasma volume (PV) expansion on substrate utilization, blood metabolites and catecholamines to prolonged, moderate intensity cycle exercise, eight untrained men mean maximal oxygen uptake VO2max 4.10 (SEM 0.32) 1.min-1 were infused (10 ml.kg-1) with a 6% dextran (DEX) solution. These responses were also compared to those elicited using a short-term training (TR) protocol involving cycling for 90 to 120 min.day-1 at 60% VO2max for 3 consecutive days. In general DEX, which resulted in a calculated expansion of PV by 23.9% was without effect in modifying exercise oxygen uptake or the reduction in the respiratory exchange ratio (R) observed during prolonged exercise. In addition, the concentrations of blood glucose, glycerol, alanine and serum free fatty acids, although altered (P < 0.05) by exercise, were not altered by DEX. Blood lactate concentration was only higher (P < 0.05) at 30 min of exercise during DEX compared to the control. With the exception of blood lactate concentration, which was reduced (P < 0.05), TR did not change R or the concentrations of other blood metabolites. The concentrations of nonadrenaline and adrenaline, were depressed (P < 0.05) by DEX and TR at 60 and 90 min of exercise. These results would suggest that mechanisms as yet undefined can compensate for the estimated 10% reduction in arterial oxygen content mediated by acute PV expansion and enable prolonged exercise to be performed without adjustments in substrate selection and substrate mobilization.
Adult↗
Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice.
1. The role of alpha2-adrenoceptor (AR) subtypes in the modulation of acute nociception, motor behaviour and body temperature, has been investigated by determining the activity of the alpha2AR selective agonist dexmedetomidine (Dex) in mice devoid of individual alpha2AR subtypes through either a point (alpha2A) or null (alpha2B/alpha2C) mutation ('knock-out'). 2. In a rodent model of acute thermal nociception, the mouse tail immersion test, Dex, in wild type (WT) control animals, produced a dose-dependent increase in the threshold for tail withdrawal from a 52 degrees C water bath with mean ED50 values of 99.9+/-14.5 (alpha2A), 94.6+/-17.8 (alpha2B) and 116.0/-17.1 (alpha2C) microg kg(-1), i.p. 3. In comparison to the WT controls, Dex (100-1000 microg kg(-1), i.p.), was completely ineffective as an antinociceptive agent in the tail immersion test in the alpha2A AR D79N mutant animals. Conversely, in the alpha2B AR and alpha2C AR knock-outs, Dex produced a dose-dependent antinociceptive effect that was not significantly different from that observed in WT controls, with ED50 values of 85.9+/-15.0 (P>0.05 vs WT control) and 226.0+/-62.7 (P>0.05 vs WT control) microg kg(-1) i.p., respectively. 4. Dex (10-300 microg kg(-1), i.p.) produced a dose-dependent reduction in spontaneous locomotor activity in the alpha2A, alpha2B and alpha2C AR WT control animals with ED50 values of 30.1+/-9.0, 23.5+/-7.1 and 32.3+/-4.6 microg kg(-1), i.p., respectively. Again, Dex (100-1000 microg kg(-1), i.p.) was ineffective at modulating motor behaviour in the alpha2A AR D79N mutants. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in spontaneous locomotor activity with ED50 values of 29.1+/-6.4 (P>0.05 vs WT control) and 57.5+/-11.3 (P>0.05 vs WT control) microg kg(-1), respectively. 5. Dex was also found to produce a dose-dependent reduction in body temperature in the alpha2A, alpha2B and alpha2C AR WT control mice with ED50 values of 60.6+/-11.0, 16.2+/-2.5 and 47.2+/-9.1 microg kg(-1), i.p., respectively. In the alpha2A AR D79N mutants, Dex had no effect on body temperature at a dose (100 microg kg(-1), i.p.) that produced a significant reduction (-6.2+/-0.5 degrees C; P<0.01 vs vehicle) in temperature in WT controls. However, higher doses of Dex (300 and 1000 microg kg(-1), i.p) produced a small, but statistically significant decrease in temperature corresponding to -1.7+/-0.4 degrees C and -2.4+/-0.3 degrees C (both P<0.01 vs vehicle), respectively. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in body temperature with ED50 values of 28.4+/-4.8 (P>0.05 vs WT control) and 54.1+/-8.0 (P>0.05 vs WT control) microg kg(-1), respectively. 6. In conclusion, the data are consistent with the alpha2A AR being the predominant subtype involved in the mediation of the antinociceptive, sedative and hypothermic actions of Dex. This profile would appear to indicate that an alpha2A AR subtype selective analgesic will have a narrow therapeutic window, particularly following systemic administration.
Adrenergic alpha-Agonists↗
Alternative definitions of disability: relationship to health-care expenditures.
The purpose of this study is to investigate the relationship between different definitions of disability and health-care expenditures in the working aged population in the United States using the 1987 National Medical Expenditure Survey (NMES). Five different definitions of disability were identified and the health-care expenditures for each group were compared using descriptive analyses. Results reveal that estimates of the prevalence of disability vary dramatically by the definition of disability. A more than three-fold difference in average total health-care expenditures is observed using different specifications of disability. These results suggest that estimates of health-care expenditures should be interpreted cautiously, since the definition influences the magnitude of estimates. Researchers and policy-makers should consider the standardization of the term 'disability'.
Activities of Daily Living↗
Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells.
A novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis, was isolated and characterized. Putative translation of the complete cDNA revealed the winged helix DNA binding domain to be centrally located within the protein, with regions on either side that contain known transcriptional regulatory motifs. Extensive Northern analysis of Genesis found that the message was exclusively expressed in embryonic stem cells or their malignant equivalent, embryonal carcinoma cells. The Genesis transcript was down-regulated when these cells were stimulated to differentiate. DNA sequences that Genesis protein would interact with were characterized and were found to contain a consensus similar to that found in an embryonic stem cell enhancer sequence. Co-transfection experiments revealed that Genesis is a transcriptional repressor. Genesis mapped to mouse chromosome 4 in a region syntenic with human chromosome 1p31, a site of nonrandom abnormalities in germ cell neoplasia, neuroblastoma, and acute lymphoblastic leukemia. Genesis is a candidate for regulating the phenotype of normal or malignant embryonic stem cells.
Amino Acid Sequence↗
Early results of laparoscopic surgery for colorectal cancer. Retrospective analysis of 372 patients treated by Clinical Outcomes of Surgical Therapy (COST) Study Group.
UNLABELLED: This study was undertaken to determine the early experience of the embers of the COST Study Group with colorectal cancer treated by laparoscopic approaches. METHOD: A retrospective review was performed of all patients with colorectal cancer treated with laparoscopy by the COST Study Group before August 1994. Tumor site, stage, differentiation, procedure completion, presence of recurrence (local, distant, trocar site), and cause of death were analyzed. RESULTS: A total of 372 patients with adenocarcinoma of the colon and rectum were treated by laparoscopic approach between October 1991 and August 1994 (170 men and 192 women): right colectomy, 170; sigmoid colectomy, 55; low anterior resection, 56; abdominoperineal resection, 44; left colectomy, 22; colostomy, 8; total colectomy, 6; transverse colectomy, 7; exploration, 2. Conversion to an open procedure was required in 15.6 percent of cases. Operative mortality was 2 percent. Tumor characteristics were as follows: TNM state: I, 40 percent; II, 25 percent; III, 18 percent; IV, 17 percent; Differentiation: well-moderate, 88 percent; poor, 12 percent; carcinomatosis, 5 percent. Local (3.6 percent) and distant implantation occurred in four patients (1.1 percent). Only one of these patients died a cancer-related death (Stage III at 36 months). Cancer-related death rates increased with increasing stage of tumor: I, -4 percent; II, 17 percent; III, 31 percent; IV, 70 percent. CONCLUSION: A laparoscopic approach to colorectal cancer results in early outcome after treatment that is comparable with conventional therapy for colorectal cancer. A randomized trial is needed to compare long-term outcomes of open and laparoscopic approaches with colorectal cancer.
Adenocarcinoma↗
Koilocytosis; an indication for conservative management.
The management of women with mild dyskaryosis continues to be the subject of debate. The management of cases with such smears could be improved if additional morphological features were found to be indicative of low/high grade cervical intraepithelial neoplasia (CIN). Our own experience in the routine audit of the diagnostic accuracy of cervical smears had suggested that cases of dyskaryosis with koilcytosis were associated with low risk of CINIII. Two hundred and forty-four cervical smears reported as showing evidence of warty virus infection were reviewed and their subsequent histories noted. Of these smears, 173 demonstrated clear evidence of koilocytosis. Irrespective of the initial grade of dyskaryosis, only 28 cases (16.2%) had underlying CIN or had progressed to CIN over a minimum follow-up period of 21 months. Only two cases (1.2%) showed evidence of CINIII. Koilcytosis is associated with a low risk of CIN and an especially low risk of CINIII. The management of women with koilocytic smears should be modified accordingly.
Colposcopy↗
The MD-PhD researcher: what species of investigator?
Though MD-PhD programs have grown rapidly since their introduction in the mid-1960s, and are widely regarded as fostering excellent young investigators and future leaders in research and academic medicine, the types of research careers their graduates can be expected to pursue have been a point of some confusion. Some regard MD-PhD programs as a flexible approach to scientific training, producing both basic scientists and clinical investigators, while others tend to view these programs as generating either one type of researcher or the other. This range of expectations associated with dual-degree programs and their graduates has perplexed observers over the years and complicated the efforts of planners and policymakers in projecting workforce needs and generating recommendations for research training. To learn more about the research careers of MD-PhDs and how these investigators fit into the larger biomedical research workforce, the authors undertook a review of the types of research proposed by dual-degree and other investigators in 12,116 applications to the National Institutes of Health in 1993 and 1994. In comparing the types of research projects proposed by investigators of various degree types (MDs, MD-PhDs, and PhDs) the authors found that the research interests of the MD-PhDs studied were more closely aligned with the laboratory pursuits of most of their PhD counterparts than with the more clinically-oriented endeavors of those with the MD degree alone. During a time when there are persistent concerns about a shortage of investigators to conduct clinical research and growing fears that America's universities may be producing more PhDs than can be meaningfully employed in the scientific enterprise, the authors' finding indicates a need for future workforce planning to better reflect the respective roles played by MDs, MD-PhDs, and PhDs in biomedical and behavioral research.
Education, Graduate↗
Effect of various irrigant and autoclaving regimes on the fracture resistance of rubber dam clamps.
Rubber dam clamps are known to break during clinical use in endodontics. This in-vitro study examined some of the variables which may contribute to the fracture. Stainless steel rubber dam clamps were subjected to various cleaning and autoclaving regimes and exposure to various solutions of sodium hypochlorite (NaOCl). Each clamp was examined after four cycles of cleaning and exposure to NaOCl. During environmental exposure to NaOCl, the clamp was stressed over a perspex rod to simulate placement onto the crown of a tooth. Clamps were examined after each test cycle visually and microscopically, or immediately after breakage. Results suggested that the fractures were because of a stress corrosion cracking phenomenon. There was evidence of intergranular and transgranular cracking of the metal. Corrosion spots were seen on the surface of the clamps and fracture occurred mainly through these spots. A number of recommendations to reduce breakage of clamps have been suggested.
Corrosion↗
Forced over-expression of the myeloid zinc finger gene MZF-1 inhibits apoptosis and promotes oncogenesis in interleukin-3-dependent FDCP.1 cells.
The myeloid zinc finger protein MZF-1 is important in hematopoiesis. Previous studies have found that reducing expression of MZF-1 inhibited G-CSF-driven human marrow colony formation assays. In this study we found that retrovirally overexpressing MZF-1 in IL-3-dependent FDCP.1 cells inhibited their apoptosis when IL-3 was withdrawn. The MZF-1-transduced FDCP.1 cells also formed tumors when injected into congenic mice, whereas control FDCP.1 cells did not.
Animals↗
Comparative effects of acute volume expansion and short-term training on thermal and cardiovascular responses to prolonged exercise.
To investigate the hypothesis that increases in plasma volume (PV) are crucial to the cardiovascular and thermal adaptations resulting from training, eight moderately active males (Vo2max = 4.10 +/- 0.32 L/min; mean +/- SE) performed prolonged cycle exercise at 60% Vo2max during a control test (CON) and following infusion (10 mL/kg) of a 6% dextran solution (DEX). These responses were also compared with short-term training (TR) involving 3 days of cycling for 90-120 min at moderate intensity (60% Vo2max). During DEX, exercise cardiac output (Q) and stroke volume (SV) were persistently higher (p < 0.05) than CON, while heart rate (HR) was unchanged. In comparison, TR resulted in a lower (p < 0.05) HR at constant Q. In contrast with TR, in which the exercise response was unchanged from CON, the DEX condition produced a lower total peripheral resistance. Rectal temperature (Tre) was lowered (p < 0.05) both by DEX and TR, but the conditions differed in the time at which the reduction occurred. For DEX, the lower Tre was manifested early and persisted throughout exercise, whereas for TR the Tre was only lower later in exercise. Forearm blood flow, mean skin temperature, and sweat rate were not affected by DEX or TR. It is concluded that acute PV expansion does not affect the time-dependent response in cardiovascular function or thermoregulation during prolonged exercise in ambient conditions. The primary effects appear to be manifested during rest or soon after the onset of exercise.
Adult↗
The HEM proteins: a novel family of tissue-specific transmembrane proteins expressed from invertebrates through mammals with an essential function in oogenesis.
We report the identification of a new family of proteins, termed the HEM family, which show distinct expression patterns in blood cells and the central nervous system. Through the isolation and characterization of the corresponding brain-specific Drosophila (dhem-2) and rat orthologues (Hem-2), and through the detection of the Caenorhabditis elegans Hem-2 orthologue in the database, we show that this family is conserved throughout evolution. HEM proteins show a conserved length ranging from 1118 to 1126 amino acid residues. Moreover, they are at least 35% identical with each other and harbour several conserved membrane-spanning domains, indicative for their location on the cell surface. One of the members, the Drosophila orthologue dhem-2, was analysed in detail for its spatial expression pattern during development and for its mutant phenotype. dhem-2 is expressed maternally in the oocyte and shows uniform expression during the first half of embryogenesis, but becomes restricted to the brain and the nervous system during late embryogenesis, consistent with the expression of its vertebrate orthologue in the brain. One P-element insertion, located 39 base-pairs downstream from the dhem-2 transcription start site, causes female sterility, due to the fact that developmental processes in the oocyte are disturbed. Of the vertebrate HEM family members, the mammalian Hem-1 gene is expressed only in cells of hematopoietic origin, while Hem-2 is preferentially expressed in brain, heart, liver and testis.
Adaptor Proteins, Signal Transducing↗
Pallidotomy increases activity of motor association cortex in Parkinson's disease: a positron emission tomographic study.
Stereotactic posteroventral pallidotomy can improve motor performance in Parkinson's disease. Interruption of inhibitory pallidal projections to ventrolateral thalamus, components of a cortical-basal ganglia motor loop allows for this clinical benefit. We hypothesized that pallidotomy would lead to increased movement related activity in motor cortical areas receiving projections from ventrolateral thalamus. This was tested in 6 Parkinson's disease patients who underwent stereotactic posteroventral pallidotomy. Each patient was imaged with positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) during performance of a simple prehension task and at rest. Scans were acquired before and 17 weeks after surgery. After pallidotomy, movement-related changes of rCBF increased significantly in both the supplementary motor area (SMA) and premotor cortex but not in primary motor cortex. The results demonstrate the importance of pallidothalamic circuitry for regulating volitional movements and confirm that disruption of inhibitory input to the ventrolateral thalamus can augment movement-related activity in motor association areas.
Adult↗