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At least 667 records · Page 37Linked to original sources
PubMed2003

Ki-67 index enhances the prognostic accuracy of the urothelial superficial bladder carcinoma risk group classification.

Approximately 80% of bladder tumors are urothelial superficial papillary carcinomas (USPC). Despite a generally good prognosis, these tumors have a strong propensity to recur and about 1/3 of them compared to disease progression. Histological assessment of these superficial tumors is not sufficiently discriminator in predicting prognosis; therefore, we decided to evaluate the prognostic significance of p53 and Ki-67 immunoexpression in low-grade (GI-II) USPC in order to predict the potential outcome of these tumors. P53 and Ki-67 immunoexpression were studied in function of recurrence-free and progression-free survival in 159 primary superficial bladder tumors. A prognostic risk model based on grade, stage and multifocality was also evaluated. P53 accumulation was significantly related to tumor progression (p=0.006). High Ki-67 index (>/=18%) and multifocality were significantly related to recurrence (both p=0.0001) and progression-free survival (both p=0.0001) and were independent prognostic factors in the multivariate analysis. The prognostic risk model based on grade, stage and multifocality was not an efficient discriminator of outcome. Adding the Ki-67 index into the risk model, single pTa/T1-GI Ki-67 positive tumors, usually classified as low risk, were reclassified as of intermediate risk. After this reclassification, the risk group model identified a subgroup of pTa/T1-G1 with a high risk of recurrence and progression. Ki-67 index is a reliable prognostic marker in urothelial superficial bladder carcinoma and, when included into a risk profile classification of the low-grade USPC, the accuracy of the prognostic discrimination is enhanced.

Biomarkers, Tumor↗
PubMed1984

Socio-economic status, indoor and outdoor work, and malignant melanoma.

Among New Zealand non-Maori men, professional, technical, administrative and managerial workers had the highest incidence and mortality rates for malignant melanoma of the skin; labourers and workers in production and transport had the lowest rates. Reclassification of occupations, in terms of both socio-economic status and a three-step scale of outdoor exposure during work, suggested that differences between occupational groups were determined by differences in socio-economic status. Outdoor work exposure seemed to have little effect on the risk of melanoma.

Adult↗
PubMed2003

Comparison of aspartate transcarbamoylase regulation in Pseudomonas alcaligenes and Pseudomonas mendocina.

The regulation of aspartate transcarbamoylase activity in cell extracts of Pseudomonas alcaligenes ATCC 14909 and Pseudomonas mendocina ATCC 25411 was compared. Under saturating substrate concentrations, pyrophosphate, CTP, UDP and ADP were highly inhibitory of the P. alcaligenes transcarbamoylase activity while pyrophosphate, UDP, ADP, ATP and GTP were the most effective inhibitors of the P. mendocina transcarbamoylase. By examining transcarbamoylase inhibition by ribonucleotide triphosphates, it was possible to differentiate these species assigned to different DNA homology groups and such an analysis might prove useful in the reclassification of Pseudomonas species.

Aspartate Carbamoyltransferase↗
PubMed2026

Biallelic VPS41 Variants in Autosomal Recessive Spinocerebellar Ataxia 29 Resolved by Long-Read Sequencing and RNA Analysis.

BACKGROUND: Biallelic variants in VPS41, encoding a subunit of the HOPS complex, cause autosomal recessive spinocerebellar ataxia 29 (SCAR29), a rare neurodevelopmental disorder with an incompletely defined phenotypic and molecular spectrum. METHODS: We investigated a 24-year-old man with cerebellar ataxia, hypotonia, and intellectual disability. Exome sequencing identified four candidate VPS41 variants. Because maternal DNA was unavailable, long-read genome sequencing was performed to determine allelic configuration, followed by RNA and protein analyses. RESULTS: In addition to typical SCAR29 features, the patient showed previously unreported findings, including swan-neck deformities and pes cavus. Long-read genome sequencing demonstrated that two VPS41 variants were in trans. RNA analysis revealed distinct splicing consequences: one allele produced an out-of-frame transcript predicted to undergo nonsense-mediated decay, whereas the other generated an in-frame exon-skipped transcript. These complementary defects reduced VPS41 expression at both transcript and protein levels, supporting pathogenicity and variant reclassification. CONCLUSION: Our findings expand the phenotypic spectrum of VPS41-related disease and highlight the value of long-read allelic resolution in clarifying pathogenic mechanisms in rare genetic disorders.

Humans↗
PubMed1991

Neuroblastoma stage IV-S: a heterogeneous disease.

Eighteen patients were diagnosed and treated for Stage IV-S neuroblastoma at The Hospital for Sick Children, Toronto between January 1971 and December 1988. All patients were 6 months of age or younger at diagnosis. Nine patients (50%) have remained disease free with a mean follow-up of 9.3 years. Of the seven patients under 6 weeks of age at presentation, four presented in the early neonatal period and died, three due to mechanical complications related to progressive disease, and one due to late recurrence. The remaining three patients under 6 weeks of age, two of whom had skin involvement at diagnosis, are alive and disease free. Six of the 11 patients over 6 weeks of age at presentation survived, combined modality therapy (CMT) being more effective than single modality treatment. N-myc was studied from tumor tissue at diagnosis in four patients and was amplified in three (25x, 25x, 100x), all of whom had late disease progression and died. The patient with a single gene copy has no evidence of disease 24 months following diagnosis. Our study confirms the heterogeneity described in this clinically defined group of patients. Because of it, management of Stage IV-S neuroblastoma cannot be uniform and until further development of a subclassification, or a reclassification based on molecular biologic markers is developed, pediatric oncologists will regularly be confronted with a decision whether or not to treat a newly presenting patient that fits into the clinical classification IV-S.

Adrenal Gland Neoplasms↗
PubMed2005

A urodynamics protocol to optimally assess men with post-prostatectomy incontinence.

AIMS: To propose a urodynamic protocol to comprehensively assess all parameters of post prostatectomy incontinence (PPI). METHODS: Sixty men with a history of PPI after radical prostatectomy prospectively underwent a standardized video urodynamics protocol. A 7F urethral catheter was used for standard cystometry, abdominal leak point pressure (ALPP), and pressure flow measurements. The International Continence Society nomogram classified obstruction and further classification of obstruction was based on fluoro voiding cystourethrography and non-invasive flow rates (free Qmax). RESULTS: Twenty-four (40%) men had detrusor overactivity with 8 (13%) also having detrusor overactivity incontinence. Only one patient had impaired compliance. All men had urodynamic stress incontinence, but 21 (35%) men demonstrated it only after removal of the urethral catheter. For men leaking with and without the urethral catheter, the respective ALPP was significantly different, 86.3 and 67 cmH2O, respectively (P = 0.002). The men who leaked only in the absence of the urethral catheter had significantly higher ALPP measurements, P < 0.001. After reclassification using the fluoroscopic images of the bladder outlet and free Qmax, only 13.3% patients were obstructed. CONCLUSIONS: The proposed urodynamic protocol allows for an optimal assessment of bladder and sphincter dysfunction and outlet obstruction in men with PPI.

Aged↗
PubMed1992

Selection of a representative set of structures from Brookhaven Protein Data Bank.

Reliable structural and statistical analyses of three dimensional protein structures should be based on unbiased data. The Protein Data Bank is highly redundant, containing several entries for identical or very similar sequences. A technique was developed for clustering the known structures based on their sequences and contents of alpha- and beta-structures. First, sequences were aligned pairwise. A representative sample of sequences was then obtained by grouping similar sequences together, and selecting a typical representative from each group. The similarity significance threshold needed in the clustering method was found by analyzing similarities of random sequences. Because three dimensional structures for proteins of same structural class are generally more conserved than their sequences, the proteins were clustered also according to their contents of secondary structural elements. The results of these clusterings indicate conservation of alpha- and beta-structures even when sequence similarity is relatively low. An unbiased sample of 103 high resolution structures, representing a wide variety of proteins, was chosen based on the suggestions made by the clustering algorithm. The proteins were divided into structural classes according to their contents and ratios of secondary structural elements. Previous classifications have suffered from subjective view of secondary structures, whereas here the classification was based on backbone geometry. The concise view lead to reclassification of some structures. The representative set of structures facilitates unbiased analyses of relationships between protein sequence, function, and structure as well as of structural characteristics.

Algorithms↗
PubMed2002

Statistical issues in the assessment of the evidence for an interaction between factors in epilepsy trials.

We examine the common clinical belief that there is an interaction between epilepsy type and the two standard anti-epileptic drugs, valproate and carbamazepine, using data from several randomized clinical trials. Epilepsy type is not always easy to define, and three possible reclassifications are investigated to see whether misclassification of epilepsy type within the trials has potentially masked such an interaction. Regression modelling is employed to investigate whether heterogeneity between trial results can be explained by patient factors. Our work suggests that uncertainty in epilepsy type classification should be recognized in future studies. We also generate the hypothesis that the interaction of drug effect with age may reflect the perceived interaction with epilepsy type. We suggest that in any context where misclassification is likely, it is worth considering the use of an explicit 'unclassified' group, and investigating whether additional covariates can answer the substantive question.

Adolescent↗
PubMed1992

Cardiovascular birth defects and prenatal exposure to female sex hormones: a reevaluation of data reanalysis from a large prospective study.

In data of the U.S. Collaborative Prenatal Study (CPS), the Drug Epidemiology Unit (DEU) reported a relative risk of about 2.3 between maternal female sex hormone exposure during months 1 to 4 of pregnancy and cardiovascular malformation in infants (Heinonen et al., '77a N. Engl. J. Med., 296:67-70). Wiseman and Dodds-Smith ('84) reexamined the original CPS data and found the DEU had made errors in classification of exposure and disease of some cases. Also they challenged the classification of cases as "exposed" in those born to mothers who received the compounds outside the day 19 to 50 window of cardiovascular embryogenesis. Wiseman and Dodds-Smith stated that their reanalysis "clearly showed that there was [in the data used by the DEU] no statistically significant association between exposure in the critical organogenic period of pregnancy and cardiac malformation in offspring." They did not undertake any statistical analysis, but their reanalysis resulted in a widespread nonacceptance of the association reported by the DEU. The study reported here reclassified the cases of the original DEU study in accord with the implications of the Wiseman and Dodds-Smith reanalysis of exposure and disease. After this reclassification, an effect magnitude measure of association, the relative risk rose from 2.33 to 2.48 and remained nominally significant statistically at the .05 level. Thus, if anything, the quantitative consequences of the Wiseman and Dodds-Smith review of the data, when applied in an unbiased manner, result in an increase in the measure of effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Data Interpretation, Statistical↗
PubMed1994

Cardiovascular birth defects and prenatal exposure to female sex hormones: a reevaluation of data reanalysis from a large prospective study.

In data of the U.S. Collaborative Perinatal Study (CPS), the Drug Epidemiology Unit (DEU) reported a relative risk of about 2.3 between maternal female sex hormone exposure during months 1 to 4 of pregnancy and cardiovascular malformation in infants (Heinonen et al., '77a N. Engl. J. Med., 296:67-70). Wiseman and Dodds-Smith ('84, Teratology, 30:359-370) reexamined the original CPS data and found the DEU had made some errors in classification of exposure and disease. Also they challenged the classification of cases as "exposed" in those born to mothers who received the compounds outside the day 19 to 50 window of cardiovascular embryogenesis. Wiseman and Dodds-Smith stated that their reanalysis "clearly showed that there was [in the data used by the DEU] no statistically significant association between exposure in the critical organogenic period of pregnancy and cardiac malformation in offspring." They did not undertake any statistical analysis, but their reanalysis resulted in a wide-spread nonacceptance of the association reported by the DEU. The study reported here reclassified the cases of the original DEU study in accord with the implications of the Wiseman and Dodds-Smith reanalysis of exposure and disease. After this reclassification, an effect magnitude measure of association, the relative risk rose from 2.33 to 2.48 and remained nominally significant statistically at the .05 level. Thus, if anything, the quantitative consequences of the Wiseman and Dodds-Smith review of the data, when applied in an unbiased manner, result in an increase in the measure of effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1996

Characterization of representative enzymes from a sulfate reducing bacterium implicated in the corrosion of steel.

This communication reports the isolation, purification and characterization of key enzymes involved in dissimilatory sulfate reduction of a sulfate reducing bacterium classified as Desulfovibrio desulfuricans subspecies desulfuricans New Jersey (NCIMB 8313) (Ddd NJ). The chosen strain, originally recovered from a corroding cast iron heat exchanger, was grown in large scale batch cultures. Physico-chemical and spectroscopic studies of the purified enzymes were carried out. These analyses revealed a high degree of similarity between proteins isolated from the DddNJ strain and the homologous proteins obtained from Desulfomicrobium baculatus Norway 4. In view of the results obtained, taxonomic reclassification of Desulfovibrio desulfuricans subspecies desulfuricans New Jersey (NCIMB 8313) into Desulfomicrobium baculatus (New Jersey) is proposed.

Corrosion↗
PubMed1999

Cis peptide bonds in proteins: residues involved, their conformations, interactions and locations.

An analysis of a non-redundant set of protein structures from the Brookhaven Protein Data Bank has been carried out to find out the residue preference, local conformation, hydrogen bonding and other stabilizing interactions involving cis peptide bonds. This has led to a reclassification of turns mediated by cis peptides, and their average geometrical parameters have been evaluated. The interdependence of the side and main-chain torsion angles of proline rings provided an explanation why such rings in cis peptides are found to have the DOWN puckering. A comparison of cis peptides containing proline and non-proline residues show differences in conformation, location in the secondary structure and in relation to the centre of the molecule, and relative accessibilities of residues. Relevance of the results in mutation studies and the cis-trans isomerization during protein folding is discussed.

Amino Acids↗
PubMed1995

Phylogenetic relationships among the true porpoises (Cetacea:Phocoenidae).

Portions of the cytochrome b gene and control region of the mitochondrial DNA molecule were sequenced to investigate systematic relationships among the six extant species of true porpoises, (Cetacea: Phocoenidae). Phylogenetic analyses of mitochondrial cytochrome b sequences support a close relationship between Burmeister's porpoise, Phocoena spinipinnis, and the vaquita, Phocoena sinus, and the association of these two species with the spectacled porpoise, Australophocaena dioptrica. The latter result is not in concordance with a recent morphological reclassification which groups A. dioptrica with Dall's porpoise, Phocoenoides dalli, in the subfamily Phocoenoidinae. The molecular analysis found no support for this grouping. A. dioptrica was originally described as a member of the genus Phocoena, and our results support returning it to that genus at this time. Finally, the data suggest that the tropical species Neophocaena phocaenoides, the finless porpoise, may represent the most basal member of the family. The control region sequences corroborated the relationships among the closely related taxa P. sinus, P. spinipinnis, and A. dioptrica, but were unable to resolve the deeper branches of the tree, probably as a result of a high level of saturation of these sequences.

Amino Acid Sequence↗
PubMed2000

Molecular phylogeny, taxonomy, and evolution of nonmarine lineages within the American grapsoid crabs (Crustacea: brachyura).

Grapsoid crabs are best known from the marine intertidal and supratidal. However, some species also inhabit shallow subtidal and freshwater habitats. In the tropics and subtropics, their distribution even includes mountain streams and tree tops. At present, the Grapsoidea consists of the families Grapsidae, Gecarcinidae, and Mictyridae, the first being subdivided into four subfamilies (Grapsinae, Plagusiinae, Sesarminae, and Varuninae). To help resolve phylogenetic relationships among these highly adaptive crabs, portions of the mitochondrial genome corresponding to the 16S rRNA gene were sequenced for all grapsoid genera occurring in America. The resulting phylogeny confirms most of the present grapsid subfamilies but suggests reclassification of some of the genera and recognition of new taxonomic units. The two American gecarcinid genera might not represent a sister group to the Grapsidae but rather appear to have evolved within the latter. Colonization of inland habitats evolved in several lineages of the grapsoids, resulting in various forms of nonmarine life and different degrees of independence from the sea.

Animals↗
PubMed1990

[Sarcoma of the gastrointestinal tract].

From 1970-1988 15 patients were operated on gastrointestinal sarcomas. Four more patients with this diagnosis had to be excluded after histological reclassification. A resection with curative intention was possible in 10 cases. Three patients initially had distant metastases, in 6 patients they appeared postoperatively. Regarding prognosis the TNMG-system proved to be useful only concerning lymph nodes. Eight patients died because of tumor progression, four have no evidence of disease 20-97 months postoperatively. One patient with liver metastases has a complete remission 32 months after chemotherapy. We found a 5-year-survival rate of 28%. Radical tumor resection and lymphadenectomy is recommended, distant metastases should be treated by chemotherapy.

Adult↗
PubMed1995

Distinctive radiological features of small hand joints in rheumatoid arthritis and seronegative spondyloarthritis demonstrated by contrast-enhanced (Gd-DTPA) magnetic resonance imaging.

A series of patients with clinically early inflammatory joint disease due to rheumatoid arthritis, psoriatic arthritis and Reiter's syndrome were examined by plain film radiography and magnetic resonance imaging (MRI). The spin echo T1-weighted precontrast, T2-weighted, and, especially, T1-weighted postcontrast images demonstrated distinct differences in the distribution of inflammatory changes, both within and adjacent to involved small hand joints. Two major subtypes of inflammatory arthritis were shown, thus providing a specific differential diagnosis between rheumatoid arthritis and some patients with seronegative spondyloarthritis. In particular, all the patients with Reiter's syndrome who were studied, and half of those with psoriatic arthritis, had a distinctive pattern of extra-articular disease involvement. The need for a new classification of clinical subsets in psoriatic arthritis has been recently suggested. The present findings suggest that magnetic resonance imaging could be useful in such a reclassification of seronegative spondyloarthritis, as well as offering considerable potential for a reappraisal of pathogenesis and therapy. In this series, it was also noted that juxta-articular osteoporosis on plain film did not correlate with bone marrow oedema on MRI. Hence the aetiology of this common radiographic finding also merits further consideration.

Adult↗
PubMed1988

The problem of determining the manner of death as suicide or accident in borderline cases.

The purpose of this study was to check the reliability of the classification of death in cases regarded primarily as accidents or undetermined. The material used for the analysis consisted of the documents of autopsies performed at our department in 1981. There were altogether 283 cases of suicides, accidents or undetermined deaths, accounting for 8.4% of total mortality, and of these 180 cases were of the two last categories. In 125 cases primarily regarded as non-suicides (accidents or undetermined) there were some features of suicide leading to reclassification as probable suicide in 24 cases. Fifteen of these were primarily poisoning "accidents", mainly alcohol intoxications. The result indicates that the suicide rate would be 3.7% instead of 3.0% of the total mortality. It may thus be concluded that the official figure for suicides could be as much as 18.9% smaller than the "actual" figure.

Accidents↗
PubMed1995

Development of simple fitness landscapes for peptides by artificial neural filter systems.

The applicability of artificial neural filter systems as fitness functions for sequence-oriented peptide design was evaluated. Two example applications were selected: classification of dipeptides according to their hydrophobicity and classification of proteolytic cleavage-sites of protein precursor sequences according to their mean hydrophobicities and mean side-chain volumes. The cleavage-sites covered 12 residues. In the dipeptide experiments the objective was to separate a selected set of molecules from all other possible dipeptide sequences. Perceptrons, feedforward networks with one hidden layer, and a hybrid network were applied. The filters were trained by a (1, lambda) evolution strategy. Two types of network units employing either a sigmoidal or a unimodal transfer function were used in the feedforward filters, and their influence on classification was investigated. The two-layer hybrid network employed gaussian activation functions. To analyze classification of the different filter systems, their output was plotted in the two-dimensional sequence space. The diagrams were interpreted as fitness landscapes qualifying the markedness of a characteristic peptide feature which can be used as a guide through sequence space for rational peptide design. It is demonstrated that the applicability of neural filter systems as a heuristic method for sequence optimization depends on both the appropriate network architecture and selection of representative sequence data. The networks with unimodal activation functions and the hybrid networks both led to a number of local optima. However, the hybrid networks produced the best prediction results. In contrast, the filters with sigmoidal activation produced good reclassification results leading to fitness landscapes lacking unreasonable local optima. Similar results were obtained for classification of both dipeptides and cleavage-site sequences.

Amino Acid Sequence↗