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Biomedical subjects

A Kemper

Publications and source records attributed to A Kemper.

At least 19 recordsLinked to original sources

First night effect in children and adolescents undergoing polysomnography for sleep-disordered breathing.

OBJECTIVE: To establish whether there is a first night effect (FNE) in children and adolescents with suspected obstructive sleep apnoea undergoing polysomnography (PSG) and whether this affects sleep and breathing, furthermore, to determine the extent to which age may influence the sleep and cardiorespiratory parameters. METHODS: One hundred and thirty-one children and adolescents (age classes-A: 2-6 years n=37; B: 7-12 years n=60; C: 13-17 years n=34) underwent PSG on 2 consecutive nights (I and II) under identical conditions for suspected sleep-related respiratory disorders. One hundred and five patients including 3 patients with obstructive sleep apnoea syndrome (OSAS) treated by adenotonsillectomy and 18 OSAS patients receiving nCPAP-therapy had no PSG-abnormalities (Group 1-A: n=28; B: n=53; C: n=24). A further 26 patients (Group 2) had clinically and polysomnographically confirmed untreated OSAS (A: n=9; B: n=12; C: n=5). RESULTS: There were no statistically significant differences between children with no PSG-abnormalities (Group 1) and those with OSAS (Group 2) in terms of sleep parameters (arousal indices excluded), oxygen saturation (SaO(2)) and heart rate (HR), and these parameters have, therefore, been pooled for the entire group (n=131) in the 3 age classes A, B and C. In the second and third age classes, sleep efficiency on the first night was reduced. In all age classes, there was significantly more wakefulness during the first night. In the second and third age ranges, the proportion of NREM 1 in the first night was significantly higher, with a correspondingly reduced proportion of NREM 4 in the third age group. In all age classes, REM sleep was significantly less during the first night, but REM latency was comparable on both nights. On the first night, the mean HR was higher. There were significant differences in apnoea/hypopnoea-index (AHI), electroencephalogram (EEG)-arousal-index (AI) and motoric arousal index (jerk index, JI) between Groups 1 and 2. In neither group, were there any significant differences in AHI, mean SaO(2) or number of EEG-arousals between nights 1 and 2. Only in the age class A, in Group 2 (n=9) was the number of motoric arousals significantly higher on the first night. Comparison of the age classes A, B, and C revealed that most polysomnographic parameters were age-dependent. Increasing age was found to correlate with a higher proportion of NREM 1, especially on the first night. Also, there was an age-dependent increase in NREM 2 on both nights, a decrease in NREM 3 on the first night, and a decrease in NREM 4 on both nights. In older children, we also found a lower proportion of REM sleep on the first night and a lower HR on both nights. In Group 1, we found a lowered AHI, AI and JI (for JI significant only on the first night) in older patients. No such age dependence of AHI, AI and JI was seen in OSAS patients (Group 2). CONCLUSIONS: In children and adolescents, there is an FNE comparable with that described in adults. In OSAS children and also in children with no PSG-abnormalities, there is night-to-night-variability in sleep parameters, but not in respiratory parameters. An adaptation night is, therefore, necessary when sleep architecture is to be studied, but not when only the nocturnal respiratory pattern is investigated. Sleep parameters, HR and arousal indices are all age-dependent.

Adolescent↗

CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells.

In this study we present new differential characteristics of NK cells expressing CD56 surface antigen in low (CD56dim) or high (CD56bright) density. In contrast to CD56bright NK cells CD56dim cells express killer cell immunoglobulin (Ig)-like receptors (KIR) such as CD158a, CD158b, and NKB1. However, c-type lectin-like receptors (KLR) CD94/NKG2 and CD161 are present on both subsets. The ability to form conjugates with susceptible targets is approximately twice as strongly pronounced in CD56dim vs. CD56bright NK cells. Last but not least, granules of CD56dim cells contain about tenfold more perforin and granzyme A enabling potentially more effective cytolysis compared to CD56bright NK cells. On the other hand, CD56bright NK cells are superior in producing the proinflammatory cytokines IFN-gamma (28.5% vs. 20.8%, p<0.05) and TNF-alpha (28% vs. 15.8%, p<0.001). The different NK cell populations retained their specific phenotype in vitro during culture in the presence of IL-2 contradicting that they simply display different stages of maturity. Taken together our data support the view that CD56bright cells are specialized NK cells that regulate immunological response mechanisms rather by cytokine supply than by their cytotoxic potential. The poor cytolytic capacity of CD56bright NK cells can be explained by weak ability in forming conjugates with target cells and low contents of perforin and granzyme A in their granules.

Antigens, CD↗

Inhibitors of ethylene synthesis inhibit auxin-induced stomatal opening in epidermis detached from leaves of Vicia faba L.

Using leaf epidermis from Vicia faba, we tested whether auxin-induced stomatal opening was initiated by auxin-induced ethylene synthesis. Epidermis was dark-incubated in buffered KNO3 containing 0.1 mM alpha-napthalene acetic acid or 1 mM indole-3-acetic acid. Maximum net opening was ca. 4 micron after 6 h. Opening was reversed by 20 microM ABA, 0.1 mM CaCl2. 1-Aminocyclopropane carboxylic acid (ACC) synthase catalyzes synthesis of ACC, the immediate precursor to ethylene. Auxin-induced stomatal opening was fully inhibited by 10 microM 1-aminoethoxyvinylglycine (AVG), an ACC synthase inhibitor. In solutions containing AVG, auxin-induced opening was restored in a concentration-dependent manner by exogenous ACC, but not in control solutions lacking an auxin. ACC-mediated reversal of AVG-inhibition of stomatal opening was inhibited by alpha-aminoisobutyric acid (AIB), an inhibitor of ACC oxidase, the last enzyme in the ethylene biosynthetic pathway, by 10 microM silver thiosulfate (STS), an inhibitor of ethylene action, and by 20 microM ABA, 0.1 mM CaCl2. CoCl2, an inhibitor of ethylene synthesis, also inhibited auxin-induced opening. Both STS and CoCl2 inhibited opening induced by light or by fusicoccin, but neither light- nor fusicoccin-induced opening was inhibited by AVG. These results support the hypothesis that auxin-induced stomatal opening is mediated through auxin-induced ethylene production by guard cells.

Amino Acid Oxidoreductases↗

Dominant negative guard cell K+ channel mutants reduce inward-rectifying K+ currents and light-induced stomatal opening in arabidopsis.

Inward-rectifying potassium (K+(in)) channels in guard cells have been suggested to provide a pathway for K+ uptake into guard cells during stomatal opening. To test the proposed role of guard cell K+(in) channels in light-induced stomatal opening, transgenic Arabidopsis plants were generated that expressed dominant negative point mutations in the K+(in) channel subunit KAT1. Patch-clamp analyses with transgenic guard cells from independent lines showed that K+(in) current magnitudes were reduced by approximately 75% compared with vector-transformed controls at -180 mV, which resulted in reduction in light-induced stomatal opening by 38% to 45% compared with vector-transformed controls. Analyses of intracellular K+ content using both sodium hexanitrocobaltate (III) and elemental x-ray microanalyses showed that light-induced K+ uptake was also significantly reduced in guard cells of K+(in) channel depressor lines. These findings support the model that K+(in) channels contribute to K+ uptake during light-induced stomatal opening. Furthermore, transpirational water loss from leaves was reduced in the K+(in) channel depressor lines. Comparisons of guard cell K+(in) current magnitudes among four different transgenic lines with different K+(in) current magnitudes show the range of activities of K+(in) channels required for guard cell K+ uptake during light-induced stomatal opening.

Arabidopsis↗

Alteration of stimulus-specific guard cell calcium oscillations and stomatal closing in Arabidopsis det3 mutant.

Cytosolic calcium oscillations control signaling in animal cells, whereas in plants their importance remains largely unknown. In wild-type Arabidopsis guard cells abscisic acid, oxidative stress, cold, and external calcium elicited cytosolic calcium oscillations of differing amplitudes and frequencies and induced stomatal closure. In guard cells of the V-ATPase mutant det3, external calcium and oxidative stress elicited prolonged calcium increases, which did not oscillate, and stomatal closure was abolished. Conversely, cold and abscisic acid elicited calcium oscillations in det3, and stomatal closure occurred normally. Moreover, in det3 guard cells, experimentally imposing external calcium-induced oscillations rescued stomatal closure. These data provide genetic evidence that stimulus-specific calcium oscillations are necessary for stomatal closure.

Abscisic Acid↗

Lymphocyte subsets and cellular immunity in patients with chronic pancreatitis.

BACKGROUND: An abnormal immune response may play a pathogenetic role in chronic pancreatitis. However, to date characterization of the systemic immunological changes in patients with chronic pancreatitis has not been undertaken. METHODS: Lymphocyte phenotypes and proliferation ((3)H-thymidine) after stimulation with mitogens and interleukin-2 were studied in peripheral mononuclear cells from 11 patients with chronic pancreatitis (alcohol-induced n = 6; idiopathic pancreatitis n = 5). The natural killer cell activity was investigated in a (51)Cr release cytotoxicity assay. In vitro cytokine release of stimulated mononuclear cells was measured. RESULTS: Flow cytometric studies showed a significant decrease in the percentage of circulating CD8+, CD56+ and CD25+ cells in patients with chronic pancreatitis independent of the etiology. Comparing all patients with chronic pancreatitis to controls, the proliferation rate was not significantly increased, but patients with pain (n = 5) showed increased proliferation in comparison to patients without pain (n = 6). No significant difference in natural killer cytotoxicity was observed. The in vitro release of tumor necrosis factor-alpha and interleukin-10 by stimulated mononuclear cells was increased. CONCLUSIONS: Chronic pancreatitis is accompanied by systemic immune dysregulation. The observed changes in peripheral mononuclear cells reveal additional evidence that the cell-mediated immune response may contribute to the development of pain and tissue destruction in chronic pancreatitis.

Adult↗

Immunologic and virologic studies in long-term nonprogressors with HIV-1 infection.

BACKGROUND: It is not known whether clinical latency in long-term nonprogressors (LTNP) with HIV-1 infection is due to a strong HIV-1 specific immune response of the host or to virologic factors. - METHODS: Peripheral blood mononuclear cells (PBMC) of 6 LTNP were analyzed for their phenotype, proliferation rates, natural killer (NK) cell activity, antibody dependent cellular cytotoxicity (ADCC), and CCR5 chemokine receptor genotype. Furthermore sequence analyses of the HIV-1 gene were performed. - RESULTS: Phenotypic analyses of lymphocyte subsets revealed increased CD8+ as well as HLA-DR+ expressing cells in LTNP and patients with progressive disease (PRO). Proliferation assays in LTNP and PRO showed a reduction of stimulation by polyclonal mitogens (PHA, ConA, PWM) of up to 60%. NK activity was within normal ranges in LTNP but reduced in PRO. 1 LTNP exhibited heterozygosity for CCR5-D32. A mutant HIV nef gene was not discovered by PCR in any of the LTNP. HIV-V3 loop PCR in 5 LTNP revealed the HIV-1B (NSI) subtype. In 2 patients further sequence analyses of the HIV-1 genome showed homozygous mutations in the Sp1 and NF-kB binding sites. CONCLUSION: The non-progression of HIV-1 infection in some LTNP seems to be due to single mutations in the viral genome resulting in a less replicative HIV-1 subtype or to a mutant chemokine receptor leading to a reduced HIV-1 entry into CD4+ cells. NK cell activity might be an additional contributing factor in controlling viremia.

Acquired Immunodeficiency Syndrome↗

Advanced transgenic and gene-targeting approaches.

Over the past two decades the techniques associated with the manipulation of the mouse genome have provided a powerful approach toward the better understanding of gene function. Conventional transgenic and gene targeting approaches have been used extensively, and these techniques have been particularly rewarding for neuroscientists. Nevertheless, the traditional approaches toward genome manipulation have certain limitations that diminish their usefulness for studying more sophisticated biological processes. Therefore, variations to these techniques have recently been developed. The improvements are focused on two areas: one provides regulated control of transgene expression using an inducible expression system; and the other provides the opportunity to inactivate genes in specific cells and at predetermined developmental stages with a conditional gene targeting system. This review summarizes the advantages as well as some of the technical difficulties of these new approaches. The application of these advanced approaches in biomedical research, particularly neuroscience, are also discussed.

Animals↗

The cytoplasmic domain of the large myelin-associated glycoprotein isoform is needed for proper CNS but not peripheral nervous system myelination.

The myelin-associated glycoprotein (MAG) is a member of the immunoglobulin gene superfamily and is thought to play a critical role in the interaction of myelinating glial cells with the axon. Myelin from mutant mice incapable of expressing MAG displays various subtle abnormalities in the CNS and degenerates with age in the peripheral nervous system (PNS). Two distinct isoforms, large MAG (L-MAG) and small MAG (S-MAG), are produced through the alternative splicing of the primary MAG transcript. The cytoplasmic domain of L-MAG contains a unique phosphorylation site and has been shown to associate with the fyn tyrosine kinase. Moreover, L-MAG is expressed abundantly early in the myelination process, possibly indicating an important role in the initial stages of myelination. We have adapted the gene-targeting approach in embryonic stem cells to generate mutant mice that express a truncated form of the L-MAG isoform, eliminating the unique portion of its cytoplasmic domain, but that continue to express S-MAG. Similar to the total MAG knockouts, these animals do not express an overt clinical phenotype. CNS myelin of the L-MAG mutant mice displays most of the pathological abnormalities reported for the total MAG knockouts. In contrast to the null MAG mutants, however, PNS axons and myelin of older L-MAG mutant animals do not degenerate, indicating that S-MAG is sufficient to maintain PNS integrity. These observations demonstrate a differential role of the L-MAG isoform in CNS and PNS myelin.

Alleles↗

Expression and in-vivo modulation of alpha- and beta-adrenoceptors on human natural killer (CD16+) cells.

Expression and in-vivo modulation of beta- and alpha-adrenoceptors on peripheral human natural killer (CD16+) cells was investigated. Ligand binding studies revealed that CD16+ lymphocytes express beta2, alpha1-, alpha2- but not beta1-adrenoceptors. Infusion of adrenaline, but not noradrenaline, significantly decreased beta2- and alpha1-adrenoceptor numbers on NK cells. Both catecholamines did not appreciably alter alpha2-adrenoceptor numbers. Additional analyses showed that adrenaline administration increases alpha2-adrenoceptor numbers on peripheral mononuclear blood cells (PBMC) and T-cell subsets (CD4+, CD8+) in contrast to decreased receptor numbers on CD16+ cells. These data demonstrate a specific effect of increasing levels of circulating catecholamines on beta2-adrenoceptors on NK cells.

Adrenergic Agonists↗

Applications in in ovo technology.

By mid-August 1995, 55% of broiler embryos in North America were vaccinated for Marek's disease using the INOVOJECT system, with 201 INOVOJECT machines placed with 16 of the top 25 poultry producers, providing the industry with the capacity to inject in excess of 400 million eggs per month or about 5 billion eggs per annum. In ovo administration of a bursal disease antibody-infectious bursal disease virus (BDA-IBDV) complexed vaccine to specific-pathogen-free (SPF) embryos was safer and more potent than conventional IBDV vaccine alone because it delayed the appearance of bursal lesions, produced no early mortality, produced higher geometric mean antibody titers against IBDV, and generated protective immunity against challenge. In ovo administration of a BDA-IBDV complexed vaccine to broiler embryos generated antibody titers against IBDV sooner than conventional virus vaccinates, and generated protective immunity against challenge Direct DNA injection of plasmid DNA encoding beta-galactosidase into breast muscle in ovo and posthatch was an effective means to achieve both gene transfer and expression, with potential for the development of gene vaccines using plasmids encoding protective antigens from poultry pathogens. In ovo administration of 800 U chicken myelomonocytic growth factor (cMGF), a chicken hematopoietic cytokine for cells of the monocytic-granulocytic lineages, significantly reduced mortality associated with Escherichia coli exposure within the hatcher when compared to PBS controls (6.1 vs 12.4, P < or = 0.05), but not when compared to a yeast expression control. A procedure was developed enabling injection prior to the onset of incubation without compromising embryo viability. This in ovo injection process has opened up the window of embryo development during incubation for intervention, as illustrated by the 100% male phenotype produced in chicks hatching from eggs injected with aromatase inhibitor prior to incubation. These data illustrate some of the in ovo applications presently in use by the poultry industry, and under development or in research at EMBREX.

Animals↗

TCR1+ large granular lymphocyte proliferation in rheumatoid arthritis.

The T gamma-lymphoproliferative syndrome is characterized by a proliferation of large granular lymphocytes (LGL). It is often associated with neutropenia, and in 30% of cases with rheumatoid arthritis (RA). Phenotypic analysis has demonstrated that in most cases of RA with T gamma-proliferative disease, the LGL represent T cells with a clonal rearrangement of the alpha/beta T cell receptor (TCR2). Here, three patients with gamma/delta TCR1+ LGL proliferation suffering from long-standing arthritis and neutropenia are described. The first patient with RA showed an expansion of a heterogeneous CD2+ CD16+ CD56- LGL population, of which 30% coexpressed TCR1 with V delta 1 rearrangement. The second patient with ankylosing spondylitis and RA was suffering from proliferation of TCR1+ (V gamma 9-, V delta 1-), CD2+ CD16- CD56- LGL with low coexpression of CD8. The third patient with RA was suffering from a proliferation of TCR1+ (V delta 1+, V gamma 9-) CD4- CD8- CD16- CD56- lymphocytes. On the basis of these unusual findings, the pathogenetic role of TCR1+ T cells in RA is discussed.

Aged↗

Simultaneous analysis of homovanillic acid, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol and vanilmandelic acid in plasma from alcoholics by high-performance liquid chromatography with electrochemical detection. Critical comparison of solid-phase and liquid-liquid extraction methods.

A method is described for the simultaneous determination of vanilmandelic acid, 3-methoxy-4-hydroxyphenylethylene glycol, 5-hydroxyindoleacetic acid, and homovanillic acid in a human plasma sample using reversed-phase high-performance liquid chromatography with column switching and amperometric detection. Two methods of sample preparation were tested. Liquid-liquid extraction yields better recoveries, is more selective and precise than solid-phase extraction and allows a shorter time of chromatographic analysis. Estimated plasma values of the metabolites from healthy controls are in good agreement with previously reported levels. Studies of alcoholics at the beginning of the delirium tremens provided different plasma levels of the metabolites, dependent on the different duration--and hence the severity--of the delirium.

Alcohol Withdrawal Delirium↗

Cortisol and beta-endorphin response in alcoholics and alcohol abusers following a high naloxone dosage.

The course of plasma cortisol and beta-endorphin-like immunoreactivity (beta-EP-IR) was determined following a single i.v. administration of 20 mg naloxone. The test subjects included 20 male alcoholics (medication-free), investigated one to three days and four weeks after the onset of abstinence, as well as 10 short-time abstinent alcohol abusers and 10 healthy control subjects. The mean baseline values of cortisol and beta-EP-IR remained within normal limits in all groups. The significant decrease in the plasma cortisol baseline values in the alcoholics after 4 weeks abstinence may indicate a lower level of the regulation of the hypothalamic-pituitary-adrenal axis (HPA) under conditions of abstinence. After naloxone administration an increase in plasma cortisol and beta-EP-IR was observed in all groups. The multivariate trend analysis showed significant differences in the time course of plasma cortisol between the three groups, however not in the course of beta-EP-IR. The changes in the dynamic regulation of the HPA axis, resulting from chronic alcohol consumption, appears to be irrespective of whether the drinking pattern is dependent or abusive. In alcoholics these changes could still be identified following a 4-week abstinence period.

Adaptation, Physiological↗

Basal activities of adenylate and guanylate cyclase in lymphocytes and platelets of alcoholics.

Basal activities of adenylate cyclase and guanylate cyclase were determined in lymphocytes and platelets of alcoholics with different severity of alcoholic withdrawal syndrome. Compared to controls, significant changes were found in the basal activities of adenylate and guanylate cyclase in all groups of patients. Adenylate cyclase activity in lymphocytes has a positive correlation to the severity of the clinical states. Although we found increased guanylate cyclase activities in lymphocytes and decreased activities in platelets compared to controls, similar values of activities were obtained in all groups of alcoholics independently of their clinical state.

Adenylyl Cyclases↗

Acute reduction in functional infarct expansion with late coronary reperfusion: assessment with quantitative two-dimensional echocardiography.

Reperfusion performed too late to salvage myocardium decreases chronic infarct expansion in experimental animals. However, the acute effects of delayed reperfusion are not known. Twenty-two dogs underwent 3 (n = 8), 4 (n = 8) or 6 h (n = 6) of circumflex artery occlusion followed by 3 h of reperfusion. Effects of reperfusion on diastolic expansion were assessed in two ways: 1) change in mean radius of curvature of the infarct segment, and 2) change in the ratio of the length of the diameter from the center of the infarct zone to the opposite wall (septal-lateral diameter) to the length of the diameter perpendicular to this (anteroposterior diameter). Effects on systolic expansion were examined with quantitative two-dimensional echocardiographic systolic thickening analysis. Delayed reperfusion produced an immediate decrease in diastolic infarct expansion. The ratio of septal-lateral/anteroposterior diameters, which had increased with occlusion from a preocclusion baseline of 0.98 +/- 0.06 to 1.13 +/- 0.08 (p less than 0.001), decreased with reperfusion to 1.02 +/- 0.07 at 15 min and 1.03 +/- 0.08 at 3 h of reperfusion (p = 0.001). This was due solely to a decrease in the septal-lateral diameter. The radius of curvature of the infarcted segment increased from 2.1 +/- 0.5 cm before reperfusion to 2.74 +/- 0.8 cm at 15 min and 2.6 +/- 0.85 cm at 3 h of reperfusion (p = 0.009). This occurred despite a significant (13.6%) decline in end-diastolic cavity area and is compatible with flattening of the reperfused infarct region. Systolic infarct expansion also improved slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗