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D A Lewis

Publications and source records attributed to D A Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2005

Synaptic targets of calretinin-containing axon terminals in macaque monkey prefrontal cortex.

The coordinated activity of specific populations of pyramidal cells and GABA-containing, local circuit neurons in the primate prefrontal cortex (PFC) appears to be critical for working memory. Different subclasses of GABA-containing neurons can be distinguished by their content of the calcium-binding proteins parvalbumin (PV) and calretinin (CR). The postsynaptic targets of PV-containing cells have been well characterized in the primate PFC, but the postsynaptic targets of CR-containing neurons in this cortical region remain unknown. In the present study, we used immuno-electron microscopy to examine the synaptic type and postsynaptic targets of CR-immunoreactive (IR) axon terminals in the superficial and deep layers of macaque monkey PFC. Labeled axon terminals formed both symmetric and asymmetric synapses. Within the superficial layers, 93% of the synapses formed by CR-IR were symmetric, whereas in the deep layers the labeled axon terminals forming synapses were more evenly divided between symmetric (57%) and asymmetric (43%). The primary postsynaptic target of these two populations of CR-IR axon terminals also differed; unlabeled dendritic shafts were the predominant target of the symmetric synapses, whereas dendritic spines were the most common target of the asymmetric synapses. In addition, the mean cross-sectional area of the terminals forming asymmetric synapses was significantly larger than that of the terminals forming symmetric synapses. The presence of CR-IR asymmetric synapses suggested that they might arise from neurons that do not utilize GABA; indeed, dual-label fluorescent immunocytochemistry revealed that a subpopulation (23%) of CR-containing neurons in monkey PFC were not GABA-IR. These findings indicate that the synaptology of CR-containing neurons is more heterogeneous than that of PV-containing cells and suggests that the contributions of CR-containing neurons to cognitive processes mediated by the PFC may be more diverse.

Animals↗
PubMed2005

Genetic polymorphisms of the RGS4 and dorsolateral prefrontal cortex morphometry among first episode schizophrenia patients.

Polymorphisms of the gene encoding the regulator of G-protein signaling subtype 4 (RGS4) may confer risk for schizophrenia.(1) DNA microarray studies of postmortem brain samples have shown RGS4 underexpression in the dorsolateral prefrontal cortex (DLPFC, area 9), motor and visual cortices in schizophrenia patients relative to control subjects.(2) Underexpression of RGS4 in DLPFC is pathophysiologically significant because DLPFC pathology in schizophrenia has been supported by neurocognitive,(3,4) structural(5) and functional(6,7) imaging, postmortem,(8) cellular(9,10) and molecular(11) pathological studies. For these reasons, we examined the association of DLPFC gray matter volume with RGS4 polymorphisms in a series of antipsychotic-naive first-episode schizophrenia patients and control subjects. We hypothesized that volumetric alterations of the DLPFC would be associated with RGS4 polymorphisms and that these differences would be more pronounced in patients than in controls. We observed robust volumetric differences across the genotypes in the pooled sample of patients and control subjects; when separately analyzed, we observed differences within the patient group (n = 30) but not in control subject (n = 27) group. The findings suggest that RGS4 polymorphisms may contribute to structural alterations in the DLPFC.

Adult↗
PubMed2005

Decreased incidence of nonmelanoma skin cancer in patients with type 2 diabetes mellitus using insulin: a pilot study.

BACKGROUND: In order to prevent the propagation of genetic mutations, human keratinocytes irradiated with ultraviolet (UV) B light in vitro undergo premature stress-induced senescence or apoptosis. This response to UVB irradiation is dependent on the functional activation of the insulin-like growth factor-1 receptor (IGF-1R). Based on this in vitro functional data, we hypothesized that the increased serum levels of insulin in patients with type 2 diabetes may activate the IGF-1R in skin and lead to a decreased frequency of skin cancer in these patients. OBJECTIVES: To determine whether the use of insulin by patients with type 2 diabetes correlated with a change in the incidence in nonmelanoma skin cancer (NMSC). METHODS: A historical cohort study identifying the incidence of NMSC following the use of two different pharmacological therapies. The patient population was restricted to caucasians who were at least 50 years old when they began the indicated pharmacological therapy. The first group consisted of 1440 patients who used insulin therapy to treat type 2 diabetes and the second group comprised 4135 patients who used cimetidine to treat their gastrointestinal ailments. An additional group of 6131 patients with diabetes who used noninsulin antidiabetics was added to examine the effect of noninsulin therapies. All patients had regular follow-up visits at the Regenstrief Clinics during the study period between 1980 and 1999. The Regenstrief Clinics is an outpatient facility which serves the general population in Metro-Indianapolis, Indiana, U.S.A. RESULTS: The incidence of NMSC in patients using insulin was significantly lower than in patients using cimetidine (1.25% vs. 2.35%, P < 0.02). The decrease in NMSC in patients with type 2 diabetes correlated specifically with the use of insulin (NMSC incidence insulin-only patients with diabetes: 1.40% vs. those with diabetes using noninsulin therapies: 2.35%, P = 0.11). CONCLUSIONS: Patients using exogenous insulin had a lower risk of developing NMSC and the protective effect of insulin use becomes more distinct with increasing age.

Aged↗
PubMed2005

Modulite: a simple solution to a difficult problem.

The development of HFA-based pMDIs has proved difficult due to differences in the physico-chemical properties of CFC and HFA propellants. However, the development of solution formulations instead of suspensions has provided a way to formulate products whose cloud characteristics can be modulated in a controlled manner by permitting different formulation and device hardware variables. The new approach has proved successful in formulating several different drugs including steroids and has now been applied to developing a formoterol Modulite solution formulation characterized by good chemical stability, delivery performance, and clinical results.

Aerosol Propellants↗
PubMed2004

Localization of calcium-binding proteins in physiologically and morphologically characterized interneurons of monkey dorsolateral prefrontal cortex.

In the primate neocortex, little is known about the possible associations between functional subclasses of GABA neurons, their morphological properties and calcium-binding protein (CaBP) content. We used whole-cell current clamp recordings, combined with intracellular labeling and fluorescence immunohistochemistry, to determine these relationships for interneurons in layers 2-3 of monkey prefrontal cortex (PFC). Eighty-one interneurons were included in the analysis. Thirty-eight of these cells showed immunoreactivity for one of the three CaBPs tested. Co-localization of more than one CaBP was not observed in any of the interneurons examined. Interneurons with different CaBPs formed distinct populations with specific physiological membrane properties and morphological features. Parvalbumin (PV)-positive cells had the physiological properties characteristic of fast-spiking interneurons (FS) and the morphology of basket or chandelier neurons. Most calretinin (CR)-containing cells had the physiological properties ascribed to non-fast-spiking cells (non-FS) and a vertically oriented axonal morphology, similar to that of double bouquet cells. Calbindin (CB)-positive interneurons also had non-FS properties and included cells with double bouquet morphology or with a characteristic dense web of axonal collaterals in layer 1. Classification of the interneurons based on cluster analysis of multiple electrophysiological properties suggested the existence of at least two distinct groups of interneurons. The first group contained mainly PV-positive FS cells and the second group consisted predominantly of CR- and CB-positive non-FS interneurons. These findings may help to illuminate the functional roles of different groups of interneurons in primate PFC circuitry.

Action Potentials↗
PubMed2004

Improved clinical status in fibromyalgia patients treated with individualized homeopathic remedies versus placebo.

OBJECTIVE: To assess the efficacy of individualized classical homeopathy in the treatment of fibromyalgia. METHODS: This study was a double-blind, randomized, parallel-group, placebo-controlled trial of homeopathy. Community-recruited persons (N = 62) with physician-confirmed fibromyalgia (mean age 49 yr, s.d. 10 yr, 94% women) were treated in a homeopathic private practice setting. Participants were randomized to receive oral daily liquid LM (1/50,000) potencies with an individually chosen homeopathic remedy or an indistinguishable placebo. Homeopathic visits involved joint interviews and concurrence on remedy selection by two experienced homeopaths, at baseline, 2 months and 4 months (prior to a subsequent optional crossover phase of the study which is reported elsewhere). Tender point count and tender point pain on examination by a medical assessor uninvolved in providing care, self-rating scales on fibromyalgia-related quality of life, pain, mood and global health at baseline and 3 months, were the primary clinical outcome measures for this report. RESULTS: Fifty-three people completed the treatment protocol. Participants on active treatment showed significantly greater improvements in tender point count and tender point pain, quality of life, global health and a trend toward less depression compared with those on placebo. CONCLUSIONS: This study replicates and extends a previous 1-month placebo-controlled crossover study in fibromyalgia that pre-screened for only one homeopathic remedy. Using a broad selection of remedies and the flexible LM dose (1/50,000 dilution factor) series, the present study demonstrated that individualized homeopathy is significantly better than placebo in lessening tender point pain and improving the quality of life and global health of persons with fibromyalgia.

Adult↗
PubMed2004

Subcortical afferents to the lateral mediodorsal thalamus in cynomolgus monkeys.

The mediodorsal (MD) nucleus of the thalamus has long been known to provide the principal source of subcortical input to the primate prefrontal cortex, as well as to other areas of the frontal lobe that are thought to contribute to higher-order cognitive functions. In this study, we used injections of retrograde tracers in the lateral portion of the monkey MD to assess the locations of labeled cells in subcortical structures. Three main patterns were identified in the distribution of subcortical connections. We found that the claustrum, superior colliculus and ventral midbrain regions were heavily labeled in the cases with injections in caudoventral MD. In these cases, labeled cells were also found in either the periaqueductal gray or zona incerta, depending on the specific case. In one case with an injection in anterodorsal MD, labeled cells were most numerous in the structures of the ventral midbrain, especially the ventral tegmental area. Finally, the claustrum and superior colliculus contained the largest percentage of labeled subcortical cells in cases with injections in ventrolateral MD. These three patterns of subcortical label corresponded to three equally distinctive trends in the distribution of MD connections with the cortex in these same cases [J Comp Neurol 473 (2004) 107]. Very few labeled cells were found in other areas such as the amygdala, globus pallidus and deep cerebellar nuclei, suggesting that pathways leading from these structures to dorsolateral and dorsomedial frontal cortices are not likely to include the lateral divisions of MD. In concert, these findings show that particular locales within lateral MD receive distinct profiles of subcortical afferents, and project into specific neocortical domains, suggesting that these different sites within lateral MD may participate in functionally distinct circuits of information processing.

Afferent Pathways↗
PubMed2004

Analysis of heat-processed corn foods for fumonisins and bound fumonisins.

Thirty retail samples of heat-processed corn foods, i.e. corn flakes, corn-based breakfast cereals, tortilla chips and corn chips, were analysed for fumonisins--fumonisin B1 (FB1), fumonisin B2 (FB2) and hydrolysed FB1 (HFB1)--as well as for protein- and total-bound FB1. Bound (hidden) fumonisins cannot be detected by conventional analysis. Improved methods for the determination of bound FB1 were developed. The protein-bound FB1 was extracted with 1% sodium dodecylsulfate (SDS) solution. The SDS, which interfered with high-performance liquid chromatography (HPLC) analysis, was then separated from protein-bound FB1 by complexing with methylene blue followed by solvent extraction and hydrolysis with 2 N KOH. To measure total-bound FB1, the sample itself was hydrolysed with KOH. In both cases, clean-up was accomplished on an OASIS polymeric solid-phase extraction column and the bound fumonisins were determined by HPLC measurement of HFB1. Fourteen of 15 samples of corn flakes and other corn-based breakfast cereals analysed contained detectable levels of FB1 with a mean in positive samples of 67ng g(-1) (13-237 ng g(-1)). Two samples also had detectable levels of FB2 (21-23ng g(-1)). Bound FB1 was found in all samples; the mean protein-bound FB1 measured was 58 ng g(-1) (22-176 ng g(-1)) and the mean total-bound FB1 measured was 106 ng g(-1) (28-418 ng g(-1)), reported as FB1 equivalents after correction for recoveries of HFB1. There was an average of about 1.3 times more FB1 in the bound form compared with extractable FB1, and this was about twice as much as protein-bound FB1. Seven of the 15 samples of alkali-processed corn-based foods, such as tortilla chips and corn chips, contained FB1 and three contained HFB1 with means in measurable positive samples of 78 (48-134) and 29 (13-47) ng g(-1), respectively. Five of these alkali-processed corn foods contained bound FB1; the mean measurable protein-bound FB1 was 42 ng g(-1) (39-46 ng g(-1)) and the mean measurable total-bound FB1 was 100 ng g(-1) (54-209 ng g(-1)). HFB1 derived from bound FB1 in selected samples was confirmed by HPLC with mass spectrometry (MS).

Carcinogens, Environmental↗
PubMed2004

Penile myiasis: a case report.

We report a case of penile myiasis in a Brazilian man caused by the larva of Dermatobia hominis. Myiasis is a parasitic disease of humans and other vertebrates caused by larvae of several fly species. Although urinary myiasis is well recognised, infestation of the genital tissue is a rare occurrence. Once the diagnosis has been made, the treatment is usually straightforward and uncomplicated.

Adult↗
PubMed2004

The 374 clinic: an outreach sexual health clinic for young men.

OBJECTIVES: To describe the establishment of a community based walk-in outreach genitourinary medicine clinic, the "374 clinic," in south London to target young men under 25 in an area with high rates of sexually transmitted infections (STIs). METHODS: The outreach clinic was set up within a Brook advisory centre, which already had gained the trust of local young people. Epidemiological, clinical, and laboratory data were obtained retrospectively for the first 24 weeks of the service. RESULTS: 134 attendances were recorded, including 94 new and 10 rebook events. The age range of the young men seen was 12-27 years (mean 18.2 years), the patients were mainly from black and ethnic minority groups, and all but one were heterosexual. Most men had heard about the clinic by "word of mouth," recommendation by Brook staff or through clinic promotional material. Condoms were used more frequently with non-regular sexual partners than with regular partners. The uptake of screening for gonococcal and chlamydial infections, mostly by urine based molecular techniques, was 98%. The uptake for HIV testing in men aged 16 or more was 72%. An overall STI prevalence rate of 26% was detected in the clinic population, which consisted almost equally of asymptomatic and symptomatic patients. The most prevalent STI was chlamydial infection (12%). CONCLUSIONS: The young men who attended the outreach clinic were happy to undergo both non-invasive urine based testing for gonorrhoea and chlamydia as well as phlebotomy to test for HIV and syphilis. The 374 clinic approach may prove to be a useful model for further outreach services to combat poor sexual health of young men in inner city areas.

Adolescent↗
PubMed2003

DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes.

Presenilin 1 (PS1) plays a critical role in the nervous system development and PS1 mutations have been associated with familial Alzheimer's disease. PS1-deficient mice exhibit alterations in neural and vascular development and die in late embryogenesis. The present study was aimed at uncovering transcript networks that depend on intact PS1 function in the developing brain. To achieve this, we analyzed the brains of PS1-deficient and control animals at embryonic ages E12.5 and E14.5 using MG_U74Av2 oligonucleotide microarrays by Affymetrix. Based on the microarray data, overall molecular brain development appeared to be comparable between the E12.5 and E14.5 PS1-deficient and control embryos. However, in brains of PS1-deficient mice, we observed significant differences in the expression of genes encoding molecules that are associated with neural differentiation, extracellular matrix, vascular development, Notch-related signaling and lipid metabolism. Many of the expression differences between wild-type and PS1-deficient animals were present at both E12.5 and E14.5, whereas other transcript alterations were characteristic of only one developmental stage. The results suggest that the role of PS1 in development includes influences on a highly co-regulated transcript network; some of the genes participating in this expression network may contribute to the pathophysiology of Alzheimer's disease.

Alzheimer Disease↗
PubMed2003

Noradrenaline-induced lipolysis in adipose tissue is suppressed at hibernation temperatures in ground squirrels.

Responsiveness of white adipose tissue (WAT) and brown adipose tissue (BAT) from hibernating and nonhibernating golden-mantled ground squirrels (Spermophilus lateralis) to the lipolytic action of the sympathetic neurotransmitter, noradrenaline, was tested in vitro at temperatures characteristic of deep torpor (5 degrees C) and euthermia (37 degrees C). Noradrenaline-stimulated lipolysis, as indicated by WAT glycerol release, of tissue from hibernating ground squirrels was six- to ten-fold greater at 37 degrees C than at 5 degrees C. Noradrenaline was ineffective in increasing lipolysis at 5 degrees C. Noradrenaline-stimulated lipolysis in BAT was similarly suppressed at 5 degrees C. Noradrenaline-stimulated lipolysis was little affected by temperature change below approximately 15 degrees C but strongly correlated with temperature above approximately 15 degrees C. Noradrenaline-induced lipolysis of WAT from nonhibernating and hibernating ground squirrels did not differ at an incubation temperature of 5 degrees C. We conclude that noradrenaline-stimulated WAT lipolytic activity is markedly suppressed at the low temperatures characteristic of deep torpor and that there is no 'hibernation-specific' adaptation of WAT to enhance its responsiveness to noradrenaline at low tissue temperatures. Temperature dependence of noradrenaline-stimulated lipolysis may in part account for the shift from lipid to carbohydrate metabolism during the earliest stage of arousal from deep torpor.

Adipose Tissue↗
PubMed2003

Chancroid: clinical manifestations, diagnosis, and management.

Chancroid is a sexually transmitted disease (STD) caused by the Gram negative bacterium Haemophilus ducreyi and is characterised by necrotising genital ulceration which may be accompanied by inguinal lymphadenitis or bubo formation. H ducreyi is a fastidious organism which is difficult to culture from genital ulcer material. DNA amplification techniques have shown improved diagnostic sensitivity but are only performed in a few laboratories. The management of chancroid in the tropics tends to be undertaken in the context of syndromic management of genital ulcer disease and treatment is usually with erythromycin. A number of single dose regimens are also available to treat H ducreyi infection. Genital ulceration as a syndrome has been associated with increased transmission of human immunodeficiency virus (HIV) infection in several cross sectional and longitudinal studies. Effective and early treatment of genital ulceration is therefore an important part of any strategy to control the spread of HIV infection in tropical countries.

Anti-Bacterial Agents↗
PubMed2003

Expression of the cytolethal distending toxin in a geographically diverse collection of Haemophilus ducreyi clinical isolates.

OBJECTIVE: To screen a collection of isolates of Haemophilus ducreyi for expression of the cytolethal distending toxin (CDT). METHODS: 45 clinical isolates of H ducreyi were screened for cytotoxic activity by examining the effect of culture supernatants on Hela cells. Expression was confirmed using immunoblotting with CDT specific monoclonal antibodies and the presence of the cdt genes determined by amplification of the cdt genes in a multiplex polymerase chain assay. RESULTS: Of the 45 clinical isolates, six isolates from differing geographical origins did not demonstrate cytotoxic activity. Expression of CDT was also not detected in these six isolates using immunoblotting and the genes cdtA, cdtB, and cdtC were not amplified using PCR. The remaining isolates demonstrated cytotoxic activity, expressed the CDT proteins, and the presence of the cdt genes was confirmed. CONCLUSIONS: CDT is considered a virulence factor of H ducreyi but was found to be absent in 13% of isolates from different geographical origins.

Bacterial Toxins↗
PubMed2002

Dopamine modulation of neuronal function in the monkey prefrontal cortex.

We developed a brain slice preparation that allowed us to apply whole-cell recordings to examine the electrophysiological properties of identified synapses, neurons, and local circuits in the dorsolateral prefrontal cortex (DLPFC) of macaque monkeys. In this article, we summarize the results from some of our recent and current in vitro studies in the DLPFC with special emphasis on the modulatory effects of dopamine (DA) receptor activation on pyramidal and nonpyramidal cell function in superficial layers in DLPFC areas 46 and 9.

Animals↗
PubMed2002

Dendritic morphology of callosal and ipsilateral projection neurons in monkey prefrontal cortex.

Subpopulations of cortical pyramidal neurons have been distinguished based on the projection target of their principal axons or by their dendritic morphology. In this study, we sought to test the hypothesis that pyramidal neurons in monkey prefrontal cortex that furnish callosal or ipsilateral projections have distinctive dendritic morphologies. Retrogradely-labeled, Fast Blue-containing callosal and ipsilateral neurons were intracellularly filled with Lucifer Yellow, immunoconverted, and reconstructed. Quantitative measurements of the size and complexity of the dendritic arbor, including total dendritic length, horizontal extent, number of branch points, maximum branch order, and number of segments, as well as spine density, were made. In general, callosal neurons had larger and more complex dendritic arbors for both apical and basilar dendritic trees than did ipsilateral neurons. The greatest difference was in total dendritic length; the apical and basilar trees of callosal neurons were 34 and 25% longer, respectively. In addition, spine density was also significantly greater on the apical and basilar dendrites of callosal neurons. These findings could not be explained by differences in somal size or completeness of dendritic filling between callosal and ipsilateral neurons. Our observations support the hypothesis that callosal and ipsilateral neurons differ on a number of measures of dendritic size and complexity. Furthermore, these findings imply that these two subpopulations of pyramidal cells differ in the number and perhaps types of excitatory inputs that they receive. Finally, differences in the dendritic morphology of callosal and ipsilateral neurons have implications for understanding the functional attributes of these two populations of cells, as well as for the characterization of pyramidal neurons in human disease states.

Amidines↗
PubMed2002

Localized decrease in serotonin transporter-immunoreactive axons in the prefrontal cortex of depressed subjects committing suicide.

A variety of postmortem brain studies and clinical investigations have provided evidence that reduced serotonin neurotransmission is associated with suicidal behavior and depression, and several serotonergic parameters have been found to be altered in the prefrontal cortex of suicide victims. However, the integrity of the serotonin innervation of the prefrontal cortex in mood disorders has not been directly investigated. The present study used immunocytochemical methods and an antibody against the serotonin transporter to examine the relative density of serotonin axons in the dorsolateral prefrontal cortex of suicide victims with a diagnosis of major depression. The mean total length of serotonin transporter-immunoreactive axons per unit area was unchanged in layers 2 and 4 of area 46 in the depressed suicide subjects compared to controls, but was significantly (P < 0.01) decreased by 24% in layer 6 in the depressed suicide group. The total length of serotonin transporter-positive axons in layer 6 was reduced in eight of the 12 depressed suicide subjects compared to their matched control subjects. These findings reveal that depressed subjects who have committed suicide exhibit a lamina-specific reduction in a marker of serotonin axons in the dorsolateral prefrontal cortex that may reflect an alteration in cortical serotonin neurotransmission.

Adult↗