Microglia emerge from the fog.
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Biomedical subjects
Publications and source records attributed to J Altman.
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OBJECTIVE: To investigate an outbreak of gram-negative folliculitis in relation to a common exposure, mud wrestling, and identify risk factors for dermatitis among those who mud wrestled. DESIGN: Case-control study. SETTING: University of Washington, Seattle. PARTICIPANTS: Two college-residence groups of students. RESULTS: Cultures from affected students and from mud similar to that used for wrestling yielded Enterobacteriaceae. The odds ratio associated with mud wrestling was 79.5 (95% confidence interval, 13.9 to 895.4). Increased time spent wrestling was associated with increased risk. Skin trauma during wrestling or immersion in the mud increased the risk of infection (odds ratio, 23.1; 95% confidence interval, 1.7 to 1440.4). CONCLUSIONS: Mud wrestling is one cause of pustular follicular dermatitis. Trauma to the skin may be a necessary cofactor for the development of infection.
An epidemic often provides an opportunity to obtain evidence of the etiologic association of a microorganism with disease. Chlamydia pneumoniae TWAR is a newly recognized organism whose relationship to disease is not completely understood. An outbreak of C. pneumoniae infections from November 1990 to February 1991 was studied in University of Washington students. Twelve TWAR infections were identified serologically in 54 students with acute respiratory disease. The organism was isolated from 7 of the 12 and identified by the polymerase chain reaction (PCR) in 2 that were isolation-negative. The organism was not found in any of the 42 serologically negative patients or in 51 control student patients without respiratory illness cultured in 1991. There was no evidence of infection with Mycoplasma pneumoniae or respiratory viruses in the 12 patients with C. pneumoniae infection. During the 4-month outbreak, there was an increase in total pneumonia cases. These findings provide evidence for an etiologic association of C. pneumoniae with pneumonia and bronchitis.
This study was performed to examine the effect calcitonin gene-related peptide (CGRP) on blood flow through well-developed coronary collateral vessels. Studies were performed in 9 adult mongrel dogs 4-6 months after embolic occlusion of the left anterior descending coronary artery (LAD) with a hollow intravascular plug to stimulate collateral vessel growth. At the time of study, the LAD was cannulated to determine inter-arterial collateral flow from measurement of retrograde blood flow. Radioactive microspheres were injected during retrograde flow collection to determine continuing tissue flow in the collateral dependent region. CGRP was infused into the left main coronary artery in a dose of 0.2 microgram/kg/min to reach collateral vessels originating from the left coronary system. Retrograde blood flow was 40 +/- 9 ml/min during basal conditions and increased 22 +/- 9% in response to infusion of CGRP (n = 9, p < 0.05). Tissue flow to the collateral-dependent myocardial region did not change in response to CGRP infusion. Isolated rings of epicardial collateral vessels contracted with prostaglandin F2 alpha (PGF2 alpha) underwent relaxation in response to CGRP which was similar in magnitude to that of normal coronary arteries of comparable size. These data demonstrate that CGRP causes vasodilation of well-developed epicardial coronary collateral vessels, resulting in an increase in collateral blood flow.
This study examined responses of coronary collateral blood flow to endothelial-dependent vasodilators. Studies were performed in 13 dogs 4-6 mo after embolic occlusion of the left anterior descending coronary artery (LAD). Collateral flow was determined as the sum of retrograde flow from the cannulated LAD, and continuing tissue flow was measured with microspheres administered during the retrograde flow collection. Agonists were introduced into the left main coronary artery to reach collaterals arising from the left coronary arterial system. The endothelial-dependent vasodilators acetylcholine and bradykinin caused 21 +/- 7 and 25 +/- 8% increases of collateral flow, respectively (each P < 0.05). This was not different from the 28 +/- 8% increase in collateral flow produced by nitroglycerin. To determine whether vasodilator prostaglandins contributed to the increased collateral flow, studies were performed after cyclooxygenase blockade with indomethacin (5 mg/kg iv). Indomethacin caused a 30 +/- 9% decrease of retrograde flow during basal conditions but did not blunt the maximum collateral flow rates produced by acetylcholine, bradykinin, or nitroglycerin. These data demonstrate intact endothelial-dependent vasodilator mechanisms in the well-developed coronary collateral circulation.
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Collateral vessels that develop after coronary artery occlusion demonstrate perivascular inflammation, subintimal hyperplasia, and endothelial proliferation. This study was performed to test the hypothesis that these abnormalities are associated with evidence for increased production of vasodilator prostaglandins. Eight dogs were studied 4-6 months after occlusion of the anterior descending coronary artery had been performed to stimulate collateral vessel growth. At the time of study, the anterior descending coronary artery was cannulated at the site of occlusion to allow measurement of retrograde blood flow as an index of interarterial collateral flow. Injection of radioactive microspheres during the retrograde flow collection allowed determination of continuing tissue flow in the collateral-dependent zone as an index of intramural microvascular collateral flow. Retrograde and tissue flows were measured before and 20 minutes after 5 mg/kg i.v. indomethacin, a dose that caused 95 +/- 3% inhibition of the coronary vasodilation in response to a 500 micrograms intracoronary bolus of arachidonic acid. Heart rate and mean aortic pressure were not significantly altered by indomethacin, and blood flow to the normally perfused myocardial region was not changed by administration of indomethacin. However, indomethacin caused a 40 +/- 7% decrease in retrograde flow (p less than 0.01), and microvascular collateral flow to the dependent myocardium decreased by 20 +/- 10% (p less than 0.05). These data indicate that, unlike the normal coronary circulation, well-developed coronary collateral vessels are under the tonic influence of vasodilator prostaglandins.
Nuclear area and orientation in the subventricular and intermediate zones was studied quantitatively in coronal vs. sagittal sections of the dorsomedial neocortex. Nissl-stained methacrylate-embedded normal rat embryos were studied between embryonic days (E) 13 and E22. The area of nuclear profiles and the degrees their long axes (defined as a straight line through the two most distant points in the nuclear profile) deviated from the horizontal (defined as parallel to the pial membrane) were determined with a computer-graphics program. Because the nucleus is the most clearly outlined structure in embryonic cells, the area and orientation of the nucleus was taken to reflect the overall size and orientation of the cell body. Nuclear area is larger in the coronal plane than it is in the sagittal plane, especially between E17 and E20. Cell body orientation in the subventricular and lower intermediate zones is predominantly horizontal in the coronal plane and predominantly vertical in the sagittal plane. In the upper intermediate zone, cell body orientation is predominantly vertical in both planes, but more so in the sagittal plane. These data indicate that the majority of cell bodies in the subventricular and lower intermediate zones have a horizontally oriented, flattened elliptical shape with their larger diameters lying within the coronal plane and their smaller diameters in the sagittal plane. Because of the flattening, the cell bodies falsely appear to be vertically oriented in the sagittal plane. Qualitative observations in horizontal sections confirmed the quantitative computer analysis. These results are related to other findings with [3H]thymidine autoradiography concerning cell migration and the sojourn of cells in the subventricular and intermediate zones.
Three-dimensional reconstructions of the normal rat embryonic (E) neocortex on days E15, E17, E19, and E21, using Skandha (software designed by J. Prothero, University of Washington, Seattle), show that the neocortical ventricular zone shrinks rapidly in the medial direction during cortical morphogenesis. [3H]thymidine autoradiography indicates that the shrinkage of the ventricular zone occurs before neurons in lateral and ventrolateral parts of layers IV-II are generated. Consequently, most of these neurons originate 400-1000 microns medial to their settling sites in the cortical plate. Embryos killed at daily intervals up to E21 after a single injection of [3H]thymidine on either E17 or E18 revealed the presence of a prominent migratory path, the lateral cortical stream, used by neurons migrating to the lateral and ventrolateral cortical plate; neurons migrating to the dorsal cortical plate follow a direct radial path. Arrival times of neurons in the cortical plate depend on the migratory path and are proportional to the overall distance travelled. Neurons that migrate only radially arrive in the dorsal cortical plate in two days (shortest route). Neurons that migrate laterally arrive in the lateral cortical plate in 3 days (longer route) and in the ventrolateral cortical plate in 4 days (longest route). [3H]thymidine autoradiography also shows that cells generated in the neocortical ventricular zone migrate in the lateral cortical stream for 5 or more days and accumulate in a reservoir. Cells leave the reservoir to enter the piriform cortex and destinations (as yet undetermined) in the basal telencephalon. The lateral cortical stream is found wherever the neocortical primordium surrounds the basal ganglia and is absent behind the basal ganglia. A computer analysis of nuclear orientation in anterior and posterior parts of the intermediate zone in the dorsal neocortex between days E17 and E22 shows that horizontally oriented nuclei are more common anteriorly where many cells are migrating laterally than posteriorly where most cells are migrating radially.
We describe a 48-year-old, previously healthy, anti-Ro/SS-A and anti-La/SS-B antibody positive black woman with negative risk factors for atherosclerosis, who developed mental status and personality changes over a 6-12-month period, and progressive cortical blindness over a 2-week period. Angiographic and computed axial tomographic studies of the brain demonstrated multiple large areas of infarction correlating with stenosis and occlusions of the internal carotid and posterior cerebral arteries. Moya moya-like findings were prominent radiographically. Results of angiographic, computed tomographic, and magnetic resonance imaging studies were interpreted as being compatible with large, medium, and small vessel disease, most likely a vasculitis.
Long-survival [3H]thymidine autoradiography was used to quantitatively determine the time of origin of neurons in the endopiriform nucleus and the claustrum in rats killed on postnatal day 60 after their dams received two consecutive daily injections of [3H]thymidine on embryonic day E13 and E14, E14 and E15, ... E21 and E22. The claustrum originates late, on E15 and E16, and has a strong gradient in the longitudinal direction, posterior (older) to anterior (younger). In contrast, the endopiriform nucleus originates early, on E14 and E15, and lacks a longitudinal gradient but has a strong one in the vertical direction, ventral (older) to dorsal (younger). Sequential-survival [3H]thymidine autoradiography was used to qualitatively determine the germinal sources and settling sites of endopiriform and claustral neurons in embryonic rats. The dams received a single injection of [3H]thymidine on either E14 (to heavily label older endopiriform neurons) or E16 (to heavily label younger claustral neurons) and were killed in sequential 24-h intervals. Neurons in the presumptive endopiriform nucleus settle within two to three days after their peak time of neurogenesis while those in the presumptive claustrum take approximately five days to settle after their peak. It is postulated that endopiriform neurons are generated in the palliostriatal ventricular angle, the neuroepithelium that forms a wedge between the primordia of the neocortex and the basal ganglia, and that claustral neurons are generated in the neocortical neuroepithelium. Divergent developmental patterns between the endopiriform nucleus and the claustrum support the anatomical evidence that these nuclei have different connections. Furthermore, neurogenetic gradients in the claustrum correlate with the pattern of anatomical connections between the claustrum and the neocortex.
The authors describe how computerization helped to improve materiel management in the OR, including inventory control and purchasing, and how they acutally enabled them to recoup lost revenue.
This study deals with the site of origin, migration, and settling of the principal cell constituents of the rat hippocampus during the embryonic period. The results indicate that the hippocampal neuroepithelium consists of three morphogenetically discrete components--the Ammonic neuroepithelium, the primary dentate neuroepithelium, and the fimbrial glioepithelium--and that these are discrete sources of the large neurons of Ammon's horn, the smaller granular neurons of the dentate gyrus, and the glial cells of the fimbria. The putative Ammonic neuroepithelium is marked in short-survival thymidine radiograms by a high level of proliferative activity and evidence of interkinetic nuclear migration from day E16 until day E19. On days E16 and E17 a diffuse band of unlabeled cells forms outside the Ammonic neuroepithelium. These postmitotic cells are considered to be stratum radiatum and stratum oriens neurons, which are produced in large numbers as early as day E15. A cell-dense layer, the incipient stratum pyramidale, begins to form on day E18 and spindle-shaped cells can be traced to it from the Ammonic neuroepithelium. This migratory band increases in size for several days, then declines, and finally disappears by day E22. It is inferred that this migration contains the pyramidal cells of Ammon's horn that are produced mostly on days E17 through E20. The putative primary dentate neuroepithelium is distinguished from the Ammonic neuroepithelium during the early phases of embryonic development by its location, shape, and cellular dynamics. It is located around a ventricular indentation, the dentate notch, contains fewer mitotic cells near the lumen of the ventricle than the Ammonic neuroepithelium, and shows a different labeling pattern both in short-survival and sequential-survival thymidine radiograms. By day E18, the reduced primary dentate neuroepithelium is surrounded by an aggregate of proliferative cells; this is the secondary dentate matrix. On the subsequent days spindle-shaped cells that have retained their proliferative capacity migrate from the progressively receding secondary dentate matrix to the dentate gyrus itself. The latter, representing a tertiary germinal matrix, becomes highly active during the perinatal period. The putative fimbrial glioepithelium is situated between the primary dentate neuroepithelium and the tip of the hippocampal rudiment. Observations in methacrylate sections and thymidine radiograms suggest that the cells of this germinal matrix, unlike typical neuroepithelial cells, do not undergo interkinetic nuclear migration.(ABSTRACT TRUNCATED AT 400 WORDS)
In radiograms of rat embryos that received a single dose of [3H]thymidine between days E16 and E20 and were killed 24 hours after the injection, the heavily labeled cells (those that ceased to multiply soon after the injection) form a horizontal layer in the intermediate zone of the hippocampus, called the inferior band. The fate of these heavily labeled cells was traced in radiograms of the dorsal hippocampus in embryos that received [3H]thymidine on day E18 and were killed at different intervals thereafter. Two hours after injection the labeled proliferative cells are located in the Ammonic neuroepithelium. The heavily labeled cells that leave the neuroepithelium and aggregate in the inferior band 1 day after the injection become progressively displaced toward the stratum pyramidale 2-3 days later, and penetrate the stratum pyramidale of the CA1 region on the 4th day. In the stratum pyramidale of the CA3 region, farther removed from the Ammonic neuroepithelium, the heavily labeled cells are still sojourning in the intermediate zone 4 days after labeling. Observations in methacrylate sections suggest that two morphogenetic features of the developing hippocampus may contribute to the long sojourn of young pyramidal cells in the intermediate zone: the way in which the stratum pyramidale forms and the way in which the alveolar channels develop. The stratum pyramidale of the CA1 region forms before that of the CA3 region, which is the reverse of the neurogenetic gradient in the production of pyramidal cells. We hypothesize that this is so because the pyramidal cells destined to settle in the CA3 region, which will be contacted by granule cells axons (the mossy fibers), have to await the formation of the granular layer on days E21-E22. Concordant with this is the observation that the hippocampal intermediate zone, which contains the sojourning young pyramidal cells, greatly enlarges between days E16 and E20, then suddenly diminishes and disappears by day E22. The other factor that may contribute to the prolonged sojourn of pyramidal cells, specifically those destined to settle in the CA1 region, is the pattern of alveolar channel development. This transient extracellular matrix begins to form several days after the onset of pyramidal cell neurogenesis, grows in a direction opposite to the settling of pyramidal cells in the stratum pyramidale, and does not reach the subicular end of Ammon's horn until day E21.(ABSTRACT TRUNCATED AT 400 WORDS)
Methacrylate-embedded sections and short-survival thymidine radiograms of the hippocampal dentate gyrus were examined in perinatal and postnatal rats in order to trace the site of origin and migration of the precursors of granule cells and study the morphogenesis of the granular layer. The densely packed, spindle-shaped cells of the secondary dentate matrix (a derivative of the primary dentate neuroepithelium) stream in a subpial position towards the granular layer of the internal dentate limb during the perinatal and early postnatal periods. By an accretionary process, the crest of the granular layer forms on day E21 and on the subsequent days the granular layer of the internal dentate limb expands progressively in a lateral direction. Granule cells differentiation, as judged by the transformation of polymorph, darkly staining small cells into rounder, lightly staining larger granule cells, follows the same gradient from the external dentate limb to the internal dentate limb. The secondary dentate matrix is in a process of dissolution by day P5. This matrix is the source of what will later become the outer shell of the granular layer composed of early generated granule cells. The thicker inner shell of the granular layer, formed during the infantile and juvenile periods, derives from an intrinsic, tertiary germinal matrix. On day E22, the dentate migration of the secondary dentate matrix becomes partitioned into two components: a) the subpial component of extradentate origin, referred to in this context as the first dentate migration, and b) the second dentate migration. The latter is distributed in the basal polymorph layer throughout the entire dentate gyrus and is henceforth recognized as the tertiary dentate matrix. The tertiary dentate matrix is prominent between days P3 and P10. It is postulated that the great increase in granule cell population during the infantile period is principally due to cells derived from this intrinsic matrix of the dentate gyrus. Between days P20 and P30 the tertiary dentate matrix disappears in the basal polymorph layer and henceforth proliferative cells become largely confined to the subgranular zone at the base of the granular layer. The subgranular zone is the source of granule cells produced during the juvenile and adult periods.
We report complete sequence-specific proton resonance assignments for the trypsin-solubilized microsomal ferrocytochrome b5 obtained from calf liver. In addition, sequence-specific resonance assignments for the main-chain amino acid protons (i.e., C alpha, C beta, and amide protons) are also reported for the porcine cytochrome b5. Assignment of the majority of the main-chain resonances was rapidly accomplished by automated procedures that used COSY and HOHAHA peak coordinates as input. Long side chain amino acid spin system identification was facilitated by long-range coherence-transfer experiments (HOHAHA). Problems with resonance overlap were resolved by examining differences between the two-dimensional 500-MHz NMR spectra of rabbit, pig, and calf proteins and by examining the temperature-dependent variation of amide proton resonances. Calculations of the aromatic ring-current shifts for protons that the X-ray crystal structure indicated were proximal to aromatic residues were found to be useful in corroborating assignments, especially those due to the large shifts induced by the heme. Assignment of NOESY cross peaks was greatly facilitated by a prediction of intensities using a complete relaxation matrix analysis based on the crystal structure. These results suggest that the single-crystal X-ray structure closely resembles that of the solution structure although there is evidence that the solution structure has a more dynamic character.
Cellular compartmentation was studied in the germinal matrices (the primary neuroepithelium and the subventricular zone) of the rat cerebral cortex at successive stages of embryonic development. Three sets of materials were used: methacrylate-embedded brain sections from normal embryos, autoradiograms from embryos labeled with [3H]thymidine, and methacrylate-embedded sections from embryos exposed to 200 R X-ray. Examination of normal specimens showed that between Embryonic Day 12 (E12) and E15 the cortical germinal matrix consists only of a primary neuroepithelium. By Day E16, a subventricular zone has formed in the early developing ventrolateral aspect of the cortex. The subventricular zone grows in depth for several days, while at the same time the depth of the neuroepithelium decreases. Examination of short-survival thymidine radiograms revealed that the labeled cells do not form a continuous band in the neuroepithelium but aggregate in patches reminiscent of bunches of grapes strung one a line. It is postulated that this vertical periodicity is due to the alternation of cell aggregates with short and long cell cycle times. Finally, examination of the cortical neuroepithelium in rats exposed to 200 R X-ray showed that there is an alternation of radiosensitive (collapsing) and radioresistant (intact) patches that roughly correspond in size to the labeled and unlabeled patches seen in autoradiograms. Additional observations concern the onset of local cell proliferation in the white matter at late stages of fetal development and the transformation of the neuroepithelium into a matrix producing ependymal cells.