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PubMed1990

Lymphokine mRNA profile and functional analysis of a human CD4+ clone with unique antitumor specificity isolated from renal cell carcinoma ascitic fluid.

We here describe the isolation, characterization, profile of lymphokine expression and T-cell-receptor gene rearrangement pattern of 444P.3, a CD3+ CD4+ CD8- 4B4+ interleukin-2 (IL-2)-dependent clone derived from the malignant ascites of a patient with renal cell cancer. The 444P.3 clone exhibited unique antitumor specificity between days 45 and 84 in culture and then lost its lytic, but not its proliferative, capacity. To our knowledge this is the first description of a specific antitumor reaction in a patient with renal cell cancer against autologous tumor. IL-2-expanded 444P.3 cells, tested on day 104 in culture, expressed mRNA for tumor necrosis factor (TNF), IL-2 and tumor growth factor beta (TGF-beta) but not for IL-1, lymphotoxin or granulocyte/macrophage-colony stimulating factor (GM-CSF). The parental noncloned population expressed mRNA for TNF, lymphotoxin, GM-CSF and TGF-beta but not for IL-1 beta or IL-2. Analysis of established human T cell clones should include profiles of lymphokine secretion in addition to growth and proliferation patterns, antitumor activity and surface phenotype. Such characterization of clones may provide a better understanding of the immunoregulatory role and functional potential of various T cell subsets involved in human antitumor reactivity.

Ascites↗
PubMed2003

Gene expression profiling and functional proteomic analysis reveal perturbed kinase-mediated signaling in genetic stroke susceptibility.

The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of heritable hypertension-associated cerebrovascular injury. This study sought to compare SHRSP to the stroke-resistant SHR strain to identify genes and protein pathways whose expression and/or function was significantly altered between the strains prior to the onset of stroke. Cerebral cortex gene expression profiles from male SHRSPs and matched SHRs were examined by Affymetrix microarray analysis. mRNAs encoding the brain-derived neurotrophic factor receptor (TrkB) and multiple kinases of the MAPK/AKT signaling pathways, including JNK2, AKT2, and PI3K, were differentially expressed between SHRSP and SHR. Because these data suggest altered function in pathways involving MAP and AKT kinase activity, we performed Western blot using phosphorylation state-specific antibodies to characterize activity of MAP kinase and PI3K/AKT pathways. Changes in the levels of the phosphorylated forms of these kinases paralleled the changes in transcript levels observed between the strains. Two-dimensional gel electrophoresis and peptide fragment mass fingerprinting were used to identify altered protein substrates of these kinases. Protein profiling of kinase substrates further supported the notion of perturbed kinase-mediated signaling in SHRSP and identified adenylyl cyclase associated protein 2, TOAD-64, propionyl CoA carboxylase, APG-1, and valosin-containing protein as kinase targets whose phosphorylation state is altered between these strains. Altered gene and protein expression patterns in SHRSP are consistent with increased vulnerability of this strain to cerebrovascular injury.

Animals↗
PubMed1994

Pulmonary function testing in the critically ill neonate, Part I: An overview.

Respiratory insufficiency, a frequent problem encountered by the critically ill neonate, has many etiologies. Pulmonary function testing can effectively diagnose, quantify, and qualify the dysfunction so as to better define a prognosis and guide appropriate therapy. Recent advances in computer-assisted technology and miniaturization of equipment now allow simple, reproducible, and rapid neonatal pulmonary function assessment at the bedside. The indications for, and benefits of, pulmonary function testing vary with gestation, age, and clinical condition of the infant. The overall description of the pulmonary function profile is discussed in this article. The general questions and approaches utilized for routine testing, the initial pulmonary function profile, and evaluation of the acutely ill infant and that of the convalescing preterm are addressed. The expertise of the intensive care nurse is invaluable in ensuring that safe, accurate, and reproducible data are obtained. The nurse can then use the data to alter the infant's care plan and to determine the necessity and timing for retesting. Specific information on methodology and examples of specific tests are given in related articles (Parts II, Vol. 13 No. 2 and III, Vol. 13 No. 4, respectively). A complete knowledge of pulmonary function assessment is important for any nurse caring for critically ill neonates.

Humans↗
PubMed1993

Anthropometric and pulmonary function test profiles of outpatients with stable chronic obstructive pulmonary disease.

PURPOSE: To determine the prevalence of abnormalities in the nutritional status, and their correlation with pulmonary function test results, in a population of outpatients with stable chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: During 1 year of study, body weight, height, triceps skinfold, arm muscle circumference, and pulmonary function parameters were assessed in 126 patients. On the basis of body mass index (BMI = weight/height2) of less than 20, 20 to 27, and greater than 27, the patients were divided into underweight (n = 29, 23%), normal weight (n = 67, 53.2%), and overweight (n = 30, 23.8%), respectively. RESULTS: Diffusing capacity for carbon monoxide (DLCO), both as absolute and percent predicted, differed significantly among the three groups, being lowest in the underweight and highest in the overweight patients. A significant and positive correlation was present between BMI as the independent variable and DLCO, forced expiratory volume in 1 second, and its ratio to forced vital capacity. A significant and negative correlation existed between BMI and residual volume and its ratio to total lung capacity. CONCLUSION: A substantial number of stable COPD patients (46.8%) have nutritional abnormalities. BMI is a simple and accurate indicator of nutritional status in these patients. BMI correlates significantly with some tests of pulmonary function.

Aged↗
PubMed2002

Transcript profiling of functionally related groups of genes during conditional differentiation of a mammalian cochlear hair cell line.

We have used Affymetrix high-density gene arrays to generate a temporal profile of gene expression during differentiation of UB/OC-1, a conditionally immortal cell line derived from the mouse cochlea. Gene expression was assessed daily for 14 days under differentiating conditions. The experiment was replicated in two separate populations of cells. Profiles for selected genes were correlated with those obtained by RT-PCR, TaqMan analysis, immunoblotting, and immunofluorescence. The results suggest that UB/OC-1 is derived from a population of nonsensory epithelial cells in the greater epithelial ridge that have the potential to differentiate into a hair-cell-like phenotype, without the intervention of Math1. Elements of the Notch signaling cascade were identified, including the receptor Notch3, with a transient up-regulation that suggests a role in hair cell differentiation. Several genes showed a profile similar to Notch3, including the transcriptional co-repressor Groucho1. UB/OC-1 also expressed Me1, a putative partner of Math1 that may confer competence to differentiate into hair cells. Cluster analysis revealed expression profiles for neural guidance genes associated with Gata3. The temporal dimension of this analysis provides a powerful tool to study genetic mechanisms that underlie the conversion of nonsensory epithelial cells into hair cells.

Animals↗
PubMedDate not supplied

[Typologic analysis of comparative effects of tobacco and Pi phenotype on the respiratory function].

Seven hundred and fourty-eight subjects from the general population were included in a transversal epidemiologic survey. The aim was the determination of a possible relationship between functional profile and Pi phenotype. Seric levels of alpha 1-antitrypsin (alpha 1 AT) and phenotypes were determined in all subjects. All underwent clinical examination, chest X-ray and functional tests (flow-volume curves and single breath nitrogen test). Distribution of the various phenotypes appeared similar to those described in other studies. No homozygote Z was found. Typologic analysis allowed identification of 7 functional profiles, among which 3 were normal and 4 had various levels of obstruction. The comparison between functional impairment and the phenotypes or smoking habits showed that smoking played the major part in the onset of obstructive disease. Mean age of the population surveyed was however rather low, which led to questions about rapidity of onset of chronic obstructive lung disease. This survey thus will lead to a longitudinal study.

Closing Volume↗
PubMed2003

Profiling the global tyrosine phosphorylation state.

Protein tyrosine kinases and protein tyrosine phosphatases play a key role in cell signaling, and the recent success of specific tyrosine kinase inhibitors in cancer treatment strongly validates the clinical relevance of basic research on tyrosine phosphorylation. Functional profiling of the tyrosine phosphoproteome is likely to lead to the identification of novel targets for drug discovery and provide a basis for novel molecular diagnostic approaches. The ultimate aim of current mass spectrometry-based phosphoproteomic approaches is the comprehensive characterization of the phosphoproteome. However, current methods are not yet sensitive enough for routine detection of a large percentage of tyrosine-phosphorylated proteins, which are generally of low abundance. In this article, we discuss alternative methods that exploit Src homology 2 (SH2) domains for profiling the tyrosine phosphoproteome. SH2 domains are small protein modules that bind specifically to tyrosine-phosphorylated peptides; there are more than 100 SH2 domains in the human genome, and different SH2 domains bind to different classes of tyrosine-phosphorylated ligands. These domains play a critical role in the propagation of signals in the cell, mediating the relocalization and complex formation of proteins in response to changes in tyrosine phosphorylation. We have developed an SH2 profiling method based on far-Western blotting, in which a battery of SH2 domains is used to probe the global state of tyrosine phosphorylation. Application to the classification of human malignancies suggests that this approach has potential as a molecular diagnostic tool. We also describe ongoing efforts to modify and improve SH2 profiling, including the development of a multiplexed assay system that will allow high-throughput functional profiling of the tyrosine phosphoproteome.

Blotting, Far-Western↗
PubMed1981

Three-dimensional dose-rate distribution of X-ray beams of linac neptun 10p and gamma-rays from Co-60 gammatron 80S for rectangular fields.

A method of calculation of the three-dimensional dose-rate distribution for X-rays of Linac Neptun 10p and gamma-rays of Gamma-tron 80S is presented. The experimental results show that the profiles function defined as the relative dose-rate across the radiation beam is useful for this purpose, and it is sufficient to determine the profile function only at one depth and for one field size. The results of measurements are presented on the graphs.

Cobalt Radioisotopes↗
PubMed1981

[Age and morphofunctional characteristics of celiac ganglia chromaffin tissue in normal and hypokinetic animals].

Accumulation of chromaffin cells (ChC) in the celiac nodes have been studied in young (6-month-old) and old (28-30-month-old) rats; 50 intact and 32 rats kept at hypokinesia for 6 weeks have been used. In the young intact rats accumulation of the ChC have been found in 51% and in the old ones-in 82% of cases. In the young rats 85% of the accumulations are localized inside the nodes, 4%-in their trunks and 12%-near the nodes, and in the old rats-69%, 8% and 23%, respectively. In the young and in the old rats the ChC section area is 133+/-4, 147+/-13 mkm2, nuclei-33.7+/-0.7 and 36.9+/=1.3 mkm2 and nuclear-plasmic relations-0.34 and 0.33, respectively. In the young rats the ChC with a high perikaryon density make 40%, with middle-32%, with low-28%, in the old rats-40%, 36% and 24%, respectively. The greater the ChC, the smaller the nuclear-plasmic ratio and perikaryon density. Low indices on the density and nuclear-plasmic ratio correspond to the excretion phase, and the high indices-to prevalence of synthesis and accumulation. These correlations reflect the morpho-functional profile of the chromaffin component in the nodes. Thus, with aging the chromaffin tissue of the celiac nodes is represented by a greater number of accumulations, while the morpho-functional indices of the ChC accumulations remain unchanged. Under hypokinesia, in the young and old rats mass of the chromaffin tissue decreases. The body and the nuclear area of the ChC decreases and by the end of the experiment it makes: in the young rats 104+/-5 and 30.6+/-1.1 mkm2, and in the old rats-100+/-3 and 29.7+/-2 mkm2. Rearrangement of the morpho-functional profile, manifested in increasing content of the ChC with high density and in decreasing congulatory role in the celiac nodes decrease. By the end of the experiment, in young rats normal function is approaching, in the old rats-the rearrangement is of stable character.

Age Factors↗
PubMed1999

[Clinical and respiratory function follow-up of 39 infants treated with neonatal respiratory extracorporeal assistance].

UNLABELLED: The aim of this prospective study was to evaluate the consequences of neonatal treatment with a venovenous extracorporeal respiratory assistance. POPULATION AND METHODS: Thirty nine neonates (28 boys) with acute respiratory failure were included. Extracorporeal respiratory assistance consisted of an apnoeic oxygenation with low frequency positive pressure ventilation and extracorporeal membrane CO2 removal through a venous single canula perfusion circuit. The causes of respiratory distress were: 15 meconium aspiration syndrome, 12 respiratory distress syndrome, six hyaline membrane disease, three sepsis, two diaphragmatic hernia, and one post-surgery Mendelson syndrome. The mean duration of mechanical ventilation was 18 days, including 5 days of extracorporeal respiratory assistance. The prospective follow-up included physical examination, chest radiographs, scintigraphy and pulmonary function tests. These tests studied the following parameters: functional residual capacity by helium dilution technique, lung resistance and dynamic lung compliance by the esophageal balloon technique and blood gases with arterialized blood samples. RESULTS: The mean duration of the follow-up was 21.3 months (6 months to 5 years). Results showed in the first year 33% of children with chronic obstructive pulmonary disease and chest (X-ray abnormalities, such as bronchopulmonary dysplasia in 23% of children. Data of pulmonary function test at the end of the first year: lung resistance and functional residual capacity were within limits of predicted values for height, and dynamic lung compliance was slightly decreased; according to the analysis of the functional profile: 31% without abnormality, 41% of obstructive syndrome and 26% with restrictive pattern. Blood gases were normal in 37 children. At the end of the second year, we noticed normal functional residual capacity, an increase of lung resistance while lung compliance was normalized; functional profile was quite different: with a decrease of the number of patients without abnormality (22%) and increase of those with obstructive syndrome (56%). CONCLUSION: The percentage of abnormalities is high but these are moderate in most cases, especially if we compare with the initial seriousness of the pulmonary pathology. We suggest a regular follow-up to study the respective incidence of pulmonary disease and/or extracorporeal respiratory assistance over these abnormalities.

Acute Disease↗
PubMed2026

Genome-resolved analysis of colonization factor repertoires reveals ecological stratification in cervid gut microbiomes.

INTRODUCTION: Colonization factors (CFs) are important microbial traits associated with persistence and host adaptation in the gut, yet their large-scale organization in cervid gut microbiomes remains unclear. METHODS: A total of 3,311 non-redundant high-quality metagenome-assembled genomes (MAGs), derived from 688 cervid gut metagenomic samples across 15 publicly available projects and one in-house dataset, were analyzed. CF-associated genes were identified by comparison against the GHA CF database, and CF repertoires were characterized at genome, host-species, and gastrointestinal-segment levels. RESULTS: A total of 138,729 CF-associated genes spanning 71 CF families were identified. MAGs from Cervinae contained richer CF repertoires than those from Caprinae, and CF47 (Peptidase_C69), CF24_29 (QueH), and CF18 (Glycos_transf_2) were among the most prevalent families. CF repertoires were strongly structured by taxonomy, showed a moderate association with bacterial phylogenetic distance, and formed two recurrent genome-level configurations with distinct KEGG functional profiles. Integration of sample metadata further revealed differentiation of CF repertoires across host species and gastrointestinal segments, representing the major ecological dimensions examined in this study. Segment-associated CF variation was accompanied by redistribution of broader functional profiles, including enrichment of carbohydrate and lipid metabolism in the jejunum, membrane transport in the ileum, xenobiotics biodegradation in the cecum, and environmental adaptation in the rumen. DISCUSSION: These findings provide a genome-resolved view of CF repertoire organization in cervid gut microbiomes and demonstrate that colonization-associated functions are structured across microbial lineages and ecological contexts. This study highlights the importance of considering microbial taxonomy and host-associated environments when interpreting the distribution of CF repertoires in mammalian gut ecosystems.

Cervidae↗
PubMed1988

Hepatitis D virus infection in children with acute or chronic hepatitis B virus infection in Taiwan.

To investigate the prevalence and clinical features of hepatitis D virus infection (HDV) in childhood, total antibody to hepatitis D antigen (anti-HD) in serum samples from 247 children (29 with acute hepatitis B, 68 with chronic hepatitis B, and 150 with asymptomatic hepatitis B surface antigen (HBsAg) carriers with normal liver function profiles) were studied using solid-phase competitive radioimmunoassay. Anti-HD was detected in three of the 29 children with acute hepatitis B and in only one of the 68 with chronic hepatitis B; none of the serum specimens from 150 asymptomatic carriers with normal liver function profile showed detectable anti-HD. All three children with HDV coinfection cleared HBsAg and seroconverted to anti-HBs, whereas one with superinfection finally had normal liver function without clearance of HBsAg. To identify possible sources of HDV infection, HBV markers and anti-HD in family members were also examined. One 4-month-old infant boy became infected through a blood transfusion from his hepatitis B e antigen (HBeAg)-positive carrier father, who had anti-HD. A 4-month-old infant girl was infected through close contact with her HBeAg-negative carrier father, who had HDV superinfection. The infection sources remained undefined in another two patients. The mothers of these four children were seronegative for anti-HD, indicating that perinatal transmission is not the usual mode of HDV infection in Taiwan. The natural course of either acute or chronic HBV infections in childhood in Taiwan may be more closely related to HBV itself, or to some other yet unrecognized factor, rather than to HDV infection.

Acute Disease↗
PubMed1997

Urodynamic evaluation of changes in urinary control after radical retropubic prostatectomy.

PURPOSE: Urodynamic evaluations were done in patients before and after radical prostatectomy to obtain more information about the factors that affect continence. MATERIALS AND METHODS: Urodynamic testing was done in 82 patients before, and 6 to 8 weeks and 6 months (9 cases) after radical prostatectomy. Evaluation included measurement of cystometric bladder capacity, compliance, functional profile length, maximal urethral closure pressure, maximal urethral closure pressure during voluntary contraction of the external sphincter, residual urine, maximal flow rate and bladder instability. RESULTS: The continence rate was 33.4, 69.4, 84.7 and 90.9% at 1, 3, 6 and 12 months after radical prostatectomy, respectively. Mean functional urethral length decreased from 61 mm. preoperatively to 25.9 mm. postoperatively, maximal urethral pressure from 89.6 to 65.2 cm. water and bladder capacity from 338.7 to 278.8 ml. Bladder instability was found in 17 and 41% of cases before and directly after radical prostatectomy, respectively. There was a statistically significant difference in maximal urethral closure pressure (68.1 versus 53.1 cm. water) as well as functional urethral length (27.6 versus 20.5 mm.) in continent versus incontinent patients, respectively. Urodynamic examination 6 months after prostatectomy showed an increase in functional profile length and maximal urethral pressure, while bladder measurements did not change significantly. CONCLUSIONS: After radical prostatectomy significant changes in bladder and sphincter measurements are noted. Urethral closure pressure, functional urethral length and bladder stability are significant urodynamic factors that influence continence after radical prostatectomy.

Adult↗
PubMed2001

Considering genetic profiles in functional studies of immune responsiveness to HIV-1.

Over the last two decades HIV-1 has spread worldwide and has now surpassed malaria as the leading cause of infectious disease mortality in adults (http://www.who.int/infectious-disease-report/pages/ch1text.html). The clinical course and outcome of HIV-1 infection are highly variable among individuals. Most individuals infected with HIV develop AIDS within 10 years. However about 1-5% remain relatively healthy for 15 years or more (long-term nonprogressors), while others progress to AIDS within the first 2-3 years after infection (rapid progressors). A small number of individuals are resistant to infection, while some individuals appear to eliminate the virus. Factors that influence susceptibility to infection and rate of disease progression are a combination of viral, host, and environmental determinants. With few exceptions, genetic resistance to infectious diseases is likely to involve a complex array of host genetic effects involving variants that have very subtle, but significant consequences on gene expression or protein function. We have gained considerable insight into the genetic effects on HIV-1 disease, yet we likely have uncovered only a fraction of the total picture. The greater our knowledge of various effects on HIV disease, the more likely we will be able to predict disease outcome on an individual-by-individual basis. While this may seem obvious, there is no standard practice of taking into account the genetic profile (i.e. genotypes at loci known to associate with rate of AIDS progression) of subjects used in functional studies of immune responsiveness to HIV-1. Here, we propose an approach for assessing overall genetic risk on an individual basis, and suggest that this information be considered when selecting comparison groups in studies of immune responses to HIV and/or in the interpretation of data derived from such studies.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Profiling protein function with small molecule microarrays.

The regulation of protein function through posttranslational modification, local environment, and protein-protein interaction is critical to cellular function. The ability to analyze on a genome-wide scale protein functional activity rather than changes in protein abundance or structure would provide important new insights into complex biological processes. Herein, we report the application of a spatially addressable small molecule microarray to an activity-based profile of proteases in crude cell lysates. The potential of this small molecule-based profiling technology is demonstrated by the detection of caspase activation upon induction of apoptosis, characterization of the activated caspase, and inhibition of the caspase-executed apoptotic phenotype using the small molecule inhibitor identified in the microarray-based profile.

Amino Acid Sequence↗
PubMed2003

Molecular basis of the selective activity of vitamin D analogues.

More than 2,000 synthetic analogues of the biological active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), are presently known. Basically, all of them interfere with the molecular switch of nuclear 1alpha,25(OH)(2)D(3) signaling, which is the complex of the vitamin D receptor (VDR), the retinoid X receptor (RXR), and a 1alpha,25(OH)(2)D(3) response element (VDRE). Central element of this molecular switch is the ligand-binding domain (LBD) of the VDR, which can be stabilized by a 1alpha,25(OH)(2)D(3) analogue either in its agonistic, antagonistic, or non-agonistic conformation. The positioning of helix 12 of the LBD is of most critical importance for these conformations. In each of the three conformations, the VDR performs different protein-protein interactions, which then result in a characteristic functional profile. Most 1alpha,25(OH)(2)D(3) analogues have been identified as agonists, a few are antagonists (e.g., ZK159222 and TEI-9647), and only Gemini and some of its derivatives act under restricted conditions as non-agonists. The functional profile of some 1alpha,25(OH)(2)D(3) analogues, such as EB1089 and Gemini, can be modulated by protein and DNA interaction partners of the VDR. This provides them with some selectivity for DNA-dependent and -independent signaling pathways and VDRE structures.

Animals↗
PubMed2003

Mechanism of continence after repair of post-traumatic posterior urethral strictures.

OBJECTIVES: To determine the mechanism of urinary continence after repair of post-traumatic posterior urethral strictures by perineal anastomotic urethroplasty. METHODS: Two groups of male patients were enrolled in this study. Group 1 consisted of 8 patients (mean age 31 years) who had undergone bulboprostatic anastomotic urethroplasty for strictures complicating a pelvic fracture urethral disruption. Group 2 consisted of 8 patients (mean age 32.5 years) with a normal urethra who were used as controls. All 16 patients underwent urethral pressure profilometry both at rest and with cough and hold maneuvers. RESULTS: In group I, urethral pressure profilometry showed much lower mean maximal urethral pressures and maximal urethral closure pressures, as well as a much shorter mean functional profile length than in group 2 (48 and 39 cm H(2)O versus 75 and 65 cm H(2)O and 2.4 versus 4 cm, respectively, P <0.0003). On cough maneuver, intra-abdominal pressure changes were transmitted along the entire functional profile length in group 1 and only along its first part in group 2. The hold maneuver increased urethral pressure in 5 patients (65%) in group 1 and in all 8 patients (100%) in group 2. CONCLUSIONS: Continence after anastomotic urethroplasty for post-traumatic posterior urethral strictures is maintained solely by the proximal urethral mechanism. Transmission of intra-abdominal pressure changes and contraction of pelvic floor musculature may augment urethral closure in these cases during stress conditions.

Adult↗