Biomedical subjects
J Rogers
Publications and source records attributed to J Rogers.
Molecular biology. CACA sequences - the ends and the means?
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A common sequence of calcium and pH signals in the mitogenic stimulation of eukaryotic cells.
When normal quiescent (G0) cells are stimulated by mitogens to enter the cell cycle, the metabolic derepression which occurs is similar in a variety of cells. The mechanisms initiating these responses and their relationship to subsequent progression through G1 to DNA synthesis in S phase, however, are generally undefined. The clearest evidence has been obtained in sea urchin eggs, where fertilization by sperm causes a rapid, transient increase in the concentration of free cytoplasmic Ca2+ [(Ca]i), followed by a sustained increase in cytoplasmic pH (pHi). It has been demonstrated clearly that these ionic responses are obligatory for progression to DNA synthesis by the normal pathway after fertilization, although the Ca2+ signal can be bypassed by parthenogenetic agents which elevate directly pHi (for example, NH+4 ions). These observations raise the questions of whether other eukaryotic cells show the same sequence of ionic responses when stimulated by mitogens and whether such signals are an obligatory component of their mitogenic pathways. We show here that a common sequence of [Ca]i and pHi responses occurs in both quiescent mouse thymocytes and Swiss 3T3 fibroblasts stimulated by appropriate mitogens. Furthermore, 'opportunistic' mitogens (those that do not act on the cells in vivo, such as concanavalin A (Con A), the Ca2+ ionophore A23187 and 12-o-tetradecanoyl phorbol 13-acetate CTPA] that are mitogenic for both mouse thymocytes and 3T3 fibroblast, each produce characteristic ionic responses that are the same in both types of cell.
Somatostatin immunoreactivity in neuritic plaques of Alzheimer's patients.
Senile dementia of the Alzheimer's type can be diagnosed with certainty only by examining neurofibrillary tangles and neuritic plaques under the microscope. Recently, it has been suggested that the condition is linked to specific neurotransmitter systems, with a decline of cortical acetylcholine, choline acetyltransferase, cholinergic neurones projecting to the cortex, cortical noradrenaline content, locus coeruleus neurones and cortical somatostatic content. Using immunocytochemical methods, we here report that somatostatin-immunoreactive processes are present in neuritic plaques in human Alzheimer's specimens. These data, as well as other reports of non-cholinergic changes, strongly imply that Alzheimer's disease cannot be linked exclusively to cortical cholinergic elements, as proposed previously. Rather, our data on plaque and somatostatin co-localization and distribution patterns suggest that Alzheimer's neuropathology may involve primarily the loss of selective cortical neurones that are targets of the implicated transmitter systems and that plaque formation may result from the degeneration of presynaptic and postsynaptic neurites of large projection neurones in layers III and V. Given the neurochemically heterogeneous input to these cells, it is not surprising that several neurotransmitter systems, one of which is somatostatin, are implicated in the pathology of Alzheimer's disease.
Exon shuffling and intron insertion in serine protease genes.
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Oncogene chromosome breakpoints and alu sequences.
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Age-impaired impulse flow from nucleus basalis to cortex.
Recent studies have renewed interest in the role of acetylcholine (ACh) in the cognitive changes associated with ageing and dementia. Deficits in cortical choline acetyltransferase (ChAT) in Alzheimer's disease have been consistently demonstrated, while other research has suggested a connection between deterioration of cortical ACh fibres and dementia. However, despite clear biochemical and anatomical evidence for a fall in ACh in dementia, results of therapeutic trials with cholinergic agonists, precursors and cholinesterase inhibitors have been inconsistent. Such findings suggest that cortical cholinergic disorders are not wholly a function of simple biochemical change; alterations of impulse flow along cholinergic fibres could well be as debilitating. An important extrinsic source of cortical ACh innervation derives from neurones diffusely located in rat basal forebrain, denoted the nucleus basalis (NB). We have now investigated the impulse conduction properties of cortically projecting, putatively cholinergic NB axons in adult and aged rats and have found that conduction latencies from NB to frontal cortex are significantly longer (by 51%) in aged animals. In addition, systematic analysis varying cortical stimulation depth revealed that these longer latencies are due entirely to decreased conduction velocities in the subcortical fibre projections. Indeed, intracortical velocities were virtually identical in the two groups. Our results indicate that ageing occasions a decrease in the temporal fidelity of impulse flow in the cholinergic input to the cortex from the NB, a previously overlooked but potentially important element in cognitive deficits that occur with age.
Modelling and reclassification of surgical procedures--experiences from the use of GALEN methods in the domain of thoracic surgery.
This paper reports on experiences from the evaluation of GALEN methods for mapping of follow-up categories in the domain of thoracic surgery to an existing classification of surgical procedures. The mapping of the aggregated levels or groups of thoracic procedures presents a genuine problem in relation to strict hierarchical classifications, since the follow-up categories do not necessarily fit in the pre-set structure of the classification. Experiences from modelling of the traditional classification and of the follow-up categories are reported, and an analysis of the results is presented along with a discussion of opportunities and potential problems and pitfalls when applying GALEN models and tools.
Chronic beryllium disease and beryllium sensitization at Rocky Flats: a case-control study.
A case-control study was conducted to evaluate the risk of chronic beryllium disease (CBD) and beryllium sensitization (SENS) associated with various levels of historical beryllium exposure at the Rocky Flats nuclear weapons facility. Fifty CBD and 74 SENS cases were matched to controls of the same age group, race, gender, and smoking status. A job exposure matrix was developed from job history data and fixed airhead (FAH) exposure data available from 1960 to 1988. Job titles and building areas were assigned factors based on exposure relative to a machinist in the Building 444 Beryllium Shop. Concurrence on these factors was obtained from past and present Rocky Flats industrial hygienists. Using the matrix, long-term mean and cumulative exposures were estimated for each subject. Both exposure estimates (p < 0.0001) and years of employment (p = 0.010) were found to be significantly higher for CBD cases as compared with their controls, but not so for the SENS cases as compared with their controls. Logistic regression analyses showed statistically significant relationships between both cumulative and mean exposure and CBD, but not for SENS. These findings suggest that reduced worker exposures might lower the future incidence of CBD, but may not necessarily lower the incidence of SENS.
Gender and patient satisfaction with primary care: tuning in to women in quality measurement.
This study analyzes the relationship between patient gender and satisfaction with primary care visits, using 1999 survey data on 1691 women and 760 men making primary care visits at multiple sites affiliated with a large academic health system designated as a National Center of Excellence in Women's Health (COE). The main findings are that in multivariate analyses controlling for patient and visit characteristics, different aspects of the content of primary care visits are important to women and men. Women's overall satisfaction with visits is more dependent than men's on informational content, continuity of care, and multidisciplinarity. Men's overall satisfaction is more dependent on the personal interest shown in them by providers. No differences in satisfaction are found between those seen in sites affiliated with the COE and other primary care sites within the health system that are not core sites of the COE. We conclude that quality improvement and research in women's primary care could benefit from gender analysis of patient satisfaction data and from more gender-sensitive patient satisfaction measures.
How risky are hot tubs and saunas for pregnant women?
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The VA psychiatric patient resocialization and community living.
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Arthritis in Saxon and mediaeval skeletons.
Examination of 400 Saxon, Romano-British, and mediaeval skeletons from seven archaeological excavations in the west of England showed an unexpectedly high incidence of osteoarthritis and osteophytosis. Three skeletons had evidence of an erosive peripheral arthritis-one with probable gout, one probable psoriatic arthropathy, and one with possible rheumatoid arthritis. The pattern and types of rheumatic disease, and the resultant disability, were apparently different. An exuberant form of large joint osteoarthritis was common and rheumatoid arthritis and similar diseases rare.
Correlation of the expression level of C1q mRNA and the number of C1q-positive plaques in the Alzheimer Disease temporal cortex. analysis of C1q mrna and its protein using adjacent or nearby sections.
We compared the expression level of C1q mRNA and the number of C1q-positive plaques in adjacent or nearby brain sections from Alzheimer disease (AD) and control cases. Small blocks of temporal cortex were fixed with 4% paraformaldehyde for 2 days at 4 degrees C. After cryoprotection with solutions containing 10-20% glycerol and 2% dimethylsulfoxide, 40-microm sections were cut from the tissue blocks. A section from each case was stained by immunohistochemistry using a C1q antibody, while RNA was purified from adjacent or nearby sections using a combination of proteinase K pretreatment followed by extraction using Trizol reagent. The expression of C1q B chain mRNA was analyzed in these samples by the reverse-transcription polymerase chain reaction (RT-PCR). The intensities of the PCR products were measured by an image analyzer. The expression of C1q B chain mRNA was significantly more abundant in AD than in control cases (p < 0.05). Immunohistochemical analysis showed that C1q protein was localized in senile plaques in the AD brain. The number of C1q-positive plaques correlated with the expression level of C1q gene (p < 0.05). The present results suggest that C1q protein in senile plaques originates is endogenously produced in the AD brain.
A statement of assumptions and principles concerning education about life-threatening illness, death, dying, and bereavement for volunteers and non-professionals. International Work Group on Death, Dying and Bereavement.
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