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Biomedical subjects

D A Lewis

Publications and source records attributed to D A Lewis.

At least 253 records · Page 14Linked to original sources

Cloning and characterization of an AAC(6') gene from Serratia marcescens.

A gene encoding AAC(6') mediated resistance to netilmicin and amikacin was cloned from the chromosome of a nosocomial strain of Serratia marcescens into the BamHI site of pACYC184. The resistance determinant was localized to a sequence of approximately 1 kb. A 490 base pair BamHI-PvuII restriction fragment from the cloned DNA was used as a probe in Southern hybridization studies. Homology with a 920 base pair fragment of PvuII digested S. marcescens DNA from AAC(6')-producing strains was observed. No homology was detected with aminoglycoside sensitive S. marcescens or Escherichia coli.

Acetyltransferases↗

A monoclonal antibody to non-phosphorylated neurofilament protein marks the vulnerable cortical neurons in Alzheimer's disease.

Various cytoskeletal proteins have been implicated in the formation of neurofibrillary tangles in Alzheimer's disease. A monoclonal antibody to non-phosphorylated neurofilament protein labels a distinct subset of pyramidal cells in the normal human cortex which have a distribution very similar to that of neurofibrillary tangles in brains from patients with Alzheimer's disease. In addition, regions and layers that normally contain a high density of such cells, in Alzheimer's disease, have large numbers of neurofibrillary tangles and few remaining immunoreactive cells.

Aged↗

Distribution of choline acetyltransferase-, serotonin-, dopamine-beta-hydroxylase-, tyrosine hydroxylase-immunoreactive fibers in monkey primary auditory cortex.

Immunohistochemical methods were used to visualize choline acetyltransferase (ChAT)-, serotonin-, dopamine-beta-hydroxylase (DBH)-, and tyrosine hydroxylase (TH)-containing fibers in the primary auditory cortex of the cynomolgus monkey (Macaca fascicularis). Each antiserum revealed a subpopulation of axons with a distinct density and laminar distribution. ChAT-immunoreactive fibers were very dense in superficial layers, particularly in layers I, deep III, and IV, and very sparse in layers V and VI. No immunoreactive cell bodies were evident. Serotonin-immunoreactive fibers were very dense in all cortical layers but exhibited some subtle laminar differences in fiber size and orientation. The densities of DBH- and TH-immunoreactive fibers were substantially lower than the densities of both ChAT- and serotonin-immunoreactive fibers, particularly in layer IV. However, there were substantial differences between the distribution of TH-immunoreactive fibers and that of DBH-immunoreactive fibers. For example, the density of TH-immunoreactive fibers was substantially greater than that of DBH-immunoreactive fibers in layer I. In addition, TH-immunoreactive fibers differed from the other three systems in that TH-immunoreactive fibers exhibited a rostral to caudal gradient of decreasing density. This is the first characterization of the innervation of a specific cortical region by all four of these systems and the first detailed description of the cholinergic innervation of a primate neocortical region utilizing a specific anti-ChAT antiserum. These striking differences in density and laminar distribution suggest that the subcortical extrathalamic systems furnishing these axons differ significantly in their modulation of cortical auditory processing. These data extend observations of previous studies which revealed that the expansion and specialization of the primate neocortex is accompanied by a pronounced regional and laminar differentiation in the intracortical distribution of these highly divergent, extrathalamic afferents.

Adrenergic Fibers↗

Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer's disease.

The distribution of cells containing messenger RNA that encodes amyloid beta protein was determined in hippocampi and in various cortical regions from cynomolgus monkeys, normal humans, and patients with Alzheimer's disease by in situ hybridization. Both 35S-labeled RNA antisense and sense probes to amyloid beta protein messenger RNA were used to ensure specific hybridization. Messenger RNA for amyloid beta protein was expressed in a subset of neurons in the prefrontal cortex from monkeys, normal humans, and patients with Alzheimer's disease. This messenger RNA was also present in the neurons of all the hippocampal fields from monkeys, normal humans and, although to a lesser extent in cornu ammonis 1, patients with Alzheimer's disease. The distribution of amyloid beta protein messenger RNA was similar to that of the neurofibrillary tangles of Alzheimer's disease in some regions, but the messenger RNA was also expressed in other neurons that are not usually involved in the pathology of Alzheimer's disease.

Alzheimer Disease↗

Clinical perspectives on neuropeptides.

Abnormalities in various neuropeptide systems have been detected in a number of neuropsychiatric disorders. Understanding the pathophysiological significance of these findings requires considering them in the context of the neural circuits involved. In both Huntington's disease and Alzheimer's disease, the reported alterations in multiple neuropeptide systems may help define the primary pathologic change, and may lead to new therapeutic strategies.

Alzheimer Disease↗

Physiologically derived critical evaporative coefficients for protective clothing ensembles.

When work is performed in heavy clothing, evaporation of sweat from the skin to the environment is limited by layers of wet clothing and air. The magnitude of decrement in evaporative cooling is a function of the clothing's resistance to permeation of water vapor. A physiological approach has been used to derive effective evaporative coefficients (he) which define this ability to evaporate sweat. We refined this approach by correcting the critical effective evaporative coefficient (K for sweating efficiency (Ke,eta') since only a portion of the sweat produced under such conditions is evaporated through the clothing. Six acclimated men and women walked at 30% maximal O2 consumption (150-200 W.m-2) at a constant dry bulb temperature as ambient water vapor pressure was systematically increased 1 Torr every 10 min. Critical pressure was defined as the partial pressure of water vapor (Pw) at which thermal balance could no longer be maintained and rectal temperature rose sharply. Each test was performed in various clothing ensembles ranging from cotton shirt and pants to "impermeable" suits. This approach was used to derive he by solving the general heat balance equation, M - W +/- (R + C) = w.he.(Psk - Pw), where M is metabolic heat production, W is external work, R is radiant heat exchange, C is convective heat transfer, w is skin wettedness, and Psk is water vapor pressure of fully wet skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices.

The number of Thioflavine S-positive neurofibrillary tangles (NFT) and neuritic plaques (NP) was determined in visual and auditory cortical regions of 8 patients with Alzheimer's disease. On both a regional and laminar basis, NFT exhibited very distinctive and consistent distribution patterns. The mean (+/- SEM) number of NFT in a 250-micron-wide cortical traverse was very low in area 17, primary visual cortex (0.9 +/- 1.0), increased 20-fold in the immediately adjacent visual association cortex of area 18 (19.7 +/- 3.6), and showed a further doubling in area 20, the higher-order visual association cortex of the inferior temporal gyrus (35.5 +/- 8.8). Similar differences in NFT number were present between primary auditory (1.6 +/- 0.5) and auditory association (18.9 +/- 5.4) regions. On a laminar basis, NFT were predominantly present in layers III and V, although there were striking regional differences in the proportion of NFT in these 2 layers. Layer III contained 79% of the NFT in layers III and V in area 18, 41% in area 20, and only 27% in area 22. In contrast, NP showed different, and less specific, regional and laminar distribution patterns. Total NP number was similar in the 3 visual areas, although there were marked regional differences in the type of NP present. Nearly 80% of the NP in area 17 was of the NPc type (i.e., contained a dense, brightly fluorescent core), whereas over 70% of the NP in both areas 18 and 21 was of the NPnc type (i.e., lacked a dense, brightly fluorescent core). NP were present in every cortical layer but were most numerous in layers III and IV. The distinctive distribution patterns of NFT are very similar to the regional and laminar locations of long corticocortical projection neurons in homologous regions of monkey neocortex. This association suggests that NFT reside in the cell bodies of a subpopulation of pyramidal neurons, namely, those that furnish long corticocortical projections. In contrast, the distribution patterns of NP suggest that multiple neuronal systems contribute to their formation.

Aged↗

The distribution of tyrosine hydroxylase-immunoreactive fibers in primate neocortex is widespread but regionally specific.

An antiserum directed against tyrosine hydroxylase (TH), an enzyme involved in dopamine and norepinephrine synthesis, was used to visualize axons immunohistochemically in monkey neocortex. Labeled fibers were distributed throughout the entire neocortex, but they had striking patterns of regional and laminar specialization. For example, primary motor cortex contained the greatest density of TH-labeled fibers, whereas primary sensory regions were sparsely innervated. Marked heterogeneity of fiber density was also present among the association regions of the frontal, parietal, and temporal lobes. In addition, the laminar pattern of innervation in a given region was correlated with its fiber density. Sparsely innervated regions had labeled fibers only in layer I and sometimes layer VI. In regions of intermediate density, labeled fibers tended to be located in layers I-superficial III and layers V-VI, whereas in densely innervated motor cortex TH-immunoreactive fibers were present in all cortical layers. Comparison of these distribution patterns with those produced by an antiserum directed against dopamine-beta-hydroxylase (DBH), a specific marker of neocortical noradrenergic axons, revealed marked differences. DBH-immunoreactive fibers were observed in some cortical locations where few or no TH-labeled fibers were present. In other regions, the density of TH-immunoreactive processes far exceeded that of DBH-labeled fibers. These findings indicate that nearly all of the immunoreactive fibers revealed by this anti-TH antiserum are dopaminergic. This interpretation was further supported by lesions of the ascending noradrenergic fibers in the brain stem, which reduced DBH immunoreactivity, but not TH immunoreactivity, in neocortex. The distinctive innervation patterns of TH-immunoreactive fibers suggest a functional specialization of the dopaminergic projections to primate neocortex.

Animals↗

Regional heterogeneity in the distribution of somatostatin-28- and somatostatin-28(1-12)-immunoreactive profiles in monkey neocortex.

The distribution of the prosomatostatin-derived peptides (PSDP), somatostatin-28 and somatostatin-28(1-12), in the cynomolgus monkey (Macaca fascicularis) neocortex was characterized in quantitative immunohistochemical studies of 3 visual areas (V1, primary visual cortex; V2, the adjacent visual association area; and AIT, a visual association area in anterior inferior temporal cortex), 2 auditory areas (AI, primary auditory cortex; and T1, an adjacent auditory association area) and anterior cingulate cortex (Area 24). The results of similar quantitative analyses in 3 homologous areas in rat neocortex (primary visual, primary auditory, and anterior cingulate) are also presented. Primate cortical areas differed significantly in both density and laminar distribution of PSDP-immunoreactive profiles. Area 24, the most densely labeled area, had nearly 6 times as many PSDP-immunoreactive neurons as V1. Both auditory areas contained approximately two-thirds the number of PSDP-immunoreactive neurons found in Area 24; however, both had nearly 4 times as many immunoreactive neurons as V1. The 3 visual areas showed incremental increases in the number of PSDP-immunoreactive neurons; V2 contained nearly twice and AIT nearly 3 times the number of immunoreactive neurons present in V1. Both the supra- and infragranular layers were densely labeled in Area 24 and Area T1, however, in AI, V1, V2, and AIT the infragranular layers were relatively sparsely labeled. In contrast to the regional heterogeneity found in the primate neocortex, the distribution of immunoreactive neurons was quite uniform across the 3 rat cortical areas. The rat cortical areas contained substantially fewer immunoreactive neurons than most of the monkey cortical areas, and a majority of these immunoreactive neurons were located in the infragranular layers. These findings suggest that the regional specialization of primate neocortex involves the selective distribution of PSDP-immunoreactive neurons. They also suggest that chemically specified intrinsic organization of neocortex is not likely to be uniform across species or across cortical areas in the primate. The distinctive regional distribution patterns of PSDP-immunoreactive profiles appear to parallel that of the long corticocortical projections (contralateral and distant ipsilateral projections), suggesting an association between these presumed inhibitory interneurons and this important extrinsic system.

Animals↗

An immunohistochemical characterization of somatostatin-28 and somatostatin-281-12 in monkey prefrontal cortex.

The distribution of the prosomatostatin-derived peptides (PSDP) somatostatin-28 (SS-28) and somatostatin-281-12 (SS-281-12) was characterized immunohistochemically in the prefrontal cortical regions of both Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). Comparison of staining with antisera specific for each peptide revealed that these antigens were segregated within immunoreactive neurons such that SS-28 was largely confined to the perinuclear region of the cell body whereas SS-281-12 was primarily found in axons and dendrites. The laminar pattern of immunoreactive fibers was similar in all areas of the prefrontal cortex. The most dense terminal arborization was in layers I, II, and superficial III. Deep III and IV were traversed by radial fibers that had little arborization. Layers V and VI contained both radial fibers and a moderately dense terminal plexus. Labeled fibers were less numerous in the white matter. There were marked regional differences in fiber density. Areas 12 and 24 had the greatest density of immunoreactive fibers, areas 9, 11, and 25 were of intermediate density, and areas 10 and 46 were the least dense. Most of the immunoreactive cells appeared to be multipolar or bitufted. They were found throughout all cortical layers and the white matter. The largest number were located in layers II, superficial III, and deep V and VI. There were also marked regional differences in cell body density, which paralleled the regional differences in fiber density. Area 24 (anterior cingulate) had the greatest density of immunoreactive cell bodies (148 +/- 14/mm2), area 9 was of intermediate density (109 +/- 13/mm2), and area 46 was the least dense (83 +/- 12/mm2). Our findings indicate that PSDP compose a complex and extensive cortical system that is largely or totally intrinsic. The substantial regional heterogeneity in density exhibited by PSDP-containing neurons has not previously been reported for an intrinsic cortical system. The laminar and regional innervation patterns of these fibers and cell bodies suggest that the PSDP cortical system may play an important role in the polymodal information processing that occurs in association regions of prefrontal cortex.

Animals↗

In vitro interactions between endogenous polyamines and superoxide anion.

Endogenous polyamines with anti-inflammatory activity scavenge superoxide and possibly other oxy-radicals produced by xanthine oxidase or from stimulated polymorphonuclear leucocytes. Polyamines incubated with stimulated cells are in part metabolised. Putrescine is converted to metabolites tentatively identified as gamma-aminobutyraldehyde, delta'-pyrolline and gamma-aminobutyric acid. The metabolism of spermidine, spermine and cadaverine was not as extensively studied but metabolites were formed that gave positive reaction to Schiffs reagent on tlc plates. The possible relevance of the results to the anti-inflammatory action of polyamines is discussed.

Animals↗

Effect of oral ciprofloxacin on the faecal flora of healthy volunteers.

The effect of oral ciprofloxacin on the intestinal flora was investigated in six male volunteers aged between 21 and 54 years. Faecal specimens were cultured quantitatively for aerobic and anaerobic micro-organisms before, during and after a five day course of ciprofloxacin. Ciprofloxacin resulted in a significant reduction in aerobic flora in all volunteers and colonisation with resistant coagulase-negative staphylococci or corynebacteria in two volunteers. The total anaerobic flora counts were significantly reduced in only one volunteer. Neither Clostridium difficile nor its toxin was detected and there was no significant colonisation with Pseudomonas spp. or yeasts; no ciprofloxacin-resistant gram-negative bacilli were detected. Peak serum levels on days 1 and 5 of 1.6-4.3 mg/l (mean 2.7) were achieved after 30-90 min and urine recovery over the five days was 27.1-44.6%.

Administration, Oral↗

A simple exercise test for the prediction of relative heat tolerance.

A medical screening exercise test is presented which accurately predicts relative heat tolerance during work in very hot environments. The test consisted of 15-20 min of exercise at a standard absolute intensity of about 600 kcal/hr (140W) with the subject wearing a vapor-barrier suit. Five minutes after the subject exercised, recovery heart rate was measured. When this heart rate is used, a physiological limit (+/- approximately 5 min) can be predicted with 95% confidence for the most intense work-heat conditions found in nuclear power stations. In addition, site health and safety personnel can establish qualification criteria for work on hot jobs, based on the test results. The test as developed can be performed in an office environment with the use of a minimum of equipment by personnel with minimal expertise and training. Total maximal test duration is about 20-25 min per person and only heart rate need be monitored (simple pulse palpation will suffice). Test modality is adaptable to any ergometer, the most readily available and least expensive of which is bench-stepping. It is recommended that this test be available for use for those persons who, based upon routine medical examination or past history, are suspected of being relatively heat intolerant.

Adolescent↗

The monoaminergic innervation of primate neocortex.

In brain, the monoamines, dopamine, norepinephrine, and serotonin, are confined to anatomically distinct neuronal systems, each of which furnishes widespread projections to neocortex. In primate, but not in rat, the terminal patterns of each of these systems have a high degree of regional and laminar specificity. These findings suggest that there are different sites of action and possibly different functional roles for each of the monoamines. This type of precise anatomic information is essential to our understanding of the possible involvement of monoamines in human disease states.

Animals↗

Mania associated with electroconvulsive therapy.

Of 94 depressed patients given electroconvulsive therapy (ECT), a manic episode developed in 6 (64%). These six patients were equally distributed across three diagnostic categories of depressive illness: primary unipolar depression, bipolar affective disorder, and schizoaffective disorder. Compared with matched controls, the patients who experienced ECT-associated mania had an earlier age of onset and a longer duration of illness. These patients also had more previous psychiatric hospitalizations. Although evidence of a direct causal relationship between the administration of ECT and the development of mania is still lacking, our data suggest that the risk of mania is higher in patients with certain clinical characteristics.

Adult↗

Therapeutic efficacy of asparaginase encapsulated in intact erythrocytes.

Asparaginase has been encapsulated in intact erythrocytes by a gentle loading technique. The loaded cells were found to survive removal by the recticuloendothelial system when returned to the circulation of mice. In addition the enzyme removed all detectable asparagine from the plasma in vivo for at least two weeks after the injection of the loaded cells. In vitro evidence suggested that the asparagine entered the cell and was metabolised by the loaded enzyme in situ. No evidence was found to suggest that the enzyme left the cell. When the encapsulated asparaginase was tested against the 6C3HED tumour in C3H mice the encapsulated preparation was superior to the free enzyme in treating the tumour and was the only treatment to produce 'cured' mice. Encapsulated asparaginase also lowered glutamine levels both in vivo and in vitro. The possibility that LDH virus was responsible for the excellent results obtained with the encapsulated enzyme was investigated and eliminated.

Animals↗