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PubMed2003

Ultrasonic tissue characterization of the myocardium in anorexia nervosa.

AIM: To determine the systodiastolic variations in the integrated backscatter (IBS) signal of the myocardium in patients with anorexia nervosa. METHODS: 25 young women (aged 22.4 +/- 4.3 y) with overt anorexia nervosa, compared with 25 age-matched thin and 25 age-matched control women with body mass index >20 kg m(-2), underwent either conventional two-dimensional echocardiography or analysis of IBS cyclic variations. RESULTS: Compared with thin and control subjects, anorectic patients showed reduced left ventricular mass (LVM: 82.9 +/- 17.1 vs 119.9 +/- 13.8 and vs 126.12 +/- 16.4 g, p < 0.0001; LVM indexed 21.4 +/- 3.3 vs 29.4 +/- 2.5 and vs 31.2 +/- 3.1 g m(-2.7), p < 0.0001), and IBS cyclic variations (septum: -0.49 +/- 2.18 vs 6.86 +/- 1.3 and vs 6.61 +/- 1.74 dB p < 0.0001; posterior wall: 2.77 +/- 2.12 vs 7.15 +/- 2.12 and vs 7.48 +/- 2.23 dB, p < 0.01). CONCLUSION: Anorexia nervosa is associated with a significant reduction in the cyclic variation in IBS, which is also related to left ventricular hypotrophy. Ultrasonic tissue characterization could give an objective approach for the detection of myocardial structural properties and represent a preclinical index of myocardial dysfunction in anorexia nervosa.

Adult↗
PubMed2004

Adenylyl and guanylyl cyclases from the malaria parasite Plasmodium falciparum.

Completion of several malaria parasite genome sequences and advances in Plasmodium gene manipulation technology, will lead to significant advances in our knowledge of the biology of these organisms. Biochemical analysis of the cyclic nucleotide signalling pathways of P. falciparum has provided important information on malaria parasite development. The Plasmodium purine nucleotide cyclase enzymes have extremely unusual structures and the regulatory mechanisms controlling parasite enzyme activity are distinct from those operating on the analogous host molecules. Study of these enzymes could therefore lead to novel strategies for anti-malarial intervention in addition to providing unique insights into the intriguing biology of the parasite.

Adenylyl Cyclases↗
PubMed2005

Enhanced statistics for local alignment of multiple alignments improves prediction of protein function and structure.

MOTIVATION: Improved comparisons of multiple sequence alignments (profiles) with other profiles can identify subtle relationships between protein families and motifs significantly beyond the resolution of sequence-based comparisons. RESULTS: The local alignment of multiple alignments (LAMA) method was modified to estimate alignment score significance by applying a new measure based on Fisher's combining method. To verify the new procedure, we used known protein structures, sequence annotations and cyclical relations consistency analysis (CYRCA) sets of consistently aligned blocks. Using the new significance measure improved the sensitivity of LAMA without altering its selectivity. The program performed better than other profile-to-profile methods (COMPASS and Prof_sim) and a sequence-to-profile method (PSI-BLAST). The testing was large scale and used several parameters, including pseudo-counts profile calculations and local ungapped blocks or more extended gapped profiles. This comparison provides guidelines to the relative advantages of each method for different cases. We demonstrate and discuss the unique advantages of using block multiple alignments of protein motifs.

Algorithms↗
PubMedDate not supplied

Repetitive ischemia-reperfusion injury: a plausible mechanism for documented clinical burn-depth progression after thermal injury.

Our previous studies confirmed the phenomenon of burn depth progression despite adequate Parkland formula resuscitation [Kim et al. J Burn Care Rehabil 2001;22960:406-6]. Repetitive ischemia-reperfusion injury (I-R) is a plausible explanation and is suggested by the concomitant swings we have observed in serum base deficit (BD) during resuscitation from burn shock. We chose to explore whether laser Doppler imaging (LDI) evidence of burn depth progression mirrored cycles of I-R (episodic swings in continuously measured BD). Positive findings would support the hypothesis that repetitive episodes of I-R is a factor in burn depth progression despite apparently adequate resuscitation. A total of 14 patients with severe life-threatening burns (median 51% TBSA) underwent continuous BD monitoring using a Paratrend 7 (Malvern PA) during 48 hours of resuscitation. Fluid needs were estimated using the Parkland formula, then were titrated to urine output. The slopes of BD changes were then analyzed. Worsening of BD greater than 0.2 mmol/l/min was noted, and a proportion derived relative to pooled data on 5-minute intervals. In four of the patients, LDI scans were performed on six representative areas sequentially every 4 hours. The analysis of median flux in these LDI images provided real-time determination of burn depth progression. Eight patients eventually died. Only four patients achieved a normal BD within 12 hours of monitoring despite exceeding the Parkland formula estimate and meeting urinary output parameters. Our analysis also showed cyclical peaks and valleys in the BD curve (P < .001), suggesting repetitive I-R insults. All increases in BD preceded changes that could be detected in vital signs or urine output. Finally, LDI confirmed that the burn depths continued to progress despite apparently adequate resuscitation, and also showed that there are similar peaks and valleys in the perfusion of the wounds (P < .0001), which mimic the changes in the BD curve. Responses to fluid resuscitation do not follow a linear pattern in the case of massive burns. These results in repetitive periods of tissue hypoperfusion evidenced by BD alterations and may contribute to progressive deepening of the burn wound.

Acid-Base Imbalance↗
PubMed2004

Disruption of the NCS-1/frequenin-related ncsA gene in Dictyostelium discoideum accelerates development.

To learn more about the function of intracellular Ca2+ in Dictyostelium discoideum, we searched databases for sequences encoding potential members of the neuronal calcium sensor (NCS) family of Ca2+-binding proteins. As a result, genes for five new putative Ca2+-binding proteins were identified. Based on amino acid sequence alignments and phylogenetic analyses, one of these genes (ncsA) was determined to be closely related to NCS-1/frequenin genes in other organisms. The protein product of ncsA (NcsA) binds 45Ca2+ and exhibits a dramatic gel mobility shift in the presence of Ca2+, suggesting that it is a Ca2+ sensor. ncsA-null cells grow normally in axenic culture. However, on bacterial lawns, the ncsA-null clones expand slowly and development begins prematurely within the plaques. In larger clones, ncsA-null cells form narrow growth zones with evenly spaced aggregates along the inner edge, and closely packed fruiting bodies. An analysis of intracellular cyclic adenosine monophosphate (cAMP) levels, developmental timing on phosphate-buffered saline (PBS) agar, and stage-specific gene expression indicate that development of ncsA-null cells is accelerated by 3-4 h. Together, these results suggest that NcsA might function in Dictyostelium to prevent cells from entering development prematurely in the presence of environmental nutrients.

Amino Acid Sequence↗
PubMed1999

Personal reflections on occupational health in the twentieth century: spiraling to the future.

The history of occupational health in the United States during the twentieth century demonstrates pendular swings, with periods of rapid progress followed by periods of reversal. Happily, the last three decades have witnessed the most impressive gains, with establishment of a near-universal system for regulating conditions in the workplace, legitimization and growth of the occupational health professions, a marked increase in scientific research, most notably epidemiology, and the transfer of knowledge about occupational health to affected workers and the larger US population. Not surprisingly, rates of injury and illness have fallen. However, analysis of these cyclical historic changes suggests that extrinsic factors--broad social currents, changes in health care financing, and societal perceptions of health and disease--have dominated over enhanced scientific knowledge, technologic changes or professional achievements, usually the determinants of medical or public health advances. Practitioners of occupational health are not, and have never been, in a particularly advantageous position to fashion future events in their own field, and the current situation, however encouraging, is likely no exception.

Forecasting↗
PubMed1990

Computer-assisted long-term measurements of urinary output and other biological data.

A computerized system is described, combining automatic collection of urine in short intervals (minutes) over long periods (days) and recordings of body temperature, MABP, and heart rate in chronically instrumented conscious dogs. During the studies the dogs are housed in metabolic cages. Indwelling catheters and electrical wires are connected to a specially designed swivel and directed out of the cage to the next room. Infusions, blood sampling, and monitoring can be performed from this room without disturbance to the dogs. Three examples of recordings are given. In one of these examples the sodium excretion patterns on 5 consecutive days under continuous saline infusion in one dog is evaluated. Urine was collected every 20 min. Sodium excretion showed cyclic variations. Fourier analysis exhibited 18-h periods and 4- to 8-h periods. The described system renders, e.g., coherent time series analysis possible for a variety of simultaneously recorded physiological variables and may thus acquire considerable importance for integrative physiology.

Animals↗
PubMed1986

Ventilatory changes of pulmonary capillary blood volume assessed by arterial density.

By use of an improved density measuring system, we found that the gravimetric density of arterial blood of dogs fluctuates at the same frequency as the spontaneous or mechanical ventilation. Similar density fluctuations were observed in the blood leaving isolated, perfused lobes of dogs that were ventilated cyclicly. Employing an analysis that balanced the erythrocyte and plasma flows through distensible capillaries containing blood with a tube hematocrit lower than the hematocrit in large blood vessels, we derived a relationship to estimate from the density fluctuation the change in pulmonary capillary blood volume (Vc). For mechanical ventilation, the maximum change in density over one ventilation cycle increased from 0.084 +/- 0.01 to 0.47 +/- 0.05 (SE) g/l as the frequency decreased from 29 to 6 cycles/min. These density changes were estimated to be the result of an 1-16% change in Vc. A larger tidal volume for the mechanical ventilation led to a larger density fluctuation. The maximum density change of spontaneous respiration of 6 cycles/min was one-sixth of the mechanical case, indicating a much smaller change in Vc during spontaneous respiration. When the airway flow resistance was increased for spontaneous respiration, larger density fluctuations were observed.

Airway Resistance↗
PubMed2004

Potential role of a novel transcriptional coactivator PELP1 in histone H1 displacement in cancer cells.

The estrogen receptor plays an important role in breast cancer progression. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), also called modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptor, modulates estrogen receptor transactivation functions. The mechanisms by which PELP1 modulates estrogen receptor genomic functions is not known. Here, using biochemical and scanning confocal microscopic analysis, we have demonstrated nuclear localization and functional implications of PELP1. Subnuclear fractionation showed PELP1 association with chromatin and nuclear matrix fractions. Ligand stimulation promoted recruitment of PELP1 to 17beta-estradiol responsive promoters, its colocalization with acetylated H3, and increased PELP1-associated histone acetyltransferase enzymatic activity. Far Western analysis revealed that PELP1 interacts with histone 1 and 3, with more preference toward histone 1. Using deletion analysis, we have identified the PELP1 COOH-terminal region as the histone 1 binding site. The PELP1 mutant lacking histone 1-binding domain acts as a dominant-negative and blocks estrogen receptor alpha-mediated transcription. Chromatin immunoprecipitation analysis showed a cyclic association and dissociation of PELP1 with the promoter, with recruitment of histone 1 and PELP1 occurring in opposite phases. PELP1 overexpression increased the micrococcal nuclease sensitivity of estrogen response element-containing nucleosomes. Our results provide novel insights about the transcription regulation of PELP1 and suggest that PELP1 participates in chromatin remodeling activity via displacement of histone 1 in cancer cells.

Bone Neoplasms↗
PubMed1995

Endogenous human renin expression and promoter activity in CALU-6, a pulmonary carcinoma cell line.

We have previously reported that transgenic mice containing the human renin gene express high levels of human renin mRNA in the lung. We show in this report that human renin expression in two lines of transgenic mice is developmentally regulated. Human renin expression is not evident in the transgenic mouse lung at 15.5 days of gestation, is detectable at 17.5 days of gestation, peaks around birth, and remains elevated into adulthood. In situ hybridization of mouse fetal lung samples at 18.5 days of gestation revealed that human renin was exclusively expressed in pulmonary type II epithelial cells. A survey of the medical literature revealed a number of clinical cases in which hypertension was caused by renin-secreting pulmonary tumors and a fairly widespread occurrence of immunoreactive renin in banked pulmonary tumors of diverse origin. This prompted us to examine a number of pulmonary tumor cell lines to determine whether they express human renin mRNA. One pulmonary carcinoma cell line, CALU-6, expressed human renin mRNA endogenously. Human renin expression in these cells was induced approximately 100-fold after treatment with forskolin, 8-bromoadenosine 3':5'-cyclic monophosphate, or N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate. Transfection analysis of human renin promoter-luciferase fusion constructs revealed the presence of cell-specific positive and negative regulatory elements in the human renin 5'-flanking DNA. This cell line is the only immortalized human cell line that expresses high levels of endogenous human renin mRNA and should provide an excellent tool for studying the regulation of human renin expression in vitro.

Animals↗
PubMed1978

Neuronal control of swimming in the medicinal leech. IV. Identification of a network of oscillatory interneurones.

Four oscillatory interneurones that appear to be the principal components of the central swim oscillator of Hirudo medicinalis have been identified on each side of the segmental ganglia of the ventral nerve cord. During 'swimming' episodes of an isolated nerve cord preparation each interneurone undergoes a polarization rhythm that is phase-locked with the impulse burst rhythm of the motor neurones known to drive the swimming movement. Passage of current into any of the interneurones can shift the phase of the swim rhythm. One of the interneurones projects its axon rearward to posterior ganglia and the other three project their axons frontward to anterior ganglia. The oscillatory interneurones are connected both intra- and interganglionically to form a topologically complex intersegmental network of concatenated ring circuits that possess the feature of recurrent cyclic inhibition. Theoretical analysis and electronic analogue models show that the network is inherently oscillatory and can produce both a cycle period and intra- and intersegmental phase relations of its elements that are appropriate for generating the body wave of the swimming movement.

Animals↗
PubMed2001

The inclusion compound of a new ionizable derivative of beta-cyclodextrin with ferrocenium drug.

A new beta-cyclodextrin (beta-CD) derivative, mono[6-deoxy-6-(2-butenedinitrile-2,3-dimercapto sodium salt)]-beta-CD (6-mnt-beta-CD), and its inclusion compound with a ferrocenium drug, have been prepared and characterized by IR, UV, 13C-NMR spectroscopy, and mass spectrometry, elemental analysis, thermogravimetry, and cyclic voltammetry (CV). The interplay between the side-arm anion of beta-CD and the ferrocenium (guest) in the inclusion compound 6-mnt-beta-CD-/Fc+ has been investigated by 13C-NMR, UV, IR, and thermogravimetric methods. Charge transfer from the anion to the cation in 6-mnt-beta-CD-/Fc+ was then experimentally identified. The interaction between the guest and the host with side-arm in 6-mnt-beta-CD-/Fc+ resulted in smaller positive potential shifts compared to that in the inclusion compound [beta-CD/Fc+]BF4-.

Antineoplastic Agents↗
PubMed2003

Role of mechanical stress in monocytes/macrophages: implications for atherosclerosis.

Hypertension is a well-known risk factor for atherosclerosis, but the molecular mechanisms that link elevated blood pressure to atherosclerosis progression remain uncertain. The interactions of mechanical forces and cells of the vasculature are relevant to many cardiovascular diseases. Once a monocyte infiltrates a tissue, it establishes extracellular matrix contacts and is subjected to deformation through those contacts. Macrophages participate in atherogenesis and commonly localize at sites of coronary plaque rupture. Although macrophages may be subjected to excess mechanical stress in these conditions, how biomechanical forces affect macrophage function remains incompletely defined. Recent work demonstrates that human monocytes/macrophages respond to mechanical deformation with selective augmentation of matrix metalloproteinases and induction of immediate-early genes. In human monocytes/macrophages and THP-1 cells, biomechanical strain can induce expression of the class A scavenger receptor, an important lipoprotein receptor in atherogenesis. In addition, DNA microarray analysis reveals that cyclic mechanical strain induces only a few genes (>2.5-fold), including interleukin-8 and IEX-1 in THP-1 cells. Thus, biomechanical deformation of monocytes/macrophages contributes to degradation of extracellular matrix, monocyte differentiation, and promotion of atherosclerosis. These findings suggest that mechanical stress in vivo, such as hypertension, may play an important role in atherogenesis and instability of coronary-artery plaques through biomechanical effects on vascular macrophages.

Animals↗
PubMed1990

Electrochemical characteristics of nitroheterocyclic compounds of biological interest. VI. The misonidazole radical anion.

The addition of four aprotic solvents to misonidazole in an aqueous buffer system has been examined electrochemically. Qualitatively they all result in separation of the initial irreversible 4 electron reduction step into two stages, the RNO2/RNO2- and RNO2-/RNHOH couples respectively. Despite some difficulties in achieving measurements for the discrete RNO2/RNO2- without interference from the following reduction step, it was clear that the various aprotic solvents influenced the lifetime of the RNO2- species to different degrees. Resolution of the two processes was best achieved using a water-acetone system and this has been employed to study the lifetimes of the misonidazole radical anion as a function of acetone content and drug concentration. Analysis of the cyclic voltammetric response showed a second order decay pathway, in line with the metronidazole system studied under similar conditions. This has been compared with results from pulse radiolysis work, which suggested a first order reaction of unknown pathway for 2-nitroimidazole radical anions.

Anions↗
PubMed2004

[The nursing labour market in Canada (1985-1999)].

This literature review analysed both published and unpublished scientific and professional studies on the nursing labour market in Canada within the period of 1985 to 1999. The goal was to conduct a situational analysis utilising statistical data and canvassing all concerned parties to extract their points of view. The analysis revealed significant cyclical variations in the evolution of the workforce, particularly with respect to auxiliary nurses, such as the perceived existence of major problems in recruiting new professionals in the field and retaining existing professionals in their organisations, the lack of homogeneity in educational training programmes, and the co-existence of several operational structures for organising nursing care, of which there is a lack of evaluation on their effectiveness. The results of the literature review identify the necessity to further develop the knowledge base on such a relevant dimension of the nursing labour market.

Canada↗
PubMed1997

[The study of chronobiology of CT features of liver cancer].

OBJECTIVE: To explore the biological cycle of malignant biological behavior of liver cancer, and to provide a research basis for the excepically specific phase of drugs for clinical treatment of liver cancer. METHODS: 24 kinds of CT features reflected varying degree of malignant biological behavior. There were 360 cases altogether from randam sampling 30 cases each month. The analytic method is each CT feature fitting a group data of yearly cycle using cosine curve made the analysis of the cyclic sequence character of each CT feature (cosinor). RESULTS: With 95% confidence, there were 10 CT features which showed biologic rhythm (P < 0.05). The acrophase of CT features for invasive growth concentrated between -60 degrees and -120 degrees (March and April). But for non-invasive growth, the CT features were relatively low and concentrated between -180 degrees and -270 degrees (July and September). No acrophase was shown in between -120 degrees and -180 degrees (May and June) and between -270 degrees and -330 degrees (October and November). CONCLUSION: Between CT features of the invasive and non-invasive growths of liver cancer, a sequential difference in biologic cycles can be observed.

Chronobiology Phenomena↗
PubMed2003

Corin-mediated processing of pro-atrial natriuretic peptide in human small cell lung cancer cells.

Corin is a recently discovered pro-atrial natriuretic peptide (ANP) convertase that is abundantly expressed in the heart. ANP is a cardiac hormone but can be secreted ectopically by certain cancers including small cell lung cancer (SCLC). In this study, we examined the role of corin in ANP production by SCLC cells. Reverse transcription-PCR detected corin mRNA expression in all nine SCLC cell lines examined and ANP mRNA expression in seven of the nine cell lines. In contrast, arginine vasopressin mRNA was detected in only five of the nine SCLC cell lines studied. Corin-expressing SCLC cells were capable of converting recombinant human pro-ANP to biologically active ANP, as determined by Western analysis and a cyclic GMP assay. Transfection of small interfering RNA duplexes directed against the corin gene completely blocked the processing of pro-ANP in the SCLC cells. Our results show that corin functions as a pro-ANP convertase in SCLC cells. We also suggest that the expression of corin may contribute to the pathogenesis of the syndrome of inappropriate secretion of antidiuretic hormone associated with certain cancers.

Arginine Vasopressin↗
PubMed1989

[The histamine-liberating action of polymyxin B and its analogs].

Histamine-releasing effect of polymyxin B1 and its deacylated analogues has been studied on purified rat mast cells. The structure-activity analysis showed that cyclic peptide fragment and acyl residue of molecule of polymyxin plays an important role in histamine-releasing activity. Histamine release, induced by polymyxin B1 and its analogue was blocked by metabolic inhibitor antimycin A. Preincubation of polymyxin B1 with lipopolysaccharide inhibits in dose-dependent manner polymyxin-induced histamine secretion from rat mast cells.

Animals↗