General practice and accident and emergency department care: does the patient know best?
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Ambulatory Care↗
Biomedical subjects
D M Baker
Publications and source records attributed to D M Baker.
Identification of the promoter of the myelomonocytic leukocyte integrin CD11b.
The CD11b (or macrophage-1 antigen; MAC-1) subunit of the leukocyte integrin family forms a noncovalently associated heterodimeric structure with the CD18 (beta) subunit on the surface of human granulocytes and monocyte/macrophages, where it enables these myeloid cells to participate in a variety of adherence-related activities. Expression of the CD11b subunit is restricted to cells of the myelomonocytic lineage and depends upon the stage of differentiation with the most mature myeloid cells expressing the highest levels of CD11b. To study the regulation of CD11b expression, a genomic clone corresponding to the 5' region of the CD11b gene was isolated from a human chromosome 16 library. Primer extension and RNase protection assays identified two major transcriptional start sites, located 90 base pairs and 54 base pairs upstream from the initiation methionine. DNA sequence analysis of 1.7 kilobases of the 5' flanking sequence of the CD11b gene indicated the absence of a "CAAT" or "TATA" box; however, potential binding sites for the transcription activators Sp1, PU.1, ets, and AP-2 are present, as well as retinoic acid response elements. The 1.7-kilobase CD11b promoter sequence displayed functional activity in transient transfection assays in the monocytic cell line THP-1 and the myeloid cell line HL-60. In contrast, this 1.7-kilobase promoter sequence did not display functional activity in the Jurkat T-lymphoid cell line. Detailed characterization of the CD11b promoter sequence should provide insight into the molecular events regulating the tissue-specific and developmental stage-specific expression of the CD11b molecule in myelomonocytic cells.
Amino Acid Sequence↗
Surgical management of the thoracic outlet compression syndrome.
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Female↗
"Transient hyperphosphatasemia of infancy and childhood" in an adult.
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Adult↗
Development of a quantitative histochemical method for determination of succinate dehydrogenase activity in autonomic neurons and its application to the study of aging in the autonomic nervous system.
An accurately validated method was developed for quantitative determination of succinate dehydrogenase (EC 1.3.99.1; SDH) activity in individual sympathetic neuron perikarya by microdensitometric measurement of an SDH-nitroblue tetrazolium-derived formazan final reaction product. Optimal incubation medium and reaction conditions were determined for measurement of reaction product in cryostat sections of rat superior cervical and celiac-superior mesenteric ganglia. The Beer-Lambert laws were verified for the ganglion tissue, and microdensitometric measurements (expressed as mean cell density readings; MCDR/min-1), characteristic of the Michaelis-Menten equation, enabled the results to be used for enzyme kinetic determinations of SDH activity. Km and Vmax values were obtained following Hans linear transformation of the readings. Between the ages of 6-24 months no significant variations in Km values were recorded, indicating an unchanged structure for SDH (overall mean Km = 0.083 +/- 0.055 mM). However, in both ganglia there were significant decreases (ranging from 43-54%) in Vmax values for SDH at 24 months. The overall mean Vmax value at 6 months was 4.01 +/- 0.61 (MCDR) and at 24 months was 2.07 +/- 0.76 (MCDR). This suggests that an overall decrease in metabolic activity takes place with age in sympathetic neurons of the rat superior cervical and celiac-superior mesenteric ganglia.
Aging↗
Isobestic wavelength determination for succinic dehydrogenase-nitroblue tetrazolium-derived formazans in autonomic neurons.
Two methods have been used to determine the isobestic (equiconcentration) wavelength of formazans derived from nitroblue tetrazolium-succinate dehydrogenase (EC 1.3.99.1) activity in cryostat sections of the rat superior cervical ganglion prior to microdensitometric measurements. Both methods indicate that maximal absorbance of the final reaction product is at a wavelength of 540-550 nm. This wavelength differs by 35-45 nm from that used to measure the same reaction product in sections of other rat tissues such as liver and implies that it may be unwise to adopt a "standard" wavelength for a particular reaction product when making microdensitometric measurements in relation to quantitative enzyme histochemistry.
Animals↗
Expression of surface antigen and mRNA for the CD11c (alpha X, p150) subunit of the human leukocyte adherence receptor family in hematopoietic cells.
We characterized the surface antigen and mRNA expression for the CD11c (alpha X, p150) subunit of the human leukocyte adherence receptor family during hematopoietic cell differentiation. The CD11c subunit antigen and mRNA are constitutively expressed in undifferentiated HL-60 promyelocytic leukemia cells, and levels increase markedly with differentiation along the monocyte/macrophage pathway using phorbol myristate acetate. Human monocyte-derived macrophages and human alveolar macrophages express elevated levels of the CD11c subunit antigen and mRNA, indicating that the changes observed in vitro are present in vivo. Dot blot analysis of immature and mature lymphoid and myeloid cells and cell lines demonstrate equivalent levels of CD11c mRNA expression. We conclude that CD11c gene expression is selectively increased during hematopoietic cell differentiation along the monocyte/macrophage pathway.
Antigens, Differentiation↗
Morphometric studies on the microvasculature of pre- and paravertebral sympathetic ganglia in the adult and aged rat by light and electron microscopy.
Morphometric measurements have been made by light and electron microscopy on sections of perfused sympathetic ganglia from rats of 6-24 months of age with special reference to the microvascular bed. Capillaries, postcapillary venules and small venules comprised the majority of the vessels studied but small arterioles were, in addition, included in the light microscopical part of the study. Light microscopical measurements using image analysis showed that there was a decrease in the density of the microvascular bed (number of vascular profiles/area) and in the total vascular luminal area with age in both ganglia. The ratio of neurons to microvessels remained constant in the superior cervical ganglion (SCG) but decreased with age in the coeliac-superior mesenteric ganglion (CSMG). However, the distribution of microvessels in relation to individual neurons remained unchanged throughout life in both ganglia. Ultrastructural studies revealed fenestrations in 12% of SCG microvessel profiles and in 38% of CSMG microvessels at 6 months, but the percentage of fenestrated profiles in the CSMG had declined by 24 months. There were no significant differences in the number of fenestrations per fenestrated profile. The basal lamina surrounding the microvessels increased significantly (almost doubling) in thickness with age. The range and distribution of microvessel wall thicknesses, expressed as harmonic mean wall thickness, were comparable in both ganglia at both ages and increased linearly according to the amount of pericyte covering present. No consistently significant relationships could be discerned between the microvessel wall thickness and luminal diameter or between the wall thickness and the area available to a given volume of blood for exchange of metabolites (luminal perimeter/luminal area). We conclude that the ganglionic capillary bed is similar in both ganglia and, in old age, accommodates structural changes that occur in the ganglion by maintaining its structure and relationship to individual neurons.
Age Factors↗
Image analysis of the sympathetic innervation of the myenteric plexus in the small intestine of mammalian species.
1. The arrangement of the sympathetic innervation of the myenteric plexus varies between mammalian species. 2. In larger mammals the density of sympathetic innervation of the myenteric plexus is significantly less than in small (less then 1 kg) species. 3. The number of varicosities on the terminal parts of sympathetic neurons innervating the gut is significantly less in larger mammals.
Animals↗
cDNA sequence for the alpha M subunit of the human neutrophil adherence receptor indicates homology to integrin alpha subunits.
The receptor on human neutrophils (polymorphonuclear leukocytes) that mediates cellular adherence consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000). We isolated a cDNA clone for the human neutrophil alpha M subunit by screening a lambda gt 11 cDNA library made from chronic myelogenous leukemia neutrophils by using an affinity-purified rabbit polyclonal antibody directed against the alpha M subunit. We used this cDNA clone to obtain additional clones from cDNA libraries made from differentiated HL-60 promyelocytic leukemia cells. Together these cDNAs constitute the complete 1137-amino acid sequence for the mature human alpha M subunit protein. The deduced amino acid sequence indicates the presence of an extensive extracellular domain with three putative metal-binding regions, (i) an amino acid region that is homologous to the A domain of von Willebrand factor, (ii) a 26-amino acid hydrophobic sequence that is a potential transmembrane domain, and (iii) a 19-amino acid cytoplasmic region. The amino acid sequence for the human neutrophil alpha M subunit contains regions that are closely related to amino acid sequences of adhesion receptors belonging to the integrin family.
Amino Acid Sequence↗
Morphometric studies on pre- and paravertebral sympathetic neurons in the rat: changes with age.
Morphometric measurements have been made on rat sympathetic neurons at ages between 6 and 24 months. In neurons of the coeliac-superior mesenteric ganglion there is a marked decrease in the neuronal packing density between 12 and 18 months which is accompanied by increases in the size of the neurons and their nuclei. In the superior cervical ganglion, no changes in packing density are seen until 18 months after which a decrease occurs, accompanied by slight increases in the neuronal parameters. These post-maturation changes occurring throughout adult life reveal a continued dynamism of sympathetic neurons into old age as well as revealing further differences between populations of sympathetic neurons.
Aging↗
A quantitative study of the effects of age on the noradrenergic innervation of Auerbach's plexus in the rat.
Noradrenergic nerves were demonstrated in stretch preparations of Auerbach's plexus and longitudinal muscle from the proximal jejunum of Wistar rats using glyoxylic acid-induced fluorescence. The density of the noradrenergic nerve plexus and the number of nerve terminal varicosities/frame area were assessed using a Quantimet 800 image analyser and the number of varicosities/unit length of nerve was measured manually with a calibrated planimeter. With increasing age, especially between 12 and 18 months there occurs a breakdown of plexus regularity and noticeably reduced levels of axonal fluorescence. Image analysis showed a decrease in the total area of the plexus of more than 50% and a decrease of almost 75% in the total number of varicosities. The frequency of varicosities per 100 micron of axon decreased from 18.79 at 12 months to 14.79 at 18 months. Significant changes in these parameters did not occur during the following 6 months. The dramatic decrease in the density of the noradrenergic innervation of Auerbach's plexus and the fall in number of varicosities with age implies a reduction in the potential of the sympathetic nervous system to influence control over motility of the jejunum in the aged rat.
Aging↗
Enteric neuron numbers and sizes in Auerbach's plexus in the small and large intestine of adult and aged rats.
Neurons in the myenteric plexus of Auerbach of the jejunum, ileum, colon and rectum in 6- and 24-month-old rats have been visualised by an enzyme histochemical method in laminar preparations of the muscularis externa. Neuron somata numbers and sizes were recorded in the preparations. Significant reductions, of at least 40%, in the numbers of neurons in the ganglia of the myenteric plexus of the 24-month animals were recorded in all regions of the intestine, especially in the colon where the neuron number decreased by over 60%. These figures do not take into account changes that might have occurred in the overall length of the intestine during adult life. Measurements of neuron sizes suggest that the neuronal fall-out with age affects all categories of neuron equally and implies that all the intrinsic neuronal systems of the gut could be equally affected in old age.
Aging↗
Persistent depression in coronary bypass patients reporting sexual maladjustment.
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Adaptation, Psychological↗
Cognitive dysfunction after coronary artery bypass surgery: a case-controlled study.
Twenty-two patients screened from a sample of 391 having coronary artery bypass grafting (CABG) showed significant declines on the Mini-Mental State Examination (MMSE) administered preoperatively and four days postoperatively. The MMSE is a 30-point cognitive function screening instrument for dementia and delirium. These patients were compared with 22 matched control subjects who exhibited intact cognitive function postoperatively. The study assessed the association between postoperative cognitive dysfunction and socioeconomic status, potential effects of selected surgical/anesthetic factors, and preoperative anxiety and depression (Zung Anxiety and Center for Epidemiologic Studies-Depression [CES-D] self-rating scales). The results indicate that a higher preoperative level of depression reported on the CES-D (mean score of study patients 22.1 versus 12.7 for controls) is significantly associated with the development of postoperative cognitive dysfunction (P less than .01). The educational and occupational levels of study patients were significantly below those of controls (P less than .01, P less than .02). Occurrence of a postoperative complication was the only surgical/anesthetic factor found to be significantly associated with cognitive dysfunction (P less than .01). These findings suggest that preoperative depression significantly increases the risk for immediate postoperative cognitive dysfunction, and that lower socioeconomic status may confer greater risk for postoperative cognitive morbidity.
Adult↗
Ethanol consumption and free operant avoidance performance following exposure to dietary lead.
Rats were exposed ad libitum to a diet containing either 500 ppm lead (Group Lead-Diet) or a control diet with no added lead (Group Control-Diet). On Day 60 both groups were presented with a 15% ethanol solution (nonchoice test) in the home cage for five days prior to placement on a choice test that presented animals with a 10% ethanol solution and tap water. Concurrently with the choice test in the home cage, animals were placed in operant chambers for one hr (pre-avoidance) prior to a 30 min free operant avoidance session (avoidance) and remained there for one hr (post-avoidance) after training. Throughout avoidance training, the choice test was conducted in the chamber as well as the home cage. In addition to evidence of greater ethanol consumption by Group Lead-Diet rats, the results showed that these animals lever pressed more frequently, but not more efficiently, than Group Control-Diet animals.
Alcohol Drinking↗
Dietary lead increases ethanol consumption in the rat.
Rats fed either a diet containing 500 ppm (parts per million) Pb (as lead acetate) or an unadulterated control diet for 50 days were offered a 15% ethanol (ETOH) solution in a nonchoice (one-bottle) test situation. The results from this test indicated that Pb-diet animals consumed greater amounts of the ETOH solution than did controls. In a subsequent choice (three-bottle, two-fluid) test situation offering a nonpreferred ETOH solution or tap water as alternatives, Pb-diet animals once again ingested greater amounts of the ETOH solution. These findings are discussed in terms of possible Pb-induced increases in emotionality and the potential stress-reduction properties of ETOH.
Alcohol Drinking↗