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At least 271 records · Page 15Linked to original sources

PubMed1987

Lymphocyte predominance Hodgkin's disease: a reappraisal based upon histological and immunophenotypical findings in relapsing cases.

The clinical, morphological and immunological findings in nine cases of relapsing lymphocyte predominance Hodgkin's disease (LPHD) are examined. Six patients had initial biopsies demonstrating nodular lymphocytic and/or histiocytic (L&H) LPHD; Leu-M1 was not expressed by any of the atypical cells in these cases. All six demonstrated one or more recurrences of nodular L & H LPHD; four are currently free of disease, one died of non-Hodgkin's lymphoma and another died of leukaemia. Two patients had initial biopsies demonstrating diffuse LPHD, with only rare multilobated atypical cells (L & H variants). Both patients had recurrences interpreted as mixed cellularity Hodgkin's disease, 10 and 15 years after initial therapy and both died with lymphocyte depleted Hodgkin's disease. The atypical cells in the initial biopsies and in subsequent recurrences failed to express Leu-M1, but did express leukocyte common antigen. The initial biopsy from the final patient was histologically interpreted as focal involvement by LPHD, but interfollicular Hodgkin's disease was considered after the Leu-M1 stain revealed additional atypical cells. The disease relapsed and the patient died with typical nodular sclerosing Hodgkin's disease. The pattern of the relapses supports the concept that the histological entity of LPHD may include several distinct clinicopathological subgroups.

Biopsy↗

PubMed1996

MTS1 gene mutations in archival oral squamous cell carcinomas.

Multiple tumor suppressor gene 1 (MTS1) has been found mutated or deleted in a variety of human cancers. Our purpose was to identify and characterize MTS1 gene mutations in primary oral squamous cell carcinomas (SCCs) in each of the three exons of the MTS1 gene. Seventeen archival samples of oral SCC were evaluated for the presence of MTS1 mutations using single strand conformation polymorphism (SSCP) and DNA sequencing. Three of 17 tumors exhibited MTS1 gene mutations: one tumor exhibited a mutation in exon 2 and two tumors exhibited mutations at the splice site junction of intron 2 and exon 3. Three tumors also exhibited a common base change in the 3' untranslated region of exon 3, which is interpreted as a likely polymorphic variant. An examination of the three tumors exhibiting MTS1 point mutations revealed no unique characteristics relative to p53 immunohistochemical activity, mitotic frequency, or degree of histologic differentiation. This study indicates that MTS1 gene mutations may be involved in at least a minor proportion of oral SCCs.

Adolescent↗

PubMed1977

Electroencephalographic variants and genetic predisposition to schizophrenia.

Schizophrenic patients (249) were divided into those with and those without a family history of major functional psychosis. The same patients were then divided into those with entirely normal electroencephalograms and those whose traces contained some variant of normal. Traces were interpreted without knowledge of the patients' identities, and the question of the presence or absence of positive heredity had been decided without knowledge of the patients' electroencephalographic status, so that the discovery that normal electroencephalograms correlated highly significantly with positive heredity, and vice versa, commands attention. It is considered in the setting of previous work on psychoses and organic and electroencephalographic findings.

Brain↗

PubMedDate not supplied

"Lumps" and "bumps" that mimic acute aortic and brachiocephalic vessel injury.

Laceration of the thoracic aorta or brachiocephalic vessels due to blunt trauma is relatively common. In such cases, prompt and accurate diagnosis followed by timely surgery is essential. These injuries typically occur at the aortic isthmus and can usually be readily identified at aortography, which remains the standard of reference for diagnosis. However, numerous anatomic variants that manifest as "lumps" or "bumps" on aortograms can mimic true vascular injury, thereby leading to false-positive or false-negative diagnosis. These variants include aortic spindle, classic or atypical ductal diverticula, and infundibula of the brachiocephalic arteries and adjacent branches or of the right third intercostal artery. Ductus diverticula typically occur at the isthmus and have smooth, uninterrupted margins with gently sloping shoulders. Infundibula are also smoothly marginated but can occur in a variety of locations and generally taper into one or more vessels at their apex. Knowledge of the imaging appearances of these anatomic variants is necessary for correct interpretation of aortograms of the aorta and brachiocephalic vessels in blunt trauma patients.

Adult↗

PubMed1981

Echocardiographic appearance of the Chiari network: differentiation from right-heart pathology.

As echocardiography is being used more often, its value and accuracy are becoming more fully appreciated. Coincident with wider application of this imaging technique is the potential for identifying normal anatomic variants and their possible erroneous interpretation as pathologic states. In this report we describe the M-mode and two-dimensional echocardiographic features of a congenital remnant known as the Chiari network. This structure can present as a highly mobile, highly reflectant echo target that can be seen in several locations in the right atrium. We report here an index case that could be well examined echocardiographically and that was a cause of considerable concern due to the presence of congestive heart failure and a history of staphylococcal endocarditis. The presence of the Chiari network was confirmed pathologically. Subsequently, we found similar echocardiographic findings in 19 of 1248 patients (1.5%) studied in our laboratory. This congenital remnant, which is found pathologically in 2-3% of normal hearts, could be confused with valve disruption, vegetation or other mass lesion, particularly when associated with a suggestive clinical situation.

Adult↗

PubMed1981

Functional interdependence of pseudopodia in Amoeba proteus stimulated by light-shade difference.

Polytactic cells of Amoeba proteus were exposed to localized photic stimulation. When a pseudopodium is stimulated to advance, by shading it, other pseudopodia are retracted. Activation of the shaded front is the primary response, and contraction of other fronts the secondary one. When a pseudopodium is inhibited by illuminating its frontal segment, or when it is allowed to enter the bright zone in the course of migration, it slows down and stops but its eventual retraction depends on the existence of other possible directions for the endoplasmic flow. Therefore, if other active pseudopodia are lacking, the front suppressed by light cannot retreat effectively until new fronts arise in other body regions kept in shade. In all experimental situations the development of new fronts or the activation of forward flow in lateral pseudopodia precedes the contraction of the former leading pseudopodium. Also the reversal of direction of the endoplasmic streaming begins at the new front, and then it gradually extends until it reaches the former front. The results confirm the interdependence of different pseudopodia in the same individual and they contradict the concept that pseudopodia behave as separate functional units. On the other hand, they indicate that formation of new pseudopodia should not be explained as a simple secondary effect of contraction of the older ones but, on the contrary, as a phenomenon that initiates the changes in the pattern of flow in amoeba. The general interpretation is based on this variant of the pressure-flow theory of amoeboid movement, which attributes the motive power to the contractile activity of the whole cell cortex and the steering role to events taking place in the front of the migrating cell.

Amoeba↗

PubMed1994

MR diagnosis of meniscal tears: analysis of causes of errors.

OBJECTIVE: MR imaging of the knee is an accurate method for diagnosing meniscal tears. However, MR findings do not always agree with surgical findings. In a retrospective study, we analyzed the various causes of incorrect MR diagnoses. MATERIALS AND METHODS: We reviewed a series of 400 MR examinations for suspected meniscal tears in which the diagnostic accuracy was 90%. In this group, we found 70 patients in whom the original MR diagnosis did not agree with the surgical findings. Three musculoskeletal radiologists independently reviewed each of the 70 MR examinations without knowledge of the original interpretation or the surgical findings. Their interpretations and the MR images then were correlated with the surgical findings. The original incorrect diagnoses were categorized as being due to unavoidable errors, errors in interpretation, or errors made because of equivocal MR findings of a tear. Unavoidable errors were defined as false-positive and false-negative diagnoses that could not be avoided, even in retrospect. RESULTS: Of the 83 original diagnostic errors made in the MR evaluation of 800 menisci, 33 (40%) were unavoidable errors, 32 (39%) were due to equivocal MR findings, and 18 (21%) were due to interpretation errors. The unavoidable errors consisted of 21 missed meniscal tears and 12 false-positive MR diagnoses. In the false-positive cases, the menisci were interpreted as torn on MR images by all three observers, but no tear was found at arthroscopy. Subtle MR findings that were equivocal for a tear caused both false-positive and false-negative diagnoses. Seven of the 18 interpretation errors occurred when normal variants were mistaken for a tear. CONCLUSION: Using conventional coronal and sagittal spin-echo MR imaging, we could not identify 21 (6%) of the 333 meniscal tears, even in retrospect. In addition, subtle findings that are equivocal for a tear may still make MR diagnosis of every torn meniscus difficult even for experienced radiologists. Unavoidable false-positive diagnoses due to healed tears or tears missed at arthroscopy are an infrequent problem occurring in only 1.5% of the original 800 menisci evaluated with MR imaging.

Diagnostic Errors↗

PubMedDate not supplied

[Structure of flower in Arabidopsis thaliana: spatial pattern formation].

Morphological analysis of flowers was carried out in Arabidopsis thaliana wild type plants and agamous and apetala2 mutants. No direct substitution of organs takes place in the mutants, since the number and position of organs in them do not correspond to the structure of wild type flower. In order to explain these data, a notion of spatial pattern formation in the meristem was introduced, which preceded the processes of appearance of organ primordia and formation of organs. Zones of acropetal and basipetal spatial pattern formation in the flower of wild type plants were postulated. It was shown that the acropetal spatial pattern formation alone took place in agamous mutants and basipetal spatial pattern formation alone, in apetala2 mutants. Different variants of flower structure are interpreted as a result of changes in the volume of meristem (space) and order of spatial pattern formation (time).

AGAMOUS Protein, Arabidopsis↗

PubMed1989

[Duodenocolonic fistula caused by carcinoma of the cecum].

Duodenocolonic fistulas of malignant origin are an uncommon finding. The point of origin of the fistula is almost always cancer of the hepatic angle of the colon. We report a patient with this rare entity which originated from a cecal carcinoma, and interpret it as an anatomic variant of the subhepatic position. The cases published are reviewed and the difficulties of reaching a therapeutic decision once the diagnosis is established are highlighted.

Carcinoma↗

PubMed1982

[Incontinentia pigmenti achromians (systematized depigmented nevus)].

Two girls of 1 1/2 und 4 years age and described with linear, arch-like depigementations which appeared in early childhood. In both children no additional abnormalities could be found. The problem of terminology is briefly discussed, and it is proposed to interpret this syndrome as a variant of a systematized naevus depigmentosus. There seems to be no justification for turning this clinical entity into a new syndrome, when the only clinical signs are the characteristic depigmentations without any additional abnormalities.

Child, Preschool↗

PubMed1994

Potential diagnostic pitfalls caused by blood film artifacts in prolymphocytic leukaemia. Observations in two cases.

The diagnosis of lymphoproliferative disorders is based on a combined evaluation of the clinical, immunological and morphological findings. Cytological details may vary with the quality of the smear. We report two cases of prolymphocytic leukaemia in which cytoplasmic hairs or protrusions were observed when the films were not dried quickly. In one case the artifacts led to an initial erroneous interpretation of hairy cell leukaemia 'variant'. The cytoplasmic outline was smooth in both cases when the smears were immediately fan-dried. The findings underscore the necessity of high standards of excellence, even for the simple technique of blood film preparation, in order to avoid undesirable artifacts which may result in diagnostic misinterpretation.

Aged↗

PubMed1976

[Vater or Vacterl syndrome (author's transl)].

Analysis of malformations in 65 newborns with limb anomalies, 39 with esophageal atresia with tracheoesophageal fistula, and 41 with anal atresia confirmed the nonrandom tendency for the defects of the VATER or VACTERL syndrome to associate together. 11 new patients with 4 or more of these anomalies were compared with 41 previously reported cases. There was good agreement with reference to the frequency of the major malformations noted in the VACTERL association. While anal atresia was not so common in our patients, cardiac anomalies and radial limb dysplasia occurred somewhat more frequently. In accordance with previous findings we also emphasize a single umbilical artery as one of the malformations in the spectrum of the VACTERL association (V = vertebral defects and vascular anomalies). Because of the high incidence of rib anomalies in our patients and in earlier cases with complete medical records it is suggested that the scope of the VACTERL association should be enlarged by this malformation. Thus the R in VACTERL would stand not only for renal defects but als for rib anomalies. Furthermore, the spectrum of anomalies could be extended by auricular defects (A = anal atresia and auricular defects). When one of these VACTERL components is found attention should be drawn to the possibility of the presence of the other associated anomalies. The developmentally correlated malformations seen in the VACTERL syndrome are generally sporadically observed. At the present time the etiology is unknown but heterogeneity is suggested. Although a causal relationship between maternal intake of progesteron/estrogen during the vulnerable period of embryogenesis and the VACTERL syndrome has been suggested, none of the mothers of our patients were exposed to these hormones during early pregnancy. Cytogenetic investigation in one patient and his mother showed a so-called marker chromosome 9 (C9qh+ variant) which is difficult to interpret at the present time.

Abnormalities, Multiple↗

PubMed1976

Human alcohol dehydrogenase ADH1, ADH2 and ADH3 loci in a mixed population of Bahia, Brazil.

1. The three structural gene loci of human alcohol dehydrogenase have been studied in liver, jejunum and lung from 300 newborns in a triracially mixed population of Bahia, Brazil. 2. The frequency of the ADH23 allele was 0-1392, suggesting that the ADH23 allele is less frequent in Negroes. 3. A new ADH2 variant was identified. The electrophoretic pattern was interpreted as due to a new allele which is provisionally called ADH2Bahia. 4. By electrophoretic classification the 'atypical' variant was found in 2-8% of the sample. A question is raised regarding the ancestral origin of the 'atypical' variant in the population. Because this variant is common in Japanese it may have reached the present day population of Bahia through their American Indian ancestors. 5. Subjective estimation of the proportions of beta chains by giving scores to the liver isozymes alphaalpha, alphabeta and betabeta showed a clear relationship between the fetal weight and the beta chain activity. 6. The proportion of beta chains in the liver is significantly less when there is no enzyme activity in the lung, indicating some synchronous 'turning on' mechanism for alcohol dehydrogenase synthesis in both tissues.

Alcohol Oxidoreductases↗

PubMed1990

Variation of some serum proteins in red deer, Cervus elaphus L.

Various electrophoretic techniques, immunoblotting and inhibitions of trypsin and chymotrypsin were used to study the variability of serum proteins in farmed red deer, Cervus elaphus L., of Czechoslovakian origin. Easily interpretable polymorphisms were observed in transferrin (variants A, B1, B2, C) and vitamin D binding protein, GC (variants D, F, I, S). Great variability was observed in the protease inhibitors PI2, PI3, PI4, PI5, and PI8 and in unidentified zones in the vicinity of albumin, but no genetical or physiological interpretation for this variability is yet available. Haemopexin, alpha 1 glycoprotein, protease inhibitors PI1, PI6 and PI7 were monomorphic.

Alleles↗

PubMed1999

Variant genotypes of the low-affinity Fcgamma receptors in two control populations and a review of low-affinity Fcgamma receptor polymorphisms in control and disease populations.

Fcgamma-receptors (FcgammaR) provide a critical link between humoral and cellular immunity. The genes of the low-affinity receptors for IgG and their isoforms, namely, FcgammaRIIa, FcgammaRIIb, FcgammaRIIIa, FcgammaRIIIb, and SH-FcgammaRIIIb, are located in close proximity on chromosome 1q22. Variant alleles may differ in biologic activity and a number of studies have reported the frequencies of variant FcgammaR alleles in both disease and control populations. No large study has evaluated the possibility of a nonrandom distribution of variant genotypes. We analyzed 395 normal individuals (172 African Americans [AA] and 223 Caucasians [CA]) at the following loci: FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb, including the SH-FcgammaRIIIb. The genotypic distributions of FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb conform to the Hardy-Weinberg law in each group. There was no strong evidence that combinations of 2-locus genotypes of the 3 loci deviated from random distributions in these healthy control populations. The distribution of SH-FcgammaRIIIb is underrepresented in CA compared with AA (P < .0001) controls. A previously reported variant FcgammaRIIb was not detected in 70 normal individuals, indicating that this allele, if it exists, is very rare (<1%). In conclusion, we present data that should serve as the foundation for the interpretation of association studies involving multiple variant alleles of the low-affinity FcgammaR.

Alleles↗

PubMed1987

Suspected intracardiac masses: evaluation with MR imaging.

Electrocardiographically gated magnetic resonance (MR) imaging was used to examine 34 patients believed or known to have intracardiac masses on the basis of results from two-dimensional (2D) echocardiography. Cardiac masses were confirmed in 15 patients on the basis of MR imaging results. In seven patients, MR imaging confirmed the absence of an intracardiac mass but demonstrated an anatomic variant or other abnormality that had been interpreted as a possible mass on the echocardiogram. In 12 patients, MR demonstrated neither an intracardiac mass nor an anatomic variant that was likely to have been misinterpreted as a mass on the echocardiogram. Clinical follow-up in these patients at 10 months to 2 years and repeat 2D echocardiography have not indicated a definite mass. In six patients tissue characterization of the mass with MR imaging added some specificity to the MR diagnosis. Thus, MR imaging can be used to verify intracardiac masses found on 2D echocardiograms and to exclude a mass as the cause of equivocal findings on 2D echocardiography.

Adolescent↗

PubMed2026

Equity in genome sequencing for rare disease diagnosis: a cross-sectional analysis of data from the UK 100,000 Genomes Project.

BACKGROUND: Genome sequencing has improved rare disease diagnosis and is now part of routine clinical care in the National Health Service in England. Automated prioritisation pipelines narrow millions of variants per patient to a small subset for clinical review, a process that relies on allele frequency resources that do not fully represent human genetic diversity. We assessed ancestry-related differences in variant prioritisation and diagnostic outcomes in patients from the UK 100,000 Genomes Project. METHODS: We analysed 29,405 rare disease probands with genome sequencing and linked clinical outcomes data. We used multivariable regression to assess ancestry-related differences in the number of variants prioritised for clinical review, the proportion of prioritised variants that were recorded as diagnostic, and diagnostic yield. We also evaluated the use of ancestry-stratified allele frequency filters derived from an independent, diverse UK cohort (n = 33,724). FINDINGS: Compared with the European ancestry group, the East African group had nearly three times more variants prioritised for clinical review (IRR 2.77, 95% CI 2.33-3.29). Other non-European groups also had significantly higher counts. Diagnostic yield was similar across ancestry groups after adjustment (LRT p = 0.1650). Prioritised variants were less likely to be recorded as diagnostic in East African (OR 0.32, 95% CI 0.22-0.46), West African (0.47, 0.39-0.57), South Asian (0.65, 0.58-0.73), and Middle Eastern (0.68, 0.54-0.86) groups. Applying ancestry-stratified allele-frequency filters removed 3.1% of prioritised variants overall-24.3% in the East African group-without loss of diagnostic sensitivity, including 29.5% of recorded VUS in this group. INTERPRETATION: Differences in the likelihood of prioritised variants being recorded as diagnostic partly reflect limitations of current allele frequency resources, which use broad population groupings that mask within-group diversity. Increased representation of diverse ancestries in reference databases and better estimation of ancestry-appropriate allele frequencies will help reduce inefficiencies and improve equity in variant prioritisation for rare disease diagnosis. FUNDING: The UK Department of Health and Social Care and the EU's Horizon 2020 Research and Innovation Programme.

Humans↗

PubMed2025

Predicting natural variation in the yeast phenotypic landscape with machine learning.

Most organismal traits result from the complex interplay of many genetic and environmental factors, making their prediction difficult. Here, we used machine learning (ML) models to explore phenotype predictions for 223 traits measured across 1011 genome-sequenced Saccharomyces cerevisiae strains isolated worldwide. We benchmarked a ML pipeline with multiple linear and non-linear models to predict phenotypes from genotypes and gene expression, and determined gradient boosting machines as the best-performing model. Gene function disruption scores and gene presence/absence emerged as best predictors, suggesting a considerable contribution of the accessory genome in controlling phenotypes. The prediction accuracy broadly varied among phenotypes, with stress resistance being easier to predict compared to growth across nutrients. ML identified relevant genomic features linked to phenotypes, including high-impact variants with established relationships to phenotypes, despite these being rare in the population. Near-perfect accuracies were achieved when other phenomics data mostly in similar conditions were used, suggesting that useful information can be conveyed across phenotypes. Overall, our study underscores the power of ML to interpret the functional outcome of genetic variants.

Genetic Variation↗