Repair of oxidative damage to DNA: enzymology and biology.
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Amino Acid Sequence↗
Biomedical subjects
L Harrison
Publications and source records attributed to L Harrison.
A technique for developing a master cast with previously made dies.
This article describes a technique for preparing final working casts to be used in the laboratory phase of restorative treatment. The goal is to produce accurate working casts that have stable dies which are easily removed from the base and reliably replaced. Most casts with removable dies are made from a single master impression. However, individual dies are sometimes made previously from individual tooth (preparation) impressions. In such cases, transfer copings are required to relate the dies and produce the final working cast. Hollow plastic casting sprues are used as temporary dowels in this technique until a transfer coping pickup impression has been made. After the dies are seated and secured in the transfer coping pickup impression, the plastic casting sprues are replaced with conventional brass dowel pins. This technique ensures well-placed dowel pins that will facilitate easy and accurate withdrawal and replacement of the dies.
Dental Casting Technique↗
Neoplastic seeding as a complication of percutaneous endoscopic gastrostomy.
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Adult↗
The effect of setup uncertainties on the treatment of nasopharynx cancer.
PURPOSE: As radiation treatment techniques become more complicated, the need to understand the effect of uncertainties on dose distributions increases. This study investigates the effect of positional uncertainities for patients with nasopharynx carcinoma treated with a multiple field conformal boost technique. Three dimensional setup errors were measured for six patients and the effect on patient dose was evaluated using dose volume histograms. METHODS AND MATERIALS: A method is presented for determining 3-dimensional translational and rotational setup errors by identifying anatomical landmarks on two treatment field images and their corresponding simulation images. Measurements were made on a daily basis for six patients undergoing conformal treatment. RESULTS: The average magnitude of the translational errors was between 1.5 and 3 mm while the average distance between simulation and treatment isocenters was 5 mm. Both systematic and random setup errors were observed. Dose volume histograms incorporating these uncertainties for standard parallel opposed and conformal techniques were generated for patients experiencing random and systematic setup errors. CONCLUSION: The data imply that positional uncertainties effect the daily dose distributions for target and critical structures differently and that the effect may be treatment technique dependent. These results demonstrate the need to measure setup uncertainties for all sites and to develop techniques for incorporating dose uncertainties in treatment plans.
Calibration↗
Evaluation of a portable prothrombin time monitor for home use by patients who require long-term oral anticoagulant therapy.
BACKGROUND: The anticoagulant activity of warfarin sodium is monitored by the prothrombin time (PT). The introduction of a portable PT monitor has raised the possibility that patients could reduce the inconvenience of anticoagulant therapy by measuring their PT at home. We performed this study to determine the feasibility and accuracy of home use of the portable PT monitor. METHODS: A prospective cohort study was performed in consecutive eligible patients who required long-term anticoagulant therapy. Patients performed multiple measurements of their PT at home by means of the portable monitor and at their usual laboratory within a 4-hour interval. The accuracy of the portable monitor was evaluated by two criteria for agreement. Standard agreement was achieved if the portable monitor and laboratory results were both either within or outside the patient's targeted therapeutic range or if the two results were within 0.4 international normalized ratio units of each other. Expanded agreement was achieved if both the portable monitor and laboratory results were within +/- 0.4 international normalized ratio units of the targeted therapeutic range. RESULTS: Forty patients (19 men and 21 women, aged 25 to 74 years) were followed up for 6 to 24 months by means of the portable PT monitor. The mean level of agreement achieved per patient was 83% (95% confidence interval, 79% to 87%) by the standard criteria and 96% (95% confidence interval, 94% to 98%) by the expanded criteria. Twenty-seven patients (68%) and 39 patients (98%) achieved more than 80% agreement by the standard and the expanded criteria, respectively. Questionnaire results revealed that 97% of the patients preferred using the portable monitor to measure their PT. CONCLUSIONS: Patients receiving long-term anticoagulant therapy achieved a high rate of clinically important agreement between self-measurements of the PT with the use of a portable monitor and laboratory PT results. Patients strongly preferred using the portable monitor to measure their PT levels. The use of the portable monitor as the primary method for measuring the PT can be recommended in selected patients receiving long-term anticoagulant treatment.
Administration, Oral↗
A phase II trial of deoxyspergualin in recurrent squamous cell head and neck cancer.
Fifteen patients with recurrent squamous cell head and neck cancer were treated with deoxyspergualin. There were no objective responses in 14 evaluable patients. The most common toxicity was reversible hypotension, which prompted dose reduction in nine patients. Deoxyspergualin is not recommended for the treatment of squamous cell head and neck cancer.
Adult↗
Dealing with child abuse: development and evaluation of a short workshop for nurses.
A 1-day workshop was evaluated in terms of its effectiveness in enhancing nurse (N = 70) understanding of child abuse. Measures of their knowledge and attitudes concerning abuse were administered before and after the workshop. The results indicated that the workshop led to a significant improvement in these two areas, in particular, a sub-sample (N = 25) who received an additional teaching aid (a programmed learning script) did better than their colleagues. Finally, a teaching evaluation form indicated a high degree of consumer satisfaction. It is concluded that the brief workshop was successful in enhancing knowledge and attitudes, and that it illustrates the kind of 'professional approach' recently advocated in the literature.
Adult↗
Investigation of the changes in neuronal distribution and phosphorylation state of MAP1X during development.
Neurite outgrowth is dependent on the presence in neurites of assembled microtubules which consist of polymerized tubulin to which microtubule-associated proteins (MAPs) are bound. This study adds to previous evidence of the similarity between the high molecular weight MAPs, MAP1X, MAP1B and MAP5, and explains the different staining patterns observed by different laboratories on frozen sections, using monoclonal antibodies against each MAP. Previous studies have shown that monoclonal antibody (mAb) G10 binds to MAP1X and labels growing but not mature axons in the rat nervous system and, therefore, expression of this MAP or molecular changes in it may be important for axon growth. It has been shown that a phosphorylated form of MAP5 can be detected by SDS-PAGE in brain areas with growing axons. This study shows that there is phosphate dependency of mAbG10 binding to MAP1X which is, however, lost during brain homogenization.
Aging↗
Demand for hospital services following admission with suspected myocardial infarction in 1983 and 1989.
Formulation of business plans by National Health hospitals requires information on likely demands for the services they provide. Two cohorts of patients admitted to the Nottingham hospitals in 1983 and 1989 with suspected myocardial infarction were sampled to determine the workload implications due to initial in-hospital tests, subsequent readmission and outpatient investigations. The results show that attendance in the first year after discharge related principally to cardiac problems, while in subsequent years non-cardiac problems predominated. An estimation of the total workload, based upon 1,000 patients admitted in 1989, suggests that demands for hospital services in the following year include over 4,000 electrocardiographs, 1,400 chest X-rays and 18,000 laboratory tests, and only 118 exercise tests and 37 cardiac catheterisations. Admission with suspected myocardial infarction makes great demand on hospital services in the year after discharge. Any change in practice, which increases the potential demand for cardiac investigations, could have important financial implications for Nottingham hospitals.
England↗
Consumption and harm: drinking patterns of the Irish, the English and the Irish in England.
There has been controversy over the relationship between alcohol consumption and related problems amongst the Irish in England. Irish migrants have high Standardised Mortality Ratios for chronic liver disease and cirrhosis and high hospital admission rates for alcohol-related diagnoses in England. Yet it has been considered that people from the Republic of Ireland, whether living in Ireland (Conniffe et al., 1990) or in England (Pearson et al., 1991), actually drink less than the English. This paper reviews the evidence. In recent years Irish per capita volume alcohol consumption has been comparable to that of the U.K., although the distribution of consumption differs. Women in Ireland are less likely to drink than women in England and Wales, while men in Ireland are more likely to drink at high-risk levels than men in England and Wales: their average weekly consumption levels are closer to those of high-consuming men in Yorkshire and Humberside, who also drink more than the U.K. national average. Men in Ireland also appear to be more likely to experience drinking problems than their counterparts in England and Wales, although this may be related to factors other than the total amount of alcohol consumed. Although a previous study of General Household Survey data indicated low-risk alcohol consumption levels for people from the Irish Republic living in Britain, a reanalysis of these data adjusting for age and gender shows drinking rates that are very high.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Issues related to the protection of human research participants.
Making ethical decisions related to the protection of human research participants is often complex and fraught with uncertainty and conflict. Awareness of the basic principles outlined in the Belmont Report as well as in federal regulations and guidelines can provide a useful framework for such decisions, although the ultimate responsibility for ensuring ethical research practices rests with the individual investigator. Ongoing dialogue and discussion about these ethical issues will provide a basis for strengthening nursing research and practice while ensuring the maximum protection for research participants who make possible the advancement of nursing science.
Confidentiality↗
Uroporphyrinogen decarboxylase in Saccharomyces cerevisiae. HEM12 gene sequence and evidence for two conserved glycines essential for enzymatic activity.
The HEM12 gene from Saccharomyces cerevisiae encodes uroporphyrinogen decarboxylase which catalyzes the sequential decarboxylation of the four acetyl side chains of uroporphyrinogen to yield coproporphyrinogen, an intermediate in protoheme biosynthesis. The gene was isolated by functional complementation of a hem12 mutant. Sequencing revealed that the HEM12 gene encodes a protein of 362 amino acids with a calculated molecular mass of 41,348 Da. The amino acid sequence shares 50% identity with human and rat uroporphyrinogen decarboxylase and shows 40% identity with the N-terminus of an open reading frame described in Synechococcus sp. We determined the sequence of two hem12 mutations which lead to a totally inactive enzyme. They correspond to the amino acid changes Gly33----Asp and Gly300----Asp, located in two evolutionarily conserved regions. Each of these substitutions impairs binding of substrates without affecting the overall conformation of the protein. These results argue that a single active center exists in uroporphyrinogen decarboxylase.
Amino Acid Sequence↗
Extrahepatic portal vein aneurysm: report of a case treated by thrombectomy and aneurysmorrhaphy.
Extrahepatic portal vein aneurysm is a rare condition with only 15 cases before ours being reported in the English literature. The etiology is thought to be congenital, secondary to portal hypertension or associated with abnormal weakness of the vein wall. It often presents in conjunction with major gastrointestinal bleeding, but may occur with minimal or no symptoms. Diagnosis is made with color duplex ultrasound, computed tomographic scan, venous phase mesenteric angiography, magnetic resonance imaging, or splenoportography. Thrombosis, rupture, and pressure effects are the major complications of portal vein aneurysm. Shunting procedures are recommended in cases with portal hypertension secondary to liver disease. We report the first case treated by thrombectomy and aneurysmorrhaphy with a successful 10 year follow-up. This procedure should be considered to preserve portal vein flow when portal hypertension is absent or is secondary to the aneurysm itself.
Adult↗
A reappraisal of the role of prophylactic cranial irradiation in limited small cell lung cancer.
The use of prophylactic cranial irradiation in limited stage small cell lung cancer remains controversial. Prospective trials have demonstrated that PCI can reduce central nervous system relapse rates, but the impact on survival remains questionable except for the possible evidence of a beneficial effect for long term survivors. With higher rates of thoracic control now obtainable with hyperfractionated radiation and concomitant chemotherapy, it becomes important to analyze the benefit of PCI in that setting. Before 1982, we included PCI in the management of all patients with limited stage small cell lung cancer; thereafter, we discontinued its use. This report compares the outcome of the two treatment approaches and addresses the role of PCI among patients who achieve durable local control. There were 36 limited stage small cell lung cancer patients treated with PCI from 1979-1982 and 26 patients treated without PCI from 1985-1989. Induction chemotherapy was followed in both groups by thoracic irradiation (45 Gy). The PCI patients received 30 Gy to the whole brain in 10 fractions. Both groups received maintenance chemotherapy. Of complete responders, brain failure was the first failure in 18% (4/22) of PCI (+) versus 45% (10/22) of PCI (-) (p = .04). Survival at 2 years was 42% for PCI (+) versus 13% for PCI (-) (p less than .05). When the analysis was limited to those patients permanently controlled in the thorax; there were 25% (4/16) brain failures PCI (+) versus 70% (7/10) PCI (-) (p = .03). For this same subset the 2-year survival was 56% PCI (+) versus 14% PCI (-) (p less than .05). There were no 5 year survivors without PCI compared to 38% (6/16) with PCI. These data suggest that PCI appears to be effective in enhancing survival of patients who achieve durable thoracic control. Prospective trials are necessary to evaluate the use of PCI combined with therapeutic regimens with a documented ability to achieve high rates of sustained control of thoracic disease.
Brain↗
Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12).
Abasic (AP) sites in DNA are produced spontaneously and by many genotoxic agents. The repair of such damages is initiated by AP endonucleases, which are evidently ubiquitous. We employed the recently cloned cDNA, APE, that encodes the major human AP endonuclease, to isolate large genomic fragments that contain the intact APE gene. The sequence of 3 kb encompassing APE was determined (GenBank Accession No. M99703). The APE gene contains four small introns (ranging 130 to 566 bp) and five exons, the first of which is untranslated. The 0.5 kb of DNA sequence upstream of APE did revealed only a possible CCAAT box, but no other regulatory sites or a TATA box, consistent with the constitutive expression of AP endonuclease activity observed in other studies. The location of APE in the human genome was mapped to chromosome 14, bands q11.2-12, by fluorescence in situ hybridization of metaphase cells with DNA from the genomic clones and subclones. Although this locus has not been associated causally with genetic diseases of DNA repair, some translocations that affect 14q11.2-12 could compromise APE and lead to genetic instability.
Base Sequence↗
Herpes simplex virus type 2 infection, syphilis, and hepatitis B virus infection in Haitian women with human immunodeficiency virus type 1 and human T lymphotropic virus type I infections. The Johns Hopkins University (JHU)/Centre pour le Developpement et la Santé (CDS) HIV Study Group.
Antibodies to herpes simplex virus type 2 (HSV-2), antibodies to hepatitis B virus (HBV) core antigen (anti-HBc), and VDRL antibodies (serologic evidence of syphilis) were evaluated in women known to be infected with human immunodeficiency virus type 1 (HIV-1) (n = 95) or human T lymphotropic virus type I (HTLV-I) (n = 45) and controls (n = 89). HIV-1-seropositive women were more likely than controls to have antibodies to HSV-2 (88% vs. 54%; P less than .001), anti-HBc (67% vs. 43%; P = .008), and VDRL antibodies (21% vs. 8%; P = .02). Similarly, HTLV-I-seropositive women were more likely than controls to have antibodies to HSV-2 (82% vs. 54%; P = .003) and anti-HBc (67% vs. 43%; P = .008). There was no evidence that HIV-1 or HTLV-I predisposed to chronic hepatitis B virus infection. The stronger associations between HIV-1 and HTLV-I with HSV-2 than the associations with syphilis or HBV are consistent with the hypothesis that recurrent disruptions of mucous membranes caused by HSV-2 infections predispose to sexual transmission of HIV-1 and HTLV-I.
Adolescent↗
Substance misuse and social work qualifying training in the British Isles: a survey of CQSW courses.
In 1989, all Certificate of Qualification in Social Work (CQSW) courses in the British Isles were included in a survey of the training offered social work students on responding to psychoactive substance misuse. There was a 74% response rate. Eleven per cent of the courses that responded provided no formal substance misuse training. Those that offered training provided a median of 8 hours, with over 70% of students receiving less than 11 hours, indicating that many students were being given the briefest of overviews. Outside of four or five 'centres of excellence', social workers and probation officers training in 1988-89 received less than adequate preparation to work with people with alcohol- and drug-related problems, despite evidence that they account for a large and growing proportion of their caseloads.
Adult↗
Transfection of the Escherichia coli nth gene into radiosensitive Chinese hamster cells: effects on sensitivity to radiation, hydrogen peroxide, and bleomycin sulfate.
The Escherichia coli nth gene encodes endonuclease III, which catalyses the glycolytic removal of various oxidized thymine residues from DNA. A truncated version of nth, with the prokaryotic regulatory sequences removed, was ligated into the retrovirus-based vector pZipneoSV(X)1 and transfected into the radiosensitive Chinese hamster ovary cell line, xrs7. Following selection with G418, two clones (x7nth1 and x7nth6) were shown by Southern analysis to contain the nth gene. No substantial difference in gamma-ray sensitivity was detected between xrs7, clones x7nth1 and x7nth6, and the parent vector transfected clone (x7neo1). However, clones containing the nth gene were more resistant to hydrogen peroxide cytotoxicity [D0's for x7nth1 and x7nth6 were 0.072 microgram/ml (4 microM) and 0.046 microgram/ml, respectively, compared with D0's of 0.034 and 0.027 microgram/ml for xrs7 and x7neo1, respectively] but markedly more sensitive to bleomycin sulfate cytotoxicity than xrs7 and x7neo1 (e.g., 1D0's for x7nth6 and xrs7 were 0.05 and 0.12 microgram/ml, while 2D0's for x7nth1 and xrs7 were 0.35 and 0.48 microgram/ml, respectively). Alterations in sensitivity to hydrogen peroxide and bleomycin sulfate could not be explained by differences in the distribution of the cell-cycle phases and growth rate of nth-containing clones and control cell lines. These results are consistent with the hypothesis that modified thymine lesions are potentially cytotoxic. Hence, when cells incur a high level of endonuclease III-repairable damage relative to strand breakage, such as after treatment with hydrogen peroxide, increased repair capacity increases survival. Gamma radiation produces a lower level of endonuclease III-repairable damage relative to all the other types of lesions produced; hence increased repair capacity has no measurable effect on cell survival. The increased sensitivity of x7nth1 and x7nth6 to bleomycin sulfate toxicity may indicate that, when thymine damage and single-strand breaks are in close proximity on opposite strands of the DNA, endonuclease III, which incises DNA at the site of damaged residues, can increase the number of double-strand breaks and hence decrease the level of cell survival.
Animals↗