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At least 667 records · Page 37Linked to original sources
PubMed1989

Platelet dysfunction in acute megakaryoblastic leukemia.

Platelet function profiles were studied in 3 patients with megakaryoblastic leukemia. All patients had a moderate decrease in platelet counts with abnormal platelet retention. One patient who developed hemorrhagic diathesis had prolonged bleeding time. In all patients platelet aggregation was defective after the addition of ADP, collagen, adrenaline, or U46619, a thromboxane A2 agonist. Malondialdehyde was reduced in all patients, as was platelet serotonin. Plasma beta-thromboglobulin levels were normal in all cases whereas PF4 was markedly elevated in one. Platelet dysfunction was not reversed by clinical remission. These studies confirm that megakaryoblastic leukemia is associated with a thrombocytopathy which may play a role in hemorrhagic diathesis and should be taken into account in the management of these patients.

Blood Platelets↗
PubMed1982

Urinary retention caused by impaction of enlarged uterus.

2 cases of urinary retention were reported which was caused by retroverted gravid uterus and a large fibroid uterus, respectively. A chain cystourethrography and an endoscopic examination were the most informative to disclose the pathogenesis of urinary retention. Urodynamically, bladder compliance was normal without any pathological contraction. Urethral function was characterized by a shortened functional profile length.

Adult↗
PubMed1996

Functional and urodynamic characteristics of Camey II ileal neobladder.

The object of this study is to evaluate the functional and urodynamic characteristics of 16 patients who had undergone the Camey II orthotopic bladder replacement after radical cystoprostatectomy. Questionnaires regarding the voiding pattern and urinary continence were answered by 14 patients. Daytime continence was achieved in 13 of 14 patients (93%) at a mean interval of 3 months postoperatively. Eight patients (62%) attained their nighttime continence at an average interval of 10 months. Six of these 8 patients had to void to keep dry at night. Urodynamic studies were completed in 13 patients at an average of 11 months (range 6-23) postoperatively. Patients with nighttime continence had a significantly higher cystometric filling capacity (323 vs. 196 ml, p < 0.001), lower basal pouch pressure (24.5 vs. 35.2 cm water, p = 0.04), lower maximal voiding pressure (62.1 vs. 88.0 cm water, p = 0.01) and higher maximal urethral closure pressure (65.5 vs. 44.0 cm water, p = 0.03). There is no significant difference among the parameters of the age at operation, the amount of residual urine and the functional profile length between these two groups of patients. The antireflux procedure was successful in 11 of 12 patients (92%). We conclude that the Camey II operation could fulfill all the criteria of ideal bladder substitution with adequate volume, low resting pressure, satisfactory continence rate and antireflux characteristic.

Cystectomy↗
PubMed1995

Effects of intravenous thyrotropin-releasing hormone on urethral closure pressure in females with voiding dysfunction.

OBJECTIVE: The aim of this work was to investigate the effects of intravenously administered thyrotropin-releasing hormone (TRH) on the urethral closure pressure in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Sixteen female subjects with either bladder outlet obstruction (BOO) or detrusor underactivity were included in the study. Following randomization, 8 subjects (3 BOO, 5 detrusor underactivity) received 200 micrograms of TRH intravenously, and 8 (4 BOO, 4 detrusor underactivity) received saline (placebo). Standard fluid fill urethral pressure profilometry was performed at baseline and 2, 3, 5, 10, 15, and 20 min following TRH injection, measuring functional profile length (FPL), maximum urethral closure pressure (UCP), and closure pressures at the proximal quarter of the FPL (1/4 UCP) and at the distal quarter of the FPL (3/4 UCP). RESULTS: Significant reductions were found in both FPL (p = 0.022) and 3/4 UCP (p = 0.014) in the 'active' group as compared with the 'placebo' group. CONCLUSIONS: TRH administration significantly reduces the distal urethral closure pressure. Clarification of the mechanism of action of TRH on the urethra may point the way towards new developments in the management of female voiding dysfunction.

Analysis of Variance↗
PubMed2001

Interactions between angiotensin-(1-7), kinins, and angiotensin II in kidney and blood vessels.

The heptapeptide angiotensin (Ang)-(1-7) is currently considered one of the biologically active end products of the renin-angiotensin system. The formation of Ang-(1-7) by pathways independent of Ang II generation, the selectivity of its actions, and its peculiar property of exhibiting effects that are partially opposite of those of the parent compound, Ang II, confer a unique biochemical and functional profile to this peptide. In this article, we will review novel aspects of the biological actions of Ang-(1-7), dealing with its interaction with Ang II and kinins, especially in the kidney and blood vessels.

Angiotensin I↗
PubMed2004

Chemokines in bronchiolar epithelium in the development of chronic obstructive pulmonary disease.

The inflammatory chemokines interleukin-8, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1, are reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although bronchiolar epithelial cells and macrophages are known to be the cellular sources, the relative contribution of each cell type remains to be elucidated. In the present study, we first quantified cytokine mRNA in human bronchiolar epithelial cells and macrophages obtained using laser-capture microdissection and explored the relationship with early-stage COPD. Only in bronchiolar epithelial cells were interleukin-8, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 mRNA levels higher in smokers with airflow limitation and/or emphysema than those in never-smokers or smokers without either airflow limitation or emphysema. No difference was observed in macrophages. Complementary DNA (cDNA) array further revealed the overexpression of CC chemokine receptor 2 in bronchiolar epithelial cells from smokers with airflow limitation and/or emphysema. This study supports the role of bronchiolar epithelium as the source of increased inflammatory chemokine levels in the early development of COPD and also demonstrates the potential use of laser-capture microdissection, combined with reverse transcriptase-polymerase chain reaction and cDNA microarrays, to investigate functional profiles of individual structural and inflammatory cells in human lungs.

Adult↗
PubMed1997

From Leros asylum to community-based facilities: levels of functioning and quality of life among hostel residents in Greece.

The pattern of mental health care in Greece is undergoing a major transformation. The Leros Projects I and II supported the development of 13 community hostels located throughout the Greek mainland. These hostels provide residential care to more than 100 former psychiatric inpatients, mainly from Leros asylum. The present study evaluates the impact of the resettlement process on the residents' perceived quality of life (QoL) together with an examination of the residents' psychiatric and behavioural functioning four years after the move from hospital. The target sample (n = 99) comprised of individuals who may be considered 'chronic' psychiatric patients with a long history of institutionalisation and many are socially deprived with few family ties. The residents' functioning profile indicates a range of different levels of abilities. The QoL findings show that the majority of residents (70%) perceived the movement from the traditional hospital regime to the community hostels as being a positive change and expressed their satisfaction (74%) with the new living situation. This study demonstrates that even the most dependent, chronic psychiatric patients in Greece can be maintained in community settings and are able to articulate generally reliable and valid responses concerning the impact of service changes.

Adult↗
PubMedDate not supplied

Developing a new generation of ongoing: Diabetes self-management support interventions: a preliminary report.

PURPOSE: The study examined the feasibility, acceptability, and potential impact of an innovative, community-based, ongoing self-management intervention aimed at enhancing and sustaining self-care behaviors over the long term among urban African Americans with type 2 diabetes. METHODS: Sixty-two African American men and women completed the study. Participants were invited to attend 24 weekly, consecutive, diabetes self-management support/ education groups. The flow of the weekly group sessions was guided by questions and concerns of the patients. Baseline and 6-month follow-up metabolic functioning, lipid profiles, cardiovascular functioning, and self-care behaviors were assessed. RESULTS: Ninety percent (n = 56) of the sample attended at least 1 session; 40% attended at least 12 or more sessions. Paired t tests found significant improvements in body mass index (P < .001), total cholesterol (P < .01), high-density lipoprotein (P < .05), and low-density lipoprotein (P < .001). Significant increases were also found for self-care behaviors (P < .05). CONCLUSIONS: Preliminary evidence suggests that participation in this weekly problem-based, self-management support intervention can yield diabetes-related health benefits.

Aged↗
PubMed1999

Validation of theoretical diffraction correction functions for strongly focused high frequency ultrasonic transducers.

Adequate correction for diffraction effects is critical to the measurement of device-independent acoustical parameters. This correction is especially important in situations where strongly focused beams are used in the measurements. Diffraction correction function profiles, for two spherically-focused high frequency transducers (50 MHz, focal distance 5.7 mm, f/number of 1.7 and 29 MHz, focal distance 10.0 mm, f/2), were determined using experimental and theoretical approaches. Experimental measurements are based on established approaches using the power backscattered by an ultrasonic tissue-equivalent calibrating phantom. These results are compared to a recently-published theoretical model. Excellent agreement between the experiment and theory is achieved. No statistically-significant difference in mean backscattered power is found between the experimental and theoretical approaches. The use of a simple normalization procedure (termed 'diffraction correction') involving the ratio of the mean power backscattered from the sample to the power for reflection from a plane reflector at the same depth, is shown to introduce significant errors.

Computer Simulation↗
PubMed2003

The Canadian Psychiatric Association practice profile survey: II. General description of results.

OBJECTIVE: To provide an overview of the results of the Canadian Psychiatric Association (CPA) practice profile survey (PPS), a national survey of psychiatrists and psychiatric practice. METHOD: Mail-in interviews were sent to all Canadian psychiatrists listed in their provincial registers and to all active CPA members (total = 3628). Respondents provided general information about their professional activities for one 24-hour day and detailed information for 1 randomly selected hour. Patient information--including sociodemographics, diagnostic profiles, functioning levels, risk of harm to self or others, and disposition--was elicited for 1 patient seen during the random hour as well as for the most seriously ill patient receiving clinical services that day. RESULTS: Psychiatrists work 10 hours daily on average and take calls for 5 hours. Sixty percent of the overall work time is in the provision of direct patient care, and fee-for-service payments account for 55% of hours worked. Forty percent of the clinical work is provided in a hospital setting, and 34% is in a private office. Agency work accounted for only 6% of clinical hours worked. Relatively few practitioners provide services to children, older, or forensic patients. The average patient seen is female, aged 40 years, unmarried or with a marital disruption, significantly impaired in multiple areas of functioning, and likely to suffer from depression (21%), schizophrenia (14%), an anxiety disorder (13%), or bipolar disorder (12%). Comorbid Axis I and Axis II disorders are common (each over 30%) and fairly high rates of suicidal (15% to 30%) and homicidal (10% to 20%) risk are present. CONCLUSIONS: This paper suggests a wide diversity of practice in psychiatry in Canada, with services being provided to a wide range of individuals with many different conditions.

Canada↗
PubMed2006

Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?

The organization and mining of malaria genomic and post-genomic data is important to significantly increase the knowledge of the biology of its causative agents, and is motivated, on a longer term, by the necessity to predict and characterize new biological targets and new drugs. Biological targets are sought in a biological space designed from the genomic data from Plasmodium falciparum, but using also the millions of genomic data from other species. Drug candidates are sought in a chemical space containing the millions of small molecules stored in public and private chemolibraries. Data management should, therefore, be as reliable and versatile as possible. In this context, five aspects of the organization and mining of malaria genomic and post-genomic data were examined: 1) the comparison of protein sequences including compositionally atypical malaria sequences, 2) the high throughput reconstruction of molecular phylogenies, 3) the representation of biological processes, particularly metabolic pathways, 4) the versatile methods to integrate genomic data, biological representations and functional profiling obtained from X-omic experiments after drug treatments and 5) the determination and prediction of protein structures and their molecular docking with drug candidate structures. Recent progress towards a grid-enabled chemogenomic knowledge space is discussed.

Animals↗
PubMed2007

Proteomic analysis of tyrosine phosphorylation during human liver transplantation.

BACKGROUND: Ischemia-reperfusion (I/R) causes a dramatic reprogramming of cell metabolism during liver transplantation and can be linked to an alteration of the phosphorylation level of several cellular proteins. Over the past two decades, it became clear that tyrosine phosphorylation plays a pivotal role in a variety of important signalling pathways and was linked to a wide spectrum of diseases. Functional profiling of the tyrosine phosphoproteome during liver transplantation is therefore of great biological significance and is likely to lead to the identification of novel targets for drug discovery and provide a basis for novel therapeutic strategies. RESULTS: Using liver biopsies collected during the early phases of organ procurement and transplantation, we aimed at characterizing the global patterns of tyrosine phosphorylation during hepatic I/R. A proteomic approach, based on the purification of tyrosine phosphorylated proteins followed by their identification using mass spectrometry, allowed us to identify Nck-1, a SH2/SH3 adaptor, as a potential regulator of I/R injury. Using immunoblot, cell fractionation and immunohistochemistry, we demonstrate that Nck-1 phosphorylation, expression and localization were affected in liver tissue upon I/R. In addition, mass spectrometry identification of Nck-1 binding partners during the course of the transplantation also suggested a dynamic interaction between Nck-1 and actin during I/R. CONCLUSION: Taken together, our data suggest that Nck-1 may play a role in I/R-induced actin reorganization, which was previously reported to be detrimental for the hepatocytes of the transplanted graft. Nck-1 could therefore represent a target of choice for the design of new organ preservation strategies, which could consequently help to reduce post-reperfusion liver damages and improve transplantation outcomes.

Journal Article↗
PubMed2001

Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model.

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.

Animals↗
PubMed2005

T cells and cytokines in atherogenesis.

Recent findings suggest that inflammation plays a key role in atherosclerosis from the earliest stage of lesion initiation, to the ultimate complication of thrombosis. In patients who died because of acute coronary syndromes (ACS), coronary atherosclerotic plaques are characterized by the presence of macrophages, and to a lesser extent T-lymphocytes, at the immediate site of either plaque rupture or superficial erosion. The rupture-related inflammatory cells are activated, indicating ongoing inflammation. ACS patients are also characterized by activated circulating lymphocytes, monocytes and neutrophils, and by increased concentrations of proinflammatory cytokines and of the highly sensitive acute phase reactant C-reactive protein. Interestingly, an unusual subset of T cells, CD4+ CD28null T cells, involved in vascular complication of rheumatoid arthritis because of their functional profile predisposing for vascular injury, are expanded in the peripheral blood and infiltrate the coronary lesions of ACS patients. The presence of activated T lymphocytes implies antigenic stimulation, but the nature of such antigen(s) remains to be investigated. Several autoantigens expressed in the atherosclerotic plaque, including oxidized LDL and heat shock proteins, and infectious agents are able to elicit an immune response. The inflammatory component is not localized to the 'culprit' plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium.

Acute Disease↗
PubMed1996

Hepatitis C viral infection in thalassemic children: clinical and molecular studies.

To determine and correlate the liver function profile, hepatitis C virus (HCV) genome, anti-HCV, genotypes, quantitation, and nucleotide sequence variability in polytransfused thalassemic children, 61 such children were studied prospectively for 4 y. Twenty-six had HCV infection. The average age, number of transfusions, and alanine aminotransferase (ALT) levels of the HCV-infected group were higher than those of the 35 children without HCV infection. None was infected after the initiation of anti-HCV screening in donor blood. Liver biopsies were performed in six HCV-infected and eight HCV-noninfected thalassemic children, and portal fibrosis was found more frequently in the HCV-infected group. Quantitation of HCV RNA was done by the competitive polymerase chain reaction method, and the titer was about 1 x 10(6) to 5 x 10(8) copies/mL. The titer did not change significantly over the 4-y follow-up period and did not correlate with ALT levels. Nineteen HCV-infected patients were genotyped; 15 were Okamoto/Simmonds type II/1b, two were type III/2a, and two were type IV/2b. The hypervariable region of the HCV genome (E2/NS1) was cloned and sequenced in two serum samples from one patient collected at a 2-y interval, as the ALT levels decreased. The variation rate was estimated to be 1.2-1.7 x 10(-2)/nucleotide/y. The results showed that, in polytransfused thalassemic children, 43% (26/61) contracted HCV. We conclude that HCV infection may cause elevated ALT levels and portal fibrosis of the liver, whereas the viral titer and genotypes do not parallel ALT levels.

Adolescent↗
PubMed2004

Ghrelin secretion in childhood is refractory to the inhibitory effect of feeding.

Ghrelin, a natural GH secretagogue, is predominantly produced by the stomach. Ghrelin has other actions including orexant activity, modulation of energy balance, and modulation of endocrine and nonendocrine functions. Ghrelin secretion is increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. Ghrelin secretion does not seem to be a function of age; in fact, morning ghrelin levels after overnight fasting in prepubertal and pubertal children are similar to those in young adults. To clarify whether children and adults have the same sensitivity to the inhibitory effect of food intake, we studied the ghrelin response to a standardized light breakfast (SLB) in 10 prepubertal lean children whose results were compared with those recorded in 19 normal-weight adults. Basal ghrelin levels in children (median, 224.5; 25th to 75th percentile, 122.0-447.7 pg/ml) and adults (338.0; 238.0-512.0 pg/ml) were similar. SLB inhibited ghrelin levels in adults (263.0; 190.0-399.0 pg/ml). However, no change in ghrelin levels after SLB (206.5; 105.0-274.0 pg/ml) was recorded in children. Thus, food intake inhibits ghrelin secretion in adults but not in children. Ghrelin refractoriness to inhibition by food intake in children would reflect a peculiar functional profile of the ghrelin system in childhood.

Adult↗
PubMed2005

Antagonist- and inverse agonist-driven interactions of the vitamin D receptor and the constitutive androstane receptor with corepressor protein.

Ligand-dependent signal transduction by nuclear receptors (NRs) includes dynamic exchanges of coactivator (CoA) and corepressor (CoR) proteins. Here we focused on the structural determinants of the antagonist- and inverse agonist-enhanced interaction of the endocrine NR vitamin D receptor (VDR) and the adopted orphan NR constitutive androstane receptor (CAR) from two species with the CoR NR corepressor. We found that the pure VDR antagonist ZK168281 and the human CAR inverse agonist clotrimazole are both effective inhibitors of the CoA interaction of their respective receptors, whereas ZK168281 resembled more the mouse CAR inverse agonist androstanol in its ability to recruit CoR proteins. Molecular dynamics simulations resulted in comparable models for the CoR receptor interaction domain peptide bound to VDR/antagonist or CAR/inverse agonist complexes. A salt bridge between the CoR and a conserved lysine in helix 4 of the NR is central to this interaction, but also helix 12 was stabilized by direct contacts with residues of the CoR. Fixation of helix 12 in the antagonistic/inverse agonistic conformation prevents an energetically unfavorable free floatation of the C terminus. The comparable molecular mechanisms that explain the similar functional profile of antagonist and inverse agonists are likely to be extended from VDR and CAR to other members of the NR superfamily and may lead to the design of even more effective ligands.

Amino Acid Sequence↗
PubMed1992

Cisplatin-DNA damage and repair in peripheral blood leukocytes in vivo and in vitro.

We have extended our studies on the relationship between cisplatin/carboplatin-induced DNA damage in readily accessible tissue(s) and clinical response to therapy. Such an approach may assist in the study of cancer drug resistance and in establishing parameters for assessing human populations for sensitivity to DNA damaging agents in the environment. Platinum-DNA adduct levels were measured by atomic absorbance spectrometry. DNA repair capacity was assessed in human T-lymphocytes by the ability to repair cisplatin lesions in cellular DNA or in transfected plasmid DNA. In a "blinded" study of 21 patients receiving combination cisplatin/carboplatin drug therapy, there was a direct relationship between DNA damage in leukocytes and disease response (summary two-sided p = 0.00011). The cohort of patients had 15 different tumor types, suggesting that blood tissue and tumor tissue of an individual may process platinum-DNA damage similarly regardless of the tissue of origin of the tumor. In leukocytes in vivo, persistence and accumulation were prominent features of the cisplatin-DNA adduct profile. Functional DNA repair capacity has been studied in eight human leukocyte cell lines in vitro (three, T-cells; three, B-cells; one, monocytic; one, promyelocytic), using a host cell reactivation assay with cisplatin-damaged pRSVcat. In the three T cell lines studied, host cell reactivation efficiency was directly related to the cells' abilities to repair cisplatin-damaged cellular DNA (correlation coefficient = 0.993).(ABSTRACT TRUNCATED AT 250 WORDS)

Carboplatin↗