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[Long-term use of Profiler in patients with dialysis intolerance: 8 months follow-up].

PURPOSE: A new method of profiled dialysis has been set up for many years in the Department of Nephrology, Dialysis and Renal Transplantation at the University of Bologna. This profiled dialysis is based on the use of a new kinetic mathematical model, in collaboration with the Faculty of Engineering at the University of Bologna, for the elaboration of individual sodium and ultrafiltration profiles. OBJECTIVE: The profiled dialysis aims are: 1) to stabilize the intradialytic blood volume, boosting the refilling of plasma water from the intracellular and the extravascular to the extracellular/intravascular compartments, to balance the ultrafiltration; 2) to counteract the disequilibrium syndrome reducing the shift of water from the extra to the intracellular compartment. The pre-dialysis elaboration of profiles is completely automatic and supported by a computerized programme, Profiler, which has been included in the software of the dialysis machine Bellco Formula 2000 Plus. METHODS: In this prospective and multicenter study, this profiled dialysis, performed according to the Profiler, was continuously applied, for an 8-month period, in a group of 13 hemodialysis (HD) patients with an intolerance to previous dialysis treatment. During the study, the following parameters were evaluated, comparatively, with the patient's basal treatment: a) sodium and water balance; b) percentage incidence of intradialytic complications such as hypotensive events, cramps, headache, and vomiting and; c) metabolic and nutritional status. RESULTS: Results evaluated in comparison with the patient's previous dialysis treatments, demonstrated: a) plasma sodium from 136.8 +/- 3 to 136.8 +/- 1.7 mEq/L (p=ns), dry body weight from 72.2 +/- 19.3 to 71.7 +/- 19.5 kg (p=ns), heart index from 3.7 +/- 0.7 to 3.1 +/- 0.5 L/min/m2 (p=ns), reactance from 5.3 +/- 15 to 4.9 +/- 11 ohm (p<0.05); b) incidence of intradialytic hypotensive events reduced from 64 to 4% (p<0.001), cramps reduced from 8 to 1% (p<0.01); c) plasma albumin from 3.5 +/- 0.2 to 3.7 +/- 0.3 g/dL (p=ns), Kt/Veq from 1.3 +/- 0.1 to 1.36 +/- 0.2 (p=ns). CONCLUSIONS: Patients treated with profiled dialysis had a higher stability of intradialytic blood pressure (BP) achieving a reduction in the incidence of disequilibrium syndrome symptoms, in comparison with previous treatment. These clinical intradialytic improvements were not correlated to clinical, instrumental or biochemical indexes of sodium-water overload nor to a worst dialysis adequacy and nutritional state.

Female↗

Use of physician profiles to influence prescribing of topical corticosteroids.

BACKGROUND: Physician profiling is a tool used to attempt to affect changes in prescribing. The Drug Evaluation Alliance of Nova Scotia (DEANS) decided to implement a physician profiling project to determine if prescribing of topical corticosteroids could be altered. OBJECTIVES: To evaluate a DEANS initiative utilizing physician prescribing profiles to shift prescribing of topical corticosteroids from higher to lower potency agents in beneficiaries of the Nova Scotia Seniors' Pharmacare Program. METHODS: Administrative claims from the Nova Scotia Seniors' Pharmacare program were used to identify prescriptions for topical corticosteroids. Prescriptions were summarized at the individual physician level, and aggregated by Anatomical Therapeutic Classification into weak, moderately potent, potent and very potent products. The number of prescriptions for topical corticosteroids was compared for the twelve-month period before and after mailing of the profiles. Overall results were aggregated by utilization and expenditures. RESULTS: The number of prescriptions for topical corticosteroids per physician profiled was 44.0 in 2000/2001 and 42.8 in 2001/2002 (p = NS) and the expenditures per physician profiled were 838.94 dollars in 2000/2001 and 826.81 dollars in 2001/2002 (p = NS). There was a small decrease in prescriptions dispensed for potent topical products over the profiling period (52.4% of prescriptions in 2000/2001 versus 51.5% of prescriptions in 2001/2002, p=0.03). Otherwise, changes in utilization or expenditures for topical corticosteroids were not statistically different between the profiling periods. CONCLUSIONS: This project showed that mailing unsolicited individual-level profiles did not alter prescribing or expenditures for topical corticosteroids over a two-year period. Further work is needed to determine physician attitudes towards such projects.

Administration, Topical↗

Lipid profiles of acute coronary syndrome patients hospitalized in ICCU of Cipto Mangunkusumo Hospital.

AIM: to see which component of the triad lipid that has more important role and frequently found in patients with acute coronary syndrome, focusing on HDL cholesterol. METHODS: a lipid profile study has been conducted in 391 patients with acute coronary syndrome (ACS), who have been hospitalized in ICCU of Cipto Mangunkusumo Hospital since January 1st, 2001 - December 31st, 2005. RESULTS: there were 294 male patients (75.2%) and 97 female patients (24.8%), from 25-89 years age group, with mean value 57.35 +/- 11.05. The mean value of total cholesterol level was 205.23 mg/dl +/- 54.84. The LDL cholesterol level was 136.16 mg/dl +/- 47.29. The mean HDL cholesterol level was 42.84 mg/dl +/- 10.28, mean triglycerides level was 157.25 mg/dl +/- 100.16. There were 82 patients (21%) with high total cholesterol (> 240 mg/dl), 102 patients (26.1%) with high and very high LDL cholesterol level (> 160 mg/dl), 152 (38.6%) patients with low HDL cholesterol level (< 40 mg/dl), consisted of 126 male patients or 42.9% of total male patients, 26 female patients or 26.8% of total female patients. The number of patients with high / very high triglycerides level (> 200 mg/dl or 500 mg/dl) was 84 patients (21.5%). The number of patients with optimal lipid level, total cholesterol level < 200 mg/dl was 191 patients (48.8%); 82 patients (21%) had LDL cholesterol level < 100 mg/dl, 23 patients (5.9%) had HDL cholesterol level > 60 mg/dl, 226 patients (57.8%) had triglycerides level < 150 mg/dl. There were 260 patients with atherogenic lipid profile (64%), 135 patients with borderline lipid profile (34.5%), and optimal lipid profile was found only in 6 patients (1,5%). The mean value of HDL cholesterol level in male patients was 41.75 mg/dl +/- 9.9, while HDL cholesterol level in female patients was 46.16 mg/dl +/- 10.74. Principally, lipid profiles of all age groups were evenly distributed. ACS patients with history of family heart disease had a more atherogenic lipid profile compared to lipid profile of patients with hypertension, diabetes mellitus, and cigarette smoking. CONCLUSION: atherogenic lipid profile is more common risk factor in ACS patients than in other non-lipid risk factors. This study also demonstrated that the atherogenic lipid is most commonly found in patient with low HDL cholesterol level and it is least frequently found in patient with optimal lipid profile.

Acute Disease↗

Ambulatory blood pressure patterns in children and adolescents: influence of renin-sodium profiles.

A renin-sodium nomogram for normotensive children and adolescents was developed at our institution. The ambulatory blood pressure patterns of subjects classified by the nomogram were then compared. A biracial sample of 159 children and adolescents were classified as having a low, intermediate, or high renin-sodium profile based on the relationship between their plasma renin activity and 24-hour urinary sodium excretion. Casual (106/58 vs 107/61 vs 106/62 mm Hg) and awake (116/69 vs 117/69 vs 116/70 mm Hg) blood pressure values were comparable among subjects with low, intermediate, and high renin-sodium profiles. Subjects with high renin-sodium profiles, however, had a smaller decline in systolic blood pressure with sleep than did subjects with low renin-sodium profiles (7 vs 11 mm Hg; P less than .04), and higher diastolic blood pressure readings during sleep than subjects with intermediate renin-sodium profiles (65 vs 62 mm Hg; P less than .05). Subjects with high renin-sodium profiles also had greater variance of diastolic blood pressure readings during sleep than either subjects with low renin-sodium profiles (P less than .01) or those with intermediate renin-sodium profiles (P less than .02). The blunted nocturnal decline and increased nocturnal variance of blood pressure among subjects with high renin-sodium profiles may be a marker or mechanism for the future development of essential hypertension.

Adolescent↗

Bactericidal effect of cefodizime against beta-lactamase-producing Neisseria gonorrhoeae in vitro. A comparison of level profiles in serum and tissue after intramuscular and intravenous administration in man.

Serum and skin suction blister fluid (SBF) level profiles as well as the profile in the hypothetical peripheral compartment in man after the single intravenous application of 1 g of cefodizime and the corresponding serum level profile after intramuscular application were simulated in the presence of beta-lactamase-producing gonococci. A rapid reduction of bacterial density was observed under each of these conditions indicating clinical efficacy of both treatment protocols in uncomplicated gonorrhoea. Considering the different level profiles in more detail both serum level profiles after intravenous and intramuscular injection turned out similarly effective: while the time needed for a 99% reduction of gonococcal density (t99%) was slightly shorter with the intravenous profile (1.45 vs. 1.68 h), the maximum relative reduction was somewhat smaller, expressed by a higher kn value (0.00024 vs. 0.00010%). The drug level profile in the hypothetical peripheral compartment proved on the whole equally effective as the serum level profiles. The suction blister fluid level profile, however, showed an inferior antigonococcal activity (kn = 0.00076%, t99% = 2.08 h). This demonstrates the value of the determination of SBF levels and their inclusion in in-vitro simulation experiments.

Cefotaxime↗

A new approach for evaluating circadian blood pressure levels and variability from 24 h ambulatory blood pressure profiles.

In 24 h blood pressure monitoring the severity of arterial hypertension is generally classified on the basis of the arithmetic mean of the diastolic blood pressure between 6 AM and 10 PM. In the present study Fourier analysis was used for evaluation of circadian blood pressure level and variability. A common reference profile was calculated on the basis of a group of 50 normotensive profiles. This reference profile is characterized by the fact that the sum of the squares of the distances between the individual profiles and the reference profile is a minimum. The individual 24 h profiles of 103 patients with untreated arterial hypertension were also each described by a Fourier series and were then compared with the normotensive reference profile. The comparison was made not only with respect to the absolute pressure over 24 h but also with respect to the circadian fluctuations in blood pressure. Our results show that the Fourier analysis of 24 h blood pressure profiles presented here can be used for more precise evaluation of 24 h blood pressure profiles.

Adult↗

Molecular profiling and the identification of genes associated with metastatic oral cavity/pharynx squamous cell carcinoma.

OBJECTIVE: To investigate differences in gene expression profiles between oral cavity/oropharynx squamous cell carcinoma (OC/OP SCC) primary tumors that have metastasized to cervical lymph nodes and nonmetastatic OC/OP SCC tumors. DESIGN: Oligonucleotide microarray analysis of primary tumors was used to produce gene expression profiles. Profile comparisons between metastatic and nonmetastatic tumors were performed using principal component analysis, t test, and fold change differences. A similar comparison between metastatic tumors and noncancer oral mucosa samples was performed to ensure tumor origin. SUBJECTS: A prospective cohort of 20 patients with previously untreated OC/OP SCC who underwent pathologic staging following surgical resection and lymphadenectomy. RESULTS: Of the approximately 9600 genes profiled, 101 demonstrated significant expression differences between the metastatic and nonmetastatic tumors (fold change > or =1.5; P<.01). Among this subset, 57 genes also exhibited significant differences between metastatic tumors and normal mucosa samples (fold change > or =1.5; P<.05). This profile included genes related to the extracellular matrix, adhesion, motility, inflammation, and protease inhibition. Collagen type 11 alpha-1 (COL11A1) demonstrated the greatest differential expression between metastatic and nonmetastatic OC/OP SCC tumors (fold change=7.61; P=.002). Tissue inhibitor of metalloproteinase 1 (TIMP-1) also demonstrated increased expression in metastatic tumors (fold change=3.3; P=.003). CONCLUSIONS: Metastatic OC/OP SCC has a distinct gene expression profile compared with nonmetastatic OC/OP SCC and normal oral mucosa. This metastatic profile includes genes related to the extracellular matrix, adhesion, motility, and protease inhibition. Knowledge gained through tumor gene expression profiling may facilitate early detection of aggressive tumors and targeted therapeutic interventions.

Carcinoma, Squamous Cell↗

Importance of blood cellular genomic profile in coronary heart disease.

Since receptor/transcription factor family especially peroxisome proliferator-activated receptors PPARs (alpha, gamma) and liver X receptor alpha (LXRalpha) have been recognized to play crucial role in both lipid metabolism and inflammation, the present study was addressed to explore the interrelationship between blood cellular genomic expression profile, serum lipid levels and severity of coronary heart disease (CHD) in human subjects. Based upon the demographic and laboratory data, the human subjects were divided into 4 groups. Genomic expression profile in the subjects belonging to these groups was determined by measuring the transcriptional expression of genes coding for PPARs (alpha, gamma), CD36, LXRalpha and low density lipoprotein receptor (LDLR) in their blood mononuclear cells. This genomic expression profile was correlated with serum lipid profile as well as with the severity of CHD (revealed by coronary angiography coupled with modified Gensini score) using standard statistical analytical methods. Further in vitro and in vivo effect of statins on such genomic profile was also explored. Although genes coding for PPARs (alpha, gamma), CD36, LDLR showed correlation with the severity of coronary atherosclerosis , blood cellular LXRalpha genomic profile showed conspicuous negative correlation with the severity of coronary atherosclerosis in subjects with or without hypercholesterolemia. This view was further confirmed in experiments directed to understand the effect of statins on the cellular genomic profile of PPARs (alpha, gamma) and LXRalpha. Based on these reported findings, we propose that blood cellular LXRalpha genomic profile has a protective effect against the development of CHD and hence may be of importance in devising synthetic therapeutic drugs for CHD in future.

Adult↗

Gene expression profiling in human endometrial cancer tissue samples: utility and diagnostic value.

OBJECTIVE: Recently, gene expression profiling techniques have been used on several human cancers to classify tumor subgroups with a specific biological behavior, which were previously undetected by the conventional histopathologic staging systems. In the current study, the clinical usefulness and prognostic value of gene expression profiling in human endometrial carcinomas were studied. METHODS: A macro cDNA array, containing cDNAs of 588 genes selected from different areas of cancer research, was used to generate gene expression profiles of tumor tissue samples. The gene expression profiles of 12 endometrial cancers, 3 benign (e.g. noncancer) endometrial tissue samples and 3 myometrial tissue samples, taken from human surgical specimen, were compared. RESULTS: The efficacy to generate a gene expression profile of these tissue samples was 77%. The RNA samples could be randomly taken from the tissue samples and were highly reproducible. Cluster analysis of gene expression profiles of the different samples showed that the benign endometrial and the myometrial samples clustered separately from the tumor samples, indicating that the gene expression profiles were tissue specific and not patient specific. Cluster analysis of the tumor samples revealed two distinct tumor clusters. Ranking of the tumors in the two clusters showed high similarity with the histopathologic classification [International Federation of Gynecology and Obstetrics (FIGO) grading]. CONCLUSION: Classification of endometrial tumors on basis of their gene expression profiles showed similarity with the FIGO grading system.

Adult↗

Profile-based string kernels for remote homology detection and motif extraction.

We introduce novel profile-based string kernels for use with support vector machines (SVMs) for the problems of protein classification and remote homology detection. These kernels use probabilistic profiles, such as those produced by the PSI-BLAST algorithm, to define position-dependent mutation neighborhoods along protein sequences for inexact matching of k-length subsequences ("k-mers") in the data. By use of an efficient data structure, the kernels are fast to compute once the profiles have been obtained. For example, the time needed to run PSI-BLAST in order to build the pro- files is significantly longer than both the kernel computation time and the SVM training time. We present remote homology detection experiments based on the SCOP database where we show that profile-based string kernels used with SVM classifiers strongly outperform all recently presented supervised SVM methods. We also show how we can use the learned SVM classifier to extract "discriminative sequence motifs" -- short regions of the original profile that contribute almost all the weight of the SVM classification score -- and show that these discriminative motifs correspond to meaningful structural features in the protein data. The use of PSI-BLAST profiles can be seen as a semi-supervised learning technique, since PSI-BLAST leverages unlabeled data from a large sequence database to build more informative profiles. Recently presented "cluster kernels" give general semi-supervised methods for improving SVM protein classification performance. We show that our profile kernel results are comparable to cluster kernels while providing much better scalability to large datasets.

Algorithms↗

Highly conserved gene expression profiles in humans with allergic rhinitis altered by immunotherapy.

BACKGROUND: Atopic diseases, resulting from hypersensitivity to a wide variety of allergens, affect 10-20% of the population. Immunotherapy is an effective treatment for atopic diseases, but its mechanisms are not fully understood. OBJECTIVE: We studied gene expression profiles in the peripheral blood mononuclear cells (PBMC) and examined whether the individuals with allergic rhinitis (AR) have a unique gene expression profile and how the immunotherapy affect the gene expression profiles. METHODS: We used cDNA microarray and 'expression analysis systemic explorer' to examine the gene expression profiles in the PBMC of atopic subjects and other groups. RESULTS: We identified a highly conserved gene expression profile in atopic subjects that permitted their accurate segregation from control or autoimmune subjects. A major feature of this profile was the under-expression of a variety of genes that encode proteins required for apoptosis and over-expression of genes that encode proteins critical for stress responses and signal transduction. We also identified 563 genes that can segregate individuals with AR based upon receipt of immunotherapy. CONCLUSION: There is a highly conserved gene expression profile in the PBMC of individuals with AR. This profile can be used to identify individuals with AR and to evaluate responses to immunotherapy. Quantitative endpoints, such as gene expression, may assist clinicians faced with clinical decisions in the diagnosis of patients and the evaluation of response to therapy. The knowledge of the possible genetic basis for immunotherapy efficacy may also lead to novel therapeutic approaches for atopic diseases.

Adult↗

Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy.

BACKGROUND: Gene expression profiling refines diagnostic and prognostic assessment in oncology but has not yet been applied to myocardial diseases. We hypothesized that gene expression differentiates ischemic and nonischemic cardiomyopathy, demonstrating that gene expression profiling by clinical parameters is feasible in cardiology. METHODS AND RESULTS: Affymetrix U133A microarrays of 48 myocardial samples from Johns Hopkins Hospital (JHH) and the University of Minnesota (UM) obtained (1) at transplantation or left ventricular assist device (LVAD) placement (end-stage; n=25), (2) after LVAD support (post-LVAD; n=16), and (3) from newly diagnosed patients (biopsy; n=7) were analyzed with prediction analysis of microarrays. A training set was used to develop the profile and test sets to validate the accuracy of the profile. An etiology prediction profile developed in end-stage JHH samples was tested in independent samples from both JHH and UM with 100% sensitivity and 100% specificity in end-stage samples and 33% sensitivity and 100% specificity in both post-LVAD and biopsy samples. The overall sensitivity was 89% (95% CI 75% to 100%), and specificity was 89% (95% CI 60% to 100%) over 210 random partitions of end-stage samples into training and test sets. Age, gender, and hemodynamic differences did not affect the profile's accuracy in stratified analyses. Select gene expression was confirmed with quantitative polymerase chain reaction. CONCLUSIONS: Gene expression profiling accurately predicts cardiomyopathy etiology, is generalizable to samples from separate institutions, is specific to disease stage, and is unaffected by differences in clinical characteristics. This strongly supports ongoing efforts to incorporate expression profiling-based biomarkers in determining prognosis and response to therapy in heart failure.

Adult↗

Expression profiling of gastric cancer samples by oligonucleotide microarray analysis reveals low degree of intra-tumor variability.

AIM: Gene expression profiling provides an unique opportunity to gain insight into the development of different types of gastric cancer. Tumor sample heterogeneity is thought to decrease the sensitivity and tumor specificity of microarray analysis. Thus, microdissection and pre-amplification of RNA is frequently performed. However, this technique may also induce considerable changes to the expression profile. To assess the effect of gastric tumor heterogeneity on expression profiling results, we measured the variation in gene expression within the same gastric cancer sample by performing a gene chip analysis with two RNA preparations extracted from the same tumor specimen. METHODS: Tumor samples from six intestinal T2 gastric tumors were dissected under liquid nitrogen and RNA was prepared from two separate tumor fragments. Each extraction was individually processed and hybridized to an Affymetrix U133A gene chip covering approximately 18 000 human gene transcripts. Expression profiles were analyzed using Microarray Suite 5.0 (Affymetrix) and GeneSpring 6.0 (Silicon Genetics). RESULTS: All gastric cancers showed little variance in expression profiles between different regions of the same tumor sample. In this case, gene chips displayed mean pair wise correlation coefficients of 0.94+/-0.02 (mean+/-SD), compared to values of 0.61+/-0.1 for different tumor samples. Expression of the variance between the two expression profiles as a percentage of "total change" (Affymetrix) revealed a remarkably low average value of 1.18+/-0.78 for comparing fragments of the same tumor sample. In contrast, comparison of fragments from different tumors revealed a percentage of 24.4+/-4.5. CONCLUSION: Our study indicates a low degree of expression profile variability within gastric tumor samples isolated from one patient. These data suggest that tumor tissue heterogeneity is not a dominant source of error for microarray analysis of larger tumor samples, making total RNA extraction an appropriate strategy for performing gene chip expression profiling of gastric cancer.

Aged↗

GABA-, glycine-, and glutamate-immunoreactive bouton profiles in apposition to neurons of the central cervical nucleus in the rat.

The neurons of the central cervical nucleus (CCN) convey information about the position and movements of the head, and receive excitatory input from dorsal neck muscles and the labyrinth. Both of these afferent sources form glutamatergic synaptic contacts with CCN neurons. However, these sensory afferent sources can also inhibit CCN neurons. To further elucidate the synaptic organization, we made an electron microscopic investigation, identifying and evaluating the relative frequency of bouton profiles containing the inhibitory transmitters GABA and glycine in apposition to identified CCN neurons. In addition, labeling for glutamate was performed. The identification of the CCN neurons was made possible by injections of retrograde tracer substances into the cerebellum. These substances were made visible by preembedding immunocytochemistry or postembedding immunogold staining. Such staining was also used to detect the three amino acids that were found in boutons apposed to the identified neurons (cf. Ornung et al., J. Comp. Neurol. 1996;365:413-426; Lindå et al., J. Comp. Neurol. 2000;425:10-23). Due to the relatively poor transport of the tracer substances into dendrites of the CCN neurons, the analysis was restricted to the cell body and included bouton profiles in direct apposition to the soma membrane. Data from 10 CCN neurons revealed that about 50% of the apposing bouton profiles were immunoreactive for GABA, and about 34% for glycine. In four neurons, the degree of colocalization of GABA and glycine was determined to be close to 30%. Thus, the vast majority of glycine-labeled profiles also contained GABA, while a considerable fraction of the profiles were immunoreactive for only GABA. The values for glycine immunoreactive bouton profiles presented here may represent somewhat low estimates, depending on the method used. Data from four neurons showed that about 18% of the profiles were labeled for glutamate. The large fraction of purely GABA immunoreactive profiles, or at least a substantial group of them, is suggestive of their derivation from axons descending from the brainstem.

Animals↗

The vaginal pressure profile.

AIMS: To describe the vaginal pressure profile in asymptomatic nulliparous women. METHODS: Fourteen nulliparous women without symptoms of anal or urinary incontinence were studied with vaginal manometry. A rapid pull-through technique utilized a four-channel water-perfused catheter on a motor-driven puller to create a pressure profile for each subject. The profiles were measured with the subject at rest and during a sustained contraction of the levator ani muscle. The individual subject's pressure profiles were averaged to create a composite profile at rest and during squeeze. RESULTS: The vaginal pressure profile at rest and during squeeze contains three pressure zones: proximal, mid, and distal. The pressure is highest in the mid pressure zone and was labeled as the vaginal high-pressure zone. In the vaginal high-pressure zone, the maximum pressure during squeeze is significantly higher than the maximum pressure at rest (P < 0.05). The length of the high-pressure zone is longer during squeeze as compared to rest (P < 0.05). The maximum pressures exhibit circumferential asymmetry with the pressures in anterior and posterior directions being significantly higher than those in the lateral directions (P < 0.05). CONCLUSIONS: The vaginal pressure profile is more complex than previously described. Understanding of the vaginal pressure profile is crucial when employing vaginal manometry to assess pelvic floor muscle strength or as a surrogate for intra-abdominal pressure.

Adult↗

Plasma protein profiling: unique and stable features of individuals.

Carefully controlled ZipTip extraction of diluted human plasma or serum was combined with MALDI-TOF-MS to produce highly reproducible protein profiles. Components detected included apolipoproteins CI, CII and CIII as well as transthyretin and several isoforms of each protein that are created by glycosylation or other modification and by proteolytic processing. Profiles of healthy individuals all contained the same 15 components. Others were found in plasma from individuals with disease. Profiles were analyzed by peak ratios within the same spectrum. Reproducibility for multiple assays was generally 4 to 10%. Within the healthy population, a given peak ratio occurred with a range of about fourfold. However, peak ratios of multiple samples from the same individual showed a much lower range, typically +/-10%. In fact, each individual displayed a personal protein profile that changed very little over time. Because of the stability of protein profiles over time within individuals, these results suggest further studies may discover that certain profile characteristics or changes in an individual's profile may be a sign of current or future disease, even when the altered profile remains within the range for healthy individuals.

Adult↗

Secondary structure-based profiles: use of structure-conserving scoring tables in searching protein sequence databases for structural similarities.

The profile method, for detecting distantly related proteins by sequence comparison, has been extended to incorporate secondary structure information from known X-ray structures. The sequence of a known structure is aligned to sequences of other members of a given folding class. From the known structure, the secondary structure (alpha-helix, beta-strand or "other") is assigned to each position of the aligned sequences. As in the standard profile method, a position-dependent scoring table, termed a profile, is calculated from the aligned sequences. However, rather than using the standard Dayhoff mutation table in calculating the profile, we use distinct amino acid mutation tables for residues in alpha-helices, beta-strands or other secondary structures to calculate the profile. In addition, we also distinguish between internal and external residues. With this new secondary structure-based profile method, we created a profile for eight-stranded, antiparallel beta barrels of the insecticyanin folding class. It is based on the sequences of retinol-binding protein, insecticyanin and beta-lactoglobulin. Scanning the sequence database with this profile, it was possible to detect the sequence of avidin. The structure of streptavidin is known, and it appears to be distantly related to the antiparallel beta barrels. Also detected is the sequence of complement component C8, which we therefore predict to be a member of this folding class.

Amino Acid Sequence↗

Relationship between soil organic C degradability and the evolution of the delta13C signature in profiles under permanent grassland.

The main objective of this research was to investigate to what extent the potential C dynamics of soil organic matter (SOM) are related to the degree of 13C enrichment with increasing depth in soil profiles under permanent grassland. The evolution of the C content and the 13C natural abundance (delta13C value) of SOM were investigated in three soil profiles (0-40 cm depth) under permanent grassland of varying texture (a loamy sand, a loam and a clay loam soil). The delta13C value of the SOM showed a gradual increase with increasing depth and decreasing C content in the profiles, ranging from 1.9 per thousand (loamy sand soil), 2.9 per thousand (clay loam soil) and 4 per thousand (loam soil) in relation to the delta13C value of SOM at the surface. The relationship between the 13C enrichment and total organic C content at different depths in the profiles (down to 40 cm depth in the loam and clay loam soil, down to 25 cm depth in the loamy sand soil) could be well described by the Rayleigh equation. The enrichment factors epsilon, associated with the Rayleigh approximation of the data, ranged from -1.57 per thousand (clay loam soil) to -1.64 per thousand (loamy sand soil) and -1.91 per thousand (loam soil). The potential C dynamics in four depth intervals from the profiles (0-10, 10-20, 20-30 and 30-40 cm depth) were determined by means of an incubation experiment. The C decomposition rate constants from the four sampling depths in the profiles showed a significant, positive correlation (y = 0.21x + 0.018, R(2) = 0.66, p < 0.005) with the corresponding Deltadelta13C values (change of the delta13C value per depth increment). A better correlation was obtained when only the data from the upper 20 cm in the profiles (y = 0.21x + 0.019, R(2) = 0.78, p < 0.05) were considered. These results suggest that the Deltadelta13C values in the surface layers of profiles under permanent grassland may serve as an indicator of the potential degradability or the stability of the SOM (in terms of C decomposition rate constants).

Algorithms↗