Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “functional profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMedDate not supplied

Total parenteral nutrition-associated cholestasis in infants: clinical and liver histologic studies.

To evaluate total parenteral nutrition-associated cholestasis (TPN-C) in infants, a retrospective clinicopathologic study was conducted of 15 infants who had received TPN. The mean gestational age and birth weight were 32.1 weeks (26-40 weeks) and 1807 g (840-5840 g) respectively. Two-thirds of the patients were kept on TPN for more than 60 days. The onset of rising direct bilirubin ranged 2-9 weeks (mean 4.5 +/- 2.4) after TPN therapy. Preterm babies less than 32 weeks of age had an earlier rise of direct bilirubin and AST. Bile sludge of the gallbladder was observed in only one case, and none had gallstone. The main histologic findings of liver biopsy or autopsy were cholestasis (intracellular and canalicular), periportal inflammation, fibrosis and bile ductular proliferation. Sixty percent of these survived, the remaining 40% died of complications unrelated to TPN-C. The liver function profile became normalized within a mean of 14.0 +/- 9.4 (8-34) weeks after discontinuation of TPN in the survival cases. It was concluded that infant TPN-associated cholestasis was mostly reversible, but that the younger preterm babies were susceptible to a prolonged TPN course with more marked clinical and pathological changes.

Cholestasis↗
PubMed1993

Characterization of T helper cell responses to the trypanosome variant surface glycoprotein.

T cell responses to the variant surface glycoprotein (VSG) previously have not been detected in animals infected with the African trypanosomes despite the fact that such animals make strong T-dependent B cell responses to VSG molecules displayed by the parasites. In the present study, we have examined B 10.BR mice for VSG-specific Th cell responses at different times after infection with Trypanosoma brucei rhodesiense clone LouTat 1. T cell populations derived from different tissues were tested for their ability to proliferate and secrete cytokines when stimulated with purified LouTat 1 VSG. Furthermore, VSG-specific T cell lines and clones were derived from immunized mice and examined for their phenotypic and functional profiles in comparison with T cell responses of infected mice. The results of this study show that VSG-specific T cells were not consistently detected in the peripheral lymphoid tissues such as spleen or lymph nodes of infected animals. In contrast, VSG Ag-specific T cells were detectable principally in the peritoneal T cell populations of infected mice. Peritoneal T cells did not proliferate in response to VSG, yet produced substantial cytokine responses when stimulated; the cytokines produced were IFN-gamma and IL-2, without detectable IL-4. The cellular phenotype of VSG-responsive T cells was that of classical Th cells in that all cells were CD4-positive and expressed the CD3 alpha/beta TCR membrane complex. Thus, the VSG appears to preferentially stimulate a Th1 cell subset response during infection. Intrinsic molecular characteristics of the VSG molecule did not induce mice to make this response, however, since VSG-specific T cell lines derived from VSG-immunized mice displayed cytokine profiles characteristic of both Th1 and Th2 cells. Isolation of Th1 clones from selected lines demonstrated that these cells displayed the same membrane-phenotypic characteristics and cytokine profiles as the T cells from infected mice. Furthermore, all Th clones were VSG type-specific, APC-dependent, and I-Ak-restricted in their responses. In summary, these experiments provide the first direct evidence for VSG-specific responses at the T cell level. T cell responses to the VSG molecule during infection appear to be anatomically compartmentalized and exhibit evidence of clonal maturation (cytokine production) but not clonal expansion (proliferation) after antigenic stimulation. The cellular phenotype and cytokine profiles predict that infection predisposes the animals to mount Th1 cell subset responses to VSG. The results of this study, including the T clones generated, provide an experimental basis for examining the regulation of VSG-specific immune responses during infection.

Animals↗
PubMed1996

Studies of the K(ATP) channel opening activity of the new dihydropyridine compound 9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridined ione in bladder detrusor in vitro.

The potassium (K+) channel opening activity of ZM244085 (9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridined ione, CAS 149398-59-4), a novel dihydropyridine (DHP), was ascertained. In a set of functional assays, its mechanoinhibitory effect on myogenic activity of guinea pig bladder detrusor muscles, either mildly or highly depolarized with 15 or 80 mmol/l KCl, was measured. ZM244085 had negligible effect on the tone of the detrusor contracted with 80 mmol/l KCl but reduced the myogenic activity induced with 15 mmol/l KCl (IC50=4.2 +/- 0.4 mumol/l). Glibenclamide, an ATP-sensitive K+ (KATP) channel blocker, competitively antagonized this action of ZM244085 with a pA2 value of 7.6. This functional profile of ZM244085 is similar to that of the prototypic K+ channel opener cromakalim but stands in contrast to that of typical DHP Ca2+ channel blockers such as nifedipine and nimodipine. The membrane potential of the guinea pig detrusor, recorded with intracellular microelectrodes, was hyperpolarized 6.8 +/- 3.1 mV by ZM244085 (10 mumol/l). This hyperpolarization was completely blocked by glibenclamide but not affected by apamin (10 mumol/l), a toxin blocking specifically small conductance and Ca2+ dependent K+ (SKCa) channels. ZM244085 (10 mumol/l) increased the whole cell KATP current in isolated guinea pig detrusor cells by 8.8 +/- 2.5 pA, but failed to activate large conductance and Ca2+ dependent K+ (BKCa) channels in excised inside-out membrane patches from those cells. The results from these studies showed that ZM244085 is a K+ channel opener which activates predominantly KATP channels in vitro to relax bladder detrusors.

Acridines↗
PubMed1996

Urodynamic evaluation of urinary incontinence following radical prostatectomy: our experience.

Thirty-four patients after retropubic radical prostatectomy, were evaluated with urodynamic studies. Patients were divided in three groups depending on the degree of urinary continence. A statistically significant difference was found between different groups for the mean functional profile length and maximal urethral closure pressure. Detrusor instability was detected in 11 patients with moderate incontinence and in 1 patient with severe incontinence. Neither differences of age, previous prostatic surgery, tumour extension, nor preservation of the neurovascular bundles had any significant influence on recovery of continence.

Aged↗
PubMed1997

Cycling status of CD34+ cells mobilized into peripheral blood of healthy donors by recombinant human granulocyte colony-stimulating factor.

In this study, we assessed the functional and kinetic characteristics of highly purified hematopoietic CD34+ cells from the apheresis products of 16 normal donors undergoing glycosylated granulocyte colony-stimulating factor (G-CSF) treatment for peripheral blood stem cells (PBSC) mobilization and transplantation in allogeneic recipients. Mobilized CD34+ cells were evaluated for their colony-forming capacity and trilineage proliferative response to selected recombinant human (rh) CSF in vitro and the content of very primitive long-term culture initiating cells (LTC-IC). In addition, the cycling status of circulating CD34+ cells, including committed clonogenic progenitor cells and the more immature LTC-IC, was determined by the cytosine arabinoside (Ara-C) suicide test and the acridine orange flow cytometric technique. By comparison, bone marrow (BM) CD34+ cells from the same individuals were studied under steady-state conditions and during G-CSF administration. Clonogenic assays in methylcellulose showed the same frequency of colony-forming unit cells (CFU-C) when PB-primed CD34+ cells and BM cells were stimulated with phytohemagglutinin-lymphocyte-conditioned medium (PHA-LCM). However, mobilized CD34+ cells were significantly more responsive than their steady-state BM counterparts to interleukin-3 (IL-3) and stem cell factor (SCF) combined with G-CSF or IL-3 in presence of erythropoietin (Epo). In cultures added with SCF, IL-3, and Epo, we found a mean increase of 1.5- +/- 1-fold (standard error of the mean [SEM]) of PB CFU-granulocyte-macrophage and erythroid progenitors (burst-forming units-erythroid) as compared with BM CD34+ cells (P < .05). Conversely, circulating and BM megakaryocyte precursors (CFU-megakaryocyte) showed the same clonogenic efficiency in response to IL-3, granulocyte-macrophage-CSF and IL-3, IL-6, and Epo. After 5 weeks of liquid culture supported by the engineered murine stromal cell line M2-10B4 to produce G-CSF and IL-3, we reported 48.2 +/- 35 (SEM) and 62.5 +/- 54 (SEM) LTC-IC per 10(4) CD34+ cells in PB and steady-state BM, respectively (P = not significant). The Ara-C suicide assay showed that 4% +/- 5% (standard deviation [SD]) of committed precursors and 1% +/- 3% (SEM) of LTC-IC in PB are in S-phase as compared with 25.5% +/- 12% (SD) and 21% +/- 8% (SEM) of baseline BM, respectively (P < .001). However, longer incubation with Ara-C (16 to 18 hours), in the presence of SCF, IL-3 and G-CSF, or IL-6, showed that more than 60% of LTC-IC are actually cycling, with no difference being found with BM cells. Furthermore, studies of cell-cycle distribution on PB and BM CD34+ cells confirmed the low number of circulating progenitor cells in S- and G2M-phase, whereas simultaneous DNA/RNA analysis showed that the majority of PB CD34+ cells are not quiescent (ie, in G0-phase), being in G1-phase with a significant difference with baseline and G-CSF-treated BM (80% +/- 5% [SEM] v 61.9% +/- 6% [SEM] and 48% +/- 4% [SEM], respectively; P < .05). Moreover, G-CSF administration prevented apoptosis in a small but significant proportion of mobilized CD34+ cells. Thus, our results indicate that mobilized and BM CD34+ cells can be considered equivalent for the frequency of both committed and more immature hematopoietic progenitor cells, although they show different kinetic and functional profiles. In contrast with previous reports, we found that PB CD34+ cells, including very primitive LTC-IC, are cycling and ready to progress into S-phase under CSF stimulation. This finding should be taken into account for a better understanding of PBSC transplantation.

Adolescent↗
PubMed1996

[Chronic obstructive bronchitis in a fodder farming setting].

Respiratory disease in agricultural workers are dominated both in terms of frequency and severity by chronic obstructive long disease. In the Doubs, in dairy cereal farmers, the prevalence of chronic bronchitis in active farm workers is around 10 per cent, and 6 per cent are non-smokers. It is twice the level of the control population of non-exposed subjects. The frequency is most elevated in the men and increases both with age and with altitude. A longitudinal study of male farm workers aged more than 45 has shown that there is an abnormally rapid loss of forced expired volume in one second (FEV1). Two different studies carried out in the Doubs have revealed epidemiological, respiratory function and immunological arguments in favour of immuno-allergic mechanisms. Notably, obstructive chronic bronchitis (OCB) occurs more frequently in agricultural workers with a previous history of farmer's lung or previous sub-acute delayed symptoms in relation to exposure. On the other hand, there are no close links between OCB and the intensity of antigenic exposure (the total quantity of fodder handled). By contrast, there is a relationship between exposure to thermophillic actinomycetes (antigen of farmer's lung) and OCB. The frequency of serum precipitins is most elevated in farm workers with OCB than in asymptomatic agricultural workers. Finally, non-smokers who are suffering from OCB without evidence of farmer's lung, have a respiratory function profile and also alveolar lavage cell pattern characteristic of extrinsic allergic alveolitis after provocation tests to mouldy hay. These arguments are in favour of immuno-allergic mechanisms in the pathogenesis of chronic bronchitis in farm workers which seems to be well differentiated from chronic bronchitis due to smoking.

Actinomyces↗
PubMed1997

Rehabilitative treatment of non-neurogenic female urinary incontinence. Clinical and urodynamic evaluation.

Thirty-two female patients affected by urinary incontinence were enrolled for rehabilitative treatment (functional electro-stimulation by vaginal electrode performed three times a week for one month followed by biofeedback performed three times a week for one month). Complete clinical and urodynamic studies, urethrocystography in order to allow Blaivas and Olsson radiologic evaluation were performed. Echography of the bladder and urine cultures were done too. Patients with severe urogenital prolaxus and obesity, neurologic urinary disorders and surgery for incontinence, were excluded. The same patients were urodynamically reassessed at the end of the treatment and a detailed clinical evaluation was obtained from each patient. 78% of patients reported a considerable improvement in clinical symptoms and only 9% reported no improvement. Urodynamic findings showed an increase of maximum cystometric capacity in 6 patients, improvement of maximum urethral closure pressure and/or functional profile length in 17 patients. Disappearance or reduction of involuntary detrusor contractions were found in 2 out of 6 patients with unstable bladder.

Adult↗
PubMed1997

Pharmacological purging of minimal residual disease from peripheral blood stem cell collections of acute myeloblastic leukemia patients: preclinical studies.

UNLABELLED: In this paper we describe an experimental model for ex vivo purging of contaminating tumor cells from peripheral blood stem cell (PBSC) collections obtained from patients with acute myeloblastic leukemia (AML). We studied the combination of the alkylating agent nitrogen mustard (NM; concentrations ranging from 0.25 to 1.25 microg/mL) and etoposide (VP-16; constant dose of 20 microg/mL), and the conventional cyclophosphamide (Cy)-derivative mafosfamide (concentrations: 20-175 microg/mL). THE AIMS OF OUR STUDY WERE: 1) To compare the toxicity of the purging protocols on bone marrow (BM) and circulating trilineage precursors collected from normal donors after priming with granulocyte colony-stimulating factor (G-CSF) or after complete remission (CR) consolidation chemotherapy and G-CSF (leukemic patients); 2) to demonstrate the survival of very primitive hematopoietic progenitors (LTC-IC) in the peripheral blood (PB) and the BM after pharmacological treatment; and 3) to evaluate the antineoplastic efficacy of purging protocols on PBSC collections using 3 well-established leukemic cell lines. Our results demonstrated that the toxicity on BM and PB progenitor cells could be correlated with the complete killing of committed granulocyte-macrophage colony-forming units (CFU-GMs) and erythroid precursors (BFU-Es), a condition reached at the concentration of 1.5 microg/mL of NM (in addition to 20 microg/mL of VP-16) and 175 microg/mL of mafosfamide. Notably, early and late megakaryocyte progenitor cells (CFU-MKs and BFU-MKs, respectively) showed higher sensitivity to NM/VP-16, but not to mafosfamide, than did CFU-GMs and BFU-Es. The dose of NM capable of inhibiting 95% of CFU-MKs and BFU-MKs (ID95) was 0.75 microg/mL. After incubation with the same dose of NM, the recovery of CFU-GMs and BFU-Es was 20 +/- 8% SD and 25 +/- 10% SD, respectively (p < 0.05). Long-term liquid cultures showed the recovery of primitive hematopoietic cells after incubation with the highest concentrations of NM/VP-16 and mafosfamide, with no significant differences between PB and BM samples. Under the same experimental conditions, we observed a more than 5-log reduction of contaminating leukemic cell lines (i.e., K-562, KG-1, and HL-60). In conclusion, we demonstrated that NM/VP-16 and mafosfamide purging agents are capable of killing leukemic cell lines that contaminate leukapheresis products from patients with AML, whereas an acceptable proportion of primitive LTC-IC is spared. Moreover, despite the different kinetic and functional profile of mobilized and steady-state BM progenitors, we did not observe any difference in toxicity of antineoplastic agents on hematopoietic cells at different levels of differentiation. These data suggest that pharmacological strategies developed for eliminating minimal residual disease (MRD) from BM autografts can be effectively and safely applied to circulating stem cell harvests.

Antineoplastic Agents↗
PubMed1998

Clinical, urodynamic, and histologic effects of urethral intussusception in clinically normal dogs.

OBJECTIVE: To evaluate clinical and histologic effects of surgically created urethral intussusception and determine whether it creates a high-pressure zone that resists passive urine flow in clinically normal dogs. ANIMALS: 8 healthy adult sexually intact female dogs. PROCEDURE: Urethral pressure profilometry was used to measure maximal urethral closure pressure (MUCP) and functional profile length (FPL) in dogs sedated with xylazine hydrochloride and atropine before and 2, 4, 7, 14, 28, 60, and 90 days after surgery. Cystourethral leak point pressure (CLPP) and cystourethral leak point volume (CLPV) were determined in anesthetized dogs immediately before and after surgery. Dogs were assigned to 4 groups of 2 dogs each; groups were euthanatized 4, 14, 28, and 90 days later, and representative tissues were examined. RESULTS: Dog 1 developed complete postoperative urethral obstruction. The procedure was altered, and all dogs recovered without complication. Mild inflammation attributable to surgical manipulation, but not ischemic damage or reduction of the intussusception, was evident. Comparison of preoperative MUCP and FPL with postoperative values did not yield significant differences. Immediate postoperative CLPP and CLPV were significantly higher than preoperative values, but were not significantly increased at euthanasia. A distinct but nonsignificant pressure spike was observed in postoperative urethral pressure profiles and persisted in 7 of 8 dogs. CONCLUSIONS: Urethral intussusception does not have deleterious effects when performed as described. Urodynamic data do not support the premise that urethral intussusception will create a high-pressure zone in the urethra that will resist passive urine flow long term in clinically normal dogs.

Animals↗
PubMed1998

[Syndrome X and microvascular angina].

The term X syndrome is used to indicate a group of patients who present anginous symptoms and ischemic-type electrocardiographic alterations which appear during exercise tolerance tests, dipiridamol tests or Holter's dynamic monitoring where coronary ultrasonography reveals no evident coronary lesions, vasospastic angina, arterial hypertension and/or diabetes mellitus, block of the left branch when resting or exercising, cardiomyopathy or valvulopathy. The highest incidence is in females with a mean age of around 50. A reduced reserve of coronary flow, highlighted both in response to vasodilatators or rapid stimulation and by positron emission tomography (PET), underlies this syndrome. It is thought to be caused by a dysfunction of the coronary microcirculation which consists in a deficit of the endothelium-dependent vasodilatory mechanisms, probably also owing to the accumulation of vasoconstrictive type substances, like endothelin-1. In addition to a dysfunction of the coronary microcirculation, one widely backed hypothesis concerns the existence of an altered perception of painful symptoms in patients with X syndrome: the anomalous constriction of prearteries might cause an increased release of adenosine, able to provoke angina despite the scarce signs of myocardial ischemia in terms of the metabolic or functional profile. From a therapeutic point of view, treatment of these patients is often ineffective: treatment should be based on the use of nitrates, calcium-antagonists or beta-blockers, if necessary moving on to other forms of therapy (aceinhibitors, xanthine methylate, estrogens, alphablockers, imipramine); the simultaneous use of tranquillizers may be useful in view of the anxious personality often characteristic of these patients.

Female↗
PubMed2004

High-throughput localization of functional elements by quantitative chromatin profiling.

Identification of functional, noncoding elements that regulate transcription in the context of complex genomes is a major goal of modern biology. Localization of functionality to specific sequences is a requirement for genetic and computational studies. Here, we describe a generic approach, quantitative chromatin profiling, that uses quantitative analysis of in vivo chromatin structure over entire gene loci to rapidly and precisely localize cis-regulatory sequences and other functional modalities encoded by DNase I hypersensitive sites. To demonstrate the accuracy of this approach, we analyzed approximately 300 kilobases of human genome sequence from diverse gene loci and cleanly delineated functional elements corresponding to a spectrum of classical cis-regulatory activities including enhancers, promoters, locus control regions and insulators as well as novel elements. Systematic, high-throughput identification of functional elements coinciding with DNase I hypersensitive sites will substantially expand our knowledge of transcriptional regulation and should simplify the search for noncoding genetic variation with phenotypic consequences.

Algorithms↗
PubMed2005

Lipoprotein profile and endothelial function in patients with subclinical and overt hypothyroidism.

The aim of the present study was to evaluate the lipoprotein profile and endothelial function in patients with overt hypothyroidism, SCH and euthyroid subjects and to assess the effects of these conditions on endothelial function. The TOSHIBA SSH-140-A unit was used to measure brachial artery (BA) diameter and blood flow velocity at rest and after occlusion by high pressure cuff. To induce FMD we used EDRF release test. BA was occluded by high pressure cuff for 2 minutes with pressure 50 mmHg higher then systolic blood pressure. 23 SCH (I group) women were recruited for study. We compared them with 21 patients with overt hypothyroidism (II group). The III group contained 26 euthyroidal women. The results of examination have shown that overt hypothyroid patients have significantly higher TC, LDLc and TG levels than controls, positively correlated with TSH and inversely correlated with FT4 levels. SCH patients have less marked changes, but significant positive relationships were found between serum TSH and TC and LDLc. It is important as a risk factor for cardiovascular disease. Flow-mediated, endothelium-dependent vasodilatation was significantly higher in control group (10.7+/-0.8%) compared with subjects SHT (6.5+/-0.5%) and patients with overt hypothyroidism (5.2+/-0.4%). TSH levels correlated inversely to endothelium-dependent dilatation. Thus, FMD, a marker of endothelial function, is impaired not only in patients with overt hypothyroidism, but also in subjects with SCH.

Adult↗
PubMed2026

Functional and Proteomic Profiles of CD3(+) Plasma-Derived Small Extracellular Vesicles Differentiate Cancer Patients From Healthy Donors.

Small extracellular vesicles (sEV) released by T cells play a key role in immune regulation. Immune capture with anti-CD3 antibodies was used to isolate and study T cell-derived CD3(+)sEV from the plasma of patients with melanoma (MPs) or healthy donors (HDs). Functional responses induced in recipient target cells by CD3(+)sEV of MPs differed from responses induced by CD3(+)sEV of HDs. Approximating functions mediated by melanoma cell-derived sEV (MTEX), CD3(+)sEV of MPs reduced metabolic activity and proliferation of T cells while promoting activity in Mel526 cell targets. Proteomics profiling confirmed functional differences between CD3(+)sEV of MPs and HDs. Of 294 sEV-specific proteins identified in CD3(+)sEV, 226 were detected in the parent T cell proteome, confirming that the CD3(+)sEV proteome mimics that of the parent T lymphocytes. Among them were 66 differentially expressed proteins (DEPs) that differentiated vesicles from MPs and HDs. These DEPs were associated with processes linked to cancer-related functions. DEPs upregulated in CD3(+)sEV of MPs were associated with RHO-GTPase, cytokine, and MAPK signaling pathways. Thus, T cells of MPs were reprogrammed by MTEX to produce CD3(+)sEV that functionally resembled MTEX, partly recapitulated features of the tumor proteome, and differed from CD3(+)sEV of HDs. In cancer, the TEX-rewired T cells produce CD3(+)sEV that potentially could serve as a liquid biopsy of patients' T cells.

Humans↗
PubMed2001

Relative contribution of resting haemodynamic profile and lung function to exercise tolerance in male patients with chronic heart failure.

OBJECTIVE: To clarify the relative contribution of resting haemodynamic profile and pulmonary function to exercise capacity in patients with heart failure. SETTING: Cardiology department and cardiac rehabilitation unit in a tertiary centre. DESIGN: 161 male patients (mean (SD) age 59 (9) years) with heart failure (New York Heart Association class II-IV, left ventricular ejection fraction 23 (7)%) underwent spirometry, alveolar capillary diffusing capacity (DLCO), and mouth inspiratory and expiratory pressures (MIP, MEP, respectively, in 100 patients). Right heart catheterisation and a symptom limited cardiopulmonary exercise test were performed in 137 patients within 3-4 days. RESULTS: Mean peak exercise oxygen consumption (VO(2)) was 13 (3.9) ml/kg/min. Among resting haemodynamic variables only cardiac index showed a significant correlation with peak VO(2). There were no differences in haemodynamic variables between patients with peak VO(2) </= or > 14 ml/kg/min. There was a moderate correlation (p < 0.05) between several pulmonary function variables and peak VO(2). Forced vital capacity (3.5 (0.9) v 3.2 (0.8) l, p < 0.05) and DLCO (21.6 (6.9) v 17.7 (5.5) ml/mm Hg/min, p < 0.05) were higher in patients with peak VO(2) > 14 ml/kg/min than in those with peak VO(2) </= 14 ml/kg/min. Using a stepwise regression analysis, the respiratory and haemodynamic variables which correlated significantly with peak VO(2) were DLCO, MEP, and cardiac index, with an overall R value of 0.63. CONCLUSIONS: The data confirm previous studies showing a poor correlation between resting indices of cardiac function and exercise capacity in heart failure. However, several pulmonary function variables were related to peak exercise VO(2). In particular, lung diffusing capacity and respiratory muscle function seem to affect exercise tolerance during heart failure.

Adult↗
PubMedDate not supplied

Factors affecting the discriminant function analysis of blood chemistry profiles.

The discriminant function analysis (DFA) of a battery of blood chemistry tests is generally more sensitive and specific than single biochemical test in detecting alcoholism or hazardous drinking. This study examined factors affecting the DFA of blood chemistry profiles (BCP) from alcoholics (ALC) in treatment, primary care outpatients (PC), and the general population (GP). Our data indicate that of the 32 variables in the BCP, 14 are not correlated with alcohol intake or consequences and can be deleted from the set considered for use in the DFA. Confounding medical conditions in the data set used in the DFA did not adversely affect the correct classification of ALC or heavy drinkers. It was not necessary to use only extreme groups (e.g., alcoholics vs. light drinkers/abstainers) to develop the discriminant function. Transformation of some blood variables greatly improved the selection of key variables in the DFA. Another finding was that there was little benefit from fitting the DFA to the demographics of subjects. When the BCP was combined with the results of a brief questionnaire, the TWEAK, it only improved slightly the classification power of the DFA based only on the TWEAK questions.

Adolescent↗
PubMed2006

Impaired functionality and phenotypic profile of dendritic cells from patients with multiple myeloma.

Multiple myeloma (MM) is a B cell cancer characterized by clonal proliferation in the bone marrow and impaired immunity. Because MM is an incurable malignancy, efficient consolidation is needed urgently. Targeting clonotypic B cells by idiotype vaccination has proved the principle to be effective and indicated that future strategies, including dendritic cell-based vaccination, could be a suitable approach. However, as MM patients suffer from a general impaired immunity, which may include dendritic cells (DCs), a careful evaluation of phenotypic traits and functionality of DCs from MM patients is necessary before an efficient vaccine can be developed. This study determined the number, phenotypic profile and functionality of myeloid and plasmacytoid DCs purified directly from blood from MM patients at diagnosis. A reduced number and lower expression of human leucocyte antigen (HLA) molecules was observed on both myeloid and plasmacytoid DCs in MM patients compared to healthy controls. Also, the expression of CCR5, CCR7 and DEC205 was lower in MM patients compared to normal donors. In addition, the capacity to stimulate allogeneic T cell proliferation and to stimulate cytokine production was decreased, suggesting that DCs from these patients are functionally impaired. Finally, the analysis of samples following chemotherapy and transplantation demonstrated an increased expression of HLA molecules, suggesting that this time-point is optimal for harvest and use in vaccination.

Antigens, CD↗
PubMed2006

Specific gene expression profiles distinguish among functional allelic variants of the mouse Pthlh gene in transfected human cancer cells.

The mouse parathyroid hormone-like hormone (Pthlh) gene encodes three allelic variants characterized by amino acid substitutions that are associated with susceptibility (Pthlh(Pro)) or resistance (Pthlh(Thr) and Pthlh(SerAspTyr)) to two-stage skin carcinogenesis and to modulation of cell migration in vitro in transfected human cancer cells. cDNA microarray hybridization analysis of 8473 transcript clones revealed a similar gene expression profile for the Pthlh(Thr) and Pthlh(SerAspTyr) alleles but a distinct pattern for the Pthlh(Pro) allele, suggesting an association between a specific gene expression profile and biological function of the Pthlh alleles. Some of the genes modulated by the Pthlh alleles, e.g., ANXA1, CCL2, FN1 and TFF3, play a role in cell migration and may represent candidate targets for this Pthlh function. Our study demonstrates the potential usefulness of gene expression profiling of genetic variants for the functional characterization of candidate cancer modifier genes.

Alleles↗
PubMed1997

Profiles of cognitive functioning in subjects with neurological disorders.

This report completes a four-year funded project designed to develop a data bank of Neurobehavioral Cognitive Status Examinations (NCSE) profiles of patients with neurological based disorders. Seven facilities participated in the study. Twenty categories of neurological/ psychological disorders were obtained from the NCSE profiles of 804 patients. Four categories had a sample large enough to permit inferences about the cognitive deficits related to the specific neurologic diagnosis. Including all diagnoses, the major areas of cognitive decline were auditory memory, visual memory and construction. Subjects with dementia had similar profiles but the severity varied depending upon the diagnoses of multi-infarct dementia, dementia of unknown origin or Alzheimer's disease. Profiles of cognitive functioning appear to differ among patients with different neurological/psychological disorders. The study also illustrated unique cognitive deficits that occur with different neurologic disorders, and how NCSE profiles were able to identify specific areas of cognitive deficits in population of patients with similar neurologic insults.

Central Nervous System Diseases↗