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↗
Fractures of the femoral neck after healed intertrochanteric fractures: a complication of too short a nail plate fixation. Report of three cases.
Three cases are described in which a femoral neck fracture developed at least 1 year after a healed intertrochanteric fracture of the femur. Trauma via osteoporotic bone is felt to be the cause. To prevent this complication, a nail extending just to the articular cartilage of the hip joint is needed. This can be accomplished by the displacement osteotomy technique or by the use of the sliding nail-plate into the more stable posterior inferior quadrant of the head.
Aged↗
Evidence for a decrease in sympathetic control of intestinal function in the aged rat.
The ability of carbachol and isoprenaline to contract and relax respectively the longitudinal layer of ileal smooth muscle has been compared in rats aged six and twenty-four months. The concentration response curve to carbachol did not vary with the age of the animal. In contrast, the ability of isoprenaline to relax longitudinal smooth muscle precontracted with carbachol was significantly (p less than 0.02) reduced in the twenty-four month age group. This reduced response was due to a decrease in the maximal relaxation induced by isoprenaline rather than by a shift to the right of its dose-response curve. These results are discussed in the context of previous histochemical and microscopical studies which have shown a marked reduction in the density of the sympathetic innervation of the rat small intestine in old age.
Adrenergic beta-Agonists↗