Monitoring ambulatory blood pressure in general practice.
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Ambulatory Care↗
Biomedical subjects
S Clark
Publications and source records attributed to S Clark.
The role of GABAB receptor activation in absence seizures of lethargic (lh/lh) mice.
Lethargic (lh/lh) mice, which function as an animal model of absence seizures, have spontaneous seizures that have behavioral and electrographic features and anticonvulsant sensitivity similar to those of human absence seizures. Antagonists of the gamma-aminobutyric acidB (GABAB) receptor suppressed these seizures in lethargic mice, whereas agonists of GABAB receptors exacerbated them. Furthermore, GABAB receptor binding and synaptically evoked GABAB receptor-mediated inhibition of N-methyl-D-aspartate responses were selectively increased in lh/lh mice. Therefore, enhanced GABAB receptor-mediated synaptic responses may underlie absence seizures in lh/lh mice, and GABAB receptor antagonists hold promise as anticonvulsants for absence seizures.
Animals↗
Correlation of insulin receptor level with both insulin action and breakdown of a potential insulin mediator precursor; studies in CHO cell-lines transfected with insulin receptor cDNA.
A phosphatidylinositol-glycan (PI-glycan) has been described previously that may serve as the precursor for a mediator of some of insulins actions. The present study further addresses the potential relevance of this compound by correlating its breakdown with other insulin actions in Chinese hamster ovary (CHO) cells which express different levels of insulin receptor. Comparisons were drawn between parent CHO cells expressing 3 x 10(3) receptors/cells and two cell-lines transfected with human insulin receptor cDNA, that expressed 600 (CHO.TH) and 300 (CHO.T) times the parent receptor level. A PI-glycan was isolated from all cells that incorporated [3H]glucosamine, [3H]galactose and [3H]inositol and was rapidly turned over upon insulin stimulation. Maximal turnover by insulin of approx. 20% was achieved in each cell line consistent with the fibroblastic nature of these cells. The effect of increased insulin receptor expression was to increase the sensitivity of the PI-glycan response to insulin. Increasing receptor number from 3 x 10(3) to 0.88 x 10(6) also increased the sensitivity of response of other insulin actions measured in this study, namely activation of pyruvate dehydrogenase (PDH), glucose utilization and transport. Thus turnover of the PI-glycan is linked closely to both metabolic actions of insulin and to cell surface insulin receptor expression further supporting its potential role in insulin action.
Animals↗
Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy, with special reference to mental ability.
We report the results of screening for molecular deletions in 164 boys with DMD and BMD and correlation of deletions with clinical features. A deletion was detected in 100 cases (61%) by Southern blot hybridization analysis with cDNA probes. Thirty-eight different deletions and two duplications were identified. All deletions except one (deletion of exons 48-53) found in males with DMD disrupted the translational reading frame of the gene; however, six deletions in boys with BMD were out of frame. The same deletion in different individuals was found to occur with or without mental impairment, and many different deletions were associated with mental retardation. We were able to ascertain a series of boys [from this study and a previous one (Hodgson S V, Hart K, Abbs S, et al. Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy. J Med Genet 1989; 26: 682-693)] without significant mental retardation who had deletions which, when combined, covered the whole region of the gene in which deletions are commonly found, and within which region individual deletions can be associated with mental retardation.
Adolescent↗
The role of NMDA receptors in in vitro epileptogenesis.
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Animals↗
Age and blood pressure measurement: experience with the TM2420 ambulatory blood pressure monitor and elderly people.
The accuracy of the TM-2420 ambulatory blood pressure monitor was assessed in elderly people. Ninety-four subjects (44 men and 50 women), aged 60-94 with systolic blood pressure (SBP) of 97-208 mmHg and diastolic blood pressure (DBP) of 45-109 mmHg, including 23 with isolated systolic hypertension, were studied in three centres. The monitor was compared simultaneously with pairs of observers using the Hawksley random zero sphygmomanometer. The standard deviation of the difference (SDD) between observers was 4.2 mmHg (SBP), 2.9 mmHg (DBP). The mean difference was 0.49 mmHg (SBP) and 0.27 mmHg (DBP). The SDD between the monitor and the average of the observers' readings was 6.7 mmHg (SBP), 5.5 mmHg (DBP); the mean differences were 4.4 mmHg (SBP) and 4.8 mmHg (DBP). There were no significant differences between the two versions of the monitor used (5 and 7) or between the three pairs of observers. The monitor was equally accurate in isolated systolic hypertension (SDD observers and monitor 6.2 mmHg for SBP, 3.9 mmHg for DBP, mean differences 4.3 mmHg for SBP, 4.5 mmHg for DBP). Twenty-four-hour ambulatory blood pressure monitoring was carried out in 129 subjects aged 60-79; 89% of the monitoring attempted were successful with error rates of < 10%. The mean error rate was 3.8%. The device was well tolerated with only 4.7% of the subjects not completing a monitoring.
Aged↗
In vivo hematological effects of seven days of rhIL-6 in neonatal rats.
Interleukin 6 (IL-6) has been demonstrated to possess a variety of biological and immunological functional properties. Recently, Interleukin 6 has been shown to stimulate in vitro fetal hematopoiesis. In the present study, we investigated the effects of 7 days of rhIL-6 on newborn rat in vivo myelopoiesis. Sprague-Dawley newborn rats (less than 24 h old) were injected (intraperitoneally) daily for 7 days with either rhIL-6 or PBS/BSA. RhIL-6 induced a mild but significant increase in the peripheral neutrophil count on day 1 (P less than 0.02), but had no significant sustained effects during the remaining 7 days of administration. Additionally, rhIL-6 had no significant effect on the bone marrow neutrophil proliferative pool, neutrophil storage pool, the liver/spleen neutrophil storage pool and neutrophil proliferative pools. Although rhIL-6 induced a significant increase in the day 1 platelet count (p less than 0.03), it failed to induce a sustained significant increase in the platelet count during the remaining 7 days of administration. RhIL-6 also failed to induce any change in the circulating hematocrit during the 7 days of administration. This study suggests that rhIL-6 failed to induce a significant and sustained increase in the peripheral neutrophil count or platelet count during in vivo administration in neonatal rats. Although rhIL-6 may possess additional immunomodulating effects in the newborn, this 7-day study of rhIL-6 failed to demonstrate any induction of neonatal peripheral neutrophilia or modulation of neonatal myeloid proliferation.
Animals↗
Decreased G-CSF and IL-3 production and gene expression from mononuclear cells of newborn infants.
Newborns are predisposed to neutropenia and thrombocytopenia during bacterial sepsis. The presence of peripheral cytopenias during overwhelming infection may be secondary to decreased hematopoietic growth factor production during states of increased demand. We therefore examined circulating levels of granulocyte-colony stimulating factor (G-CSF) and IL-3, production of G-CSF and IL-3 from unstimulated and stimulated mononuclear cells (MNC), expression of G-CSF and IL-3 genes during unstimulated and stimulated conditions, and equilibrium and binding of G-CSF receptors on mature effector peripheral blood cells of adults and neonates. Serum from cord and adult peripheral blood contained negligible amounts of both G-CSF (less than or equal to 50 pg/mL) and IL-3 (less than or equal to 5 pg/mL). Constitutive supernatant levels of G-CSF and IL-3 from cord and adult unstimulated MNC were also undetectable. However, there was a significant difference in G-CSF and IL-3 production from stimulated cord and adult MNC. Supernatants from stimulated adult MNC had significantly more G-CSF (p less than 0.007) and IL-3 (p less than 0.02). Additionally, Northern blot hybridization and densitometry of autoradiographs demonstrated significantly more G-CSF and IL-3 mRNA transcripts from adult than from cord MNC. Lastly, affinity, binding, and number of G-CSF receptors on cord and adult peripheral effector cells were equal. These data suggest that, during states of increased demand, cord MNC produce less G-CSF and IL-3 than do adult MNC and have an associated reduction in their respective mRNA transcripts. These findings may have implications in the pathogenesis of neonatal cytopenias during states of increased demand, such as sepsis.
Adult↗
Hypoxemic respiratory failure complicating nosocomial measles in a healthy host.
Since 1983 there has been a steady increase in the number of cases of measles reported to the Centers for Disease Control (CDC), and recent large-scale outbreaks have heightened public awareness. Although mortality from measles is considered rare, systemic complications occur frequently. This case highlights the significant morbidity and potential mortality of measles infection in a normal adult host who did not meet CDC guidelines for measles vaccination.
Adult↗
Spark erosion technology.
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Dental Polishing↗
Tongue in cheek.
Apyogenic granuloma is an innocent lesion commonly found on the gingiva, but can occur at other oral sites. A case is reported of a tongue lesion which had been present for 20 years and is unusually large.
Aged↗
The use of a synthetic tRNA gene as a novel approach to study in vivo transcription and chromatin structure in yeast.
To monitor in vivo transcription and chromatin structure of yeast tRNA genes, we constructed a synthetic tRNA gene that can be used as a reporter. Constructs in which this synthetic tRNA gene is combined with different flanking regions can be integrated into the genome as single copies. The artificial tRNA gene is tagged by the insertion of an intron-like sequence that cannot be spliced out from the precursor and transcripts can thus be identified and quantitated. By several criteria, the artificial tRNA gene behaves like a resident tRNA gene. By measuring the accessibility towards DNaseI in chromatin, we found that the artificial tRNA gene exhibits the same characteristic pattern as resident tRNA genes. Three DNaseI-sensitive sites across the transcribed part of the gene and the immediate flanking regions reflect the formation of the stable transcription complex; positioned nucleosomes are observed in the upstream flanking region. We are confident that the system we have established will prove useful for studying regulatory aspects of tRNA gene expression as well as aspects of pre-tRNA processing and splicing.
Animals↗
In vitro production of granulocyte-macrophage colony-stimulating factor in aplastic anemia: possible mechanisms of action of antithymocyte globulin.
Various abnormalities of lymphokine production have been described in patients with aplastic anemia. To determine if abnormal production of hematopoietic growth factors could contribute to the process of aplastic anemia we studied the in vitro production of human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) by phytohemagglutinin (PHA)- and antithymocyte globulin (ATG)-stimulated peripheral blood lymphocytes from 29 patients with aplastic anemia and 15 normal controls. GM-CSF production in response to 1% PHA was seen in nearly all samples (43 of 44) and similar amounts of GM-CSF were produced by patients with aplastic anemia and normal controls. Production of GM-CSF by ATG-stimulated lymphocytes was seen in 7 of 23 patients with aplastic anemia (30%); two of these patients also demonstrated low-level spontaneous production of GM-CSF. Production of GM-CSF in response to ATG was also seen in 2 of 11 normal controls (18%) and barely detectable spontaneous production of GM-CSF was seen in both. Biologically active IL-3 could also be detected in PHA- or ATG-stimulated peripheral blood mononuclear cells in several patients and normal controls. Our results indicate that lymphocytes from patients with aplastic anemia can be stimulated in vitro to produce normal quantities of GM-CSF, suggesting that impaired potential for production of T-cell derived hematopoietic growth factors is unlikely to account for the marrow hypoplasia seen. In several patients overproduction of GM-CSF was observed, consistent with the notion that some patients with aplastic anemia may have circulating activated T cells. We also demonstrate that ATG can stimulate the production of growth factors such as IL-3 and GM-CSF, supporting the role for ATG in stimulating hematopoiesis.
Adult↗
Changes in insulin-receptor structure associated with trypsin-induced activation of the receptor tyrosine kinase.
The tyrosine kinase of the insulin receptor can be activated by trypsin treatment. The concomitant abolition of insulin binding has been postulated to result from proteolytic destruction of the receptor. A discrepancy between the decrease in insulin binding and receptor immunoreactivity after trypsin treatment led us to investigate more closely the structure of the trypsin-treated receptor. After trypsin treatment of the CHOT cell line, which over-expresses transfected human insulin receptors, insulin binding was significantly decreased, but reactivity with five alpha-subunit monoclonal antibodies was either unaffected or only moderately decreased, indicating that the alpha-subunit was substantially intact. Examination of receptor structure after trypsin treatment, receptor autophosphorylation and gel electrophoresis revealed a single band at 110 kDa in non-reduced gels, comprising a small fragment (21 kDa) of the alpha-subunit linked to the beta-subunit by class II disulphides. When the receptor was radio-labelled with 125I, two additional alpha-subunit bands of 142 kDa and 81 kDa (composed of identical reduced bands) were observed on non-reduced gels, which contained disulphide-linked (class I) fragments. All fragments could be precipitated by antibodies to both alpha- and beta-subunits. However, only antibodies directed towards the N-terminus of the receptor could immunoblot trypsin-treated fragments. Thus activation of the receptor tyrosine kinase by trypsin occurs after cleavage, but not loss of the alpha-subunit. This finding has implications for the mechanism of transmembrane activation of the receptor kinase by insulin.
Animals↗
Modulation of phospholipase A2 activity by epidermal growth factor (EGF) in CHO cells transfected with human EGF receptor. Role of receptor cytoplasmic subdomain.
Activation of phospholipase A2 (PLA2) in response to external stimuli may play a pivotal role in signal-transduction pathways via the generation of important cellular intermediates, including prostaglandins. Epidermal growth factor (EGF) has been shown to modulate prostaglandin production, possibly via direct activation of PLA2 or indirectly via interaction with a PLA2-modifying protein such as lipocortin I. We have investigated these pathways with two CHO cell-lines, one (CHOwt) transfected with the full-length human EGF receptor and the second (CHO 11) with a deletion mutant, delta 990, that has lost the autophosphorylation sites and part of the internalization domain. CHOwt cells responded to EGF with a rapid rise in lysophosphatidylcholine and arachidonic acid release concomitant with an increase in prostaglandin production. However, in the non-internalizing CHO 11 cells no such activation of PLA2 was observed. This was not due to an intrinsic lack of PLA2 in these cells, as PLA2 activation was shown on melittin addition, nor was this difference due to a defect in intracellular pathways, as arachidonic acid was released from both cell types by Ca2+ and protein kinase C modulators. However, only in CHOwt cells were these responses potentiated by concomitant addition of EGF. Thus the cytoplasmic subdomain of the EGF receptor, containing the major sites of autophosphorylation and the internalization domain, seems to be involved in the activation of PLA2 by EGF. In addition, we have shown that phosphorylation of lipocortin I is unlikely to play a role in PLA2 activation. In CHOwt cells and a positive control cell line, A431, activation of PLA2 was complete by 10 min, at which time there was no evidence of lipocortin I phosphorylation.
Animals↗
Fertility of workers chronically exposed to chemically contaminated sewer wastes.
Few studies have investigated the reproductive effects of exposure to chemical mixtures. The purpose of this study was to assess fertility in males exposed to mixed industrial and domestic wastes. A detailed reproductive history was obtained from the wives of 231 employees in order to evaluate fertility. Daily work records were used to define exposure status. To ascertain problems of infertility, the ratios of observed live births to expected live births (generated from U.S. birth probabilities) for exposed and nonexposed groups were calculated, and the ratios of these Standardized Fertility ratios (SRFs) were compared. Other analyses considered the couples' contraceptive history and preexposure versus postexposure experience. Though multiple statistical approaches were used to examine the data, the conclusion of this study was that exposure to chemical mixtures was not associated with a decrease in the couples' fertility.
Air Pollutants, Occupational↗
The effectiveness of ice- and Freon-based personal cooling systems during work in fully encapsulating suits in the heat.
The use of cooling garments in conjunction with fully encapsulating suits offers the potential for reducing the heat strain for workers at hazardous waste sites and chemical emergencies. This study examined the use of ice- and Freon-based cooling garments during exercise in the heat while wearing a U.S. Coast Guard chemical response suit (CRS), a fully encapsulating, Teflon-coated, Nomex suit. Responses of nine healthy men (mean age 28.8 yr) were measured during moderate exercise at 30% of their maximal oxygen consumption in an environmental chamber maintained at 33.9 degrees C (93 degrees F) and 82% relative humidity. The four randomly assigned experimental conditions were (1) the CONTROL, consisting of a self-contained breathing apparatus (SCBA) worn in conjunction with shorts, shirt, helmet, and shoes; (2) the CRS, consisting of the Coast Guard CRS worn with shorts, shirt, SCBA, helmet, gloves, and boots; (3) the ICE, which was identical to the CRS ensemble, with the addition of an ice and water cooling system; and (4) the FREON, which was also identical to the CRS ensemble, with the addition of a Freon-based cooling system. To the author's knowledge, this paper is the first to quantify and compare a Freon-based system with a circulating ice water system. The subjects performed repeated rest/work intervals for 45 min, followed by a 10-min recovery period. Measured physiological responses, including heart rate, skin, rectal, and axillary temperatures, were recorded at 1-min intervals during the tests.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗