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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 163 records · Page 9Linked to original sources
PubMed1999

Effects of sleep and sleep deprivation on catecholamine and interleukin-2 levels in humans: clinical implications.

The objective of this study was to evaluate the effects of nocturnal sleep, partial night sleep deprivation, and sleep stages on catecholamine and interleukin-2 (IL-2) levels in humans. Circulating levels of catecholamines and IL-2 were sampled every 30 min during 2 nights: undisturbed, baseline sleep and partial sleep deprivation-late night (PSD-L; awake from 0300-0600 h) in 17 healthy male volunteers. Sleep was monitored somnopolygraphically. Sleep onset was associated with a significant (P < 0.05) decline of circulating concentrations of norepinephrine and epinephrine, with a nocturnal nadir that occurred 1 h after nocturnal sleep. On the PSD-L night, levels of norepinephrine and epinephrine significantly (P < 0.05) increased in association with nocturnal awakening. During stage 3-4 sleep, levels of norepinephrine, but not epinephrine, were significantly lower (P < 0.05) compared to average levels during the awake period, stages 1-2 sleep, and rapid eye movement sleep. Nocturnal levels of circulating IL-2 did not change with sleep onset or in relation to PSD-L or the various sleep stages. We conclude that sleep onset is associated with changes in levels of circulating catecholamines. Loss of sleep and disordered sleep with decreases in slow wave sleep may serve to elevate nocturnal catecholamine levels and contribute to cardiovascular disease.

Adult↗
PubMed1999

Effect of cannabis use on cognitive functions and driving ability.

BACKGROUND: Neither experimental nor epidemiologic approaches have so far given definitive answers to the question of the potential effect of cannabis on driving ability. METHOD: To shed more light on this topic, we conducted a placebo-controlled double-blind study including 60 healthy volunteers (a negative urine drug screening test was prerequisite). On the first day, baseline data were obtained from a physical examination and a psychological test battery for the investigation of visual and verbal memory as well as cognitive perceptual performance. On the second day, subjects received a regular cigarette or one containing 290 microg/kg body weight of tetrahydrocannabinol. Physical and psychological assessments were performed immediately (15 minutes) after subjects smoked their cigarettes. Twenty-four hours later, physical and psychological examinations were repeated. RESULTS AND CONCLUSION: Our results suggest that perceptual motor speed and accuracy, 2 very important parameters of driving ability, seem to be impaired immediately after cannabis consumption.

Adult↗
PubMed1999

Genetically engineered Mengo virus vaccination of multiple captive wildlife species.

Encephalomyocarditis virus (EMCV), has caused the deaths of many species of animals in zoological parks and research institutions. The Audubon Park Zoo, (New Orleans, Louisiana, USA) attempted vaccination of several species with a killed EMCV vaccine with mixed results. This paper reports an attempt at vaccination against EMCV using a genetically engineered, live attenuated Mengo virus (vMC0) at the Audubon Park Zoo and Miami Metro Zoo, (Miami, Florida, USA) from December 1996 to June 1997. Several species of animals were vaccinated with vMC0, which is serologically indistinguishable from the field strain of EMCV. Serum samples were taken at the time of vaccination and again 21 days later, then submitted for serum neutralization titers against EMCV. The vaccinate species included red capped mangebey (Cercocebus torquatus), colobus (Colobus guereza), angolan colobus (Colobus angolensis), ruffed lemur (Lemur variegatus ruber and Lemur variegatus variegatus), back lemur (Lemur macaco), ring-tailed lemur (Lemur catta), siamang (Hylobates syndactylus), diana guenon (Cercopithicus diana), spider monkey (Ateles geoffroyi), common marmoset (Callithrix jacchus), talapoin monkey (Cercopithecus talapoin), Brazilian tapir (Tapirus terrestris), Baird's tapir (Tapirus bairdii), Malayan tapir (Tapirus indicus), dromedary camel (Camelus dromedarius), bactrian camel (Camelus bactrianus), gerenuk (Litocranius walleri), guanaco (Lama glama guanicoe), black duiker (Cephalophus niger), Vietnamese potbellied pig (Sus scrofa), babirusa (Babyrousa babyrussa), collard peccary (Tayass tajacu), and African crested porcupine (Hystrix africaeaustralis). The vaccine response was variable, with high virus neutralizing antibody titer responses in some primate species and mixed to poor responses for other species. No ill effects were seen with vaccination.

Animals↗
PubMed1999

Indinavir-induced nephropathy.

We report the case of a 38-year-old male who developed renal insufficiency while on the protease inhibitor, indinavir. This patient had an increase in serum creatinine over a period of approximately one year, along with persistently abnormal urinalysis. A renal biopsy was performed and showed marked tubular crystal deposition. The indinavir was discontinued, and after two months the patient's serum creatinine and urinalysis returned to normal. To our knowledge this is the second case of indinavir associated nephropathy.

Adult↗
PubMed1999

Marked alteration of sterol metabolism and composition without compromising retinal development or function.

PURPOSE: To evaluate the consequences of altering retinal sterol metabolism and composition on the development, histologic organization, and electrophysiological function of the retina, under conditions that mimic the biochemical hallmarks of the Smith-Lemli-Opitz (SLO) syndrome. METHODS: Pregnant Sprague-Dawley rats were fed cholesterol-free chow containing AY9944 (treated group), an inhibitor of 3beta-hydroxysterol delta7-reductase, from gestational day 6 through postnatal day (P)28. Control animals were fed the same chow, but without AY9944. In addition, progeny in the treated group were injected subcutaneously every other day from birth to P28 with an olive oil emulsion containing AY9944; control animals received olive oil emulsion alone. At various postnatal times, tissues from treated and control animals were harvested, and their sterol profiles were analyzed by reversed-phase high-performance liquid chromatography. Companion eyes from animals of both groups were examined histologically at P1. At P28, animals were evaluated by electroretinography; tissues were then harvested for biochemical analysis and companion eyes were subjected to histologic and ultrastructural analyses. RESULTS: Treatment of developing rats with AY9944 caused markedly abnormal accumulation of 7-dehydrosterols and severely reduced cholesterol levels in all tissues examined, relative to control animals. Despite this, treated animals exhibited normal retinal development and had no overt ocular defects or decrease in electroretinographic function, up to P28. CONCLUSIONS: These results were unexpected, given the known biophysical effects of such sterol alterations on membrane properties and the profound dysmorphic and cognitive abnormalities associated with genetic defects in 3beta-hydroxysterol delta7-reductase that have been linked to the SLO syndrome. The results suggest that 7-dehydrosterols can substitute functionally for cholesterol in the retina or perhaps can act synergistically with subthreshold levels of residual cholesterol to allow normal cellular structure and function to be achieved.

Animals↗
PubMed1999

Knowledge and use of the food label among senior women in the management of type 2 diabetes mellitus.

Food selection is a key component in the management of diabetes. The foods selected affect the caloric and nutrient composition of the diet and blood glucose levels among people with diabetes. The nutrition information on the food label can guide decisions for food purchases. Whether senior women with diabetes use and comprehend the nutrition information on the food label has not been determined. Therefore, the purpose of this study was to assess knowledge and beliefs about the food label and diabetes management among women with type 2 diabetes mellitus =65 years of age. Focus groups were conducted and participants (n=24) completed a knowledge test about the food label. Analysis involved extensive review of the videotapes and transcripts of the focus groups. Participants reported that they referred to the nutrition information on the label when grocery shopping. Yet, comprehension of terms and product claims on the label was poor. The mean score on the food label knowledge test was only 49%. Misconceptions about the nutritional management of diabetes also were noted. Thus, senior women with diabetes need additional education about the food label to facilitate application of the information in meal planning and to manage diabetes successfully.

Aged↗
PubMed1998

CDO, a robo-related cell surface protein that mediates myogenic differentiation.

CDO, a member of the Ig/fibronectin type III repeat subfamily of transmembrane proteins that includes the axon guidance receptor Robo, was identified by virtue of its down-regulation by the ras oncogene. We report here that one prominent site of cdo mRNA expression during murine embryogenesis is the early myogenic compartment (newly formed somites, dermomyotome and myotome). CDO is expressed in proliferating and differentiating C2C12 myoblasts and in myoblast lines derived by treating 10T1/2 fibroblasts with 5-azacytidine, but not in parental 10T1/2 cells. Overexpression of CDO in C2C12 cells accelerates differentiation, while expression of secreted soluble extracellular regions of CDO inhibits this process. Oncogenic Ras is known to block differentiation of C2C12 cells via downregulation of MyoD. Reexpression of CDO in C2C12/Ras cells induces MyoD; conversely, MyoD induces CDO. Reexpression of either CDO or MyoD rescues differentiation of C2C12/Ras cells without altering anchorage-independent growth or morphological transformation. CDO and MyoD are therefore involved in a positive feedback loop that is central to the inverse relationship between cell differentiation and transformation. It is proposed that CDO mediates, at least in part, the effects of cell-cell interactions between muscle precursors that are critical in myogenesis.

Animals↗
PubMed1998

Transcriptional induction of cyclooxygenase-2 gene by okadaic acid inhibition of phosphatase activity in human chondrocytes: co-stimulation of AP-1 and CRE nuclear binding proteins.

The involvement of serine/threonine protein phosphatases in signaling pathways that control the expression of the cyclooxygenase-2 (COX-2) gene in human chondrocytes was examined. Okadaic acid (OKA), an inhibitor of protein phosphatases 1 (PP-1) and 2A (PP-2A), induced a delayed, time-dependent increase in the rate of COX-2 gene transcription (runoff assay) resulting in increased steady-state mRNA levels and enzyme synthesis. The latter response was dose dependent over a narrow range of 1-30 nmol/L with declining expression and synthesis of COX-2 at higher concentrations due to cell toxicity. The delayed increase in COX-2 mRNA expression was accompanied by the induction of the proto-oncogenes c-jun, junB, junD, and c-fos (but not FosB or Fra-1). Increased phosphorylation of CREB-1/ATF-1 transcription factors was observed beginning at 4 h and reached a zenith at 8 h. Gel-shift analysis confirmed the up-regulation of AP-1 and CRE nuclear binding proteins, though there was little or no OKA-induced nuclear protein binding to SP-1, AP-2, NF-kappaB or NF-IL-6 regulatory elements. OKA-induced nuclear protein binding to 32P-CRE oligonucleotides was abrogated by a pharmacological inhibitor of protein kinase A (PKA), KT-5720; the latter compound also inhibited OKA-induced COX-2 enzyme synthesis. Calphostin C (CalC), an inhibitor of PKC isoenzymes, had little effect in this regard. Inhibition of 12P-CRE binding was also observed in the presence of an antibody to CREB-binding protein (265-kDa CBP), an integrator and coactivator of cAMP-responsive genes. The binding to 32P-CRE was unaffected in the presence of excess radioinert AP-1 and COX-2 NF-IL-6 oligonucleotides, although a COX-2 CRE-oligo competed very efficiently. 32P-AP-1 consensus sequence binding was unaffected by incubation of chondrocytes with KT-5720 or CalC, but was dramatically diminished by excess radioinert AP-1 and CRE-COX-2 oligos. Supershift analysis in the presence of antibodies to c-Jun, c-Fos, JunD, and JunB suggested that AP-1 complexes were composed of c-Fos, JunB, and possibly c-Jun. OKA has no effect on total cellular PKC activity but caused a delayed time-dependent increase in total PKA activity and synthesis. OKA suppressed the activity of the MAP kinases, ERK1/2 in a time-dependent fashion, suggesting that the Raf-1/MEKK1/MEK1/ERK1,2 cascade was compromised by OKA treatment. By contrast, OKA caused a dramatic increase in SAPK/JNK expression and activity, indicative of an activation of MEKK1/JNKK/SAPK/JNK pathway. OKA stimulated a dose-dependent activation of CAT activity using transfected promoter-CAT constructs harboring the regulatory elements AP-1 (c-jun promoter) and CRE (CRE-tkCAT). We conclude that in primary phenotypically stable human chondrocytes, COX-2 gene expression may be controlled by critical phosphatases that interact with phosphorylation dependent (e.g., MAP kinases:AP-1, PKA:CREB/ATF) signaling pathways. AP-1 and CREB/ATF families of transcription factors may be important substrates for PP-1/PP-2A in human chondrocytes.

Antioxidants↗
PubMed1998

Fourier transform infrared spectroscopy reveals a rigid alpha-helical assembly for the tetrameric Streptomyces lividans K+ channel.

The structure of the tetrameric K+ channel from Streptomyces lividans in a lipid bilayer environment was studied by polarized attenuated total reflection Fourier transform infrared spectroscopy. The channel displays approximately 43% alpha-helical and 25% beta-sheet content. In addition, H/D exchange experiments show that only 43% of the backbone amide protons are exchangeable with solvent. On average, the alpha-helices are tilted 33 degrees normal to the membrane surface. The results are discussed in relationship to the lactose permease of Escherichia coli, a membrane transport protein.

Lipid Bilayers↗
PubMed1998

Formation of CLC-0 chloride channels from separated transmembrane and cytoplasmic domains.

CLC-0, a member of the CLC family of Cl(-)-conducting ion channels, consists of an N-terminal hydrophobic core and a C-terminal region that is thought to be cytoplasmic. This study provides evidence that the C-terminal region is a mechanistically relevant cytoplasmic domain of the CLC-0 ion channel. Both a point mutation and a 37-residue deletion in this region cause drastic alterations in voltage-dependent gating of CLC-0 current expressed in Xenopus oocytes. CLC-0 current is not observed when the entire C-terminal region is deleted, but functional channels are efficiently reconstituted by co-injection of separate cRNA constructs encoding the N-terminal transmembrane and the C-terminal cytoplasmic domains. Moreover, reconstitution of CLC-0 can be achieved by co-injection of cRNA encoding the transmembrane domain along with Escherichia coli-expressed C-terminal domain polypeptide.

Animals↗
PubMed1998

Changes in the cytokine regulation of stem cell self-renewal during ontogeny.

The last 10 years have seen the development of a quantitative assay that is specific for transplantable totipotent murine hematopoietic cells with durable in vivo blood-forming ability. Recently, this assay has been successfully adapted to allow the detection and enumeration of an analogous population of human hematopoietic stem cells using myelosuppressed immunodeficient (nonobese diabetic/severe-combined immunodeficiency) mice as recipients. Characterization of the cells detected by this assay indicates their close relationship in both mice and humans with cells detected in vitro as long-term culture-initiating cells (LTC-IC). Culture conditions have now been identified that support a significant net expansion of these cells from both species. More detailed analyses of the cytokine requirements for this response indicate that the viability, mitogenesis and maintenance of LTC-IC function by human CD34+ CD38- cells can be independently regulated by exogenous factors. Superimposed on this uncoupling of hematopoietic stem cell "self-renewal" and proliferation control is a change during ontogeny in the particular cytokines that regulate their responses. These findings unite stochastic and deterministic models of hematopoietic stem cell control through the concept of a molecular mechanism that actively blocks stem cell differentiation and must be maintained when these cells are stimulated to divide by exposure to certain types and concentrations of cytokines.

Animals↗
PubMed1998

Ultrastructural, physiological, and molecular defects in the inner ear of a gene-knockout mouse model for autosomal Alport syndrome.

The cochleae from a COL4A3-deficient mouse line were examined for defects that might shed light on the molecular mechanism of otopathology observed in humans with Alport syndrome. At the light microscopic level no obvious defects were observed. Immunohistochemical analysis using antibodies specific for the basement membrane collagen chains revealed the absence of the COL4A3 and COL4A4 chains throughout the membranous labyrinth. The COL4A5 chain was absent from all cochlear basement membranes except those in the vessels of the stria vascularis. Expression of the COL4A1 and COL4A2 chains was unchanged in the mutant. Electron microscopic examination of the cochlear basement membranes revealed significant thinning of the basement membrane running from the spiral limbus, down the inner sulcus, across the basilar membrane and up to the spiral prominence. Basement membranes that normally ensheathe the root cells were not detectable. In contrast, the basement membranes surrounding the vessels of the stria vascularis were significantly thickened in the mutant. This was associated with endothelial cell swelling and a marked decrease in internal capillary diameter. In severe cases, pathology was observed in the marginal cells with a loss of basolateral infoldings. Immunohistochemical analysis of the strial vessels revealed an increase in entactin and collagen COL4A1 and COL4A2 chains. Auditory-evoked brainstem response measurements suggest a small increase in thresholds across all frequencies when successive measurements on individual mutant mice were examined between 6 and 8 postnatal weeks. Combined, these results illustrate changes in the basement membranes of the strial vessels that bear resemblance to Alport glomerular basement membrane pathology. A closer look at this compartment in human Alport biopsy specimen may be warranted.

Animals↗
PubMed1998

Differential expression patterns of Wnt genes in the murine female reproductive tract during development and the estrous cycle.

The murine female reproductive tract differentiates during postnatal development. This process of cytodifferentiation and morphogenesis is dependent upon specific mesenchymal-epithelial interactions as well as circulating steroid hormones (Cunha, G.R., 1976. Int. Rev. Cytol. 47, 137-194; Pavlova, A. et al., 1994. Development 120, 335-346). Members of the Wnt family of signaling molecules have been recently identified in this system (Pavlova, A. et al., 1994. Development 120, 335-346; Bui, T.D. et al., 1997. Br. J. Cancer 75, 1131-1136; Miller, C., Sassoon, D.A., 1998. Development, in press). We describe the expression patterns of Wnt genes in the developing and adult female reproductive tract. Additionally, we note that changes in the levels of expression occur during the estrous cycle. Wnt gene expression patterns are regulated by the presence of epithelium in tissue graft experiments, suggesting that Wnt genes may indeed play roles in the mesenchymal-epithelial interactions critical for female reproductive tract development and function.

Animals↗