Holmes and Watson on 'Sherlock'.
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Brain↗
Biomedical subjects
J D Watson
Publications and source records attributed to J D Watson.
Resident continuity clinics: a learning design for group private practice.
Continuity clinics are required for residents in obstetrics and gynecology in the U.S., but are costly and difficult to administer. Organizing them into group resident continuity clinic programs which emulate the group private practice most residents will join, creates a design that is parsimonious of clinic resources, while providing a type of continuity with which patients, nurses, and physicians are familiar and comfortable.
Continuity of Patient Care↗
Locations for renal services--patient satisfaction surveys.
Renal services have been given priority in recent years in an attempt to align them with levels of provision in other European countries. A survey of patients receiving renal replacement therapy in the Northern Ireland Regional Centre, Belfast, was carried out to ascertain their views on services (survey I). After the establishment of a Northern Health and Social Services Board (NHSSB) sub-regional unit in 1995, the survey was repeated for patients attending the new unit (survey II). In survey I, 53% NHSSB patients responded. Travelling time to and from hospital was a major issue for the majority of patients, with 33% of haemodialysis patients receiving twice weekly treatment unwilling to attend more frequently, even if clinically advised to do so. In survey II, 60% of patients responded. Travel times to the sub-regional unit were significantly shorter and patients felt it provided a similar or better standard of service, compared with the regional centre. All the twice weekly haemodialysis patients would increase to thrice weekly if clinically advised to do so. The study underlines the importance of locating dialysis facilities closer to patients' homes.
Chi-Square Distribution↗
Microcystic adnexal carcinoma: a report of three cases.
Microcystic adnexal carcinoma is an uncommon adnexal neoplasm. It is highly aggressive locally and its importance lies in the fact that it can be easily confused with benign adnexal tumours, particularly desmoplastic trichoepithelioma, trichoadenoma and syringoma. We report three cases of microcystic adnexal carcinoma of the skin, all three being on the face: two on the lips and one on the left eyebrow. Clinically, the neoplasms were slow growing indurated nodules or plaques. Two of the cases displayed benign features on initial biopsy and their malignant potential could not be established at that stage. On subsequent review, the three neoplasms showed all the characteristic features of microcystic adnexal carcinoma as described by Goldstein et al. and the University of Virginia study. All three patients were treated by surgery in the form of wide excision. They behaved in a highly locally malignant manner with excisions being incomplete in two of the lesions, in spite of taking an adequate margin around the clinically assessable margins. The other recurred after three years in spite of a histologically proven complete excision. Two of the tumours showed infiltration into the underlying muscle with perineural spread. Wider excision in the next stage with frozen section control achieved good clearance and after a five year follow-up period all are symptom free. None of these tumours showed any evidence of distant spread.
Aged↗
The dilemma of the incapacitated patient who has previously refused consent for surgery.
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Critical Illness↗
Images of the working brain: understanding human brain function with positron emission tomography.
In the past 15 years positron emission tomography (PET) has become a settled method of imaging the functioning human brain, both in normal volunteers and in patients with various disorders. Much of the work on sensory systems has been on the visual system, a conveniently studied and very important part of the brain. The motor system in health and disease has attracted as much interest. In this short review I will explain some of the technical aspects of PET, and illustrate some of the research that has been done on visual and motor brain function in the human.
Brain↗
The activity in human areas V1/V2, V3, and V5 during the perception of coherent and incoherent motion.
We have used the technique of positron emission tomography to study and compare the cortical activity produced when humans view a pattern of small squares moving incoherently with respect to one another and when the same pattern moves coherently and unidirectionally. A stationary version of the stimulus acted as a control. Our choice of paradigm was inspired by psychophysical models and physiological studies in the macaque monkey which show that directionally selective cells in V5 respond optimally to unidirectional coherent motion, whereas those of V1 respond to motion within their receptive fields, regardless of the motion in surrounding parts. Our results show that human V1/V2, V3, and V5 are all activated by both types of motion stimuli. Incoherent motion, however, proved to be more effective than coherent motion in activating V1/V2 and V5. Thus the higher perceptual salience of unidirectional coherent motion in comparison to incoherent motion is not reflected by any increased activation of human area V5.
Adult↗
Genes and politics.
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Biological Evolution↗
Antigen-induced interferon-gamma and interleukin-2 responses of cattle inoculated with Mycobacterium bovis.
Bovine purified protein derivative (PPD)-induced interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) mRNA expression was measured in peripheral blood lymphocyte cultures of cattle inoculated with Mycobacterium bovis and compared to cytokine protein levels as measured by IFN-gamma enzyme-linked immunosorbent assay and IL-2 bioassay. For individual animals, positive correlations were observed between mRNA and protein levels of bovine PPD-induced IFN-gamma and IL-2, although the correlations were stronger for IFN-gamma. Expression of these two cytokines also correlated with responses from a comparative intradermal test and a M. bovis antibody test. At 7 and 20 weeks after inoculation, bovine PPD-induced IFN-gamma and IL-2 mRNA expression was detected in all animals with tuberculous lesions and in a proportion of the M. bovis-inoculated animals with no lesions. Correlation of antigen-induced IFN-gamma and IL-2 with other immune parameters suggests that these two cytokines play an important role in the immune response to bovine tuberculosis.
Animals↗
Priming to mycobacterial antigen in vivo using antigen-pulsed antigen presenting cells generated in vitro is influenced by the dose and presence of IL-4 in APC cultures.
Antigen presenting cells (APC) similar to immature dendritic cells can be generated in vitro from bone marrow precursors. The authors have compared the yield, the phenotype and the function of murine bone marrow cells cultured for 7 or 11 days in either granulocyte macrophage colony stimulating factor alone (GM BMAPC) or in combination with interleukin-4 (GM/IL-4 BMAPC). The results showed that GM/IL-4 BMAPC expressed the highest levels of MHC Class 2 molecules, CD86/B7-2 and CD80/B7-1 co-stimulatory molecules and the lowest levels of F4/80 macrophage marker. However, when these APC were pulsed with BCG culture filtrate antigen or PPD they were not correspondingly more effective at stimulating activated T lymphocytes in vitro or priming naive T lymphocytes in vivo. Also, in contrast to GM BMAPC, high backgrounds recorded following injections of GM/IL-4 BMAPC without antigen were not consistently reduced by lowering the dose and irradiating the cells prior to administration. The authors conclude that the degree of maturity of BMAPC varies with culture conditions and that this may be an important consideration where BMAPC are to be used in vivo in immunotherapeutic regimens.
Animals↗
Immunization with heat-killed Mycobacterium vaccae stimulates CD8+ cytotoxic T cells specific for macrophages infected with Mycobacterium tuberculosis.
Immune responses to Mycobacterium tuberculosis are analyzed in mice which have been immunized with Mycobacterium vaccae to examine novel ways of altering protective immunity against M. tuberculosis. The spleen cells of mice immunized with M. vaccae proliferate and secrete gamma interferon (IFN-gamma) in response to challenge with live M. tuberculosis in vitro. Immunization with M. vaccae results in the generation of CD8+ T cells which kill syngeneic macrophages infected with M. tuberculosis. These effector cytotoxic T cells (CTL) are detectable in the spleen at 2 weeks after immunization with M. vaccae but cannot be found in splenocytes 3 to 6 weeks postimmunization. However, M. tuberculosis-specific CTL are revealed following restimulation in vitro with heat-killed M. vaccae or M. tuberculosis, consistent with the activation of memory cells. These CD8+ T cells secrete IFN-gamma and enhance the production of interleukin 12 when cocultured with M. tuberculosis-infected macrophages. It is suggested that CD8+ T cells with a cytokine secretion profile of the Tc1 class may themselves maintain the dominance of a Th1-type cytokine response following immunization with M. vaccae. Heat-killed M. vaccae deserves attention as an alternative to attenuated live mycobacterial vaccines.
Animals↗
Sacrospinous ligament colpopexy: new instrumentation applied to a standard gynecologic procedure.
Sacrospinous ligament colpopexy continues to be underutilized because of its technical difficulty. The Endo Stitch, a new laparoscopic suturing instrument, was used as a surgical adjunct in the performance of sacrospinous ligament colpopexy in nine patients with vaginal vault prolapse after hysterectomy. The procedures were performed with surprising technical ease.
Female↗
Expression of atrial natriuretic peptide by third-trimester placental cytotrophoblasts in women.
Atrial natriuretic peptide (ANP) is a vasoactive molecule with a potential role in modulating uteroplacental blood flow. We examined the expression of ANP in the third-trimester fetomaternal interface by immunohistochemistry performed on sections of placental tissue as well as by reverse transcriptase-polymerase chain reaction (RT-PCR) and RIA performed on isolated, purified term trophoblasts. Results from immunohistochemical studies on ten normal term placental samples revealed labeling of extravillous interstitial and cytotrophoblastic shell trophoblasts. The trophoblastic identity of the cells was determined by labeling of adjacent serial sections with anti-cytokeratin antibody. Labeling of decidual tissue was also observed in some samples (3 of 10 samples), whereas villous trophoblastic tissue showed no labeling. RT-PCR analysis of RNA extracted from isolated third-trimester trophoblasts revealed the presence of a 0.45-kb and band corresponding to ANP mRNA. Sequencing of the amplified cDNA confirmed its identity. RIA on lysates of isolated trophoblasts revealed the presence of ANP at a level of 41 pg +/- 8 pg/10(7) cells (n = 4; range = 16.8-50.4 pg/10(7) cells). These results indicate that placental cytotrophoblastic tissue is a source of ANP. This molecule might play a role in the regulation of uteroplacental and/or fetoplacental blood flow.
Atrial Natriuretic Factor↗
Nonparametric analysis of statistic images from functional mapping experiments.
The analysis of functional mapping experiments in positron emission tomography involves the formation of images displaying the values of a suitable statistic, summarising the evidence in the data for a particular effect at each voxel. These statistic images must then be scrutinised to locate regions showing statistically significant effects. The methods most commonly used are parametric, assuming a particular form of probability distribution for the voxel values in the statistic image. Scientific hypotheses, formulated in terms of parameters describing these distributions, are then tested on the basis of the assumptions. Images of statistics are usually considered as lattice representations of continuous random fields. These are more amenable to statistical analysis. There are various shortcomings associated with these methods of analysis. The many assumptions and approximations involved may not be true. The low numbers of subjects and scans, in typical experiments, lead to noisy statistic images with low degrees of freedom, which are not well approximated by continuous random fields. Thus, the methods are only approximately valid at best and are most suspect in single-subject studies. In contrast to the existing methods, we present a nonparametric approach to significance testing for statistic images from activation studies. Formal assumptions are replaced by a computationally expensive approach. In a simple rest-activation study, if there is really no activation effect, the labelling of the scans as "active" or "rest" is artificial, and a statistic image formed with some other labelling is as likely as the observed one. Thus, considering all possible relabellings, a p value can be computed for any suitable statistic describing the statistic image. Consideration of the maximal statistic leads to a simple nonparametric single-threshold test. This randomisation test relies only on minimal assumptions about the design of the experiment, is (almost) exact, with Type I error (almost) exactly that specified, and hence is always valid. The absence of distributional assumptions permits the consideration of a wide range of test statistics, for instance, "pseudo" t statistic images formed with smoothed variance images. The approach presented extends easily to other paradigms, permitting nonparametric analysis of most functional mapping experiments. When the assumptions of the parametric methods are true, these new nonparametric methods, at worst, provide for their validation. When the assumptions of the parametric methods are dubious, the nonparametric methods provide the only analysis that can be guaranteed valid and exact.
Algorithms↗
Developmental expression of the collagen-binding heat-shock protein GP46 and collagen types I and IV in rat tissues.
The temporal expression of protein and mRNA encoding the collagen-binding heat-shock glycoprotein, gp46, were determined in the heart, kidney, and lung during early rat postnatal development. The steady-state levels of collagen types I and IV mRNA expression were also examined to determine if gp46 and these collagen types are co-regulated during ontogenesis. Western blot analysis using a monoclonal antibody to gp46 revealed that gp46 levels are developmentally regulated. In heart and kidney, gp46 levels were high on days 3 and 8, reduced significantly on day 25, and low to undetectable on day 69. Protein levels of gp46 in the lung exhibited a similar temporal pattern except on day 3, when very low levels of gp46 were detected. mRNA expression of gp46 during early postnatal development did not correlate with gp46 protein accumulation in these tissues, suggesting a complex pre- and post-translational regulatory scheme. In the heart, protein levels of gp46 correlated well with collagen type I alpha 1(I) mRNA expression but not with collagen type IV alpha 1(IV). In contrast, gp46 protein levels closely paralleled alpha 1(IV) expression in the kidney. Gp46 levels exhibited no apparent correlation with either alpha 1(I) or alpha 1(IV) levels in the lung. These results show that gp46 is developmentally regulated at both the protein and mRNA levels in a tissue specific manner. The relationship between gp46 and collagen alpha 1(I) and alpha 1(IV) chain mRNA expression also has been shown to be tissue specific.
Animals↗
Hyperpnoea during and immediately after exercise in man: evidence of motor cortical involvement.
1. The neurophysiological basis for the increase in breathing associated with exercise remains obscure. The present study uses positron emission tomography (PET) to measure relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during and immediately following exercise. 2. Male volunteers underwent H2(15)O PET scanning during two complementary studies. Firstly, six subjects performed right leg exercise, adequate to increase oxygen uptake 2.5-fold. Secondly, five different subjects were scanned immediately following bicycle exercise (adequate to increase oxygen uptake 5-fold) while breathing was still increased. In each study, as a control, scanning was also performed during matched passive isocapnic positive pressure ventilation; additionally, in the first study, passive right leg movement was performed. 3. Increases in relative rCBF were obtained in each individual and co-registered with their magnetic resonance image of the brain defining individual gyral morphology. 4. During exercise, individual and group analysis revealed significant relative rCBF increases in the left and right superomedial primary motor cortex (the motor cortical 'leg' areas) and also in the left and right superolateral primary motor cortex in areas previously shown to be associated with volitional breathing. After exercise, there was no significant increase in relative rCBF in the superomedial areas but such increases were still present bilaterally in the superolateral areas which had been activated during the exercise. Other relative rCBF increases were also found, both during and after exercise, in cortical and subcortical areas known to be involved in motor control. 5. The results from PET scans during and after exercise, taken together, provide evidence for motor cortical involvement in the exercise-related hyperpnoea in man.
Adult↗
Time-dependent decreases of atrial natriuretic peptide release from the isolated rat atrium: evidence for a readily releasable pool.
In vitro, atrial distension causes a rapid increase in atrial natriuretic peptide (ANP) release. This stretch-induced release, however, declines to baseline levels within minutes without significant depletion of the total hormone stores. It has been observed that the basal rate of ANP release from isolated atria also declines over time despite evidence that the tissue retains its viability. We examined this time-dependency of ANP release from isolated rat atria and some parameters that may explain the diminishing release. Mean ANP secretion was 60 pg/min for both spontaneously beating and electrically paced preparations. Although ANP secretion steadily declined over time, there was no time-dependent effect on the amplitude of intracellularly recorded action potentials. The total ANP content in atria obtained after dissection was 133 +/- 28.9 micrograms/g (n = 3) which was not significantly different from atria that were perfused for 3 h (137 +/- 21.2 micrograms/g; n = 3). Only the 28 amino acid circulating form of ANP was released. The ANP mRNA appeared to be partially degraded in atria after 30 min equilibration or after perfusion for 3 h. These results demonstrated that ANP release from isolated atrial preparations declines steadily despite the maintenance of normal electrophysiological activity. This decline was not due to significant depletion of the ANP stores suggesting that a readily releasable pool of ANP exists and represents only a small fraction of the total hormone stores. Finally, degradation of ANP mRNA implies a reduction of de novo synthesis in our preparation which suggests that the observed depletion of the releasable pool was related to a decline in newly synthesized ANP.
Action Potentials↗
Production of the 19-kDa antigen of Mycobacterium tuberculosis in Escherichia coli and its purification.
The 19-kDa antigen (19Ag) of Mycobacterium tuberculosis (Mt) is a lipoprotein which is released from the organism during growth. In order to study the possible involvement of this antigen in the host protective response against Mt infection, it would be helpful to obtain high-level production of 19Ag from a recombinant organism. We have found that overexpression of the native 19Ag gene in Escherichia coli or yeast leads to products which are aggregated and insoluble. By site-directed mutagenesis of the 19Ag lipoprotein leader sequence, we have generated a mutant gene which directs the production of 19Ag into the periplasmic space of E. coli, from where it can be easily purified in high yield. 19Ag obtained from this mutant construct lacks the lipid-modified N-terminal Cys residue found in the native 19Ag, and is not glycosylated, but is otherwise indistinguishable from 19Ag isolated from Mt culture supernatant.
Amino Acid Sequence↗