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Folding pattern recognition in proteins using spectral analysis methods.

Divergence in sequence through evolution precludes sequence alignment based homology methodologies for protein folding prediction from detecting structural and folding similarities for distantly related protein. Homolog coverage of actual data bases is also a factor playing a critical role in the performance of those methodologies, the factor being conspicuously apparent in what is called the twilight zone of sequence homology in which proteins of high degree of similarity in both biological function and structure are found but for which the amino acid sequence homology ranges from about 20% to less than 30%. In contrast to these methodologies a strategy is proposed here based on a different concept of sequence homology. This concept is derived from a periodicity analysis of the physicochemical properties of the residues constituting proteins primary structures. The analysis is performed using a front-end processing technique in automatic speech recognition by means of which the cepstrum (measure of the periodic wiggliness of a frequency response) is computed that leads to a spectral envelope that depicts the subtle periodicity in physicochemical characteristics of the sequence. Homology in sequences is then derived by alignment of spectral envelopes. Proteins sharing common folding patterns and biological function but low sequence homology can then be detected by the similarity in spectral dimension. The methodology applied to protein folding recognition underscores in many cases other methodologies in the twilight zone.

Algorithms↗

4A randomized trial of prolonged prone positioning in children with acute respiratory failure.

STUDY OBJECTIVE: To compare the effect of the prone position (PP) vs supine position (SP) on oxygenation in children with acute respiratory failure (ARF). DESIGN: Prospective, randomized controlled trial. SETTING: A 36-bed pediatric critical-care unit in a tertiary-care, university-based children's hospital. PATIENTS: Ten children (mean [SD] age, 5 +/- 3.6 years) with ARF with a baseline oxygenation index (OI) of 22 +/- 8.5. INTERVENTIONS: Following a period of stabilization in the SP, baseline data were collected and patients were randomized to one of two groups in a two-crossover study design: group 1, supine/prone sequence; group 2, prone/supine sequence. Each position was maintained for 12 h. Lung mechanics and acute response to inhaled nitric oxide were examined in each position. MEASUREMENTS AND MAIN RESULTS: OI was significantly better in the PP compared to the SP over the 12-h period (analysis of variance, p = 0.0016). When patients were prone, a significant improvement in OI was detected (7.9 +/- 5.3; p = 0.002); this improvement occurred early (within 2 h in 9 of 10 patients) and was sustained over the 12-h study period. Static respiratory system compliance and resistance were not significantly affected by the position change. Inhaled nitric oxide had no effect on oxygenation in either position. Urine output increased while prone, resulting in a significantly improved fluid balance (+ 6.6 +/- 15.2 mL/kg/12 h in PP vs + 18.9 +/- 13.6 mL/kg/12 h in SP; p = 0.041). No serious adverse effects were detected in the PP. CONCLUSION: In children with ARF, oxygenation is significantly superior in the PP than in the SP. This improvement occurs early, remains sustained for a 12-h period, and is independent of changes in lung mechanics.

Acute Disease↗

Maganese retention in rat brain.

Manganese retention was observed in brains and in several other tissues of female Wistar rats after the intratracheal instillation of an inorganic manganese compound: manganese dioxide. Two categories of rats, younger (180 to 200g) and older (330 to 350g), were divided into a control group, in which animals received vehicle only (0.5 mL physiological saline), and an experimental group, in which rats received a dose of 0.48 mg of Mn/kg body weight (in 0.5 mL saline), twice a week for 3 months, for a total dosage of 11.80 mg of Mn/kg body weight. At the end of the exposure period, manganese retention in selected rat organs, brain, liver, kidney, and lung, was analyzed using atomic absorption spectrophotometry. At the end of the 6-wk or 12-wk manganese dioxide exposure period, analysis of variance of the manganese retention results revealed significant differences between Mn-exposed and unexposed rats in brain, kidney, and lung tissues (p<0.01) for both experimental age categories. Moreover, at the end of the 12-wk exposure period, significant results (p<0.05) between younger and older rats were obtained for both brain and kidneys. In both types of tissue, the manganese retention in the younger group was higher than that in older animals.

Aging↗

On the intercorrelation of some frequency and amplitude parameters of the human EEG and its functional significance. Communication. I: Multidimensional neurodynamic organization of functional states of the brain during intellectual, perceptive and motor activity in normal subjects.

In 95 normal subjects, a separate evaluation of the amplitude and frequency parameters of EEG by period analysis made it possible to reveal, using factor analysis, four independent groups of parameters--the EEG factors, two of which being independent of the amplitude fluctuations. They were considered as integral EEG characteristics of qualitatively different neurophysiological processes. Decrease of Factor I values during mental activity (called 'general activation') reflected an intercorrelated desynchronization of the wave amplitudes in all the bands, a decrease of alpha-index (percentage presence in epoch) and regularity together with parallel increase of the indices and mean periods of delta- and theta-waves. This generalized reaction has shown 'non-specific' dependence upon novelty and difficulty of the tasks and stimuli with certain task-specific topographical distribution. An increase of values of regional Factor Ia in the anterior areas was caused by delta- and theta-amplitude synchronization, more pronounced during matching the rhymes (MR) than in mental multiplication (MM). An increase of Factor II values (related to increase of the index, frequency and regularity of beta-activity and called 'cortical excitation', CE) was more expressed during MR, whereas an increase of Factor III values (an increase of mean alpha-period and theta-index called 'active selective inhibition', ASI) was characteristic of MM, the latter reaction being evident in the right hemisphere. During analysis of external sound stimuli and rhythmical clenching of a fist, an increase of Factor III values was accompanied by decrease of Factor II values [corrected]; in the motor activity, such reciprocal reaction being localized in the central areas contralateral to the hand moved . Neuropsychological analysis suggests that CE correlates with associative and successively organized mental operations involving search for memory traces and ASI presumably relates to different aspects of mental selectivity such as simultaneous mental operations, voluntary attention and mental automation, the latter two cases being supported by parallel reduction of CE.

Acoustic Stimulation↗

In vivo and in vitro debromination of decabromodiphenyl ether (BDE 209) by juvenile rainbow trout and common carp.

Decabromodiphenyl ether (BDE 209), the major congener in the high volume industrial flame retardant mixture "DecaBDE", has recently been shown to be metabolized by carp. To further explore this phenomenon, juvenile rainbow trout were exposed to BDE 209 via the diet for a five month period. Analysis of the whole body homogenate, liver, serum, and intestinal tissues revealed that BDE 209 accumulated in rainbow trout tissues and was most concentrated in the liver. In addition to BDE 209, several hepta-, octa-, and nonaBDE congeners also accumulated in rainbow trout tissues over the same period as a result of BDE 209 debromination. Based on the total body burden of the hepta- through decaBDE congeners, uptake of BDE 209 was estimated at 3.2%. Congener profiles were different among whole body homogenate, liver, and serum, with the whole body homogenates having a greater contribution of the debrominated biotransformation products. Extracts of the rainbow trout whole body homogenates were compared with extracts from a previous experiment with common carp. This comparison revealed that BDE 202 (2,2',3,3',5,5',6,6'-octabromodiphenyl ether) was a dominant debromination product in both studies. To determine whether the observed debromination was metabolically driven, liver microsomal fractions were prepared from both common carp and rainbow trout. Analysis of the microsomal fractions following incubation with BDE 209 revealed that rainbow trout biotransformed as much as 22% of the BDE 209 mass, primarily to octa- and nonaBDE congeners. In contrast, carp liver microsomes biotransformed up to 65% of the BDE 209 mass, primarily down to hexaBDE congeners. These microsomal incubations confirm a metabolic pathway for BDE 209 debromination.

Animals↗

Association of 24-hour activity levels with the clinical severity of chronic venous disease.

INTRODUCTION: The pathophysiology underlying the skin changes seen in chronic venous insufficiency (CVI) is multifactorial. Sedentary lifestyle and prolonged sitting and standing at work have been proposed by some authors to be influential in the development of CVI skin changes. This study compared the 24-hour activity profiles in patients with different clinical severities of CVI and normal controls. METHODS: Patients were classified into groups according to CEAP clinical severity classes: mild (C2&C3), moderate (C4) and severe (C5&C6). Activity profiles were measured in 60 patients and 15 controls using a Newcastle Universities Medical Activity (NUMACT) monitor, which recorded the duration spent in supine, sitting, and standing postures as well as duration spent walking and the walking intensity over a 24-hour period. Analysis was performed by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. RESULTS: Walking intensity was significantly different between the controls and patient groups during prolonged walking (P < .001). The controls spent significantly more time standing in a 24-hour period than any of the CVI clinical groups (P = .036), and the percentage time spent sitting was significantly higher in the patient groups (P = .025). No significant differences were found in the total number of steps taken or total duration spent walking in the 24-hour period between any of the groups. CONCLUSION: This study shows that walking intensity is lower in the more severe clinical groups and may be influenced by the clinical severity of CVI. The study provides evidence that prolonged sitting and reduced standing is associated with increased severity of CVI, which may by an effect of the patient's symptoms rather than a cause of disease progression.

Adult↗

Changes and associations in healthy diet among the Finnish elderly, 1985-2001.

BACKGROUND: diet is related to health and studies of transitions in diet among elderly people are scarce. The aim of this study was to monitor any recent changes in healthy diet among the 65- to 79-year-old population of Finnish citizens. Possible disparities in 5-year age groups, occupation and marital status were examined. METHODS: biennially conducted nationwide monitoring cross-sectional surveys among Finnish elderly people were used to study 11,793 (response rate 82%) men and women from 1985-2001. Data were pooled into three time periods. Analysis of logistic regression was used to compare and test for changes in healthy diet in categories of sociodemographic factors. RESULTS: the diet of the elderly population clearly improved from the mid-1980s to the early 2000s. The change over the monitoring period was slightly steadier among women than men. The youngest respondents, especially women, retired office employees and married persons had the healthiest diet. CONCLUSIONS: continuing improvement in diet might indicate positive health outcomes in the future. Nevertheless, there are still subgroups with unhealthier diets that include persons who are also underprivileged as far as functional ability is concerned.

Age Factors↗

The effects of family policies in the German Democratic Republic: a re-evaluation.

The author examines "the impact which various pro-natalist measures adopted since 1976 in the German Democratic Republic have had on women's birth cohorts....A period analysis of subsequent birth and fertility trends would seem to indicate that this policy was remarkably effective. The annual number of births...started to rise rapidly in 1976 and reached a peak of 245,132 births in 1980, an increase of 37%....Furthermore, comparison with the period fertility trend in the Federal Republic of Germany...shows that the gap between the two Germanys has widened since 1977...whereas the trends had been very similar in the two countries before that date....However...other factors should be taken into account: in particular, the number of marriages has fallen steeply during the last few years, and at the same time the number of births outside marriage has soared. These changes, which were in all probability prompted by the adoption of social legislation which favoured single mothers (or fathers)...must be taken into account when assessing the consequences of the new family policy."

Age Factors↗

Tetracosactrin vs. methylprednisolone in the prevention of emesis in patients receiving FEC regimen for breast cancer.

0.5 mg tetracosactrin is considered to be equivalent to 40 mg methylprednisolone with regard to the induced cortisol secretion. 97 female breast cancer patients who received their first two FEC courses (epirubicin 50-75 mg/m2, 5-fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2) entered this randomised crossover study (76 had previously received an adjuvant treatment); tetracosactrin was administered intramuscularly and methylprednisolone intravenously immediately before chemotherapy administration. The tolerability was evaluated using a diary card during 5 days and patients were asked for their preference at the end of the two cycles. There was no difference either for vomiting (dry heaves were included) or nausea between the two treatments (the analysis was performed on day 1, the worse day of days 2 and 3 and the worse day of days 4 and 5). At day 1, 49% of the patients experienced no or mild nausea after tetracosactrin and 62% after methylprednisolone (not significant) (first period analysis); a complete control of vomiting (including dry heaves) was observed in 49% of the patients after tetracosactrin and 53% after methylprednisolone (not significant). No difference was observed between patients with or without previous chemotherapy. However, slightly more patients preferred tetracosactrin (P = 0.048).

Antineoplastic Combined Chemotherapy Protocols↗

DNA synthesis and nucleolar organizer regions circadian rhythm in mouse regenerating liver hepatocytes.

DNA synthesis and Nucleolar Organizer Regions (NORs) were studied in C3HS inbred mice standardized for periodicity analysis. Immunohistochemical detection of Bromodeoxyuridine (BrdU) incorporated into DNA with a monoclonal antibody and silver staining of NORs (AgNORs) were assessed by means of a digital image analysis system in histological sections of regenerating liver. Tissue samples were obtained at different times after hepatectomy along a circadian span. The results showed a strong correlation of values between DNA synthesis (BrdU labelling index) and AgNOR numbers, with higher counts during the activity period of animals at 00:00/38 and 04:00/42 hours Time of Day/Hours Post-Hepatectomy (TD/HPH), being the differences with other time points highly significant. Our observations demonstrate the existence of a strong correlation of DNA synthesis measured by BrdU incorporation and AgNOR numbers with a defined circadian rhythm in mouse regenerating hepatocytes.

Animals↗

Structural features of the sulphated polysaccharide from a green seaweed, Cladophora socialis.

A sulphated heteropolysaccharide, [alpha]27D + 59.9 degrees, has been isolated from a green seaweed, Cladophora socialis, by extraction with dilute acid and purified by fractional precipitation. The polymer is composed of galactose (58.3%), arabinose (31.8%), xylose (10.6%) and sulphate (16.9%). The results of methylation analysis, periodate oxidation and partial acid hydrolysis studies indicate that the polymer is a branched one and is composed of 1,3-linked galactose and 1,4-linked arabinose units. Xylose is present at the non-reducing end position of the branches. Both arabinose and galactose carry branches. Desulphation and subsequent analysis of the polymer show that some of the arabinose units carry sulphate groups at C-3 and some of the galactose units carry the sulphate groups at C-4 and some at C-4 and C-6 as well.

Carbohydrate Sequence↗

Isotope ratio analysis of lead in biological materials by inductively coupled plasma mass spectrometry.

Inductively coupled plasma mass spectrometry (ICP-MS) allowed 0.2-0.3% imprecision (1 sigma) in 204Pb/206Pb, 207Pb/206Pb, and 208Pb/206Pb measurements at the 20-100 ppb level, which was precise enough to detect some of the isotopic variations observed in nature. Mass discrimination could be corrected within +/- 0.5% of the true value by periodical analysis of standard reference material of known lead isotopic composition. As a separation method for lead in human bone, which contains enormous amounts of calcium and phosphorus, anion exchange of the Pb-Br complex was found to be effective. Lead isotope ratios in bone, measured by ICP-MS after separation, were consistent with those measured by thermal ionization mass spectrometry. Hair matrix did not have any influence on the accuracy and precision of the analysis; a digested sample could be directly analyzed and this offered rapid sample throughput. Preliminary data on lead isotope ratios in bone and hair from prehistoric and contemporary Japanese are presented.

Archaeology↗

Dyslipidemia treatment among patients with coronary artery disease in a managed care organization.

PURPOSE: The statin-prescribing patterns in a large managed care organization and the effectiveness of statin prescriptions in lowering low-density-lipoprotein (LDL) cholesterol levels in patients with coronary artery disease (CAD) or risk-equivalent patients were examined. METHODS: A retrospective review of the records in an integrated medical, pharmacy, and laboratory database was performed. The qualifying period for the study began January 1, 1999, and ended December 31, 2000; the reporting period extended from January 1, 2001, to December 31, 2001. Patients included in this study had a medical claim indicative of a diagnosis of CAD or risk equivalence during the qualifying 18-month period. The data were examined to determine percentages of patients who were tested for circulating LDL cholesterol levels, were prescribed statins, and achieved the LDL cholesterol goal recommended by the National Cholesterol Expert Panel. Physician prescribing patterns were also examined. RESULTS: During the 12-month analysis period of the study, 24% of patients were tested for circulating LDL cholesterol levels, and 39.8% received at least one statin. Of patients whose LDL cholesterol values were documented and who received statins, 44.5% achieved goal LDL cholesterol levels. Of patients who were tested and did not receive statins, 29.8% achieved the LDL cholesterol goal. Cardiologists prescribed statins to CAD patients at a higher rate than other specialists or primary care providers. CONCLUSION: Patients with a diagnosis of CAD or risk equivalence, who would benefit from treatment to reduce circulating LDL cholesterol levels, were significantly undertreated.

Anticholesteremic Agents↗

Spontaneous regression in murine hypersensitivity pneumonitis: lack of immunological tolerance.

We have reported a murine model of hypersensitivity pneumonitis (HP) by transnasal administration of Thermoactinomyces vulgaris (Tv) antigen and shown a potential usefulness in the study of the immunopathogenesis of HP. Since we observed spontaneous regression (SR) of the lung lesions with continuous administration of Tv antigen in our model of HP, attempts were made to study if SR is caused by immunological tolerance. The titers of anti-Tv IgG antibody in serum and bronchoalveolar lavage fluid (BALF) did not show any decrement during the period of SR, at the 6th and 9th weeks after the first administration of the antigen. A delayed-type hypersensitivity reaction, i.e. footpad swelling with Tv antigen, did not change significantly during the SR period. Analysis of BALF cells disclosed that Lyt-2-positive cells, i.e. suppressor/cytotoxic T lymphocytes, did not increase to predominate Lyt-1-positive cells. The lymphocyte proliferation test with Tv antigen showed that the lung lymphocytes reacted to Tv antigen as well as concanavalin A during the period of SR in a similar magnitude as in the development period (3 weeks after the first treatment with the antigen). Treatment with cyclophosphamide before the period of SR resulted in no delay of SR. Finally, the adoptive cell transfer of spleen T cells obtained from mice during the SR period did not manipulate the development of granulomatous pneumonitis in the recipient mice. We concluded that the events causing SR in our murine model of HP may not involve the induction of immunological tolerance in humoral or cellular immunity.

Alveolitis, Extrinsic Allergic↗

Molecular ecological analysis of planktonic bacterial communities in constructed wetlands invaded by Culex (Diptera: Culicidae) mosquitoes.

The succession of the planktonic bacterial community during the colonization by Culex (Diptera: Culicidae) mosquitoes of 0.1-ha treatment wetlands was studied using denaturing gradient gel electrophoresis (DGGE) methodology. Relationships between apparent bacterial diversity and ecological factors (water quality, total bacterial counts, and immature mosquito abundance) were determined during a 1-mo flooding period. Analysis of DGGE banding patterns indicated that days postflooding and temporal changes in water quality were the primary and secondary determinants, respectively, of diversity in bacterial communities. Lower levels of diversity were associated with later postflood stages and increases in ammoniacal nitrogen concentration and total bacterial counts. Diversity was therefore most similar for bacteria present on the same sampling date at wetland locations with similar flooding regimes and water quality, suggesting that wastewater input was the driving force shaping bacterial communities. Comparatively small changes in bacterial diversity were connected to natural processes as water flowed through the wetlands. Greater immature mosquito abundance coincided with less diverse communities composed of greater total numbers of bacteria. Five individual DGGE bands were directly associated with fluctuations in mosquito production, and an additional 16 bands were associated with hydrological aspects of the environment during the rise and fall of mosquito populations. A marked decline in mosquito numbers 21 d after inundation may have masked associations of bacterial communities and mosquito recruitment into the sparsely vegetated wetlands. DGGE was an effective tool for the characterization of bacteria in mosquito habitat in our study, and its potential application in mosquito ecology is discussed.

Analysis of Variance↗

Monitoring a mouse colony for Helicobacter bilis using a Helicobacter-genus-specific nested PCR.

Although Helicobacter infections of laboratory mice are usually subclinical, they may interfere with in vivo experiments and thus may lead to misinterpretation of data. As such, it is important to provide a means to unequivocally identify infections with murine Helicobacter spp. In the present study, a nested polymerase chain reaction (PCR) was established and shown to be 10 to 100 times more sensitive than the single-step PCR commonly used for routine diagnosis of Helicobacter spp. Experimental infection of Helicobacter-free mice demonstrated that faeces, caecum, colon and rectum but not liver are equally suitable for the detection of H. bilis. However, use of faecal pellets is advantageous since detection of H. bilis is possible one week after infection and analysis of faeces instead of tissues avoids euthanasia of animals. Furthermore, it generates representative data for all animals housed in the same cage and analysis can be repeatedly performed. Use of samples from breeding pairs but not offspring provides representative information about the Helicobacter status of a mouse colony. Both C3H/HeJ and C57BL/6 mice appear to be susceptible to H. bilis and persistent infection was observed during the 20-week experimental period. Analysis of pooled faecal pellets by nested PCR seems to be the most sensitive approach for H. bilis monitoring of the given breeding colony.

Animals↗

Rett syndrome: the late infantile regression period--a retrospective analysis of 91 cases.

The late infantile regression period of Rett syndrome was analysed in a consecutively collected series of females, born 1945-87 (median 17 1/2 years), fulfilling the diagnostic criteria for classic Rett syndrome. For general information, data from 91 girls and women were used (group A), while more detailed analysis was based on the youngest 20, all born during the last decade (group B). Median ages at onset of developmental stagnation (stage I) were 11 (5-24) and 10 (5-18) months for groups A and B, respectively. Loss of acquired skills (stage II) began at 19 (12-36) and 17 (13-25) months, and lasted for 19 (2-53) and 13 (2-32) months. Onset of the period of loss was distinctly marked in 43%, dramatic in 16% and insidious in 41%. Gross motor delay and aberrant behaviour raised the first suspicions of disease, while a more specific pattern comprising a triad of manifestations, i.e. contact/communication, hand use/skill, babble/words, characterized the loss of acquired skills. Although development invariability came to a definite break at a crucial stage of maturation, an "awakening" (stage III) and return of interest to act and interact astonishingly followed the period of withdrawal. Apraxia was found in all, but some use of the hands could be enticed in engaging and non-demanding situations. The observed preference for use of the left hand (9/11), compared to the right (2/11), suggested a reflection of an underlying dysfunction/disease process, also displayed as spike activity in left central leads in EEGs from 13/20 girls.

Adolescent↗

Sawtooth wave density analysis during REM sleep in normal volunteers.

OBJECTIVE: Sawtooth waves (STW) are a characteristic EEG feature of REM sleep but their source and function are unknown. We previously reported stereotypical properties of STW at stage REM onset, and alterations in bulbar postpolio syndrome. This study analyzes STW features throughout REM, in order to test the hypothesis that sawtooth wave activity may be predictable and have a consistent relationship across REM periods. METHODS: Twenty polysomnographic recordings were scored for occurrence, duration, and frequency of STWs. STW density was calculated based on the number of bursts/min REM and duration of STW activity/min REM. The density measurements were statistically analyzed to assess for differences across REM periods. RESULTS: STW density mean was 0.97 bursts/min REM (95% CI [0.85, 1.09]); 6.85 s/min REM (95% CI [5.95, 7.76]). STW frequency range was 1.5-5 Hz, mean 2.5 Hz. STWs occurred in bursts with a mean duration of 7 s (range 2-26 s). There was a lower density of bursts of STW activity per minute in the first REM period compared to the second, third, and fifth cycles. CONCLUSIONS: This study reports STW density characteristics throughout REM sleep in normal subjects. Our density measurements suggest a difference in STW activity between the first REM period and later periods. Analysis of STW and related phenomena may increase the understanding of REM sleep mechanisms and may be useful to evaluate brainstem function during normal and pathological sleep.

Journal Article↗