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The functional status of ESRD patients as measured by the Sickness Impact Profile.

This study describes and compares the perceived sickness-related behavioral dysfunction of 859 end-stage renal disease (ESRD) patients from 11 centers according to treatment modality via the Sickness Impact Profile (SIP). The unadjusted functional status of ESRD patients differed significantly by treatment modality. Transplantation patients were least functionally limited followed in order by home dialysis, continuous peritoneal dialysis, and in-center dialysis patients. The largest overall differences were for the sleep and rest, work, recreation and pastimes, and home management SIP categories. Regression analysis revealed that many of the large observed intermodality differences in functional status may have resulted from casemix variations (e.g. age and comorbidity differences). Only SIP score differences between transplantation and other treatment modality patients remained significant following the introduction of casemix controls. Results do not justify choosing one dialysis modality over another because of differences in perceived dysfunction.

Adult↗

Transcriptome profiling to identify genes involved in peroxisome assembly and function.

Yeast cells were induced to proliferate peroxisomes, and microarray transcriptional profiling was used to identify PEX genes encoding peroxins involved in peroxisome assembly and genes involved in peroxisome function. Clustering algorithms identified 224 genes with expression profiles similar to those of genes encoding peroxisomal proteins and genes involved in peroxisome biogenesis. Several previously uncharacterized genes were identified, two of which, YPL112c and YOR084w, encode proteins of the peroxisomal membrane and matrix, respectively. Ypl112p, renamed Pex25p, is a novel peroxin required for the regulation of peroxisome size and maintenance. These studies demonstrate the utility of comparative gene profiling as an alternative to functional assays to identify genes with roles in peroxisome biogenesis.

Gene Expression Profiling↗

Receptor-selective, peptidase-resistant agonists at neurokinin NK-1 and NK-2 receptors: new tools for investigating neurokinin function.

The pharmacological profiles of two novel neurokinin agonists have been investigated. delta Ava[L-Pro9,N-MeLeu10]SP(7-11) (GR73632) and [Lys3,Gly8-R-gamma-lactam-Leu9] NKA(3-10) (GR64349) are potent and selective agonists at NK-1 and NK-2 receptors respectively. In the guinea-pig isolated trachea preparation, contractions induced by these agonists were largely unaffected by inclusion of peptidase inhibitors in the bathing medium, indicating that these agonists are resistant to metabolism by peptidases. In the anaesthetised guinea-pig, both agonists were more potent bronchoconstrictor agents than either NKA or the SP analogue, SP methylester. In the anaesthetised rat, the NK-1 agonist, GR73632 was more potent than SP, NKA or NKB at causing the histamine-independent extravasation of plasma proteins into the skin after intradermal administration. The NK-2 agonist, GR64349 and the NK-3 agonist, senktide were without significant effect in this model. These agonists are useful tools for characterizing neurokinin receptor-mediated actions both in vitro and in vivo.

Administration, Cutaneous↗

Acute fatty liver and HELLP syndrome: two distinct pregnancy disorders.

OBJECTIVE: to report the experience clinical, biochemical findings, complications and the maternal-perinatal outcome in patients with HELLP syndrome and acute fatty liver of pregnancy (AFLP) during the same period. MATERIALS AND METHODS: during the period between January 1996 and December 1999, medical records of patients with the discharge diagnosis of AFLP and HELLP syndrome were reviewed for presenting symptoms, laboratory findings, maternal and perinatal complications. Routine laboratory evaluation included serial measurement of liver function tests, complete blood cell count, coagulation profile and renal function tests. RESULTS: during the study period 10 patients had AFLP and 75 women had HELLP syndrome as the discharge diagnosis. Patients with HELLP syndrome had major parity than AFLP (P<0.006). The most common presenting symptom for patients with AFLP was malaise noted in all patients, nausea and/or vomiting, abdominal pain and jaundice were very common. Headache, abdominal or epigastric pain and hematuria were the most common symptoms of patients with HELLP syndrome. Women with AFLP had major hypoglycemia, hypocholesterolemia, hypotriglyceridemia, serum transaminase activity and low antithrombin III. Disseminated intravascular coagulation, acute renal insufficiency, ascites, seroma and encephalophaty were more common with AFLP. CONCLUSIONS: our opinion is that AFLP had clinical presentation, biochemical findings and complications clearly distinguished of HELLP syndrome.

Abdominal Pain↗

[Measurement of pressure and force as a basis of the postoperative evaluation of abdominal wall function].

By quantifying profiles of pressure and effects of forces in the operating area of inguinal hernia operations we found coughing to be the extreme burden for the abdominal wall and Bassini suture. The described technique of measuring the forces exercised in the suture spot by using an expanding wire can be used in principle such as the measurement of pressure in the rectum, for similar cases of general care in surgery.

Abdominal Muscles↗

Systemic lupus erythematosus--a medical and social profile.

The social functioning of 120 patients (114 women) with systemic lupus erythematosus (SLE) was studied. The proportion of Chinese, Japanese and Native Indians was greater than expected. Familial incidences of SLE (12.5%) and rheumatoid arthritis (17.5%) were high. Sixty-one women had 76 pregnancies after the onset of SLE; although fetal wastage was common, outcomes were otherwise satisfactory. Social difficulties worsened with disease exacerbations, drug reactions and delay in diagnosis. Thirty-three percent completed their education after the onset of SLE. Sixty-three percent with a work history were employed and 52% were totally or partially self-supporting. Patients experienced problems with self-image (20%), sexual functioning (4%) and lifestyle (17%). SLE was not a barrier to marriage or a primary cause of divorce: 40% married after the onset of SLE and 12.5% had a history of divorce. In summary, SLE patients can function well socially; it is imperative to recognize the difficulties and provide support.

Adolescent↗

On the dosimetric accuracy of a Sievert integration model in the proximity of 192Ir HDR sources.

PURPOSE: To investigate the efficacy of a Sievert integration model in dosimetry close to 192Ir high-dose-rate brachytherapy sources and validate its accuracy and potential to resolve dosimetric differences between these sources in the cm and mm distance ranges relevant to interstitial and intravascular brachytherapy applications, respectively. METHODS AND MATERIALS: The dosimetric quantities of the generalized Task Group 43 formalism, as well as dose rate profiles in polar and Cartesian coordinates, are calculated, and results are compared to corresponding Monte Carlo data in the literature. RESULTS: Sievert calculations were found in excellent agreement with corresponding Monte Carlo published results. Dose rate polar angle profiles in the cm distance range depended significantly on corresponding anisotropy function data, whereas in the mm distance range, dose rate polar angle profiles are governed by the corresponding geometry function profiles, because anisotropy proved insignificant. Radial dose functions of the sources were found comparable. A simple equation for the calculation of the dose rate constant of the sources within clinically acceptable accuracy is provided. CONCLUSIONS: The particular Sievert model proved capable of resolving dosimetric differences of the sources and provides results within clinical accuracy. Therefore, it constitutes a useful tool for dosimetry in clinical practice and especially in intravascular applications, where there is currently a lack of available dosimetric data.

Anisotropy↗

Divergence between motoneurons: gene expression profiling provides a molecular characterization of functionally discrete somatic and autonomic motoneurons.

Studies in the developing spinal cord suggest that different motoneuron (MN) cell types express very different genetic programs, but the degree to which adult programs differ is unknown. To compare genetic programs between adult MN columnar cell types, we used laser capture microdissection (LCM) and Affymetrix microarrays to create expression profiles for three columnar cell types: lateral and medial MNs from lumbar segments and sympathetic preganglionic motoneurons located in the thoracic intermediolateral nucleus. A comparison of the three expression profiles indicated that approximately 7% (813/11,552) of the genes showed significant differences in their expression levels. The largest differences were observed between sympathetic preganglionic MNs and the lateral motor column, with 6% (706/11,552) of the genes being differentially expressed. Significant differences in expression were observed for 1.8% (207/11,552) of the genes when comparing sympathetic preganglionic MNs with the medial motor column. Lateral and medial MNs showed the least divergence, with 1.3% (150/11,552) of the genes being differentially expressed. These data indicate that the amount of divergence in expression profiles between identified columnar MNs does not strictly correlate with divergence of function as defined by innervation patterns (somatic/muscle vs. autonomic/viscera). Classification of the differentially expressed genes with regard to function showed that they underpin all fundamental cell systems and processes, although most differentially expressed genes encode proteins involved in signal transduction. Mining the expression profiles to examine transcription factors essential for MN development suggested that many of the same transcription factors participate in combinatorial codes in embryonic and adult neurons, but patterns of expression change significantly.

Animals↗

[Functional and esthetic cephalometric analysis of the profile].

We report a new cephalometric method for profile analysis, which uses strictly exobasicranial landmarks: 13 anatomic points, 9 bone points and 4 skin points. The analysis is based on phylogenetic, ontogenetic, anatomic and biomechanical data. The face is comprised between a new exobasicranial plane represented by the Nasion-Glenion (Na-Gl) and the classical mandibular plane. These two planes form the angle of facial divergence. Orthogonal projection of the axis of the maxillary incisors and the axis of facial growth on the new basicranial plane is then performed. The upper and lower levels of the facial mass are divided sagittally by four vertical anatomic planes perpendicular to the Francfort plane, accounting for the facial skin profile (cutaneous facial plane), the anterior and posterior facial pillars (premaxillary and postmaxillary planes), and the craniospinal postural plane. The ideal occlusion plane is undistinguishable from the curve of Spee. This new cephalometric method for functional and esthetic profile analysis enables simple rapid and efficient study of the main facial and cervical structures.

Adult↗

Use of plasma progesterone profiles for the assessment of reproductive functions in indigenous Nigerian Zebu cattle.

The reproductive performance of Zebu cattle is generally low. However, blood concentrations of progesterone may be of practical value in assessing the reproductive status of the Zebu female. This paper reviews recent findings regarding plasma progesterone profiles during different phases of the reproductive cycle of some Nigerian Zebu cattle. The reproductive phases examined include the estrous cycle, early pregnancy and the postpartum periods. Our findings describe variations in plasma progesterone profiles observed under field conditions. The practical implications of these findings in assessing reproductive functions in indigenous Nigerian Zebu cattle are examined.

Journal Article↗

A convolution method for constructing primary beam profiles in the presence of beam modifiers.

Empirical functions that describe primary beam profiles for radiotherapy treatment planning systems generally account for finite source size only on beams unmodified by blocks, wedges, or compensating filters. To incorporate the effects of extended sources on such modified beams and to treat the effect of an extended source consistent with the manner in which the unmodified beam is treated, the unmodified beam profile can be written as a convolution of an unknown source function with a collimator transmission profile. Using Fourier transforms, one can then solve for the source function. This source function is then convolved with a beam transmission function that has been modified by blocks, wedges, or compensating filters to obtain a primary beam profile. A number of examples are presented that demonstrate the calculations of the effects of beam modifiers on primary beam profiles.

Algorithms↗

Prevalence of residual B-cell function related to age at onset and genetic profile in newly diagnosed type I diabetics.

Patients with type I (insulin-dependent) diabetes mellitus maintain B-cell function for a varying period of time after onset. This is commonly held to account for post-initial remission. To estimate residual B-cell function we measured plasma and 24-h urinary C-peptide in 68 type I diabetic patients (age range 4-35 years, within 10-180 days of the onset of symptoms, typed for HLA-A, -B, -C and DR loci. A positive correlation (r = 0.26; p less than 0.05) was found between urinary C-peptide levels and the age of the patient. The analysis of variance of urinary C-peptide values on the basis of the presence or absence of DR3 and DR4 antigens revealed that the DR3-positive patients had reduced excretion (15.2 +/- 9.2 SD micrograms/24h) with respect to the others (22.7 +/- 15.5 SD micrograms/24h) (F = 6.35; p less than 0.05). No interaction effect was found in DR3/4 positive patients. Hence, late onset patients appear to have higher residual C-peptide secretion. In the light of these findings, the assessment of B-cell function and genetic profile may be useful in predicting which patients are likely to have remission periods and identifying the metabolic consequences of even minimal endogenous insulin secretion.

Adolescent↗

Chemistry-based functional proteomics: mechanism-based activity-profiling tools for ubiquitin and ubiquitin-like specific proteases.

Determining the biological function of newly discovered gene products requires the development of novel functional approaches. To facilitate this task, recent developments in proteomics include small molecular probes that target proteolytic enzyme families including serine, threonine, and cysteine proteases. For the families of ubiquitin (Ub) and ubiquitin-like (UBL)-specific proteases, such tools were lacking until recently. Here, we review the advances made in the development of protein-based active site-directed probes that target proteases specific for ubiquitin and ubiquitin-like proteins. Such probes were applied successfully to discover and characterize novel Ub/UBL-specific proteases. Ub/UBL processing and deconjugation are performed by a diverse set of proteases belonging to several different enzyme families, including members of the ovarian tumor domain (OTU) protease family. A further definition of this family of enzymes will benefit from a directed chemical proteomics approach. Some of the Ub/UBL-specific proteases react with multiple Ub/UBLs and members of the same protease family can recognize multiple Ub/UBLs, underscoring the need for tools that appropriately address enzyme specificity.

B-Lymphocytes↗

Species-specific analysis of protein sequence motifs using mutual information.

BACKGROUND: Protein sequence motifs are by definition short fragments of conserved amino acids, often associated with a specific function. Accordingly protein sequence profiles derived from multiple sequence alignments provide an alternative description of functional motifs characterizing families of related sequences. Such profiles conveniently reflect functional necessities by pointing out proximity at conserved sequence positions as well as depicting distances at variable positions. Discovering significant conservation characteristics within the variable positions of profiles mirrors group-specific and, in particular, evolutionary features of the underlying sequences. RESULTS: We describe the tool PROfile analysis based on Mutual Information (PROMI) that enables comparative analysis of user-classified protein sequences. PROMI is implemented as a web service using Perl and R as well as other publicly available packages and tools on the server-side. On the client-side platform-independence is achieved by generally applied internet delivery standards. As one possible application analysis of the zinc finger C2H2-type protein domain is introduced to illustrate the functionality of the tool. CONCLUSION: The web service PROMI should assist researchers to detect evolutionary correlations in protein profiles of defined biological sequences. It is available at http://promi.mpimp-golm.mpg.de where additional documentation can be found.

Amino Acid Motifs↗

Use of latent profile analysis to identify eating disorder phenotypes in an adult Australian twin cohort.

CONTEXT: The relationships among the different eating disorders that exist in the community are poorly understood, especially for residual disorders in which bingeing or purging occurs in the absence of other behaviors. OBJECTIVE: To examine a community sample for the number of mutually exclusive weight and eating profiles. DESIGN: Data regarding lifetime eating disorder symptoms and weight range were submitted to a latent profile analysis. Profiles were compared regarding personality, current eating and weight, retrospectively reported life events, and lifetime depressive psychopathology. SETTING: Longitudinal study among female twins from the Australian Twin Registry in whom eating was assessed by a telephone interview. PARTICIPANTS: A community sample of 1002 twins (individuals) who had participated in earlier waves of data collection. MAIN OUTCOME MEASURES: Number and clinical character of latent profiles. RESULTS: The best fit was a 5-profile solution with women who were (1) of normal weight with few lifetime eating disorders (4.3%), (2) overweight (10.6% had a lifetime eating disorder), (3) underweight and generally had no eating disorders except for 5.3% who had restricting anorexia nervosa, (4) of low to normal weight (89.0% had a lifetime eating disorder), and (5) obese (37.0% had a lifetime eating disorder). Each profile contained more than 1 type of lifetime eating disorder except for the third profile. Women in the first and third profiles had the best functioning, with women in the fourth and fifth profiles having similarly poorer functioning. The women in the fourth group had a symptom profile distinctive from the other 4 groups in terms of severity; they were also more likely to have had lifetime major depression and suicidality. CONCLUSION: Lifetime weight ranges and the severity of eating disorder symptoms affected clustering more than the type of eating disorder symptom.

Adult↗

Functional changes in vascular amputee patients: evaluation by Barthel Index, PULSES profile and ESCROW scale.

This study evaluated the changes made by 60 peripheral vascular amputees from one month prior to admission to six months after attending a rehabilitation hospital. The Barthel index, PULSES profile, and ESCROW profile were used to measure functional status, social support, and rehabilitation progress. Statistical analysis consisted of t-tests to determine significant differences between the means of scores at varying intervals, and analysis of variance was added to determine interactions between amputation level, age, and sex as related to functional change. Amputees showed significant gains in Barthel scores from admission to discharge; this was attributed to rehabilitation intervention. They showed a significant decrease by the PULSES profile over the study period, indicating a decrease in independence from their premorbid function. Changes in ESCROW scores showed patients to have a greater need for social supports as they moved from admission to discharge. Age was a significant factor in mobility at discharge as measured by the Barthel index. As measured by the PULSES profile, men did better than women at six months follow-up. Unexpected results were that neither amputation level nor the presence or absence of diabetes mellitus had a significant impact on functional status as measured. The lack of significant differences by amputation level may be due to factors of age and sex, as well as to more depression in the below-knee group.

Activities of Daily Living↗

Aqueous stability of recombinant human thrombopoietin as a function of processing schemes.

Preformulation studies conducted with recombinant human thrombopoietin (rhTPO), a 332 amino acid glycoprotein which stimulates platelet production, show distinctions in degradation profiles as a function of processing schemes. The stability-limiting degradation pathways change as a function of purification stage and method and are dependent upon the presence of contaminating protease. The stability-limiting degradation pathway of affinity-purified and in-process rhTPO preparations is primarily attributed to proteolysis initiated by a protease present as a fermentation contaminant. The proteolysis increases with increasing pH as a function of temperature. The degradation profiles for these preparations show that bioactivity initially increases and then decreases with increasing pH as a function of temperature. This is consistent with proteolysis to active forms which ultimately undergo degradation to less active forms. Similar studies conducted with rhTPO preparations purified by a combination of more conventional chromatographic steps show different stability-limiting degradation pathways and a different pH-stability profile when compared to affinity purified or in-process preparations. In this case, degradation is accompanied by decreases in activity under all conditions, consistent with the conversion to less active forms. These results illustrate the importance of preformulation and stability characterization of protein pharmaceuticals in support of both process and formulation development. Issues related to storage and handling of inprocess preparations differ from those with formulated product since the stability-limiting degradation pathways change as a function of purification stage.

Animals↗

Expression profiling of human renal carcinomas with functional taxonomic analysis.

BACKGROUND: Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. RESULTS: We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors) and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p < 0.001) gene expression changes in clear cell renal carcinomas compared to normal kidney. These genes were classified with a tool to conceptualize expression patterns called "Functional Taxonomy". Each tumor type had a distinct "signature," with a high number of genes in the categories of Metabolism, Signal Transduction, and Cellular and Matrix Organization and Adhesion. CONCLUSIONS: Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data.

Adenocarcinoma, Clear Cell↗