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PubMed1981

[Studies of vesico-urethral function by urethral pressure profile during drug treatment (author's transl)].

The urethral closure pressure profile (UPP) examination was performed routinely together with the administration of alpha-blockers. By the measurement of UPP, we can understand whether the organic changes at the bladder neck have already occurred or not. Further, by calculating the decreasing rate of the pressure at the bladder neck (BNP) and the maximum urethral closure pressure (MP), we can determine which nerve component is affected. Particularly, when we want to detect the affected nerve component in a mild disorder of vesico-urethral function, the measurement of UPP is quite useful as one of the screening urodynamic tests.

Adrenergic alpha-Antagonists↗
PubMed2006

Cognitive and symptom profiles in high-functioning pervasive developmental disorder not otherwise specified and attention-deficit/hyperactivity disorder.

Age- and IQ-balanced 27 children with high-functioning (IQ>or=70) pervasive developmental disorder not otherwise specified (HPDDNOS) and 27 children with attention-deficit/hyperactivity disorder (ADHD) were compared on the Japanese version of Wechsler Intelligence Scale for Children Third Edition (WISC-III) and the Childhood Autism Rating Scale-Tokyo Version (CARS-TV). Compared with the ADHD children, the HPDDNOS children scored significantly lower on verbal comprehension, vocabulary, and comprehension, but significantly higher on block design. After controlling for the total CARS-TV score, the HPDDNOS children were significantly more abnormal on "relationships with people," "nonverbal communication," and "general impressions," but less abnormal on "near receptor responsiveness" and "activity level." These differences in cognitive and autistic symptom profiles may help professionals to distinguish clinically between both conditions.

Adolescent↗
PubMed1983

Natural killer cell function and lymphocyte subpopulation profiles in inflammatory bowel disease.

Peripheral blood natural killer (NK) cell activity and lymphocyte subpopulation profiles were studied in 23 patients with inflammatory bowel disease (IBD) and in 16 healthy control subjects. NK activity was assessed by a 4-hr 51Cr release assay using K-562 erythroleukemia cell line targets. Both monocyte depleted and nondepleted lymphocyte preparations were tested using 50:1 and 25:1 effector to target cell ratios. Lymphocyte subpopulation profiles were determined by incubation of cell suspensions with the monoclonal anti-lymphocyte antibodies (OK-M1, OK-T4, Leu-4 and Leu-2) labeling with goat anti-mouse FITC and sorting by flow cytometry on the fluorescence-activated cell sorter (FACS). NK activity in patients with IBD showed wide variation, but mean activity was not significantly different from normal controls. Analysis of patient subgroups by disease activity, disease type, duration or treatment also failed to reveal significant differences from controls. Parallel measurements of peripheral blood lymphocyte subpopulations using these phenotypic markers revealed no significant differences between patients with IBD and control subjects.

Adolescent↗
PubMed1999

Pharmacological characterization of the bradykinin B2 receptor: inter-species variability and dissociation between binding and functional responses.

1. The present study addresses the differences in binding profiles and functional properties of the human and rat bradykinin (BK) B2 receptor using various kinin receptor peptide derivatives as well as the non-peptide receptor antagonists WIN 64338 (phosphonium, [[4-[[2-[[bis(cyclohexylamino)methylene]amino]-3-(2-naphtalenyl)1- oxopropyl]amino]-phenyl]-methyl]tributyl, chloride, monohydro-chloride), and FR173657 (E)-3-(6-acetamido-3-pyridyl)-N-[-N-[2,4-dichloro-3-[(2-methyl-8-quinoli nyl)oxymethyl]-phenyl]N-methylamino carbonyl methyl] acrylamide. 2. [3H]-BK bound with a similar affinity to membranes of Chinese hamster ovary cells (CHO-K1) expressing the cloned human (hB2-CHO) or rat (rB2-CHO) B2 receptor, human embryonic intestine cells (INT407) expressing the native B2 receptor, human umbilical vein (HUV) and rat uterus (RU). WIN 64338 and FR173657 bound with a 3.8-6.6 fold and 7.0-16.3 fold higher affinity the rat than the human B2 receptor, respectively. The affinity values of BK derivatives as well as non-peptide antagonists were reduced by 6-23 fold in physiological HBSS compared to low ionic strength TES binding buffer. 3. BK (0.01-3000 nM) increased inositol triphosphates (IP3) levels in hB2-CHO, rB2-CHO and INT407 cells. The B2 receptor antagonist, Hoe 140 (D-Arg0-[ Hyp3, Thi5, D-Tic7, Oic8]-BK) at 10(-7) M, significantly shifted to the right the IP3 response curves to BK giving apparent pKB values of 8.56, 9.79 and 8.84 for hB2-CHO, rB2-CHO and INT407 cells, respectively. 4. In human isolated umbilical vein, Hoe 140, D-Arg0-[Hyp3, D-Phe7, Leu8]-BK and NPC 567 had a lower potency in functional assays (pKB 8.18, 5.77 and 5.60, respectively) than expected from their affinity in binding studies (pKi 10.52, 8.64 and 8.27, respectively). 5. FR173657 behaved as a high affinity ligand with pKi values of 8.59 and 9.81 and potent competitive antagonist with pKB values of 7.80 and 8.17 in HUV and RU, respectively. FR173657 bound with a similar affinity the cloned and native bradykinin B2 receptor in human (pKi of 8.66 and 8.59, respectively) and in rat (pKi 9.67 and 9.81, respectively). 6. In conclusion, we suggest that the binding buffer composition has to be taken into account when screening new compounds and that inter-species differences should be considered when setting up animal models with the aim of developing bradykinin B2 receptor antagonists as therapeutic agents.

Adrenergic beta-Antagonists↗
PubMed2006

Essential structural profile of a dual functional inhibitor against cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and 3D-QSAR analyses on DHDMBF analogues.

It is recently proposed that compounds with equal capabilities of inhibiting COX and 5-LOX, both are key enzymes involved in the arachidonic acid (AA) cascade, are expected to be safer non-steroidal anti-inflammatory drugs (NSAIDs). To dig out helpful information in designing dual functional inhibitors against the two enzymes, homology modeling, molecular dynamics (MD) simulations, automated docking, and 3D-QSAR analyses were performed in this study on 21 COX-2/5-LOX dual inhibitors, namely, 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran (DHDMBF) analogues. A 3D-model of 5-LOX was built based on the high-resolution X-ray structure of rabbit reticulocyte 15-lipoxygenase. Molecular docking was then applied to locate the binding orientations and conformations of DHDMBF analogues with COX-2 and 5-LOX, respectively, leading to highly predictive CoMFA models constructed on the basis of the binding conformations with q2 values of 0.782 and 0.634 for COX-2 and 5-LOX, respectively. In addition, CoMFA field distributions were found in good agreement with the structural characteristics of the corresponding binding sites. Both the docking simulations and QSAR analyses suggest that new potent dual inhibitors should share a structural feature with a moderately bulky group at R2 position and a rather negatively charged group around the position of the carbonyl group of DHDMBFs. Therefore, the final 3D-QSAR models and the information of the inhibitor-enzyme interaction should be useful in developing new NSAIDs as anti-inflammation drugs with favorable safety profile.

Amino Acid Sequence↗
PubMed2006

Functionally relevant coupled dynamic profile of bacteriorhodopsin and lipids in purple membranes.

The dynamics of bacteriorhodopsin (bR) and the lipid headgroups in oriented purple membranes (PMs) was determined at various temperatures and relative humidity (rh) using solid-state NMR spectroscopy. The 31P NMR spectra of the alpha- and gamma-phosphate groups in methyl phosphatidylglycerophosphate (PGP-Me), which is the major phospholipid in the PM, changed sensitively with hydration levels. Between 253 and 233 K, the signals from a fully hydrated sample became broadened similarly to those of a dry sample at 293 K. The 15N cross polarization (CP) NMR spectral intensities from [15N]Gly bR incorporated into fully hydrated PMs were suppressed in 15N CP NMR spectra at 293 K compared with those of dry membranes but gradually recovered at low temperatures or at lower hydration (75%) levels. The suppression of the NMR signals, which is due to interference with proton decoupling frequency (approximately 45 kHz), coupled with short spin-spin relaxation times (T2) indicates that the loops of bR, in particular, have motional components around this frequency. The motion of the transmembrane alpha-helices in bR was largely affected by the freezing of excess water at low temperatures. While between 253 and 233 K, where a dynamic phase transition-like change was observed in the 31P NMR spectra for the phosphate lipid headgroups, the molecular motion of the loops and the C- and N-termini slowed, suggesting lipid-loop interactions, although protein-protein interactions between stacks cannot be excluded. The results of T2 measurements of dry samples, which do not have proton pumping activity, were similar to those for fully hydrated samples below 213 K where the M-intermediates can be trapped. These results suggest that motions in the 10s micros correlation regime may be functionally important for the photocycle of bR, and protein-lipid interactions are motionally coupled in this dynamic regime.

Bacteriorhodopsins↗
PubMed2006

A factor analysis model for functional genomics.

BACKGROUND: Expression array data are used to predict biological functions of uncharacterized genes by comparing their expression profiles to those of characterized genes. While biologically plausible, this is both statistically and computationally challenging. Typical approaches are computationally expensive and ignore correlations among expression profiles and functional categories. RESULTS: We propose a factor analysis model (FAM) for functional genomics and give a two-step algorithm, using genome-wide expression data for yeast and a subset of Gene-Ontology Biological Process functional annotations. We show that the predictive performance of our method is comparable to the current best approach while our total computation time was faster by a factor of 4000. We discuss the unique challenges in performance evaluation of algorithms used for genome-wide functions genomics. Finally, we discuss extensions to our method that can incorporate the inherent correlation structure of the functional categories to further improve predictive performance. CONCLUSION: Our factor analysis model is a computationally efficient technique for functional genomics and provides a clear and unified statistical framework with potential for incorporating important gene ontology information to improve predictions.

Algorithms↗
PubMed1991

Acute recovery profile of lung volumes and function after running 5 miles.

The purpose of this study was to characterize the acute changes and recovery profile of lung volumes and function subsequent to strenuous aerobic exercise. Eight experienced runners (X age = 25 yrs; wt = 73 kg; ht = 181 cm) completed three identical 5 mile runs. Determinations were made of forced vital capacity (FVC), residual volume (RV), closing capacity (CC), and pulmonary diffusion capacity (DLCO). Measurement of cardiac output (Q) and stroke volume (SV) occurred simultaneously with the 10 second DLCO breathhold maneuver. Measurements were obtained before and 5, 15 and 25 minutes after each run. FVC was reduced (-4.5%) 5 min post-run with a return to pre-run values by 15 min. CC (+16%) and RV (+18%) remained elevated for at least 30 min post-run. DLCO did not appear to be effected by the run. However, the single-breath DLCO breathhold maneuver consistently caused a fall in SV at rest and during recovery. The hypothesis has been forwarded that an increase in central blood volume post-run accounted for the acute reduction in FVC. The sustained elevation in RV resulted from early closure of the small airways possibly due to an increase in extra-vascular lung water.

Adult↗
PubMed2005

Longitudinal assessment of immune response and viral characteristics in HIV-infected patients with prolonged CD4(+)/viral load discordance.

Although suppression of HIV-1 RNA below the limit of detection is associated with optimal outcomes, many patients can maintain or increase their CD4(+) count for prolonged time periods in the presence of persistent low-level viremia. We followed seven patients with prolonged (>5 years) discordant CD4(+)/viral load (VL) responses on protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) prospectively for 1 year to assess evolution of immune function, viral phenotype, replication capacity (RC), and resistance profile. Immune function was assessed by qualitative and quantitative measurement of cellular activation (CD38(+)HLA-DR(+) and CD38 antibodies bound per cell), and the interferon (IFN)-() ELISpot assay. Presence of syncytium-inducing (SI) or nonsyncytium-inducing (NSI) viral strains was determined by MT-2 cell culture. RC was measured by a modified rapid recombinant virus assay. The resistance profile was characterized by both genotypic and phenotypic analysis. Over the year of follow-up, IFN-() production to gag persisted, responses to other HIV antigens increased, and markers of cellular activation did not change. NSI virus predominated. The genotypic (GSS) and phenotypic (PSS) susceptibility scores remained stable. Evolution of RC was variable over the year of follow-up, but the RC of viruses remained well below that of wild-type clinical isolates. Thus, CD4(+)/VL discordance can be maintained for periods exceeding 5 years in some patients receiving PI-based HAART without significant evolution of HIV resistance.

Adolescent↗
PubMed1992

[Trophoblast: its functional regulation and pathophysiological profiles].

The trophoblast of the human placenta is composed of two layers: syncytiotrophoblast and cytotrophoblast. Cytotrophoblast displays highly proliferative and invasive properties, while syncytiotrophoblast displays little potential for proliferation. Regulatory factors involved in processes of proliferation and differentiation of the trophoblast still remain to be elucidated. Immunohistologically, myc product was predominantly localized to cytotrophoblastic cells. A close similarity between cytologic localization of myc product and tritiated thymidine labeling of placental explant suggests that myc protein expression is linked to trophoblast proliferation. A similar pattern of cytological localization was observed with the use of anti-PDGF antibody, supporting a possibility that PDGF also plays a role in the trophoblast proliferation. Human trophoblast produces two major proteins, hCG and hPL. hCG stimulates progesterone production by corpus luteum. hPL exerts lipolytic action which assures glucose supply to the fetus. In situ hybridization with cDNA probes for hCG(alpha, beta) and hPL revealed that mRNA expression of hCG alpha and probably hCG beta are initiated before syncytial formation, whereas hPL mRNA is expressed only in fully differentiated syncytiotrophoblast. hCG levels in maternal serum are the highest in early pregnancy and thereafter decline, while hCG alpha and hPL levels increase throughout pregnancy. In patients with choriocarcinoma, serum hPL levels are extremely low despite high levels of hCG. In this context, hCG beta mRNA levels remarkably declined in term placenta compared to early placenta, and hPL mRNA was little observed in choriocarcinoma. EGF and EGF receptor (EGF-R) in 4-5 weeks placenta were almost exclusively localized to cytotrophoblasts, whereas EGF and EGF-R in 6-12 weeks placenta were predominantly localized to syncytiotrophoblasts. In the second and third trimester placentas, EGF was mainly localized to cytotrophoblasts, while EGF-R was predominantly localized to syncytiotrophoblasts. It is of great interest that the cytologic localization of EGF and EGF-R in human placenta varies according to the age of gestation. The fact that mitotically active cytotrophoblasts in 4-5 weeks placenta were positive for both EGF and EGF-R expression suggests that EGF and EGF-R may be involved in the control of multiplication of cytotrophoblasts very early in the first trimester. On the other hand, the fact that mitotically inactive syncytiotrophoblasts in 6-12 weeks placenta were positive for both EGF and EGF-R expression suggests that EGF and EGF-R may play a role in the induction of differentiated function of trophoblast in 6-12 weeks gestation. In fact, EGF stimulated hCG and hPL production and secretion by cultured early placental tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗
PubMed1994

Effect of octreotide on gastrointestinal pressure profiles in health and in functional and organic gastrointestinal disorders.

The somatostatin analogue, octreotide, restores normal pressure profiles in disorders of upper gut motility. This study aimed to evaluate the acute effects of octreotide in five healthy subjects and in 50 consecutive patients with functional (n = 22) or organic (n = 28) dysmotility. Antroduodenojejunal manometry was performed during three hours' fasting, for two hours after a standard meal, and 30 minutes after subcutaneous injection of 50 micrograms octreotide. Antral motility, before and after octreotide, and characteristics of spontaneous migrating motor complexes and octreotide induced activity fronts were compared. Octreotide inhibited antral motility and induced a small intestinal activity front followed by motor quiescence in all healthy subjects and patients. The duration and propagation velocity of activity fronts were greater than those of spontaneous migrating motor complexes. Thirty per cent of activity fronts began simultaneously at different levels of small bowel, and in 20%, a second, normally propagated activity front developed within 30 minutes of octreotide injection. Octreotide induces rapidly propagated, long activity fronts, even in patients with neuropathology, and this may initially facilitate the intestinal propulsion of chyme. Propulsion may not occur, however, if octreotide induces simultaneous activity fronts or if the activity front is followed by prolonged quiescence. Inhibition of antral motility suggests that octreotide may not be effective in gastroparesis.

Adolescent↗
PubMed2006

The effects of clozapine on cognitive function and regional cerebral blood flow in the negative symptom profile schizophrenia.

OBJECTIVE: Cognitive function and regional cerebral blood flow (rCBF) were studied in negative symptom profile schizophrenic patients by using WCST and SPECT. METHODS: Twenty-one schizophrenic patients who matched the criteria of Andreason's negative symptom profile received SPECT and WCST, and then were treated with clozapine for 8 consecutive weeks. There were 28 and 12 normal subjects as the control groups of WCST and SPECT, respectively. RESULTS: Compared with controls, significantly poorer performance on total trials of category (TT), persevering errors (PE), and non-persevering errors (NPE) of WCST were found in schizophrenia (p < 0.05). The total score of the scale for assessment negative symptoms (SANS) was significantly related with poor TT (r = 0.45, p < 0.01) and PE performance (r = 0.45, p < 0.01). The poor TT, PE, and NPE tasks of WCST and SANS scores in the negative schizophrenic patients were significantly improved through clozapine treatment (p < 0.05). The schizophrenic patients had a significantly lower rCBF in bilateral frontal and temporal lobes and lower change rate of rCBF in bilateral frontal lobes during WCST compared to normal controls (p < 0.05). CONCLUSIONS: Negative symptom profile schizophrenia has cognitive deficits and lower rCBF in bilateral frontal and temporal lobes, which suggests that negative symptom profile schizophrenic patients have hypofrontality. Clozapine can improve negative symptoms and improve cognitive dysfunction, although it cannot improve reduced rCBF in the frontal lobes.

Adult↗
PubMed1993

Neurobehavioral effects of the fragile X premutation in adult women: a controlled study.

Although previous studies have suggested that the fragile X premutation (fra [X] pM) does not cause deleterious effects, methodological constraints have prevented more definitive conclusions from being reached. In this report, we describe the neuropsychiatric and cognitive-neuropsychological status of 34 adult women with the fra (X) pM, as compared with a well-matched control group of 41 mothers of fra (X)-negative children with developmental disability. The results indicate that there are no meaningful differences between adult women with the fra (X) pM and control subjects with respect to cognitive abilities or profile, neuropsychological function, psychiatric diagnoses or symptoms, and self-rated personality profile. No measure for either group showed evidence of functioning outside the normal range except for a high lifetime prevalence of major depression in both groups. Additional exploratory analyses within the fra (X) group showed no significant effect of either the size of the fra (X) insert or X chromosome inactivation pattern in leukocytes, on any measure of neurobehavioral function. These findings provide additional information to professionals providing genetic counseling to, and assessment of, fra (X) families.

Adult↗
PubMed1992

[Functional sensory and motor asymmetry profile in patients with neuroses and those with diseases of the digestive system].

Functional sensorimotor asymmetry (FSMA) was analyzed in 21 healthy volunteers, 19 neurotic patients and 29 patients suffering from alimentary diseases. Among the neurotic patients, there prevailed those with the left profile of FSMA as compared to the group of healthy persons. As to the group of the patients with alimentary diseases, a subgroup of persons with no disturbances of emotional information perception by the neurotic type was distinguished according to the psychophysiological characteristics. Among those persons in the given representative sample, none showed the left and symmetric profiles of FSMA.

Adult↗
PubMed1988

Studies of transformer repair workers exposed to PCBs: II. Results of clinical laboratory investigations.

Thirty-eight transformer repairmen currently exposed to polychlorinated biphenyls (PCBs), 17 former transformer repairmen, and 56 comparison workers not known to be exposed to PCBs were studied. Measurements were made of serum liver function tests, gamma-glutamyl transpeptidase (GGT), lipid profile, thyroid function tests, and other serum biochemistry; hemoglobin; white cell count; 24-hour excretion of delta-aminolevulinic acid, porphyrins, 17-hydroxycorticosteriods and 17-ketosteroids; sperm count; spirometry; and antipyrine half-life to evaluate microsomal mixed function oxidase induction. The total exposed group differed significantly from the comparison group in albumin, LDH, T4, T4-RT3 index, and actual/predicted FEV1. Significant differences among all three exposure groups were seen for albumin, T4, T4-RT3 index, and 17-hydroxycorticosteroid excretion. Differences in FEV1 were attributable to smoking. Significant correlations between serum PCBs and serum lipids were removed by adjustment for confounding variables. After adjustment for confounding variables, there was a statistically significant positive correlation between serum PCBs and GGT and a negative correlation between adipose PCBs and 17-hydroxycorticosteroid excretion. These may reflect subtle metabolic effects of PCBs.

Analysis of Variance↗
PubMed1993

Functional combination of tapering profiles and overlapping arrangements in nonspanning skeletal muscle fibers terminating intrafascicularly.

Using digital image analysis and several anatomical methods, morphometric analysis of nonspanning fibers which had tapering profiles at their intrafascicular termination sites and represented overlapping arrangements within the fiber fascicles was performed in the rat rectus abdominis. Special emphasis was focused on dimensional relationships occurring between overlapping portions and tapering segments and sarcomere lengths in non- and overlapping portions. Nonspanning fibers were found to overlap each other for more than 40% of their length. In length, their overlapping portions generally corresponded to their tapering segments, which were also greater than 40% of the fiber length. In addition, despite the presence of overlapping linkages, nonspanning fibers maintained a fairly uniform length irrespective of their overlapping and nonoverlapping portions. Overlapping linkages in fibers without tapering profiles have a larger cross-sectional area in the overlapping portion than in the non-overlapping one, resulting in a phenomenon which will cause different sarcomere lengths between the two portions during fiber stretching. The present results suggest that tapering profiles in the overlapping portion ensure uniform sarcomere lengths within nonspanning fibers, thereby providing mechanical stability in each fiber.

Abdominal Muscles↗
PubMed1992

Marker profile, enzyme activity, and function of a human myelomonocytic leukemia cell line.

Morphological and functional characteristics of a permanent human leukemia cell line (DD) that possesses myelomonocytic features were investigated. The cells bear a second type Fc gamma receptor and form rosettes with sheep erythrocytes sensitized with rabbit IgG (EA). However, the surface-bound EA is not internalized. The cell line lacks the surface markers CD2, CD19, CD14, HLA-DR, Fc gamma receptor I, Fc gamma receptor III, and CR3. alpha 1-Antitrypsin, lysozyme, Factor XIII a subunit of blood coagulation, and acid phosphatase reactions were negative. A terminal differentiation of the DD cell line was observed when the expression of CD14, CR3, Fc gamma receptor I, and Fc gamma receptor III was induced. The DD cells induced with 12-O-tetradecanoylphorbol-13-acetate or Escherichia coli lipopolysaccharide can internalize EA via Fc gamma receptor II and complement-coated yeast in the function of the inducers. The phagocytic ability appears to be parallel with the appearance of enzymes which participate in phagocytosis.

Antigens, Surface↗