A case of self-inflicted craniocerebral penetrating injury.
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Adult↗
Biomedical subjects
M Duff
Publications and source records attributed to M Duff.
Overlapping CRE and E-box promoter elements can independently regulate COX-2 gene transcription in macrophages.
Macrophage cyclooxygenase-2 (COX-2) transcription is mediated through the collaboration of different promoter elements. Here, the role of an overlapping cyclic AMP responsive element (CRE)/E-box was investigated. Nuclear proteins bound both the CRE and E-box, which synergized with other promoter elements to induce COX-2 transcription. Endotoxin induced binding of nuclear proteins to the CRE and E-box and each element independently induced higher COX-2 transcription levels than the overlapping CRE/E-box. Transcription factors associated with the CRE binding complex included c-Jun and CRE binding protein and with the E-box binding complex USF-1; their overexpression significantly induced COX-2 transcription. Therefore, both CRE and E-box promoter elements regulate COX-2 transcription in macrophages.
Animals↗
Cathepsin S regulates the expression of cathepsin L and the turnover of gamma-interferon-inducible lysosomal thiol reductase in B lymphocytes.
Loading of antigenic peptide fragments on major histocompatibility complex class II molecules is essential for generation of CD4(+) T cell responses and occurs after cathepsin-mediated degradation of the invariant chain chaperone molecule. Cathepsins are expressed differentially in antigen presenting cells, and mice deficient in cathepsin S or cathepsin L exhibit severely impaired antigen presentation in peripheral lymphoid organs and the thymus, respectively. To determine whether these defects are due solely to the block in invariant chain cleavage, we used cathepsin-deficient B cells to examine the role of cathepsins S and B in the degradation of other molecules important in the class II presentation pathway. Our data indicate that neither cathepsin S nor B is critical for H-2M degradation or processing of precursor gamma-interferon-inducible lysosomal thiol reductase (GILT) to a mature thiol reductase, but suggest a role for cathepsin S in the turnover of mature GILT and in regulating levels of mature cathepsin L protein in B cells. Despite the presence of mature cathepsin L protein, no enzyme activity could be detected in B cells or dendritic cells. These experiments suggest a novel mechanism by which these functionally important enzymes may be regulated.
Animals↗
Recognition and source memory for pictures in children and adults.
The present experiment investigated the developmental aspects of source compared to item memory. College students and 7-8-year-old children viewed pictures drawn in red or green during a study phase, and were asked either to remember the pictures for a subsequent recognition test, or to remember both the pictures and their associated colors for a subsequent source memory test. In the test phase, new and old pictures were presented in black. In the recognition task, participants were asked to make binary old/new recognition judgments, while in the source task, they were asked to make trinary old-green/old-red/new source judgements. Performance on all tasks improved with increasing age, but the age difference for source was much larger than that for item memory. It has been suggested that the frontal lobes play a critical role in the retrieval of source information, and that this brain region relative to the medial temporal lobes continues to develop into late adolescence. Thus, it is possible that immaturity of the frontal lobes may be causally related to the children's lower performance on the source memory task.
Adolescent↗
Prospective evaluation of the morbidity of axillary clearance for breast cancer.
BACKGROUND: Axillary clearance, despite its morbidity, retains an essential role in the management of patients with breast cancer. The aim of this prospective study was to document the development of arm swelling and limitation of shoulder movement following complete axillary clearance. METHODS: One hundred patients who had axillary clearance to level III, for treatment of breast cancer, were followed prospectively for over 1 year. Arm volumes were measured using an optoelectronic volometer and shoulder movements with a goniometer. RESULTS: Ten patients had significant arm swelling at 1 year. The swelling was mild in eight and moderate in two. No patient developed severe swelling. Reduced arm movements were noted in the first week after operation but had returned to normal at 6 months. CONCLUSION: This study provided accurate documentation of the morbidity associated with axillary clearance, together with a reproducible method of arm volume measurement.
Adult↗
Helicobacter pylori: has the killer escaped from the institution? A possible cause of increased stomach cancer in a population with intellectual disability.
Advancing knowledge of the existence of Helicobacter pylori and its association with gastrointestinal tract malignancy, and previous research showing higher-than-expected gastrointestinal tract malignancy in institutionalized adults with intellectual disability (ID) prompted a review of all deaths as a result of cancer in the Stoke Park group of hospitals for people with ID between 1946 and 1996. A 50-year, retrospective case note analysis of all deaths from cancer in an institution for people with ID was undertaken. Death from stomach cancer accounted for up to 48% of all cancer deaths. A further 25 residents had died of perforated stomach ulcers. The higher proportion of deaths specifically caused by stomach cancer in a population with ID has not been noted previously. It is postulated that the high levels of H. pylori infection found in institutionalized populations may be instrumental in this higher mortality rate and that the closure of the institutions without evaluation of H. pylori status transfers the problem unresolved to the community. Existing guidelines for the screening and eradication of H. pylori developed for the general population are inadequate when applied to people with ID, and therefore, the value of population screening and mass eradication programmes is explored.
Cause of Death↗
Breast cancer screening for older women with intellectual disability living in community group homes.
Breast cancer is one of the commonest cancers to affect women. Present health service guidelines call for screening and mammography for all women aged between 50 and 65 years in an effort to increase early detection and improve survival rates. Nulliparity is one of the associated risk factors for breast cancer. Women with intellectual disability (ID) are increasing in longevity and are frequently nulliparous, and therefore, they are at increased risk of developing breast cancer. The aim of the present study was to review the uptake and knowledge of women with ID living in the community of breast screening programmes. A postal survey of women aged > or = 50 years with ID living in community group homes was used to gather data. Only one-third of the women carried out regular breast examination and a similar proportion had received invitations to mammography. General practitioners and practice nurses were currently playing very minor roles in breast screening these women. Primary health care professionals may be missing opportunistic health promotion opportunities and the support services for women with ID living in the community could be provided with better training and resources to improve breast cancer screening in this vulnerable group.
Aged↗
More training is needed in health care of people with learning disabilities.
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Curriculum↗
Helicobacter pylori and the learning disabled.
Those with a learning disability previously cared for in institutions have now been discharged into smaller community homes. This has meant that an increased burden has been placed on general practitioners (GPs) to evaluate and treat those who have symptoms that may be difficult to interpret. This report presents the prevalence of Helicobacter pylori in those still awaiting discharge and discusses the possible symptoms that GPs may encounter.
Adolescent↗
Role of biotin-containing membranes and nuclear distribution in differentiating human endometrial cells.
Human Ishikawa endometrial cells form domes when confluent monolayers are stimulated with fresh fetal bovine serum. Extensive structural and biochemical changes have been detected during the approximately 30 h differentiation period. The earliest detectable change involves the formation of multinucleated structures and the appearance of "granules" that stain for biotin within those structures. Nuclei become associated with each other and are ultimately enclosed within a biotin-containing membrane. Aggregated membrane-sheathed nuclei and the cells containing them begin to elevate from the dish as biotin staining becomes apparent in apical membranes. The elevated structures are called predomes and consist of one or more very large cells containing the sheathed nuclei. Apical membranes of these unusual cells extend far out into the medium in structures that resemble endometrial pinopods. A lumen under the elevated cells fills with transcytosed fluid. As differentiation proceeds, highly concentrated chromatin material that was flattened against apical and lateral membranes of the predome cells begins to disperse. Small mononuclear cells evolve from larger predome cells. Apical membranes of predome and dome cells continue to stain for biotin. Gel electrophoresis of SDS-solubilized biotin-containing membranes, followed by Western blot analysis using avidin-linked peroxidase, resulted in three stained bands with molecular weights similar to those of the mitochondrial carboxylases: propionyl carboxylase, methylmalonyl carboxylase, and pyruvate carboxylase.
Biotin↗
A comparison of purging and nonpurging eating-disordered outpatients: mediating effects of weight and general psychopathology.
OBJECTIVES: The present study compared purging and nonpurging eating-disordered outpatients on key behavioral and psychological features of their disorder. It also investigated the possible mediating effects of current level of depression, anxiety or general psychopathology, and current weight on differences between purgers and nonpurgers. METHOD: Seventy-seven patients from an outpatient eating disorder clinic who purged were compared to 48 clinic patients who did not purge on measures of eating behavior disturbances and specific psychopathology while controlling for weight, level of depression, anxiety, and general distress. RESULTS: Purgers reported significantly more eating behavior disturbance and higher scores on measures of specific psychopathology than the nonpurgers. These differences were unrelated to current weight, level of anxiety, or general distress. However, severity of depression did moderate some of the difference between the groups. CONCLUSION: These data provide further support for the proposition that purging is a distinctive clinical marker in all types of eating-disordered patients.
Adolescent↗
The effect of presemantic acoustic adaptation on semantic "satiation".
A decrement in the strength of the meaning of a word after rapid repetition of that word has been called "semantic satiation." This study asked whether this "satiation" might be produced by presemantic acoustic adaptation. Category words were utilized to prime the meaning of target words. The adaptation or "satiation" procedure, 30 rapid repetitions of the primes, was compared with a control condition of 3 repetitions. Participants listened to a series of prime words, each repeated by either the same speaker or many speakers, and then made semantic decisions on target words. When all the repetitions of a prime word are produced by the same speaker, presemantic and semantic repetitions are confounded. When the repetitions are produced by different speakers, presemantic acoustic repetition is abolished. A semantic decrement was detected with single-speaker, but not with multiple-speaker, repetitions of prime words. This study concluded that the semantic "satiation" observed here was a decrement in the activation level of semantic representations induced by presemantic acoustic adaptation.
Analysis of Variance↗
Released chromatin: linearized DNA for high resolution fluorescence in situ hybridization.
Free DNA was prepared from routinely harvested and fixed cells for high resolution FISH mapping using either a sodium hydroxide/ethanol mixture or 70% formamide. Hybridization signals from cosmid probes appeared as extended lines. The average length of signals on DNA prepared with sodium hydroxide was significantly greater than with formamide. A set of overlapping cosmids from the HLA class II region was used to determine how precisely the actual overlap or gap between probes can be calculated from the measured overlap or gap between their signals. Lengths of the probe signals and their known kilobase lengths were used as an internal ruler. The mean values calculated from the measured length from 30 or more signals for each probe pair showed remarkable conformity with the known kilobase lengths of their overlaps and gaps. Immediately adjacent probes could also be ordered on the released DNA. These simple procedures dramatically increase the speed with which relationships between probes can be determined during contig construction.
Chromatin↗
Epicardial sites for vagal mediation of sinoatrial function.
The posterior atrial fat pad (PAFP) has been described as the probable anatomic location of parasympathetic ganglia mediating sinoatrial (SAN) and atrioventricular nodal function in the mammalian heart. This contrasts with recent localizations of such control elements in the pulmonary vein fat pad (PVFP) and in fatty tissues overlying the junction of inferior vena cava-inferior left atrium (IVC-ILA), respectively. Short bursts (5-8 pulses/burst, 3 bursts/train) of electrical current (1-16 Hz, 400 ms, 1-5 mA) applied directly to the ventral right atrial epicardium via a concentric bipolar electrode (separation 0.3-0.6 mm) during the atrial muscle refractory period, activated subepicardial postganglionic pathways from PVFP and entering the SAN; identical stimulation of dorsal right atrial epicardium between PAFP and SAN excited few or no fiber pathways controlling SAN discharge rate or patterns. In a second series of experiments, injection of a neuronal marker (Fast Blue) into and around SAN, with time (5-10 days) allowed for retrograde transport, resulted in staining of many soma in PVFP but none in IVC-ILA or PAFP. These data strongly affirm the primary, and perhaps exclusive, localization of ganglia that mediate parasympathetic regulation of SAN function in PVFP of the dog's heart, with little or no such participation by ganglia within PAFP or IVC-ILA.
Adipose Tissue↗
Surgical interruption of postganglionic innervation of the sinoatrial nodal region.
Recent experiments have revealed synapses that selectively mediate right and left vagal regulation of sinoatrial function in the fat pad overlying and surrounding the right pulmonary vein complex. However, precise vagal postganglionic pathways to the sinoatrial region have remained obscure. Such pathways, including critically important neural inputs to sinoatrial and atrioventricular nodal regions, may be vulnerable to surgical approaches to atrial or intracardiac repair. The present experiments seek to delineate specific autonomic pathways to the sinoatrial region of the canine heart. The distal ends of the cut right and left cervical vagi and the right and left ansae subclaviae were electrically stimulated (10 to 20 Hz, 1 msec, 2 to 3 V) before and after surgical incisions were placed. Cut No. 1 was made longitudinally along the ventral caval surface from the pericardial reflection caudally to the pulmonary vein fat pad, cut No. 2 was made from the caudal end of cut No. 1 transversely across the sulcus terminalis to a point midway across the anterior (ventral) surface of the right atrium. Each incision was closed with 4-0 silk, with care being taken to avoid injury to either the sinoatrial nodal or the pulmonary fat pad regions. In four of seven animals, these two incisions totally interrupted vagal input to the sinoatrial node, whereas in the remaining three dogs a residual inhibitory influence remained. These residual fibers were surgically ablated by excision of globular fat pads situated on the rostrodorsal surfaces of the right superior pulmonary vein, suggesting a dorsorostral route into the interatrial septum and thence to the sinoatrial node. There was little or no interruption of either right or left vagal input to the atrioventricular nodal region; sympathetic supplies to both sinoatrial nodal and atrioventricular nodal regions remained essentially intact after the two incisions. Thus the major parasympathetic postganglionic projections to the sinoatrial node in the dog heart are by way of the free wall of the right atrium and are vulnerable to surgical interventions in this portion of the heart.
Animals↗
Assessing cultured colonies automatically.
The number of colonies formed by macrophage colony-forming cells and high proliferation potential colony-forming cells was assessed by an image processor. The processor counted and sized colonies accurately, reproducibly, rapidly (2 s/dish) and objectively. The processor also measured the amount of light (in grey levels) the colonies transmitted. The optical density of a colony (the sum of its grey levels) was related to its cellularity. Thus the image processor compared both the number of colonies in samples and their cellularity. Samples of marrow containing high proliferation potential colony-forming cells of different proliferative capacity were prepared by injecting fluorouracil into mice and collecting their marrow 2-10 days later (marrow samples called FU2-FU10). These samples were cultured with one of three sources of synergistic factor titrated over seven dilutions. Colonies contained approx. 5 X 10(4) cells after 11 days culture but the way that FU2-FU10 marrow grew depended on the interval between treating donors with fluorouracil and collecting their marrow. Samples collected 2-4 days after fluorouracil formed more colonies containing more cells with small increases of synergistic factor whereas samples collected after 8-10 days did neither. It was important to culture samples of marrow with the appropriate synergistic factor for the interval after fluorouracil. Factor(s) derived from the 5637 cell line acted optimally on high proliferation potential colony-forming cells in samples collected 2-8 days after fluorouracil, and factor(s) derived from Wehi 3B cells on high proliferation potential colony-forming cells in samples collected 6-10 days after fluorouracil. Factor(s) derived from placental conditioned medium acted well on samples collected between 2 and 10 days. The proliferative capacity of samples of marrow could also be compared by estimating growth curves for high proliferation potential colony-forming cells in samples collected at successive intervals after fluorouracil.
Animals↗