Incidence of and mortality from breast cancer since introduction of screening. Scottish figures show higher incidence and similar mortality.
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Adult↗
Biomedical subjects
J Warner
Publications and source records attributed to J Warner.
Molecular analysis of the TK locus in L5178Y large and small colony mouse lymphoma cell mutants induced by hycanthone methanesulfonate.
Mouse lymphoma cells of the L5178Y TK + /-3.7.2C line were exposed to varying concentrations of the anti-schistosomal drug hycanthone methanesulfonate. The trifluorothymidine (TFT)-resistant cells fell into two classes based on colony size. Southern blot analyses were performed using NcoI-digested DNA from a number of large and small mutant colonies from each treatment group. Two different restriction fragment banding patterns were identified in these analyses, those colonies that contained the 6.4 kb NcoI restriction fragment and those that did not. A total of 471 mutant colonies were analyzed and 84.5% (398) of these colonies did not exhibit the 6.4 kb fragment. There did not appear to be a hycanthone methanesulfonate dose response effect in the number of colonies that did not contain the 6.4 kb fragment among the treated groups. In addition, 82% (154 out of 188) of spontaneous mutants did not contain the 6.4 kb fragment. The results imply that greater than 80% of all spontaneous mutations found in the mouse lymphoma assay regardless of colony size do not contain the 6.4 kb fragment and each may be considered to be a large scale mutation. In addition, greater than 80% of the hycanthone induced mutations in the mouse lymphoma assay do not contain the 6.4 kb fragment and thus may be considered to be a large scale mutation.
Animals↗
Simultaneous initiation of degranulation and inhibition of leukotriene release by soman in human basophils.
Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.
Basophil Degranulation Test↗
Inhibitory motor seizures: correlation with centroparietal structural and functional abnormalities.
Six adults and 2 children with focal inhibitory motor seizures (ictal paralysis) were evaluated during a 4-year period. Paresthesias at seizure onset occurred during some seizures in all patients, and focal clonic activity followed paralysis in 4. EEG-CCTV recordings of the seizures in 2 patients showed that ictal paralysis coincided with an ictal discharge starting in one centroparietal area. MRI showed centroparietal structural lesions in six patients. One patient with a normal MRI scan had right centroparietal hypometabolism on PET. Inhibitory motor seizures must be differentiated from transient ischemic attacks and migraine. In our patients a centroparietal epileptogenic focus was suggested by neuroimaging studies, and in 2 instances by ictal EEG.
Adolescent↗
Role of elevated plasma soluble ICAM-1 and bronchial lavage fluid IL-8 levels as markers of chronic lung disease in premature infants.
BACKGROUND: Pulmonary neutrophilia characterises both the relatively transient inflammation associated with infant respiratory distress syndrome (IRDS) and the persistent inflammation of chronic lung disease. The possibility that persistently raised markers of inflammation indicate the development of chronic lung disease in low birth weight (< 1730 g) preterm (< 31 weeks) infants was therefore investigated. METHODS: Soluble ICAM-1 (sICAM-1) levels in plasma, and interleukin (IL)-8 and myeloperoxidase (MPO) levels in bronchial lavage fluid (BLF) obtained from 17 infants on days 1, 5, and 14 following birth were measured and correlations with the number of neutrophils in BLF sought. Peripheral neutrophils were isolated on Polymorphoprep and chemotactic responsiveness to IL-8 was assessed using micro Boyden chambers. RESULTS: Sixteen infants developed IRDS and, of these, 10 infants subsequently developed chronic lung disease. Levels of IL-8 in BLF at 14 days of age correlated with the long term requirement for intermittent positive pressure ventilation (IPPV). Interleukin 8 levels in BLF correlated with neutrophil numbers and MPO concentration, suggesting both recruitment and activation in response to this cytokine. Antibody depletion studies showed that approximately 50% of total neutrophil chemotactic activity in BLF was due to IL-8. No difference in peripheral neutrophil chemotactic responsiveness at any age was observed for infants with IRDS or chronic lung disease. Plasma soluble intercellular adhesion molecule (sICAM-1) was higher at 14 days of age in infants who developed chronic lung disease than in those with resolving IRDS, and correlated with severity of disease, as indicated by duration of IPPV. CONCLUSIONS: The results indicate that high levels of plasma sICAM-1 and IL-8 in BLF at day 14 correlate with the development of chronic lung disease and indicate the severity of disease.
Biomarkers↗
Results of conservative management of clinically localized prostate cancer.
BACKGROUND: The selection of treatment for patients with localized prostate cancer requires reliable information about the outcome of conservative management. Previous studies of this question are generally considered unreliable because they were uncontrolled and nonrandomized. METHODS: We performed a pooled analysis of 828 case records from six nonrandomized studies, published since 1985, of men treated conservatively (with observation and delayed hormone therapy but no radical surgery or irradiation) for clinically localized prostate cancer. A Cox regression analysis was performed to determine which factors influenced survival among patients who did not die of causes other than prostate cancer (disease-specific survival). Kaplan-Meier curves for overall and metastasis-free survival among such patients were compared with use of the log-rank method and the Mantel-Haenszel test. RESULTS: Factors that had a significant effect on disease-specific survival were grade 3 tumors (risk ratio, 10.04), residence in Israel (risk ratio, 2.48) or New York (risk ratio, 0.37), and age under 61 years (risk ratio, 0.32). Ten years after diagnosis, disease-specific survival (with data on men who died from causes other than prostate cancer censored) was 87 percent for men with grade 1 or 2 tumors and 34 percent for those with grade 3 tumors; metastasis-free survival among men who had not died of other causes was 81 percent for grade 1, 58 percent for grade 2, and 26 percent for grade 3 disease. These findings were not affected by the inclusion of men who had early-stage cancer, were older, had worse-than-average health, or underwent delayed radiation therapy or radical prostatectomy. CONCLUSIONS: The strategy of initial conservative management and delayed hormone therapy is a reasonable choice for some men with grade 1 or 2 clinically localized prostate cancer, particularly for those who have an average life expectancy of 10 years or less. New treatment strategies are needed for men with grade 3 prostate cancer.
Aged↗
Expectant management of clinically localized prostatic cancer.
Among approximately 4,000 prostatic cancer registrations 75 patients with clinical stage B histologically proved prostatic cancer receiving no therapy for at least 1 year after diagnosis were identified and managed expectantly. Of the patients 29 had stage B1, 37 stage B2 and 9 stage B3 lesions. Eight patients ultimately elected definitive radiation treatment. First evidence of tumor progression was local in more than 90% of the cases. Overall median intervals were 78 months to local progression, 186 months to metastasis, 108 months to initiation of any treatment and 156 months to death. The rate of tumor progression was often consistent with protracted survival. Prostatic cancer and co-morbidity were each significant forces of mortality.
Aged↗
Validation of a croup score and its use in triaging children with croup.
The Syracuse croup scoring system was validated in 165 children with croup who were admitted to an intensive therapy unit for assessment over a one year period. The unit served as a croup triage point for Cardiff and its environs. A score of > 5 was taken as an indication that a patient was at risk of upper airway obstruction and was used to support a triage decision by the junior hospital doctor to admit a patient to the intensive therapy unit. All patients with an initial score < or = 5 were considered safe for transfer to a general paediatric ward and none of these required subsequent admission to intensive care. This score was then tested on a further 134 children with croup, in order to identify those patients who required specialised monitoring, observation or treatment in intensive care. A score of > 5 gave a specificity of 100% and a sensitivity of 80%. Croup scoring continued after admission on the general paediatric wards. Two patients who were originally admitted to the intensive therapy unit with a score > 5 improved within 6 h and were transferred to the general ward with a score < or = 5. These children subsequently required readmission to the intensive therapy unit. Our tracheal intubation rate of 2% was low and may relate to the routine use of regular adrenaline nebulisation. We recommend this scoring system to other paediatric departments for initial triaging decisions and for documenting progress on the wards.
Child↗
Reliability of clinical diagnosis of Huntington's disease.
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Aged↗
"Resolv'd to drink no more": addiction as a preindustrial construct.
The notion that alcohol is potentially addictive dates not from the late eighteenth century but from the early seventeenth century at the very least, as does the related notion that habitual drunkenness constitutes a "disease" in its own right. English pamphlets and sermons from the latter period would suggest that the two notions were first advanced by clergymen and other moralists, and only later found acceptance in the British and American medical communities. Seen in this light, the American physician Benjamin Rush (c. 1745-1813) was less an innovator in advancing the notion of addiction than the last great voice in a tradition already 150 years old.
Alcoholism↗
Neuro-ophthalmology of multiple sclerosis.
Neuro-ophthalmic manifestations are important in multiple sclerosis. Optic neuritis is a frequent harbinger of the disease, and is characterized by subacute painful visual loss, with disproportionate loss of color and contrast sensitivity, central or cecocentral scotoma, and an afferent pupillary defect. Visual recovery is the rule, but tests have been developed to detect most cases of recovered optic neuritis. Intraocular inflammation has come to be recognized as a frequent accompaniment of multiple sclerosis. Because of the predilection of multiple sclerosis for the infratentorial white matter, defects in eye movement control are common, particularly internuclear ophthalmoplegias and nystagmus.
Humans↗
Mechanisms of airways inflammation which may be amenable to prophylaxis.
The presence of mucosal inflammation in the lower airways of atopic asthmatics and to a milder degree of atopic nonasthmatics suffering from rhinitis points to atopy and allergen exposure as risk factors for lower airways disease. The study of mechanisms which regulate the degree of inflammation should enable the understanding of why some individuals suffer from rhinitis alone whereas others go on to develop bronchial disease. This information should enable the development of prophylactic strategies to prevent atopy from expressing itself in the lower airways.
Air Pollutants↗
Functional expression of soluble ICAM-1 by baculovirus-infected Sf9 cells.
Inflammation, metastasis and ischemia are processes that require lymphocyte or leukocyte cell recognition and adherence to endothelial counter receptors such as ICAM-1. Mapping the sites of interaction of ICAM-1 with LFA-1, the receptor for ICAM-1 on lymphocytes, may lead to the design of novel inhibitors of inflammation or metastasis. To this end, recombinant soluble ICAM-1 cDNA was engineered into the baculovirus expression system, which is capable of expressing large amounts of proteins. These constructs were designed to contain a protein leader sequence so that the transfected insect cells would secrete the recombinant polypeptide into the culture media for ease of isolation. We engineered four constructs of ICAM-1 into the baculovirus system and obtained relatively high expression of two soluble forms of ICAM-1, a two domain and a five domain form. These truncated proteins were isolated and shown to promote adherence of HL-60 cells and Molt-4 cells. These recombinant soluble proteins also inhibited cell adherence to purified intact ICAM-1 isolated from K562 cells.
Amino Acid Sequence↗
Incidence of leukaemia and other cancers in birth and schools cohorts in the Dounreay area.
OBJECTIVE: To determine whether a raised incidence of leukaemia in the Dounreay area occurred in children born to local mothers (birth cohort) or in those who moved to the area after birth (schools cohort) and also whether any cases of cancer have occurred in children born near Dounreay who may have moved elsewhere. DESIGN: Follow up study. SETTING: Dounreay area of Caithness, Scotland. SUBJECTS: 4144 children born in the area in the period 1969-88 and 1641 children who attended local schools in the same period but who had been born elsewhere. MAIN OUTCOME MEASURES: Cancer registration records linked to birth and school records with computerised probability matching methods. RESULTS: Five cancer registrations were traced from the birth cohort compared with 5.8 expected on the basis of national rates (observed to expected ratio 0.9, 95% confidence interval 0.3 to 2.0). All five cases were of leukaemia (2.3, 0.7 to 5.4). In the schools cohort three cases were found (2.1, 0.4 to 6.2), all of which were of leukaemia (6.7, 1.4 to 19.5). All eight children were resident in the Dounreay area at the time of diagnosis; thus no cases were found in children who were born in or had attended school in the study area but who subsequently moved away. CONCLUSION: The raised incidence of leukaemia in both the birth and schools cohorts suggests that place of birth is not a more important factor than place of residence in the series of cases of leukaemia observed near Dounreay area.
Child↗
Linkage of Emery-Dreifuss muscular dystrophy to the red/green cone pigment (RGCP) genes, proximal to factor VIII.
Further DNA linkage studies on two previously described X-linked recessive Emery-Dreifuss muscular dystrophy (EMD) families are reported, which refine the localization of the gene responsible for EMD. Two recombination events indicate that the most likely localization for the EMD gene lies in the interval between DXS15/DXS52 and F8C. A maximum LOD score of 3.44 at theta = 0 is obtained for EMD vs the red and green cone pigment genes (RCP and GCP). Our data provide additional support for one of the two proposed orientations of genes and markers distal to DXS15/DXS52, with respect to the telomere. Given this favoured orientation, our data best fit a localization of EMD to within a 2 megabase (Mb) interval between DXS15/DXS52 and F8C.
Adolescent↗
IgE-mediated anaphylactic degranulation of isolated human skin mast cells.
Isolated human skin mast cells (HSMC) were prepared and cultured overnight before functional and electron microscopic studies. Mast cell suspensions were examined after stimulation with anti-IgE to produce anaphylactic degranulation or examined in buffer-incubated controls. Histamine release was measured in replicate samples. Control, isolated HSMC studied by electron microscopy were well preserved and fully granulated. Although all granule patterns reported for human mast cells were found, crystal granules were the most prevalent, as is true for HSMC in situ. Individual mast cells containing both crystal and scroll granules occurred. Lipid bodies were rare, as in HSMC in situ. Control, isolated mast cells did not express granule changes associated with either piecemeal degranulation or recovery during wound healing in situ; nor were morphologic changes of anaphylactic degranulation present. Spontaneous histamine release was 0% in control samples. Anaphylactic degranulation of isolated HSMC was accompanied by 24% maximum histamine release and characteristically showed extrusion of altered, membrane-free granules through multiple pores in the plasma membrane to the exterior of the cell. Other morphologic aspects of anaphylactic degranulation, as expressed in isolated human lung mast cells, were also present. These events included granule swelling, fusion, alteration of matrix contents, degranulation channel formation, pore formation, and shedding of granules, membranes, and surface processes. The ultrastructural morphology of isolated HSMC and their IgE-mediated degranulation shows some differences from similar studies of isolated human lung mast cells and of human lung and gut mast cells in biopsy samples. These differences include crystal granules as the predominant granule pattern, minor numbers of lipid bodies, and extrusion of granules during anaphylactic degranulation as characteristic for HSMC. By contrast, isolated human lung and gut mast cells have more scroll granules and particle granules, respectively, and more lipid bodies. In isolated human lung mast cells, anaphylactic degranulation is almost exclusively an intracellular fusion event characterized by the formation of complex degranulation channels within which altered granule matrix materials solubilize. In addition to morphologic differences between mast cells of skin, lung, or gut origin, functional differences have also been reported among mast cells of these organs. The ultrastructural morphology of isolated HSMC is identical to that of skin mast cells in biopsy samples, thereby validating the usefulness of this new source of HSMC for correlative functional and morphologic studies.
Anaphylaxis↗
Longitudinal changes in forearm bone mineral content in primary hyperparathyroidism.
Forearm bone mineral content was measured in 28 patients with primary hyperparathyroidism before and 1 year after successful parathyroidectomy. The forearm bone mineral content rose from a mean value of 1.068 to 1.092 g/cm (P less than 0.05, paired t-test). Those patients with the lower initial values had the largest rise. In an additional study, the forearm bone mineral content was measured in 10 women over the age of 40 years (mean age 58.6 +/- 7.9SD years) with hyperparathyroidism before and for 2 years after successful parathyroidectomy and compared with the forearm bone mineral content measured over 2 years in 12 women (mean age 56.3 +/- 5.5SD years) with continuing hyperparathyroidism and with the forearm bone mineral content of 12 eucalcemic control women (mean age 58.8 +/- 8.2SD years), also measured over 2 years. The parathyroidectomized group gained bone, whereas the ongoing hyperparathyroid group and the eucalcemic control group lost bone. The difference between the parathyroidectomized group and the ongoing hyperparathyroid group was significant after 2 years (P less than 0.05). The percentage loss of forearm bone mineral in the eucalcemic control subjects was not significantly different from the percentage loss of forearm bone mineral in the ongoing hyperparathyroid group, although the initial mean bone mineral content in the eucalcemic group was significantly higher than in the ongoing hyperparathyroid group, suggesting that a possible determinant of bone mineral loss in women in this age group is the initial bone mineral content.
Adult↗