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Differential contributions of the two hemispheres in intra-modal proprioceptive sensory matching in 7-10-year-old boys.

This study explores putative differential contributions of the two hemispheres when 7-10-year-old right-hand and left-hand preferent boys are required to carry out a 'foot-hand' target location and matching task. The task required subjects to locate a target pin with the big-toe (felt target), and match the located target position with the hand, without vision. Right-handed (n=25) and left-handed (n=22) boys were tested in a four-condition design. Two intra-hemispheric conditions (right foot locating-right hand matching, left foot locating-left hand matching), and two inter-hemispheric conditions (right foot locating-left hand matching, left foot locating-right hand matching) were used. When the criterion for handedness was writing hand only the results were found to be confounded by the large number of subjects with indeterminate handedness (isolated by use of the Edinburgh Handedness Inventory) originally assigned to the left-handed group. Reclassification of the handedness groups, on the basis of this inventory, showed the pure-left handers to be as good on those conditions mediated by the right hemisphere as pure right handers were with those conditions mediated by the left. These findings are discussed with respect to the contention that left handers are not just 'reversed' right handers.

Child↗

Genomic organization and regulation of the vav proto-oncogene.

Vav and vav2 are members of the dbl family of guanine nucleotide exchange factors (GEF) for the rho/rac family of GTP binding proteins. Vav is expressed primarily in hematopoietic cells, while vav2 has a wider tissue distribution. The genomic structure of the human vav proto-oncogene was studied by identifying and sequencing all 27 exons of the gene from overlapping P1 and cosmid clones. The gene spans a 77-kb region on chromosome 19. In contrast, the coding region of vav2 is distributed over 30 exons spanning 227-kb. The overall organization of the exons which encode both proteins was found to be similar. In humans, alternative splicing of exons 6, 16 and 28 generated at least two distinct vav2 mRNA species. Several differences from the original vav cDNA sequence were noted. The most important difference was the identification of amino acid 718 as isoleucine, rather than threonine. This change warrants the reclassification of the vav SH2 domain as a type 3 SH2, instead of a type 2 SH2 as originally proposed by Songyang et al. (Mol. Cell. Biol. 14 (1994) 2777-2785). A series of vav promoter deletions were constructed using the enhanced green fluorescent protein (EGFP) as a reporter gene. A 23-bp segment that included a potential CBF/AML-1 binding site was found to be essential for EGFP expression in U937 cells. The same constructs were not active in HeLa cells, which do not express vav. A potential c-myb DNA binding site within the vav promoter was not required for EGFP expression.

3T3 Cells↗

Enterobacter sakazakii: a review.

Enterobacter sakazakii, previously referred to as a yellow-pigmented Enterobacter cloacae was designated as a unique species in 1980. This reclassification was based on differences from E. cloacae in DNA relatedness, pigment production and biochemical reactions. E. sakazakii has been implicated in a severe form of neonatal meningitis. Although studies have failed to identify an environmental source for the organism, dried-infant formula has been implicated in both outbreaks and sporadic cases of E. sakazakii meningitis. The high mortality rate (40-80%), the severity of the infection in infants, plus the scarcity of information on the ecology and pathogenicity of this organism warranted a review of the clinical and microbiological features of this putative foodborne pathogen.

Enterobacter↗

Sequencing of prototype viruses in the Venezuelan equine encephalitis antigenic complex.

The 5' nontranslated region (5'NTR) and nonstructural region nucleotide sequences of nine enzootic Venezuelan equine encephalitis (VEE) virus strains were determined, thus completing the genomic RNA sequences of all prototype strains. The full-length genomes, representing VEE virus antigenic subtypes I-VI, range in size from 11.3 to 11.5 kilobases, with 48-53% overall G+C contents. Size disparities result from subtype-related differences in the number and length of direct repeats in the C-terminal nonstructural protein 3 (nsP3) domain coding sequence and the 3'NTR, while G+C content disparities are attributable to strain-specific variations in base composition at the wobble position of the polyprotein codons. Highly-conserved protein components and one nonconserved protein domain constitute the VEE virus replicase polyproteins. Approximately 80% of deduced nsP1 and nsP4 amino acid residues are invariant, compared to less than 20% of C-terminal nsP3 domain residues. In two enzootic strains, C-terminal nsP3 domain sequences degenerate into little more than repetitive serine-rich blocks. Nonstructural region sequence information drawn from a cross-section of VEE virus subtypes clarifies features of alphavirus conserved sequence elements and proteinase recognition signals. As well, whole-genome comparative analysis supports the reclassification of VEE subtype-variety IF and subtype II viruses.

5' Untranslated Regions↗

Characterization of the agent of swine dysentery based on deoxyribonucleic acid homology.

Chromosomal deoxyribonucleic acids (DNAs) of five strains formally assigned to Treponema hyodysenteriae and Treponema innocens have been compared. The results of DNA-DNA-hybridization indicate that all the strains belong to the same species. The very low guanine-plus-cytosine values between 24.7 and 29.7 mol% are regarded as further evidence in favour of the reclassification of the swine dysentery agent as Borrelia hyodysenteriae (comb. nov. Blaha).

Animals↗

Feline hemotropic mycoplasmosis (feline hemobartonellosis).

Hemotropic mycoplasmas represent an important cause of anemia in cats worldwide. Previously known as Haemobartonella species, sequencing of the 16S rRNA genes of these organisms has led to their reclassification as mycoplasmas. Two species have been identified in cats, M haemofelis and "Candidatus M haemominutum." The latter organism alone has not been associated with disease in naturally infected cats but may cause anemia in FeLV-infected cats and accelerate development of FeLV-induced myeloproliferative disease. The mode of transmission of these organisms remains enigmatic. Nevertheless, development of sensitive DNA-based tests for these unculturable organisms has improved the understanding of the epidemiology and pathogenesis of FHM. Cats with clinical signs and laboratory abnormalities consistent with FHM should be treated with doxycycline; enrofloxacin may represent an effective alternative. Transfusion with packed red blood cells after cross-matching may be required for severely anemia cats, and addition of prednisone may be required if the diagnosis of FHM is uncertain, or response to antimicrobials alone is insufficient. Affected cats should be tested for FeLV, the most common concurrent infection in cats with FHM.

Anaplasmataceae↗

Ehrlichiosis and related infections.

Ehrlichiosis is a term that has been used to describe infection with any of a number of related intracellular, vector-borne pathogens. A recent reclassification has resulted in the transfer of several species previously known as Ehrlichia to the genus Anaplasma or Neorickettsia. Ehrlichia and Anaplasma are transmitted largely through the bite of infected ticks, while vectors for Neorickettsia include trematodes and the intermediate hosts (i.e., fish, snails, and insects) involved in the trematode life cycle. Dogs (and cats) are susceptible to infection with several of these pathogens, and veterinarians should be aware of the similarities and differences between E canis and related infections. Pets with suggestive clinical signs and laboratory abnormalities may be started on doxycycline pending specific diagnostic testing. The veterinarian practicing in endemic areas must understand the implications and limitations of serologic and molecular testing to confirm a diagnosis. For animals in endemic areas, prevention of exposure to vectors can lessen the risk of disease for pets and might lessen the potential for animals to become carriers of disease for their human companions.

Anaplasma↗

[AIDS patients with an unclassified risk factor for HIV].

OBJECTIVES: In the surveillance of the AIDS epidemic via registries there is a small proportion of cases whose route of HIV transmission is unknown (5% for Catalonia, Spain). For reclassification purposes, the aim of this study is to detect similarities between these cases with "not qualified risk" (NQR) with the other main HIV transmission groups. METHODS: All Aids cases (> 12 years) resident in Catalonia and reported between 1988 and 1996 to the AIDS registry (n = 8,559) were compared according to their distribution of "age at diagnosis" and "first indicative AIDS disease". ANOVA and log-linear regression models were applied separately by sex. RESULTS: Evidence of similarity with the NQR group was only found for men; in terms of age at diagnosis, the NQR group was similar to both groups of sexual transmission whilst in terms of Aids indicative disease it was similar to the heterosexual transmission group. As from 1994, a reduction in the incidence of NQR cases was observed and coincided with an increase in the heterosexual group. CONCLUSIONS: According to the characteristics of the NQR cases, it can be concluded that all cases acquired HIV via one of the classic routes of infection, primarily through heterosexual contacts. For this reason, it is advisable that the criteria that define heterosexual HIV transmission be relaxed.

Acquired Immunodeficiency Syndrome↗

Do national medicinal drug policies and essential drug programs improve drug use?: a review of experiences in developing countries.

Increasing concerns regarding access to and appropriateness of medicinal drug use have led many governments in developing countries to develop national policies and regulations intended to increase the affordability, supply, safety, and rational use of pharmaceuticals. However, little is known about the intended and unintended impacts of these social experiments on actual drug use. We conducted a critical review and synthesis of the international literature in an attempt to define the current state of knowledge regarding drug policy effects on drug use, and to extract from the evidence important lessons for future policy and research. Literature sources included the archives and computerized databases, articles published in medical and pharmacy journals, as well as published annotated bibliographies. The evaluated interventions included three broad categories: (1) multi-component national drug policies including essential drug programs; (2) drug supply and cost-sharing programs; and (3) regulatory measures. Most of these studies utilized weak research designs that evaluated programs solely on the basis of post-intervention measures. Only two studies measured pre-policy utilization, but did not include a control group. Thus, none of the results are conclusive, and the findings represent, at best, hypotheses for more rigorous studies of policy impacts. Some suggestive findings include an association between increases in the supply of essential drugs (combined with training) and more appropriate use of medications in primary care settings. In addition, preliminary data suggest some unintended effects of de-registration of drugs or upward reclassification of specific medicines. Similarly, loosening restrictions have sometimes been accompanied by increased dispensing of specific drugs by unqualified personnel. The available studies focused only on a few categories of national and regulatory policies. Because of poor study design, the results do not provide valid data to determine whether national drug policies improve drug use. Moreover, no studies have evaluated the effects of major and recent changes, such as increased use of product patents, national pharmaceutical insurance policies, and increased privatization of pharmaceutical products and services. Future studies need to explore the consequences of these emerging developments on drug access and use. Despite the difficulties inherent in evaluation of national policies, stronger research designs can and should be carried out. Interrupted time-series analysis and other more rigorous designs should become standard designs for policy evaluation in the same way that standard treatment guidelines are intended to guide medical practice.

Developing Countries↗

[Diagnosis, classification and cathogenesis of diabetes mellitus].

Diabetes mellitus (DM) is a metabolic disorder characterized by the presence of chronic hyperglycemia accompanied by greater or lesser impairment in the metabolism of carbohydrates, lipids and proteins. The origin and etiology of DM can vary greatly but always include defects in either insulin secretion or response or in both at some point in the course of disease. When characteristic symptoms of DM are clearly present and blood glucose levels are high enough, the diagnosis is usually unequivocal. However, it is important to remember that the diagnosis is made in asymptomatic patients in most cases, based on the results of routine tests. The prevalence of DM, its specific complications and the presence of other diseases that often accompany DM make this disease one of today's main social and public health problems. The great increase in information available on the etiology and pathophysiology of DM and its chronic complications has led necessarily to the revision of diagnostic criteria and reclassification of the processes involved. Revised diagnostic criteria and classifications were agreed upon in 1997 and 1998 by the American Diabetes Association and the World Health Organization, respectively, and new recommendations were published. Thanks to cross-representation on the committees, the conclusions and final recommendations are, in general, very similar, although a few minor differences are present. Clarification of diagnostic criteria and better classification of patients suffering from DM should allow us to make better choices among the various treatment options available and to improve prognosis.

Blood Glucose↗

Polybrene increases retrovirus gene transfer efficiency by enhancing receptor-independent virus adsorption on target cell membranes.

Cationic polymers, such as polybrene and protamine sulfate, are typically used to increase the efficiency of retrovirus-mediated gene transfer, however, the mechanism of their enhancement of transduction has remained unclear. As retrovirus transduction is fundamentally limited by the slow diffusion of virus to the target cell surface, we investigated the ability of polybrene to modulate this initial transport step. We compared the ability of both envelope (gp70) and capsid (p30) protein based assays to quantitate virus adsorption and found that p30 based assays were more reliable due to their ability to distinguish virus binding from free gp70 binding. Using the p30 based assay, we established that polybrene concentrations, which yielded 10-fold increases in transduction also, yielded a significant increase in virus adsorption rates on murine fibroblasts. Surprisingly, this enhancement, and adsorption in general, were receptor and envelope independent, as adsorption occurred equivalently on receptor positive and negative Chinese hamster ovary cells, as well as with envelope positive and negative virus particles. These findings suggest that the currently accepted physical model for early steps in retrovirus transduction may need to be reformulated to accommodate an initial adsorption step whose driving force does not include the retrovirus concentration, and the reclassification of currently designated 'receptor' molecules as fusion triggers. The implication of these findings with respect to the development of targeted retrovirus-mediated gene therapy protocols is discussed.

3T3 Cells↗

Histomorphometry in paraffin sections of thyroid tumors.

Planimetric features of cell nuclei in paraffin-embedded histological sections of benign and malignant thyroid tumors, as well as normal thyroid tissue as control, were determined by means of a semiautomatic system. The main aim was to objectify possible quantitative differences between adenomas and carcinomas of the thyroid gland, which had recently been reported by several authors. For each nuclear profile, the area, the maximum diameter as well as two form factors were calculated. Statistical analyses of morphometric differences between normal controls, oxyphilic adenomas and carcinomas, and between follicular adenomas and carcinomas were performed using the T-test, a multivariate test, and a discriminant analysis. The tests revealed significant differences between controls and all other groups. The most striking result, however, was the total discrimination between follicular adenomas and carcinomas, with no false reclassification. Carcinomas had a higher mean nuclear area and diameter and a lower form factor. A similar reliability of discrimination could be obtained by comparing these morphometric values in oxyphilic adenomas and carcinomas. When using a test set of 9 cases (4 adenomas, 5 carcinomas), only one adenoma was falsely reclassified as a carcinoma by the discriminant analysis. Our results thus allow the conclusion that planimetric nuclear measurements indeed seem to be useful for the objectivation of cytomorphologic differences between adenomas and carcinomas of the thyroid gland.

Adenoma↗

Neighborhood analysis of low magnification structures (glands) in healthy, adenomatous, and carcinomatous colon mucosa.

A new algorithm analyzing neighborhood conditions of adenomatous tissue is is introduced. Using O'Callaghan's definition of neighborhoods, a graph theory approach for measuring histomorphological structures can be created as follows: glands are defined as vertices and the coherence of neighboring glands as edges. The procedure leads to an unoriented, well-defined graph which contains information usually not measurable by conventional morphometric analysis. Measurements on healthy mucosa, tubulo-villous adenoma and highly to moderately differentiated adenocarcinoma of colon revealed statistically significant differences (p less than or equal to 0.05) for the following parameters: number of vertices, number of edges, frequency distribution of n-stars and of n-closed paths. Correct separation and reclassification of 83% of cases could be carried out using discriminant analysis. 11/15 cases (73%) could be classified correctly in a prospective group based upon the learning set. The significance of these findings for automatic pattern recognition in histopathology is discussed.

Adenocarcinoma↗

CD 15 antigen in Hodgkin's disease.

A retrospective analysis of 117 cases of Hodgkin's disease treated at the Centre G.F. Leclerc between 1976 and 1985 was performed with three objectives: 1): to re-evaluate the histologic subtype by the Lukes-Rye classification according to recent data; 2): to demonstrate the frequency of CD 15 antigen by an indirect, three stage immunoperoxidase technique on initial node biopsy histologic sections; 3): to study the prognostic value of this antigen. Histologic reclassification disclosed that 9 cases were in fact non Hodgkin's lymphoma. The remaining 108 cases were classified as lymphocyte predominant (n = 11), nodular sclerosis (n = 77), and mixed cellularity (n = 17), with no cases of either lymphocyte depletion or nodular paragranuloma of Poppema and Lennert identified. In these specimens, fixed in Bouin's solution and embedded in paraffin, CD 15 antigen was detected in the Reed-Sternberg cells and the mononuclear variety of Hodgkin cells in 64 patients (59%). The presence of this antigen was independent of histologic subtype, patient age or sex, clinical stage and the presence of systemic symptoms. Both actuarial disease-free and overall survivals showed that the prognosis of Hodgkin's disease is more favorable in CD 15 positive cases.

Antigens, Differentiation↗

Pika and vole mitochondrial genomes increase support for both rodent monophyly and glires.

Complete mitochondrial genomes are reported for a pika (Ochotona collaris) and a vole (Volemys kikuchii) then analysed together with 35 other mitochondrial genomes from mammals. With standard phylogenetic methods the pika joins with the other lagomorph (rabbit) and the vole with the other murid rodents (rat and mouse). In addition, with hedgehog excluded, the seven rodent genomes consistently form a homogeneous group in the unrooted placental tree. Except for uncertainty of the position of tree shrew, the clade Glires (monophyletic rodents plus lagomorphs) is consistently found. The unrooted tree obtained by ProtML (Protein Maximum Likelihood, a program in MOLPHY) is compatible with a reclassification of mammals [Syst. Biol. 48, 1-5 (1999)] which is also supported by other recent studies. However, when this tree is rooted with marsupials plus platypus, the outgroup often joins the lineage leading to the three murid rodents, so the rodents are no longer monophyletic. Apart from misplacing the root, the presence of the outgroups also distorts other parts of the unrooted tree. Either constraining the tree to maintain rodents monophyletic, or omitting murids, maintains the ingroup tree and sees the outgroup join on the edge to Xenarthra, to Afrotheria, or to these two groups together. This emphasises the importance of carrying out both an unrooted and a rooted analysis. It is known from cancer research that murid rodents have reduced activity in some DNA repair mechanisms and this alters their substitution pattern - this may be the case for mitochnodrial DNA as well. Comparing nucleotide compositions may identify taxa that differ in aspects of their DNA repair mechanisms.

Animals↗

Optimized ribotyping protocol applied to Hungarian Bordetella bronchiseptica isolates: identification of two novel ribotypes.

We reported previously that ribotype patterns generated with PvuII and a probe derived from the Escherichia coli rrnB gene could be used to differentiate isolates of Bordetella bronchiseptica. In the present study we report modifications made to the original ribotyping procedure that permit detection in the formerly characterized isolates of an additional 8 fragments with homology to rrnB. Ribotypes were redefined to include these fragments. Although this modification did not permit the detection of novel ribotypes from the previously characterized isolates, it did result in a more accurate reclassification of five of these isolates to other existing ribotypes. It was hypothesized that the additional fragments could form the basis for novel ribotypes in future analyses, and this was supported by the subsequent evaluation of 101 previously uncharacterized pig, rabbit, and dog B. bronchiseptica isolates from Hungary. A total of six different patterns were detected from this group, including two previously not identified that were designated ribotypes 17 and 18. The profile of ribotype 17 includes a novel fragment not associated with any other ribotype. A subset of the fragments constituting ribotype 18, essential for its differentiation from other ribotypes, is only detectable under the modified conditions reported here. Hungarian swine isolates are highly clonal, since 98.2% were identified as ribotype 3. Similarly, 83.7% of rabbit isolates from Hungary are also ribotype 3. Cluster analysis revealed that despite the existence of numerous ribotypes, B. bronchiseptica isolates display limited heterogeneity. The ability to detect additional ribotypes under the modified conditions described in this study strengthens the usefulness of ribotyping as an epidemiologic tool.

Animals↗

Fatal drug poisonings: medico-legal reports and mortality statistics.

The entire fatal drug poisoning panorama in Finland is considered in terms of three catergories: accidental, self-inflicted and undetermined (whether accidental or with intent to harm) deaths. The study material consisted of all 500 deaths in 1997 that medical examiners, after examination(s) at the Forensic Toxicology Division (FTD) of the Department of Forensic Medicine, University of Helsinki, officially certified as resulting from drug poisoning. These deaths were matched with data on the same deaths registered at Statistics Finland (SF), the national mortality statistics office. The SF register included 72 additional instances of deaths resulting from drug poisoning. In all but two of these cases, the cause-of-death determination was based on a medico-legal inquest with autopsy and forensic toxicological examination(s) and was certified, in most of the cases, as due to the alcohol component in multiple-toxicant combinations. Reclassifying these deaths at SF to the category of drug component is in accordance with current International Classification of Diseases (ICD-10) regulation of coding "to the medicinal agent when combined with alcohol"; the principle and practice, which is recommended to be amended to equalize the status of alcohol and drug when explicitly stated by a forensic examiner as the principal toxicant in combined poisonings. With regard to manner-of-death, the agreement rates between medico-legally proven deaths from drug poisoning and those registered at SF were 79.8% for accidents, 98.5% for suicides and 0% (nil) for undetermined deaths, at the level of three-character external cause codes (E-code). All deaths originally certified as undetermined were re-assigned, most frequently to the category of accidental death. Since within an advanced and sophisticated medico-legal system, a medical examiner's evidence-based statement, even when the conclusion reached is undetermined (as to intent), should be taken as a compelling argument, the practice of reclassification cannot be considered advisable because assembled information is lost. Concerning the assigned drug-specific groups, the agreement according to the manner-of-death between certifications and registrations was fairly good. From among the accidents, however, opioid poisonings were re-assigned in 11 (29.7%) cases, mostly to the drug abuse/dependence categories, i.e. they were considered as natural deaths by the statistics office. The drug-specific observations were possible only by using the codes from the Anatomical Therapeutic Chemical (ATC) classification of drugs. This is why the incorporation of ATC codes into the ICD system, whenever reasonable, is recommended.

Adult↗

Nuclear morphometry of the myocardial cells as a diagnostic tool in cases of sudden death due to coronary thrombosis.

Sudden cardiac death due to underlying coronary artery thrombosis is one of the leading causes of death. However, in a significant percentage of individuals who died suddenly, no indication of myocardial infarction is found during post-mortem examination, especially when the time interval between appearance of symptoms and death is short. In the present study, we have evaluated certain nuclear morphometric parameters, such as, minimum, maximum, mean and standard deviation of perimeter and area in 20 individuals who died of coronary artery thrombosis, within 1 h from symptoms onset. Furthermore, the above parameters were compared with those of a control population of 20 individuals whose sudden death was caused by traffic accidents. Statistical elaboration of the results by means of t-test, Mann-Whitney (U-test) and analysis of covariance (adjusting for age), showed a statistically significant difference for all variables except for the minimum area. With stepwise discriminant analysis method, the mean perimeter was selected as the best predictor of cardiac death. Mean perimeter achieved a correct reclassification percentage (based on Fisher's linear discriminant function) of 92.5% (85% and 100% for cases and controls, respectively). Moreover, by applying the cut-off of 172 microns, we could identify the individuals who died suddenly because of coronary artery thrombosis with a specificity of 100% (sensitivity 85%, P < 0.001). Our results show that nuclear morphometry of the myocardial cells is a reliable diagnostic tool for the diagnosis of coronary thrombosis based lesion in cases of sudden death, even when methods trying to verify the presence of infarction fail to do so.

Case-Control Studies↗