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PubMed1997

Complete coding regions of two novel HLA-B alleles detected by phototyping (PCR-SSP) in the British caucasoid population: B5108 and B5002.

Two previously reported PCR-SSP variants of the HLA-B locus, B51GAC and B45v, were investigated by RT-PCR cloning and nucleotide sequence analysis of their complete coding regions. They have been shown to correspond to the new alleles B*5108 and B*5002, both of which differ from the common B*5101 and B*5001 subtypes, respectively, by amino acid replacements at their alpha-2 domain alpha-helices. The primary structure of B*5002, intermediate between those of B*4501 and B*5001, raises further concern about the current classification of B*45 as a B12 rather than as a B*50 subtype.

Alleles↗

PubMed1984

Different forms of AT-III congenital defect: a study by crossed immunoelectrofocusing.

Antithrombin III (AT-III) deficiency may be due to quantitative or qualitative AT-III reduction. The diagnosis of qualitative disorder is suspected when a discrepancy is found between immunological and functional levels of AT-III. Heterogeneity has been hypothesized in both quantitative and qualitative deficiency of AT-III. A technique based on crossed immunoelectrofocusing (CIEF) was applied to investigate molecular variants of AT-III. 3 families with low functional and immunological levels of AT-III and 1 family with only a low functional AT-III level were investigated. An abnormal AT-III pattern was found with CIEF in the family with suspected qualitative disorder and in 1 of the families with quantitative disorder. The 2 abnormal patterns were different. Thus the use of CIEF AT-III patterns could help to define congenital AT-III deficiencies and could serve as a basis for classification of different forms of AT-III deficiency.

Adult↗

PubMed1994

Glandular odontogenic cyst: analysis of cytokeratin expression and clinicopathological features.

The glandular odontogenic cyst (GOC) is a rare odontogenic cyst which is still controversial in regard to classification, terminology, and origin. The first Japanese case of GOC is reported. Immunohistochemical examination for expression of cytokeratins and epithelial membrane antigen by monoclonal antibodies suggested that the lining epithelium was of odontogenic origin with metaplastic mucus-laden cells. We have reviewed the literature and compared the clinicopathological findings of the reported case of GOC with those of botryoid odontogenic cysts (BOC). The anatomical location, age range, and sex of GOC cases were very similar to those of BOC. GOC appears to be a multiocular and mucoepidermoid variant of non-keratinizing odontogenic cysts, which also includes BOC. GOC should be separated from the other types of odontogenic cyst and central mucoepidermoid tumours of salivary gland origin.

Aged↗

PubMed1989

[Molecular pathology of the erythrocyte membrane. Erythrocyte membrane defects as a cause of congenital hemolytic anemia].

Recently numerous defects of erythrocyte membrane proteins have been described in hereditary hemolytic anemias. An exact biochemical characterization of some different types of hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and the hemolytic anemias with increased cation permeability (hereditary stomatocytosis) is possible after analysis of membrane proteins with SDS-polyacrylamide gel electrophoresis, quantitative determination of spectrin, the relation of dimeric to tetrameric spectrin, and partial tryptic digestion of the spectrins. The known clinical heterogeneity of the mentioned disorders is now partially explained by the different biochemical defects of the erythrocyte membrane. In classical hereditary spherocytosis a close relationship between erythrocyte spectrin content and clinical severity has been found. The clinical manifestation in hereditary elliptocytosis and hereditary pyropoikilocytosis mainly depends on the functional disturbance of variant spectrins, especially their ability to form tetramers, i.e. their ability for self-association of the spectrin chains. In the hydrocytic form of stomatocytosis a deficiency of the integral protein band 7.2b has been documented. Besides the analysis of erythrocyte membrane proteins the classical methods used in the study of congenital hemolytic anemias cannot be missed. Signs of increased hemolysis, erythrocyte morphology, osmotic fragility, autohemolysis, heat and mechanical stability of the erythrocyte membrane, intracellular cation concentration and studies of other family members, are indispensable prerequisites for classification, prognosis, and indication of therapeutic efforts, especially splenectomy.

Anemia, Hemolytic, Congenital↗

PubMed1985

Extracellular matrix and epithelial differentiation of Wilms' tumor.

Different histologic types of 82 Wilms' tumors were graded on the basis of the histologic pattern. Representative tumors of each group were analyzed by the immunoperoxidase method for evaluation of the histogenesis of Wilms' tumor and the value of antibodies against extracellular matrix (ECM) components (collagens I and III, laminin, fibronectin) in differential diagnosis of different types of Wilms' tumors. The tubules of classic Wilms' tumor expressed laminin, which could be seen also in and around some blastemal cells. Blastema and tubules were negative for interstitial collagens, but Type I and III collagen were prominent in the fibrovascular stroma. The monomorphous tubular, psammomatous and rosetting tumors expressed laminin, but no interstitial collagens. In sarcomas, only the blastemal variant of spindle-cell sarcomas was negative for interstitial collagens, which were abundantly seen in all other sarcomas. While spindle-cell sarcomas were devoid of laminin, the highly malignant rhabdoid and clear-cell sarcomas expressed laminin in a characteristic dotted fashion. Staining for fibronectin gave varying results and had therefore only a limited value in distinguishing different types of Wilms' tumors. However, the antibodies against interstitial collagens and against the basement membrane glycoprotein laminin turned out to be a useful adjunct in differential diagnosis and classification, especially of sarcomatoid Wilms' tumors. The basement membrane of normal nephrons is similar to that in tubules of triphasic Wilms' tumor, but the ECM of blastemas is different. This transformed phenotype might represent a maturation arrest of the blastemal cell when compared with the expression of proteins during normal nephrogenesis.

Adenocarcinoma↗

PubMed1988

[Papillary carcinoma of the thyroid: development of the histological criteria for diagnosis. Study of 29 cases and review of the literature].

Papillary carcinoma (PAP) is the most frequent malignant tumour of the thyroid. PAP and follicular carcinoma of the thyroid are two biologically different tumours, without any intermediate or mixed form. Therefore the differentiation between PAP and follicular carcinoma is essential. The histological diagnosis of PAP is based upon several criteria, the most important being the papillae, the "ground glass" nuclei, and the psammoma bodies. The value of the "ground glass" nuclei in the diagnosis of PAP has been particularly emphasized in the last 10 years. The need to take into account all the diagnostic histological criteria of PAP is necessary in the definition of the different variants of PAP, particularly its follicular variant. We report 28 cases of PAP and one case of insular carcinoma, the latter probably originating from a PAP. "Ground glass" nuclei often associated with "grooved nuclei", were identified in the paraffin sections of 7 PAP. One case was classified as a follicular variant of PAP. Psammoma-bodies were seen in 6 PAP. Eleven PAP were less than 1 cm in diameter (microPAP). One microPAP presented with important lymph node metastases and blood vessels' involvement; 2 others microPAP arose in a vesicular adenoma. Six PAP were entirely encapsulated, without any lymph node metastasis or vessel invasion. Six PAP presented with lymph node metastases associated with lymphatic and/or blood vessels invasion. Lymphatic and blood vessel invasion was seen more often in association with PAP extending to the thyroid capsule. The histological classification and prognostic criteria are discussed and compared with those previously described in the literature.

Adenocarcinoma↗

PubMed1986

Equine herpesvirus type 1 (EHV-1) induced abortions and paralysis in a Lipizzaner stud: a contribution to the classification of equine herpesviruses.

Out of 30 cases of abortion and perinatal deaths in a Lipizzaner stud in Austria 10 mares died after having shown central nervous system disturbances, ataxias and paralysis. The etiological agent of this "abortion storm" was equine herpesvirus type 1 (EHV-1). The restriction enzyme pattern of the DNA from 5 isolates recovered from fetuses has been analyzed and compared with the known reference strains of EHV-1, -2, -4 and an Austrian vaccine strain. The DNA restriction profiles of the Lipizzaner isolates as well as of the vaccine strain could be identified as being typical of abortigenic strains with minor variations. Such variations on the molecular biological level of the DNA do not justify characterization of the strains as neuro-variants. The vaccine strain differed from other isolates investigated with 4 restriction endonucleases (Bam HI, Bgl II, EcoRI, Kpn I) which was due to a deletion in the unique short segment of the genome. The lack of similar DNA bands in two EHV-1 viruses, causing mild respiratory disease, as well as in the vaccine strain Prevaccinol is suggestive of lowered virulence. In contrast to one Lipizzaner isolate tested (strain Austria IV) the Austrian vaccine strain proved to be of strong neurovirulence for suckling mice.

Abortion, Veterinary↗

PubMed1992

Error in radiology: classification and lessons in 182 cases presented at a problem case conference.

The authors review and classify errors in 182 cases that were presented at problem case conferences between August 1986 and October 1990. Errors were classified by means of a system developed 20 years ago and by means of a system developed within the past several years. The authors found that sources of error have changed very little. Errors usually involved failure to consult old radiologic studies or reports, limitations in imaging technique, acquisition of inaccurate or incomplete clinical history, location of a lesion outside the area of interest on an image, lack of knowledge, failure to continue to search for abnormalities after the first abnormality was found, and failure to recognize a normal biologic variant. Errors included 126 perceptual errors (64 false-negative, 15 false-positive, and 47 misclassification errors) and 56 mishaps, including 38 complications and 18 communication errors. In seven cases nonperception errors occurred because established departmental routines were not followed, and in nine cases a new departmental routine was established after a complication occurred. Departmental policy exerts less effect on perception and interpretation errors.

Diagnostic Errors↗

PubMed1991

Characterization and classification of leishmanial parasites from humans, wild mammals, and sand flies in the Amazon region of Brazil.

Ninety-four leishmanial isolates from the Brazilian Amazon Region (Amapá, Amazonas, Pará, and Rondônia) were identified and classified using specific monoclonal antibodies and an indirect radioimmunoassay (serodeme analysis); eighty-two were also characterized by enzyme electrophoresis (zymodeme analysis), the results of which were subjected to a numerical phenetic analysis. Six isolates from humans (3), Didelphis marsupialis (1), Lutzomyia olmeca nociva (1), and Lu, reducta (1) showed reactivity patterns and isoenzyme profiles similar to those obtained with the Leishmania amazonensis reference strains, and were identified as this species. Eighty-six stocks were classified as members of the L. braziliensis complex; of these, 61 were L. guyanensis or variants, which presented three serodeme subtypes, but whose isoenzyme profiles were all similar to the reference strain. A total of 15 isolates were distinguished as L. braziliensis or variants and were classified into five serodeme subtypes. The isolate from Psychodopugus davisi appeared, from the numerical analysis, to be a distinct parasite species. Ten isolates showed reactivity patterns and isoenzyme profiles similar to those obtained with the L. naiffi reference strain. A parasite isolated from Ps. claustrei appeared to be different from all reference strains by both techniques, and was classified as probably being a new species. The importance of these results with respect to the taxonomic status of the New World Leishmania, and their implications for both clinical and epidemiologic data are discussed.

Animals↗

PubMed1991

Computer-assisted statistical analyses of enzyme and ribosomal DNA electrophoretic polymorphism in Yersinia.

The intra- and inter-species differentiation of 90 strains of Yersinia belonging to six species were studied independently by computer-assisted statistical analysis of data from enzyme electrophoretic polymorphism and ribosomal DNA (rDNA) restriction fragment length polymorphism. Two correspondence analyses (CA) demonstrated the concordance between the bacterial classification obtained from enzymatic and genomic data. This concordance was reinforced by an algorithm of the correspondence established between the two dendrograms drawn from previous computations. Comparison of CA with similarity analysis (also called "numerical taxonomy") indicated that the intra- and inter-species differentiation obtained by the two methods are similar. The advantage of CA is that it gives a synthetic geometrical representation of the results (factorial planes), displaying both the main features of the clusters of strains (location and dispersion) and their essential character (i.e.: enzyme electrophoretic variant, rDNA fragment size).

Algorithms↗

PubMed2000

Clinical consequences of molecular diagnosis in families with mismatch repair gene germline mutations.

Hereditary nonpolyposis colorectal cancer (HNPCC), clinically defined by the Amsterdam criteria, is associated with mismatch repair gene germline mutations. This study was performed to evaluate the efficiency of combined clinical and molecular diagnostics in identifying carriers of a mutated gene in families meeting criteria of the Bethesda guidelines and to examine the influence of molecular diagnosis on clinical decision-making in carriers and noncarriers. Seventy-two patients meeting criteria of the Bethesda guidelines were tested for microsatellite instabilities (MSI). MSI-H tumors were found in 38 (52.8%) index patients. Complete sequencing of hMLH1 and hMSH2 in 38 MSI-H patients and of hMSH6 in one of these patients revealed 15 pathogenic germline mutations, including three novel mutations, and three novel unclassified germline variants. Twelve of the 15 pathogenic mutations were found in patients fulfilling the Amsterdam I/II criteria. Surgical and genetic counseling was offered to the affected families; as a result of molecular diagnosis in the 15 families, 26 index patients and affected carriers and 8 asymptomatic carriers of a mutated mismatch repair gene were included in the surveillance program, and 26 noncarriers were excluded from this program. Although germline mutations are detected in only 20.8% of patients fulfilling criteria of the Bethesda guidelines, family history and MSI-H tumor classification are both strong indicators for germline mutations in hMSH2, hMLH1, and hMSH6 genes, resulting in a 51.9% mutation detection rate. Identification of individual mutation status allows clear-cut decisions on whether or not inclusion in surveillance programs is indicated.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Down-regulation of beta(1C) integrin in breast carcinomas correlates with high proliferative fraction, high histological grade, and larger size.

beta(1C) integrin is an unspliced form of the integrin beta(1) subfamily, which has been shown to inhibit cell proliferation in vitro. Using an affinity-purified rabbit antibody, we have investigated 283 previously untreated breast carcinomas, with the aim of ascertaining the actual prevalence of beta(1C) expression in these tumors and of defining its pathological correlates. Immunoblotting and reverse transcriptase-polymerase chain reaction experiments have also been performed in selected cases, to confirm the immunocytochemical findings. Overall, beta(1C) immunoreactivity was down-regulated (ie, expressed in < 50% of the neoplastic cells) in 114 cases (40.3%). Down-regulation of beta(1C) expression in breast carcinomas correlated significantly with the tumor grade, the proliferative fraction (as evaluated by Ki-67 immunostaining with the MIB-1 monoclonal antibody), the estrogen and progesterone receptor status, and the tumor size (pT classification) and marginally with the node status. In a multivariate analysis with all available measures fitted simultaneously, tumor grade (P = 0.004), Ki-67 immunolabeling (P = 0.01), and pT categories (P = 0.04) were significantly associated with beta(1C) immunoreactivity. Although the short follow-up time (2-3 years) of the current series of patients does not allow the performance of survival analyses, the correlation of beta(1C) expression with tumor size, grade, and proliferative fraction and its alleged role as an upstream regulator of p27(kip1) make this integrin variant a likely novel prognostic parameter for invasive carcinomas of the breast.

Breast↗

PubMedDate not supplied

Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review.

Medium chain acyl-CoA dehydrogenase (MCAD) is a tetrameric flavoprotein essential for the beta-oxidation of medium chain fatty acids. MCAD deficiency (MCADD) is an inherited error of fatty acid metabolism. The gene for MCAD is located on chromosome one (1p31). One variant of the MCAD gene, G985A, a point mutation causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD protein, has been found in 90% of the alleles in MCADD patients identified retrospectively. There is a high frequency of MCADD among people of Northern European descent, which is believed to be due to a founder effect. MCADD is inherited in an autosomal recessive manner. Of patients clinically diagnosed with MCADD, 81% who have been identified retrospectively are homozygous for K304E, and 18% are compound heterozygotes for K304E. Clinical data on the probability of clinical disease indicates that MCADD patients are at risk for the following outcomes: hypoglycemia, vomiting, lethargy, encephalopathy, respiratory arrest, hepatomegaly, seizures, apnea, cardiac arrest, coma, and sudden and unexpected death. Long-term outcomes include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit disorder (ADD). Differences in clinical disease specific to allelic variants have not been documented. Factors that may increase risk for disease onset or modify disease severity are age when the first episode occurred, fasting, and presence of infection. Acute attacks must be treated immediately with appropriate intravenous doses of glucose. For those diagnosed, long-term management of the disease includes preventing stress caused by fasting and maintaining a high-carbohydrate, reduced-fat diet, and carnitine supplementation. Hospitalization costs attributable to morbidity and mortality from MCADD are unknown; MCADD is not a diagnosis in the International Classification of Disease, 10th Revision (ICD-10) codebook. Furthermore, the penetrance of the MCAD genotypes is unknown; there appears to be a substantial number of asymptomatic MCADD individuals and some uncertainty regarding which individuals will manifest symptoms and which individuals will remain asymptomatic. Several technologies are available to detect MCADD. Diagnostic technologies include DNA-based tests for K304E mutations using the polymerase chain reaction (PCR), and the detection of abnormal metabolites in urine. Screening technologies include tandem mass spectrometry (MS/MS), which detects abnormal metabolites mostly in blood. State programs are beginning to offer screening in newborns for MCADD using MS/MS. In addition, a private company currently offers voluntary supplemental newborn screening for MCADD to birthing centers.

Acyl-CoA Dehydrogenases↗

PubMed2004

Feline immunodeficiency virus subtypes A, B and C and intersubtype recombinants in Ontario, Canada.

Knowledge of the geographical distribution of feline immunodeficiency virus (FIV) subtypes is important for understanding different disease courses and for vaccine design. Intersubtype recombination may develop in areas where more than one subtype is prevalent and has the potential to create new transmittable variants with novel pathogenic properties. In this study, 40 FIV-positive DNA samples were classified by sequence analysis of the LTR-gag region. Phylogenetic analysis indicated that 32 Canadian FIV isolates clustered with previously identified subtypes A, B and C and that subtype A was most frequent in Ontario. Four strains with inconsistent clade assignment were further analysed by sequencing of the env-LTR regions. Comparisons of phylogenetic trees constructed from the two different regions of the genome and analysis of similarities to reference sequences yielded classification of three samples as A/B and one as A/C intersubtype recombinants. Although the A/B recombinant samples were obtained from unrelated cats in geographically disparate regions, a common breakpoint was consistently identified within gag. In addition, there was no evidence of co-infection with parental strains of subtypes A and B as indicated by PCR-based limiting dilution assays, although these assays allowed for the identification of two different recombinant viruses co-existing in one sample. Both sequences contained the same breakpoint. These findings suggested that a new circulating recombinant FIV may be enzootic in Ontario.

Animals↗

PubMed2006

Aptitude-treatment interactions revisited: effect of metacognitive intervention on subtypes of written expression in elementary school students.

We examined the effectiveness of a metacognitive intervention for written language performance, based on the Hayes model of written expression, for 73 fourth-grade (n = 38) and fifth-grade (n = 35) students. The intervention consisted of twenty 45-min writing lessons designed to improve their awareness of writing as a problem-solving process. Each of the lessons addressed some aspect of planning, translating, and reflecting on written products; their self-regulation of these processes; and actual writing practice. All instruction was conducted in intact classrooms. Prior to the intervention, all students received a battery of neurocognitive tests measuring executive functions, attention, and language. In addition, preintervention writing samples were obtained and analyzed holistically and for errors in syntax, semantics, and spelling. Following the intervention, the writing tasks were readministered and cluster analysis of the neurocognitive data was conducted. Cluster analytic procedures yielded 7 reliable clusters: 4 normal variants, 1 Problem Solving weakness, 1 Problem Solving Language weaknesses, and 1 Problem Solving strength. The response to the single treatment by these various subtypes revealed positive but modest findings. Significant group differences were noted for improvement in syntax errors and spelling, with only spelling showing differential improvement for the Problem Solving Language subtype. In addition, there was a marginally significant group effect for holistic ratings. These findings provide initial evidence that Writing Aptitude (subtype) x Single Treatment interactions exist in writing, but further research is needed with other classification schemes and interventions.

Aptitude↗

PubMed1972

Isolation and classification of extranuclear mutants of Neurospora crassa.

Four extranuclear mutants, [exn-1], [exn-2],[exn-4], and [stp-C], were obtained from N-methyl-N'-nitro-N-nitrosoguanidine-treated conidia and mycelium of Neurospora crassa. The three exn mutants grow with a pronounced lag from conidia and ascospores and are female fertile, whereas [stp-C] has a stop-start growth phenotype and is female sterile. The mitochondria from all four mutants are deficient in cytochromes a+a(3) and b, but contain an excess of cytochrome c. On the basis of growth and fertility, nuclear suppressors and complementation in heteroplasmons, 16 of the extranuclear mutants now available in Neurospora can be divided into three groups. Group I consists of 8 female-fertile variants with both poky-like growth and cytochrome defects. Their slow growth is suppressed by the nuclear factor, f, but not by a second nuclear suppressor, su-1([mi-3]). They complement with group III mutants in mixed cytoplasmons. Group II is represented by a single variant, [mi-3]. It is phenotypically modified by the su-1([mi-3]) factor, but not by f. Its unique cytochrome spectrum shows a deficiency of cytochrome a, but c and b are present. It complements in heteroplasmons with group I and III mutants. Group III included 7 female-sterile variants with stopper growth phenotypes and the same cytochrome defects as group I. Group III mutants complement both with group I and II isolates, but they are unaffected by either f or su-1.

Crosses, Genetic↗

PubMed1997

Detection of CBFbeta/MYH11 fusion transcripts in acute myeloid leukemia: heterogeneity of cytological and molecular characteristics.

Pericentric inversion of chromosome 16, translocation (16;16) and del(16q), resulting in a chimerical fusion of CBFbeta and MYH11 genes, are typically seen in the M4Eo French-American-British (FAB) classification subset of acute myelogenous leukemia (AML). In this study, we analyzed 70 cases of acute non-lymphoblastic leukemia, mainly of the M4 or M5 type. We report the very unusual presence of the t(16;16) and CBFbeta/MYH11 fusion transcript in an M7 patient. Ten M4Eo and four non-M4Eo patients presented an inv(16), t(16;16) or CBFbeta/MYH11 fusion transcript. In most cases, the common 'A-type' CBFbeta/MYH11 fusion transcript was detected. In addition to the eight different breakpoints and the three alternative splicing variants already described, evidence of a new CBFbeta/MYH11 fusion transcript was found which involves a 785-bp deletion of MYH11. Moreover, two patients had an unusual transcript, to our knowledge only observed once. Only one patient had abnormal eosinophilic differentiation without chromosome 16 cytogenetic abnormalities or detectable CBFbeta/MYH11 fusion. Conversely, only one patient presented CBFbeta/MYH11 fusion without abnormal eosinophilic differentiation. Altogether, our data suggest a correlation between the CBFbeta/MYH11 fusion transcript and characteristic abnormal eosinophilic differentiation, whatever the FAB subtype or the percentage of abnormal eosinophils

Adult↗

PubMed2005

African origin of GB virus C determined by phylogenetic analysis of a complete genotype 5 genome from South Africa.

GB virus C (GBV-C), a positive-strand RNA virus, currently infects approximately one-sixth of the world's population. This virus exists as a collection of genotypes whose global distribution correlates with geographical origin. Genotyping of GBV-C isolates by phylogenetic analysis has relied upon the use of 5'-untranslated region (5'-UTR) sequences, however, complete genome sequences are used to demonstrate definitively their existence and geographical correlation. Initial identification of the fifth genotype from South Africa was based upon phylogenetic analysis of the 5'-UTR. It was sought to confirm this classification by analysis of full-length E2 genes from South African isolates and by analysis of a complete genotype 5 genome. Analysis of full-length E2 genes from 28 GBV-C-infected South African individuals revealed the existence of a unique group of 18 isolates, distinct from the other four genotypes. Bootstrap analysis provided strong support (95 %) for this fifth group. The remaining isolates were either genotype 1 (n=8) or 2 (n=2). Analysis of human E2 gene sequences, with the E2 gene from the chimpanzee variant GBV-Ctro included as the outgroup, produced a tree rooted on the genotype 1 branch. The complete genome nucleotide sequence of South African genotype 5 isolate D50 was determined. Phylogenetic analysis of the 5'-UTR and open reading frame produced congruent trees that grouped the sequences into five major genotypes. Inclusion of the corresponding region of the chimpanzee isolate GBV-Ctro in the analysis produced trees rooted on the branch leading to the genotype 5 isolate D50, suggesting an ancient African origin of GBV-C.

Flaviviridae Infections↗