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Biomedical subjects

D A Lewis

Publications and source records attributed to D A Lewis.

At least 235 records · Page 13Linked to original sources
PubMed1990

The management of lead exposure in pediatric populations.

Chronically elevated lead levels are a common problem affecting children. Although this problem occurs most frequently in the inner city, no community is safe from excessive pediatric lead exposure. Screening by erythrocyte protoporphyrin is a sensitive early indicator of rising lead levels. A Centers for Disease Control report recommends that all children be screened starting at 9 to 12 months. A classification system of various lead levels helps determine proper treatment. Health care practitioners need to be well-informed about lead exposure and how it occurs in order to educate parents.

Child, Preschool↗
PubMed1989

Corticotropin-releasing factor immunoreactivity in monkey neocortex: an immunohistochemical analysis.

Corticotropin-releasing factor (CRF) has been implicated in the pathophysiology of certain human neuropsychiatric disorders that affect neocortical function. However, the anatomical organization of CRF-containing structures in the expanded and highly differentiated primate neocortex has not been previously described. In this study, the distribution of CRF-immunoreactive neurons and processes was characterized in the neocortex of New World squirrel monkeys (Saimiri sciureus). Substantial regional differences were present in the density, laminar distribution, and morphological appearance of CRF-immunoreactive neurons. The greatest density of labeled neurons was present in anterior cingulate cortex. A wide range of intermediate densities of CRF-immunoreactive neurons was evident in the association regions of the prefrontal, parietal, and temporal cortices. The lowest numbers of CRF-immunoreactive neurons were observed in the primary visual and primary motor cortices. For example, the density of labeled neurons was nearly five times greater in the anterior cingulate cortex than in the precentral cortex. CRF-immunoreactive neurons were also distributed in at least four different laminar patterns. For example, in the agranular anterior cingulate cortex, labeled cell bodies were distributed throughout layers II, III, and V. In other regions, such as the posterior cingulate cortex, labeled neurons were present in layers II, III, and IV. In contrast, labeled neurons were predominantly present in layers II and superficial III of the visual cortex, whereas in the inferior temporal cortex, they were present predominantly in layer IV. Regional and laminar differences were also present in the relative distributions of the two major morphological types (as defined by cell body shape) of CRF-immunoreactive neurons. Vertically oriented oval neurons, which frequently had a single dendritic process arising from each somal pole, were most frequently found in layer III. In contrast, the labeled neurons in layers II and IV tended to have a round- or triangular-shaped soma. In layer IV of some association cortices, these multipolar neurons were associated with a high density of rod-like structures composed of large immunoreactive varicosities clustered together in vertical arrays. These structures were frequently found to be located immediately below the soma of pyramidal neurons. Comparison of these findings with Golgi impregnation studies strongly suggests that CRF is present in the soma and axonal cartridges of a subset of chandelier neurons. The heterogeneous distribution and morphological diversity of CRF-containing neurons suggest that CRF may mediate distinct functions in different regions and layers of monkey neocortex.

Animals↗
PubMed1989

Antibodies directed against tyrosine hydroxylase differentially recognize noradrenergic axons in monkey neocortex.

In previous immunohistochemical studies of monkey neocortex, we found that antisera directed against tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) appeared to label distinct populations of neocortical axons, which presumably were dopaminergic and noradrenergic, respectively. In the present study, we further evaluated the apparent selectivity of this rabbit anti-TH antiserum for cortical dopaminergic fibers in monkeys by comparing it with two other anti-TH antibodies, a mouse monoclonal and a sheep polyclonal. In addition, the latter two anti-TH antibodies were used in double-labeling studies with a rabbit anti-DBH antiserum. In both single- and dual-label studies, each anti-TH antibody visualized a similar population of cortical axons, although the number of labeled fibers differed across antibodies. That is, in some cortical regions and layers, both the sheep and mouse anti-TH antibodies labeled more cortical fibers than did the rabbit anti-TH antiserum. Thus, the former two antibodies appeared to identify a subpopulation of TH-containing fibers that the latter antibody did not. Dual-label experiments, involving the rabbit anti-DBH antiserum and either the sheep or mouse anti-TH antibodies, demonstrated numerous neocortical DBH-immunoreactive axons in which TH was not detectable immunohistochemically. The percentage of DBH-immunoreactive fibers that were single-labeled differed across cortical regions and with the anti-TH antibody employed. For example, in primary motor cortex the mouse anti-TH antibody did not label 99.4% of the DBH-positive fibers, whereas in primary visual cortex, 76.4% of the DBH-immunoreactive axons were identified by the sheep anti-TH antibody. The results of these studies indicate that many DBH-immunoreactive, presumably noradrenergic, axons in monkey neocortex are not visualized by anti-TH antibodies, and that the ability of anti-TH antibodies to identify noradrenergic cortical axons in monkeys differs substantially among anti-TH antibodies and across cortical regions. These findings may be consistent with previous reports suggesting that the TH molecule is present in different concentrations or molecular forms in dopaminergic and noradrenergic cortical fibers. Finally, this study demonstrates that the labeling characteristics of a particular anti-TH antibody must be carefully evaluated, particularly in studies of primate neocortex, in order to properly interpret the results of those studies.

Adrenergic Fibers↗
PubMed1989

Investigation of the mechanism of CTP synthetase using rapid quench and isotope partitioning methods.

The UTP-dependent ATPase reaction and the glutamine-dependent overall reaction of Escherichia coli CTP synthetase have been studied by rapid quench and isotope partitioning kinetics. The effect of GTP, an allosteric effector, on the pre-steady-state kinetics of both reactions has also been examined. The time courses of the UTP-dependent ATPase reaction in the presence and absence of GTP are both characterized by a burst of acid-labile phosphate equivalent to 0.93 and 0.43 subunits, respectively. The time course of the glutamine-dependent reaction in the absence of GTP is also characterized by a burst of acid-labile phosphate corresponding to 0.8 subunit; however, in the presence of GTP, no burst was observed. These results along with positional isotope exchange experiments [von der Saal, W., Anderson, P. M., & Villafranca, J. J. (1985) J. Biol. Chem. 260, 14997] provide evidence that the mechanism of CTP formation involves phosphorylation of UTP followed by attack of NH3, and finally release of phosphate, producing CTP, ADP, and Pi. A kinetic model for the first stages of the enzymatic reaction was developed from the rapid quench data, and the internal equilibrium constant for the formation of the phosphorylated UTP intermediate was determined. The internal equilibrium constants for the UTP-dependent reaction in the presence and absence of GTP were found to be 1.1 and 18, respectively. By contrast, the internal equilibrium constant for the reaction in the presence of glutamine was 50. Thus, the presence of glutamine shifts the internal equilibrium constant to favor formation of the phosphorylated UTP intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1989

Noradrenergic innervation of monkey prefrontal cortex: a dopamine-beta-hydroxylase immunohistochemical study.

Norepinephrine has been implicated in the regulation of a number of cortical functions, yet relatively little is known about the anatomical organization of noradrenergic axons in the expanded and highly differentiated prefrontal cortex of primates. In this study, the distribution of fibers containing dopamine-beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was characterized immunohistochemically in the prefrontal cortical regions of Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density of DBH-labeled fibers were detected both across and within many prefrontal cytoarchitectonic regions. In cynomolgus monkeys, area 8B had the greatest density of DBH-immunoreactive fibers; within this region, the medial surface had a greater density of labeled processes than the dorsal surface. Areas 9 and 24 also had a high density of DBH-labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and portions of areas 10 and 46 had the lowest density of immunoreactive fibers. Regional differences in the density of DBH-immunoreactive fibers were also present in squirrel monkey prefrontal cortex. Despite the regional variations in the density of DBH-immunoreactive fibers, the laminar distribution of these fibers was very similar across cytoarchitectonic areas of cynomolgus prefrontal cortex. Layer I contained a low density of labeled fibers which were primarily tangential in orientation. The predominantly radially oriented fibers in layers II-IV were slightly higher in density. The density of both radially and tangentially oriented immunoreactive fibers increased substantially in layer V. Fiber density decreased in layer VI; a band of tangentially oriented fibers was present in the deep portion of this layer. With a few exceptions, the laminar distribution of DBH-immunoreactive fibers in the prefrontal regions of squirrel monkey cortex was similar to that of cynomolgus monkey. Since other data suggest that anti-DBH selectively labels noradrenergic axons in monkey neocortex, the distinctive innervation patterns exhibited by DBH-immunoreactive fibers reveal the regions and layers that may be the principal sites of action of norepinephrine in exerting its effects on prefrontal cortical function.

Animals↗
PubMed1989

Pharmacokinetics of FCE 22101 in man following different modes of administration.

Twelve healthy volunteers received single iv doses of either 500 and 1000 mg or 750 and 1500 mg of the sodium salt of FCE 22101; in addition, five of the volunteers received a further dose of 2000 mg. In the second part of the study, 11 of the volunteers received 1000 mg doses of FCE 22101 in a four-way randomized fashion by iv bolus (1000 mg, with and without probenecid), im injection (1000 mg plus lignocaine) and a continuous infusion (280 mg/h) to steady state. All doses were well tolerated by the volunteers with no serious side effects and no significant haematological or biochemical changes following drug administration. Plasma and urine concentrations of FCE 22101, and in the cross-over study also its open ring metabolites P1 and P2, were determined by HPLC. Good linearity was observed between the peak plasma levels or AUC and the dose given. Plasma concentrations were fitted to a two-compartment model and the mean pharmacokinetic parameters determined after iv bolus were: Cmax 117 mg/l, T1/2 beta 36 min, Vss 181, AUC 2179 mg/min/l with urinary recoveries of FCE 22101 37%, P1 36% and P2 6%. With probenecid the values were Cmax 116 mg/l, T1/2 beta 47 min, Vss 141, AUC 4540 mg/min/l and urinary recoveries of FCE 22101 20%, P1 40% and P2 7%. Following im injection the mean values were Cmax 15 mg/l, Tmax 30 min, T1/2abs 14 min, T1/2 beta 61 min, AUC 2117 mg/min/l and urinary recoveries of FCE 22101 33%, P1 37% and P2 6%. At steady state during continuous infusion, mean values were Css 12.7 mg/l, Vss 131 and T1/2 beta after steady state was 22 min. Although urinary recoveries varied widely between volunteers there was a tendency towards consistency of recovery within individual volunteers. We conclude that FCE 22101 is a well tolerated penem with pharmacokinetic properties broadly similar to those of other penem and carbapenem antibiotics.

Adolescent↗
PubMed1989

The transport of microspheres from the gastro-intestinal tract to inflammatory air pouches in the rat.

The distribution of latex microspheres (1.1 microns diam) has been investigated in-vivo, as a potential passive targeted system for the treatment of inflammation. Microspheres administered orally were found in the circulation and in inflamed tissues and exudates of inflammatory air pouches in rats. Oral absorption was also found in a rabbit. Particles administered directly into the circulation also penetrated into the air pouch tissues and fluids. The possibility of using microspheres as a passive targeted system for the treatment of inflammation is discussed.

Administration, Oral↗
PubMed1989

Ironies of inclusion: social class and deinstitutionalization.

This paper discusses changes in the social organization of mental institutionalization as they relate to developments in the wider social and economic environment. Despite dramatic changes in the system of inpatient psychiatric care during the last three decades, the historic division of labor between the private and the public system (with the latter treating the poor, the unemployed, and the nonwhite) has not ceased to exist. At the same time, under the influence of the postwar trend towards greater political integration of disadvantaged and marginal groups into society's central value systems, treatment of the mentally ill has become less segregated and more voluntary. An important implication of these two interacting trends--the changed legal position of the patient vis-à-vis the provider and the deteriorating economic position of the user of public psychiatric facilities--has been the exceeding irrelevance of one of the basic tenets of psychiatric care: that clinical treatment precedes social functioning. With two vignettes of chronic patients the article illustrates how symptoms and survival are fused in the contemporary, inclusionary system of care.

Adult↗
PubMed1989

An outbreak of Clostridium difficile associated diarrhoea in urological practice: a potential consequence of excessive antibiotic prophylaxis?

During an outbreak of Clostridium difficile associated diarrhoea, 17 patients on a urological ward developed symptoms in a 17-day period. Of these patients, 15 had received antibiotics during their admission. In order to eradicate the infection, it was necessary to close the unit for 1 month. Antibiotic associated diarrhoea is a serious complication of the prophylactic and therapeutic use of such agents and, because of the common use of antimicrobials on urological units, there is potential for similar epidemics.

Aged↗
PubMed1988

The dopaminergic innervation of monkey prefrontal cortex: a tyrosine hydroxylase immunohistochemical study.

The distribution of tyrosine hydroxylase (TH)-immunoreactive fibers was characterized immunohistochemically in the prefrontal cortical regions of both Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density and/or laminar distribution of TH-labeled fibers were detected both across and within almost every prefrontal cytoarchitectonic region. In cynomolgus monkeys, areas 9 and 24 had the greatest density of TH-labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and areas 10 and 46 had the lowest density of immunoreactive fibers. Differences in fiber density within many of these regions were also consistently observed. On a laminar basis, the distribution of labeled fibers in a given area of cynomolgus prefrontal cortex was systematically related to the overall fiber density of that area. For example, in the lightly innervated fundus of the principal sulcus (area 46), labeled fibers were primarily present in layer I and layers V-VI, whereas in area 9, the most densely innervated region, TH-labeled fibers were present in all cortical layers. Similar regional differences in the density and laminar distribution of TH-immunoreactive fibers were also present in squirrel monkey prefrontal cortex. In previous studies, we have analyzed the regional and laminar distributions of fibers immunoreactive for TH and dopamine-beta-hydroxylase (DBH), a specific marker for noradrenergic cortical fibers, in multiple areas of cortex from both normal and locus ceruleus-lesioned animals. These comparisons, which have been confirmed in the present report, indicate that anti-TH and anti-DBH label distinct populations of axons in monkey neocortex, which presumably are dopaminergic and noradrenergic, respectively. Thus, the distribution of TH immunoreactivity described in the present report suggests that dopaminergic fibers are distributed in a very heterogeneous fashion in monkey prefrontal cortex. The distinctive innervation patterns exhibited by these fibers reveal the regions and layers that may be the principle sites of action of dopamine in exerting its effects on prefrontal cortical function.

Animals↗
PubMed1988

Brainstem dopaminergic neurons project to monkey parietal cortex.

In this study, retrograde transport of Fast blue was combined with tyrosine hydroxylase immunohistochemistry to reveal the presence of projections from both dopaminergic and non-dopaminergic neurons of the substantia nigra-ventral tegmental area to the parietal cortex of cynomolgus monkeys (Macaca fascicularis). These findings confirm the results of previous studies demonstrating the existence of a dopaminergic innervation of monkey parietal cortex.

Amidines↗
PubMed1988

Antioxidant effects of exogenous polyamines in damage of lysosomes inflicted by xanthine oxidase or stimulated polymorphonuclear leucocytes.

Active oxygen species produced by the action of xanthine oxidase or stimulated guinea-pig polymorphonuclear leucocytes have a lytic action of lysosomes possibly due to lipid peroxidation. Polyamines give some protection against lysis with putrescine being the most effective polyamine. The possible relevance to inflammatory disease is discussed.

Acid Phosphatase↗
PubMed1988

Differential regulation of amyloid-beta-protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer disease.

We have mapped the neuroanatomical distribution of amyloid-beta-protein mRNA within neuronal subpopulations of the hippocampal formation in the cynomolgus monkey (Macaca fascicularis), normal aged human, and patients with Alzheimer disease. Amyloid-beta-protein mRNA appears to be expressed in all hippocampal neurons, but at different levels of abundance. In the central nervous system of monkey and normal aged human, image analysis shows that neurons of the dentate gyrus and cornu Ammonis fields contain a 2.5-times-greater hybridization signal than is present in neurons of the subiculum and entorhinal cortex. In contrast, in the Alzheimer disease hippocampal formation, the levels of amyloid-beta-protein mRNA in the cornu Ammonis field 3 and parasubiculum are equivalent. These findings suggest that within certain neuronal subpopulations cell type-specific regulation of amyloid-beta-protein gene expression may be altered in Alzheimer disease.

Aged↗
PubMed1988

Distribution of precursor amyloid-beta-protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques.

Neurofibrillary tangles (NFT) and neuritic plaques (NP), two neuropathological markers of Alzheimer disease, may both contain peptide fragments derived from the human amyloid beta protein. However, the nature of the relationship between NFT and NP and the source of the amyloid beta proteins found in each have remained unclear. We used in situ hybridization techniques to map the anatomical distribution of precursor amyloid-beta-protein mRNA in the neocortex of brains from three subjects with no known neurologic disease and from five patients with Alzheimer disease. In brains from control subjects, positively hybridizing neurons were present in cortical regions and layers that contain a high density of neuropathological markers in Alzheimer disease, as well as in those loci that contain NP but few NFT. Quantitative analyses of in situ hybridization patterns within layers III and V of the superior frontal cortex revealed that the presence of high numbers of NFT in Alzheimer-diseased brains was associated with a decrease in the number of positively hybridizing neurons compared to controls and Alzheimer-diseased brains with few NFT. In contrast, no correlation was found between the densities of NP and neurons containing precursor amyloid-beta-protein mRNA transcripts. These findings suggest that the expression of precursor amyloid-beta-protein mRNA may be a necessary but is clearly not a sufficient prerequisite for NFT formation. In addition, these results may indicate that the amyloid beta protein, present in NP in a given region or layer of cortex, is not derived from the resident neuronal cell bodies that express the mRNA for the precursor protein.

Aged↗
PubMed1988

Psychrometric limits to prolonged work in protective clothing ensembles.

When work is performed by workers in protective clothing, sweat evaporation is limited and body temperature rises. In an attempt to quantify the limits such ensembles place on safe work, 6 acclimated men and women walked at 30% VO2max (150-200 W/m2) in 2 protocols involving environmental transients. In one, ambient water vapor pressure (Pw) was fixed at 10 torr, and after rectal temperature (Tre) plateaued, ambient dry-bulb temperature (Tdb) was raised 2 degrees C every 10 min. In the second, Tdb was constant and Pw was increased 2 torr every 10 min. Critical temperature (Tcrit) and pressure (Pcrit) were defined as the Tdb or Pw at which thermal balance could no longer be maintained and Tre rose sharply. Each test was performed in various clothing ensembles ranging from light cotton work clothes to "impermeable" suits. Lines connecting mean Tcrit and mean Pcrit define a limit for safe prolonged exposure/exercise for approximately 50% of the population in each ensemble. Similar lines, drawn to represent values 2 standard deviations below the mean, should provide critical environmental limits for 95% of the population.

Body Temperature↗