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PubMed1990

[Pathology of inflammatory diseases of the central nervous system--an autopsy analysis 1967-1988].

This paper deals with investigations of CNS-inflammations based on 23,338 autopsies in the period from 1967 to 1988. Inflammatory CNS-findings were observed in 210 cases (0.9 per cent). Their etiology was caused bacterially in 66 per cent and viral infections were found in 20 per cent. Additionally multiple sclerosis appeared in 14 per cent of all CNS-inflammations. The meningitis dominated among the bacterial infections and the leukencephalitis and nekrotizing polioencephalitis of Herpes type among the viral inflammations. The histological classification of the nonbacterial inflammations was difficult or impossible in 9 per cent. A clinical diagnosis was established only in 70 per cent of all cases. Especially babies and patients at the age about 60 or 70 were involved.

Adult↗

PubMed1999

Multiple inositol polyphosphate phosphatase: evolution as a distinct group within the histidine phosphatase family and chromosomal localization of the human and mouse genes to chromosomes 10q23 and 19.

Multiple inositol polyphosphate phosphatase is the only enzyme known to hydrolyze the abundant metabolites inositol pentakisphosphate and inositol hexakisphosphate. We have previously demonstrated that the chick homolog of multiple inositol polyphosphate phosphatase, designated HiPER1, has a role in growth plate chondrocyte differentiation. The relationship of these enzymes to intracellular signaling is obscure, and as part of our investigation we have examined the murine ((MMU)Minpp1) and human ((HSA)MINPP1) homologs. Northern blot analysis demonstrated expression of ((MMU)Minpp1 in a variety of mouse tissues, comparable to the expression of other mammalian homologs, but less restricted than the expression of HiPER1 in chick. A purified (MMU)Minpp1 fusion protein cleaved phosphate from inositol (1,3,4,5)-tetrakisphosphate and para-nitrophenyl phosphate. When the presumptive active site histidine was altered to alanine by site-directed mutagenesis, enzyme activity was abolished, confirming the classification of (MMU)Minpp1 as a histidine phosphatase. The amino acid sequences of the murine and human MINPP proteins share >80% identity with the rat enzyme and >56% identity with HiPER1, with conservation of the C-terminal consensus sequence that retains proteins in the endoplasmic reticulum. The intron/exon structure of the mammalian (MMU)Minpp1 and (HSA)MINPP1 genes is also conserved compared to the chick HiPER1 gene. Sequence analysis of plant and fruit fly MINPP homologs supports the hypothesis that the MINPP enzymes constitute a distinct evolutionary group within the histidine phosphatase family. We have mapped (HSA)MINPP1 to human chromosome 10q23 by fluorescence in situ hybridization, YAC screening, and radiation hybrid mapping. This assignment places (HSA)MINPP1 in a region of chromosome 10 that is frequently mutated in human cancers and places (HSA)MINPP1 proximal to the tumor suppressor PTEN, which maps to 10q23.3. Using a radiation hybrid panel, we localized (MMU)Minpp1 to a region of mouse chromosome 19 that includes the murine homolog of Pten. The evolutionary conservation of this novel enzyme within the inositol polyphosphate pathway suggests a significant role for multiple inositol polyphosphate phosphatase throughout higher eukaryotes.

Amino Acid Sequence↗

PubMed2004

[Clinical analysis of 91 cases with articulation error].

OBJECTIVE: To study classification of the articulation errors, find the related factors which affect the therapy effect, and compare the therapy effect in the different patterns of the phonemic errors and build up a clinical model of the speech therapy on the basis of more than 4 years speech therapy in the clinic. METHOD: After excluding the organic articulation disorders, 91 cases of consonant phonemic errors were classified into different patterns according to the phonemic placement errors. The 91 cases were divided into two groups as effective one and ineffective one depending on whether the symptoms disappeared or not after the speech therapy. Ten factors including sex, age, oral-motor function problem, developmental delay, history of language development delay, history of middle ear affection, lingua frenata, mental retardation, the therapy frequency and times, were analyzed. The statistics software SPSS (SPSS Inc, 1997) was applied to show the factors related to the therapy effect by logistic multiple stepwise regression analysis. The therapy effect was compared between the single pattern (phonemic error < 2 groups) and multiple pattern (phonemic errors > or = 2 groups). RESULTS: The 91 cases with consonant phonemic errors were classified into four groups. The multiple pattern of the articulation errors was the most common (37 cases, 41%) among the 4 groups, followed by velar errors (33 cases, 36%). The third one was the apico-dental errors (12 cases, 13%) and the last one was the linguo-alveolar errors (8 cases, 9%). Only one case had labiodental error (/f/). The logistic multiple stepwise regression analysis showed that the history of the positive developmental delay, language delay and the frequency of the speech therapy were related to the therapy effect. The effective rate of the speech therapy in the single pattern of the phonemic error was as high as 87% while the one in the multiple pattern group was only 2.7%. The difference was significant (P < 0.000 1) when the therapy effect in these two groups was compared. The clinical model of the speech therapy included speech assessment, designing of the goal, choice of the target sound, sound production and oral-motor functional training. CONCLUSION: The consonant phonemic errors in the clinic represent four groups. The developmental delay, the language delay and frequency of the speech therapy influence the therapy effect. The frequency of the speech therapy should be increased every week, for example not less two times a week. The therapy effect of the single pattern of the phonemic errors is much better than that of the multiple pattern. The primary model of the speech therapy has been built in the clinics.

Articulation Disorders↗

PubMed2005

Sensorimotor rhythm-based brain-computer interface (BCI): feature selection by regression improves performance.

People can learn to control electroencephalogram (EEG) features consisting of sensorimotor rhythm amplitudes and can use this control to move a cursor in one or two dimensions to a target on a screen. In the standard one-dimensional application, the cursor moves horizontally from left to right at a fixed rate while vertical cursor movement is continuously controlled by sensorimotor rhythm amplitude. The right edge of the screen is divided among 2-6 targets, and the user's goal is to control vertical cursor movement so that the cursor hits the correct target when it reaches the right edge. Up to the present, vertical cursor movement has been a linear function of amplitude in a specific frequency band [i.e., 8-12 Hz (mu) or 18-26 Hz (beta)] over left and/or right sensorimotor cortex. The present study evaluated the effect of controlling cursor movement with a weighted combination of these amplitudes in which the weights were determined by an regression algorithm on the basis of the user's past performance. Analyses of data obtained from a representative set of trained users indicated that weighted combinations of sensorimotor rhythm amplitudes could support cursor control significantly superior to that provided by a single feature. Inclusion of an interaction term further improved performance. Subsequent online testing of the regression algorithm confirmed the improved performance predicted by the offline analyses. The results demonstrate the substantial value for brain-computer interface applications of simple multivariate linear algorithms. In contrast to many classification algorithms, such linear algorithms can easily incorporate multiple signal features, can readily adapt to changes in the user's control of these features, and can accommodate additional targets without major modifications.

Adult↗

PubMed1992

Artificial neural network classification of Drosophila courtship song mutants.

Courtship songs produced by Drosophila males--wild-type, plus the cacophony and dissonance behavioral mutants--were examined with the aid of newly developed strategies for adaptive acoustic analysis and classification. This system used several techniques involving artificial neural networks (a.k.a. parallel distributed processing), including learned vector quantization of signals and non-linear adaption (back-propagation) of data analysis. "Pulse" song from several individual wild-type and mutant males were first vector-quantized according to their frequency spectra. The accumulated quantized data of this kind, for a given song, were then used to "teach" or adapt a multiple-layered feedforward artificial neural network, which classified that song according to its original genotype. Results are presented on the performance of the final adapted system when faced with novel test data and on acoustic features the system decides upon for predicting the song-mutant genotype in question. The potential applications and extensions of this new system are discussed, including how it could be used to screen for courtship mutants, search novel behavior patterns or cause-and-effect relationships associated with reproduction, compress these kinds of data for digital storage, and analyze Drosophila behavior beyond the case of courtship song.

Algorithms↗

PubMed2000

Predictors of adverse events with intramuscular ketamine sedation in children.

STUDY OBJECTIVE: Ketamine is a safe and effective sedative for emergency department procedures in children. However, the use of ketamine sometimes is associated with airway complications, emesis, and recovery agitation. We wished to identify predictors of these adverse events that clinicians might use to risk-stratify children who are candidates for ketamine sedation. METHODS: We analyzed data from 1,021 ED intramuscular ketamine sedations in children 15 years of age or younger at a university medical center and an affiliated county hospital over a 9-year period. Five potential predictor variables (age, gender, American Society of Anesthesiologists' [ASA] risk classification, quantity of first ketamine dose, and number of ketamine doses administered) were compared between children with and without complications. We used multiple logistic regression analyses to determine the association of these 5 variables with emesis and recovery agitation, and validated these analyses with bootstrap resampling techniques. We compared children with and without airway complications using univariate statistics alone, as there were too few patients with airway complications to support a multivariate analysis. RESULTS: No study variables had significant univariate associations with airway complications (all P values >.40). We found emesis to be associated with increasing age in multivariate analysis (odds ratio [OR] 1.25 per year, bias-corrected 95% confidence interval [CI] 1.17 to 1.34, P<.001). The incidence of emesis was 12. 1% in children aged 5 years or older, and 3.5% in those younger than 5 years (Delta8.6%, 95% CI 4.9% to 12.1%). Recovery agitation was associated with the presence of an underlying medical condition (ie, ASA class > or =2, OR 3.05, bias-corrected 95% CI 1.65 to 7.30, P=.004) and inversely associated with increasing age (OR 0.79 per year, bias-corrected 95% CI 0.69 to 0.89, P<.001). The incidence of recovery agitation was 17.9% in ASA class 1 children and 33.3% in children in ASA class 2 or greater (Delta-15.4%, 95% CI 0.0% to -30. 7%). The incidence of recovery agitation was 12.1% in children aged 5 years or older, and 22.5% in those younger than 5 years (Delta-10. 4%, 95% CI -3.0% to -17.7%). Bootstrap resampling techniques validated the importance of the significant variables identified in the regression analyses. CONCLUSION: No study variable was predictive of ketamine-associated airway complications. Emesis that occurred after ketamine administration was modestly associated with increasing age. Recovery agitation was modestly associated with decreasing age and the presence of an underlying medical condition. The discriminatory power of these variables was low enough as to be unlikely to alter clinical decisions regarding patient selection for ketamine administration. No evidence of a significant ketamine dose relationship was noted for airway complications, emesis, or recovery agitation.

Adolescent↗

PubMed2006

Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers.

OBJECTIVE: To examine the hypothesis that results of the QuantiFERON-TB Gold assay (QFT-G), a whole-blood test for detection of tuberculosis infection, are more significantly related to known risk factors for tuberculosis infection in healthcare workers (HCWs) who have received bacille Calmette-Guerin vaccine than are results of the Mantoux tuberculin skin test (TST). DESIGN: All HCWs (approximately 510) from a 370-bed general hospital in Tokyo where patients with and patients without tuberculosis are treated were invited to participate in the study. All study participants completed a questionnaire about their Mycobacterium tuberculosis infection risk factors as HCWs at the general hospital. They were then tested for LTBI by means of the QFT-G, followed by the TST. Statistical analyses were performed to compare results of each test with M. tuberculosis infection risk factors (age, length of employment in the healthcare industry, history of working with tuberculosis-positive patients in a tuberculosis ward or in the outpatient department of the hospital's tuberculosis clinic for more than 1 year, chest radiograph evidence of healed tuberculosis, history of performing bronchoscope procedures, and job classification), and for TST-positive HCWs, to compare the QFT-G result with the TST induration diameter. RESULTS: A total of 332 HCWs (95% of whom had been vaccinated with BCG) participated in the study, and 33 had positive QFT-G results, suggesting a prevalence of LTBI of 9.9%. Of 304 HCWs who underwent TST, 283 (93.1%) had an induration diameter of 10 mm or more. Multiple logistic regression analysis revealed that positive QFT-G results were significantly associated with age and with a history of working in a tuberculosis ward or an outpatient department of a tuberculosis clinic. TST results were not correlated with any of the tuberculosis infection risk factors we evaluated. CONCLUSIONS: Positive QFT-G results were closely associated with the presence of risk factors for LTBI in a hospital setting, suggesting that the QFT-G can detect LTBI in a population composed predominantly of BCG vaccinees. Because most HCWs worldwide have been vaccinated with BCG, the QFT-G offers a significant improvement over the TST in tuberculosis screening programs and minimizes unwarranted use of tuberculosis prophylaxis.

Adult↗

PubMed2000

Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma.

PURPOSE: We assessed the influence of clinical and pathological factors on multifocality of renal cell carcinoma. MATERIALS AND METHODS: Between June 1995 and September 1999 radical nephrectomy was performed in 71 men and 32 women with a mean age of 56.5 years. The 103 removed kidneys with renal cell carcinoma were sectioned at 3 mm. intervals and inspected microscopically for satellite carcinomas. We evaluated pathological stage, grade, cell type, histological pattern, vascular involvement, tumor size and the incidence of multifocality. To determine cell type we used several classification systems. RESULTS: The primary tumor was 2 to 20 cm. (mean plus or minus standard deviation 7.10 +/- 3.48). Overall satellite carcinomas were present in 22 of the 103 cases (21.4%). When the predominant lesion was 5 cm. or smaller, the incidence of multifocality was 19%. The incidence of multifocality was statistically higher in patients with stage pT3 than in those with stage pT1 or pT2 disease (p = 0.022). Multiple logistic regression analysis demonstrated that only primary tumor pathological stage was a significant predictor of renal cell carcinoma multifocality in stages T3 versus T1 and T3 versus T2 cancer (odds ratio 3.45, 95% confidence interval 1.15 to 10.39 and 5.75, 1.31 to 25.29, respectively). Other parameters, such as tumor size, grade, vascular invasion, cell type and histological pattern, did not correlate with multifocality. CONCLUSIONS: Our results imply that primary tumor stage is a significant factor for multifocal disease. Therefore, more precise preoperative staging of the primary lesion is required if nephron sparing surgery is indicated.

Adult↗

PubMed1992

[Utility of the examination of plasma-cell morphology in the study of multiple myeloma].

PURPOSE: To assess the classification of Greipp et al in a group of multiple myeloma (MM) patients, in an attempt to correlate the morphological patterns with the clinico-biological features of the disease. MATERIAL AND METHODS: Bone marrow aspirates from 135 patients with multiple myeloma were examined by two different observers. RESULTS: Full accordance existed in 122 cases (90%). The four morphological MM subgroup distribution was: mature, 38%; intermediate, 30%; immature, 18%, and plasmoblastic, 14%. The analysis of the M component types with regard to morphology showed increased IgA cases within the intermediate (40%) and immature (48%) MM (p = 0.01), and Bence-Jones cases within the plasmoblastic MM (32%). On the contrary, no differences were found with regard to the clinical stage, although none of the plasmoblastic MM was in stage I. The incidence of renal insufficiency and of high bone-marrow infiltration progressively increased from mature to plasmoblastic MM, the difference between the extreme morphological groups being significant. The incidence of hypercalcaemia and lower paraprotein rates was higher in plasmoblastic myeloma, with significant difference with respect to mature myeloma (p = 0.05). The median survival was longer in intermediate (27.8 months) and mature (22.5 months) myelomas than in plasmoblastic (17.9 months) and immature (13.6 months) myelomas. After grouping the mature forms (intermediate plus mature) and the immature ones (plasmoblastic plus immature) the survival differences approached statistical significance (p = 0.07). CONCLUSIONS: This study suggests that the morphological examination of plasma cells should be included in the prognostic criteria of multiple myeloma.

Aged↗

PubMed2004

IRIS II study: the IRIS II score--assessment of a new clinical algorithm for the classification of insulin resistance in patients with Type 2 diabetes.

AIMS: With the increasing availability of new drugs for the treatment of insulin resistance in patients with Type 2 diabetes, simple methods for their identification is an important challenge. The aim of our study was to compute a new algorithm for estimating insulin resistance in a routine clinical setting. METHODS: Clinical data and blood samples were collected from 4265 Type 2 diabetic patients from 149 clinical sites. A clinical algorithm to estimate insulin resistance was developed by stepwise multiple regression analysis. The new generated score was compared with the HOMAIR-score, calculated from fasting insulin and glucose levels measured in a central laboratory. In a subgroup of 48 patients, the score was verified against a frequently sampled intravenous glucose tolerance test with subsequent modified minimal model analysis according to Bergman. RESULTS: Multiple regression analysis revealed fasting blood glucose, BMI, triglycerides and HDL as the most powerful predictors of insulin resistance which were used for further computation of the IRIS II score. A significant overall correlation was found between the HOMAIR-score and the new clinical IRIS II score (r = 0.42; P < 0.0001). Compared with HOMAIR, the new score revealed a specificity of 0.95, a sensitivity of 0.34 and a positive predictive value of 0.95. This was in good agreement with the subset analysis of the intravenous glucose tolerance test, where a sensitivity of 0.37 and a specificity of 0.85 of the IRIS II score was calculated. Patients with insulin resistance according to the IRIS II score revealed an increased odds ratio for overall vascular complications (1.28; 1.11-1.46; P < 0.001). CONCLUSIONS: The new IRIS II score can identify insulin resistance in Type 2 diabetic patients with high predictive value and high specificity.

Algorithms↗

PubMed1989

[Superficial bladder carcinoma: clinical and epidemiological analysis of 250 patients].

The neoplasms of bladder are an important part of genitourinary tumors. Superficial forms represent 70-80% of their overall number. We have carried out a retrospective clinical and epidemiological study of 250 patients seen in our service during a 12-year period. We found that the disease was more common in males aged 60-70 years, usually being multiple tumors and mostly in the lateral walls of the bladder. Most tumors were in grades 1 and 2 of UICC and in stage O of Jewett's classifications, with a clear association between the degree of cell differentiation and the stage of infiltration. There was no correlation of age and sex with the number of tumors, their localization, cellular degree and tumor stage. There was a correlation between the number of tumors and their localization; thus, single tumors had a preference for lateral walls, while multiple tumors predominated in the bladder fundus.

Adult↗

PubMed2003

Blunt liver injuries in polytrauma: results from a cohort study with the regular use of whole-body helical computed tomography.

The estimated prevalence of liver injury in patients with blunt multiple trauma ranges from 1% to 8%. The objective of this study was to investigate the profile of accompanying liver injury in a cohort of polytraumatized patients who had regularly undergone contrast-enhanced, whole-body helical computed tomography (CT). We enrolled consecutive patients admitted between September 1997 and January 2001 to a level I trauma center. Clinical baseline data were compiled as part of a nationwide trauma registry. Morphologic features were evaluated descriptively, whereas prognostic variables were assessed by logistic regression analysis. We identified 218 patients [149 men, mean age 35 +/- 18 years, mean injury severity score (ISS) 35 +/- 10], 55 of whom had sustained blunt liver trauma [25.2%, 95% confidence interval (CI) 19.6-31.5%]. The prevalence of Moore III to V lesions was 10.1%. There were 99 parenchymal contusions, 15 capsular tears, and 2 liver fractures. Surgery was required in 15 patients and was best predicted by the classification of the American Association for the Surgery of Trauma [odds ratio (OR) 3.91, 95% CI 1.59-9.61]. The mortality rate was 0.0035/person/day. Patients requiring surgical repair had fourfold increased relative odds of case fatality (OR 4.50, 95% CI 1.01-19.96). Sevenfold increased relative odds were observed if liver laceration was considered the leading injury (OR 7.17, 95% CI 1.17-43.97). The prevalence of liver lacerations among multiple-trauma patients is likely to be underestimated and must be determined by the independent application of reference standards, such as helical CT. High-grade hepatic injuries and the need for surgical repair are associated with poorer survival prognosis.

Adult↗

PubMed2002

Autonomic dysfunction in multiple sclerosis: correlation with disease-related parameters.

Cardiovascular autonomic functions were investigated in a prospective, controlled study of 22 consecutive relapsing-remitting multiple sclerosis (MS) patients and 22 healthy subjects using 5 simple noninvasive tests and sympathetic skin response testing. Tests included the heart rate response to deep breathing, valsalva maneuver and standing, blood pressure response to standing and sustained hand grip, and were graded according to the Ewing and Clark classification as early, definite or severe impairment. The relationship between autonomic dysfunction and disease-related parameters such as the expanded disability status scale (EDSS) and disease duration was studied. Ninety percent of the patients had symptoms related with autonomic dysfunction, and 45.5 % had abnormal results in cardiovascular autonomic function testing with 4 patients also having abnormal sympathetic skin responses. Statistical analysis indicated that patients with a long disease duration rather than high EDSS carried a risk of autonomic involvement in MS. Both parasympathetic and sympathetic functions were impaired and this could have been easily overlooked by a standard EDSS follow-up. In this regard, autonomic function testing seems necessary in order to detect subclinical changes in MS patients and should be considered in outcome measures.

Adult↗

PubMed1995

OMENS-Plus: analysis of craniofacial and extracraniofacial anomalies in hemifacial microsomia.

This review of 121 patients with hemifacial microsomia (HFM) revealed that 67 (55.4%) had extracraniofacial anomalies. Sixteen patients (13%) had one extracraniofacial anomaly and 51 patients (42.4%) had anomalies of multiple organ systems. There was no gender or side predominance in the cohort with the HFM "expanded spectrum." Central nervous system (CNS), cardiac, and skeletal anomalies were "associated" (i.e., had frequencies of 10% or more). Pulmonary, gastrointestinal, and renal deformities were equivocally associated. Statistical analysis indicated significant associations between several orbital, mandibular, ear, neural, and soft tissue (OMENS) variables and extracraniofacial anomalies. Patients with extracraniofacial structural defects had higher OMENS grades for individual craniofacial anatomic categories. Furthermore, patients with expanded spectrum had higher total OMENS scores. The frequency of cardiac anomalies (26%) supports the model of neural crest involvement in the pathogenesis of both hemifacial microsomia and conotruncal defects. The majority of the heart defects in this study were of either the outflow or septal type. We propose that the OMENS classification system for craniofacial anomalies of HFM be expanded to OMENS-Plus (+) to designate the presence of associated extracraniofacial anomalies.

Abnormalities, Multiple↗

PubMed2006

Protein disorder prediction by condensed PSSM considering propensity for order or disorder.

BACKGROUND: More and more disordered regions have been discovered in protein sequences, and many of them are found to be functionally significant. Previous studies reveal that disordered regions of a protein can be predicted by its primary structure, the amino acid sequence. One observation that has been widely accepted is that ordered regions usually have compositional bias toward hydrophobic amino acids, and disordered regions are toward charged amino acids. Recent studies further show that employing evolutionary information such as position specific scoring matrices (PSSMs) improves the prediction accuracy of protein disorder. As more and more machine learning techniques have been introduced to protein disorder detection, extracting more useful features with biological insights attracts more attention. RESULTS: This paper first studies the effect of a condensed position specific scoring matrix with respect to physicochemical properties (PSSMP) on the prediction accuracy, where the PSSMP is derived by merging several amino acid columns of a PSSM belonging to a certain property into a single column. Next, we decompose each conventional physicochemical property of amino acids into two disjoint groups which have a propensity for order and disorder respectively, and show by experiments that some of the new properties perform better than their parent properties in predicting protein disorder. In order to get an effective and compact feature set on this problem, we propose a hybrid feature selection method that inherits the efficiency of uni-variant analysis and the effectiveness of the stepwise feature selection that explores combinations of multiple features. The experimental results show that the selected feature set improves the performance of a classifier built with Radial Basis Function Networks (RBFN) in comparison with the feature set constructed with PSSMs or PSSMPs that adopt simply the conventional physicochemical properties. CONCLUSION: Distinguishing disordered regions from ordered regions in protein sequences facilitates the exploration of protein structures and functions. Results based on independent testing data reveal that the proposed predicting model DisPSSMP performs the best among several of the existing packages doing similar tasks, without either under-predicting or over-predicting the disordered regions. Furthermore, the selected properties are demonstrated to be useful in finding discriminating patterns for order/disorder classification.

Amino Acid Sequence↗

PubMed2006

Pathologic and nicotinic receptor binding differences between mild cognitive impairment, Alzheimer disease, and normal aging.

BACKGROUND: Neurochemical and pathologic studies show that mild cognitive impairment (MCI) is frequently a transitional state between normal aging and Alzheimer disease (AD). Neuropathologic sample sizes have been limited because relatively few individuals with MCI die before dementia develops. Decreased neocortical nicotinic receptor binding is characteristic of AD but has not been investigated in subjects with MCI. OBJECTIVE: To assess nicotinic receptor binding and pathologic differences in control subjects with no dementia (ND) and in subjects with clinically and pathologically described MCI or Alzheimer disease. DESIGN: This was a clinicopathologic analysis. Subjects with ND had no demonstrable cognitive or functional impairment. Subjects with MCI met Petersen clinical criteria for single- or multiple-domain amnestic MCI and died before the disorder progressed to AD. Subjects with AD met National Institute for Neurological Diseases and Stroke/Alzheimer's Disease and Related Disorders Association clinical criteria for AD. All subjects underwent a complete diagnostic and semiquantitative neuropathologic examination. Data were examined after both clinical and histopathologic classification of subjects. SETTING: Sun Health Research Institute Brain Donation Program, and Arizona Alzheimer Disease Center. PARTICIPANTS: Twenty-one control subjects with ND, 8 subjects with MCI, and 70 subjects with AD, prospectively followed up to autopsy. MAIN OUTCOME MEASURES: Nicotinic acetylcholine receptor binding value, total tangle density, total plaque density, and Braak stage. RESULTS: At the last examination before death, subjects with AD were significantly younger, less educated, and more cognitively and globally impaired compared with subjects with ND. When categorized by clinical diagnosis, MCI was always intermediate between ND and AD. On the whole, MCI was pathologically intermediate between ND and AD for senile plaque density, neurofibrillary tangle density, and Braak stage, but some subjects with MCI lacked neuritic plaques entirely. Binding for nicotinic acetylcholine receptors did not differ between the ND and MCI groups, but it was significantly less in the AD group. CONCLUSIONS: Most MCI may be considered a transitional state between ND and AD clinically and neuropathologically, but in some MCI cases there is lack of neuritic plaques, and, therefore, it cannot be considered early AD. Nicotinic receptor binding seems to be lost during the transition from MCI to AD.

Aged↗

PubMed2004

New satellite DNA in Lacerta s. str. lizards (Sauria: Lacertidae): evolutionary pathways and phylogenetic impact.

A new tandemly repeated (satellite) DNA family namely Agi160, from Lacerta agilis and Lacerta strigata (Lacerta sensu stricto (s. str.), Linnaeus 1758) have been cloned and sequenced. Agi160 is found in the above two species, as well as two other representatives of the same genus, L. viridis and L. media. DNA hybridization did not reveal it in Darevskia, Podarcis, Zootoca, Eremias, Ophisops, and Gallotia - the other genera of the family Lacertidae. The results suggest that Agi160 is a Lacerta s. str. specific family of tandem DNA repeats. However, a comparison between sequences of Agi160 and CLsat repeat units revealed 60 bp regions 62-74% identical. The latter is a satellite DNA family typical for Darevskia (syn. "L. saxicola complex") (Grechko et al., Molecular-genetic classification and phylogenetic relatedness of some species of Lacertidae lizards by taxonoprint data. Mol Biol 32:172-183, 1988.). Both Agi160 and CLsat tandem repeats share several common features (e.g., the same AT content and distribution of multiple short A-T runs, internal structure of repeated units, the presence of conservative regions). These data are indicative of their common origin and a possibly strong selective pressure upon conserving both satellites. A comparative analysis of structure, organization, and abundance of these two families of satDNA reveals evolutionary pathways that led to their formation and divergence. The data are consistent with the hypotheses of the concerted evolution of satellite DNA families. The possibility of use of Agi160 as a phylogenetic tool, defining relationships within Lacerta s. str., as well as within the whole family of Lacertidae is discussed.

Animals↗

PubMed2006

A novel model-free approach for reconstruction of time-delayed gene regulatory networks.

Reconstruction of genetic networks is one of the key scientific challenges in functional genomics. This paper describes a novel approach for addressing the regulatory dependencies between genes whose activities can be delayed by multiple units of time. The aim of the proposed approach termed TdGRN (time-delayed gene regulatory networking) is to reversely engineer the dynamic mechanisms of gene regulations, which is realized by identifying the time-delayed gene regulations through supervised decision-tree analysis of the newly designed time-delayed gene expression matrix, derived from the original time-series microarray data. A permutation technique is used to determine the statistical classification threshold of a tree, from which a gene regulatory rule(s) is extracted. The proposed TdGRN is a model-free approach that attempts to learn the underlying regulatory rules without relying on any model assumptions. Compared with model-based approaches, it has several significant advantages: it requires neither any arbitrary threshold for discretization of gene transcriptional values nor the definition of the number of regulators (k). We have applied this novel method to the publicly available data for budding yeast cell cycling. The numerical results demonstrate that most of the identified time-delayed gene regulations have current biological knowledge supports.

Algorithms↗