Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Variant classification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85Linked to original sources
PubMed1997

Expression of wild-type alpha-catenin protein in cells with a mutant alpha-catenin gene restores both growth regulation and tumor suppressor activities.

Recent studies indicate that disruption of the E-cadherin-mediated cell-cell adhesion system is frequently associated with human cancers of epithelial origin. Reduced levels of both E-cadherin and the associated protein, alpha-catenin, have been reported in human tumors. This report describes the characterization of a human ovarian carcinoma-derived cell line (Ov2008) which expresses a novel mutant form of the alpha-catenin protein lacking the extreme N terminus of the wild-type protein. The altered form of alpha-catenin expressed in Ov2008 cells fails to bind efficiently to beta-catenin and is localized in the cytoplasm. Deletion mapping has localized the beta-catenin binding site on alpha-catenin between amino acids 46 and 149, which encompasses the same region of the protein that is deleted in the Ov2008 variant. Restoration of inducible expression of the wild-type alpha-catenin protein in these cells caused them to assume the morphology typical of an epithelial sheet and retarded their growth in vitro. Additionally, the induction of alpha-catenin expression in Ov2008 cells injected into nude mice attenuated the ability of these cells to form tumors. These observations support the classification of alpha-catenin as a growth-regulatory and candidate tumor suppressor gene.

Amino Acid Sequence↗
PubMed1991

Enzymologic studies on patients with methylmalonic aciduria: basis for a clinical trial of deoxyadenosylcobalamin in a hydroxocobalamin-unresponsive patient.

Eleven patients with methylmalonic aciduria have been classified on the basis of detailed enzymology on cultured skin fibroblasts. Nine were classified as mutase deficiencies and were unresponsive to hydroxocobalamin in vivo or in vitro. One was classified as a Cbl A variant and was responsive to hydroxocobalamin therapy in vitro and in vivo. Patient 11 was classified as having deoxyadenosyltransferase deficiency (Cbl B). However, a clinical therapeutic trial of deoxyadenosylcobalamin resulted in no clinical or biochemical improvement. Further studies on the patient's cultured fibroblasts suggested that deoxyadenosylcobalamin fails to reach the mitochondria in an intact form. These studies show that detailed enzymologic classification is essential for the reliable evaluation of the response to therapeutic maneuvers; complementation studies alone may be inadequate to completely classify these patients. Therapy with deoxyadenosylcobalamin offers no advantages over the use of hydroxocobalamin in the treatment of patients with methylmalonic aciduria.

Alkyl and Aryl Transferases↗
PubMedDate not supplied

[A faunistic approach to the classification of an animal population (exemplified by small terrestrial mammals of the Kopet-Dag)].

A floristic method of vegetation classification (after Braun-Blanquet) is applied for classification of animal communities. The latter, by analogy with vegetation, can be dividend into classificatory units differing mutually by their composition. Diagnostic species are used as a basis for such classification. Their names are used in producing syntaxonomic nomenclature of the animal population. Assembly is suggested as a principal classificatory unit within this approach. It is defined as multispecies assemblage of animals from various trophic levels, which form stable population combinations and are similar in their geographic and habitat distributions. The assembly can be further divided into subunits called subassembly and population variant. Five assemblies are identified and described for population of insectivores, rodents and lagomorphs in Kopet-Dag Mts (S. Turkmenistan).

Altitude↗
PubMed1987

Astrocytomas: old and newly recognized variants, their spectrum of morphology and antigen expression.

The relationship between the morphology of astrocytomas and their prognosis is complex, with the localization of the tumour, the predominant cell type and the degree of anaplasia all playing an important part in determining the patient's future. Since many astrocytomas have a diversity of patterns, small needle biopsies taken from just one or a few areas may fail to elucidate the principal features of a given tumour. In addition to the astrocytoma subtypes listed in the WHO's International Histological Classification of brain tumours, new entities have been observed in the last few years. These include lipidized forms, such as the relatively benign pleomorphic xanthoastrocytoma and the highly malignant lipidized glioblastoma. Neoplastic astrocytes are capable of forming basal laminae and of phagocytosis, and often contain alpha-1-antitrypsin, features that may lead to confusing them with histiocytes. They may be arranged in a whorled pattern imitating meningiomas, their myxoid intercellular stroma may assume the morphology of cartilage and closely packed tumour cells in "epithelioid" astrocytomas come close to imitate metastatic carcinoma. Some astrocytomas contain cells indistinguishable from those of granular cell tumours of other tissues. The presence of reactive lymphocytes in astrocytomas and reactive astrocytes in malignant lymphomas can be the source of confusion between those two kinds of neoplasms.

Animals↗
PubMed2001

[Morphological variants of neutrophilic granulocytes in blood of practically normal humans].

Verification of presumed inertness of blood neutrophil granulocytes revealed their morphological heterogeneity in practically healthy donors. At light microscopic level it was expressed as a varying degree of cell cytoplasm granularity--58% of the cells were highly granular, 30% contained moderate amount of granules and 12% were completely devoid of granules. According to the ultrastructural analysis, neutrophils were subdivided into four groups: intact cells (60%), cells with slight (26%), moderate (12%) and severe (2%) changes. The criteria for this classification included changes in neutrophil shape and ultrastructure during its activation: formation of pseudo- and lobopodia, spatial redistribution of organelles, degranulation etc. Presence of neutrophils with the signs of activation in the circulation suggests that the neutrophil system normally is not inert, but is in a state of so-called working tone, thus providing high antibacterial resistance of the macroorganism exposed to natural bacterial environment.

Adult↗
PubMed1975

Unusual intracardiac tumor in a child. Inflammatory pseudotumor or "granulomatous" variant of myxoma?

An intracardiac tumor arising in the right atrium of a young child is reported. Morphologically, the lesion was reminiscent of "plasma cell granulomas," but unprecedented in this location. Based on clinical manifestations, laboratory findings, histologic and ultrastructural characteristics of the mass, the speculation is put forth that this lesion may represent a cardiac myxoma with atypical structural features. An extension of this proposal is a pathogenetic sequence that would try to reconcile the complex clinical course of some myxomas with the described structural observations. Alternative choices for classification of the lesion are also given consideration.

Child, Preschool↗
PubMed2006

Congenital hypothyroidism: from paracelsus to molecular diagnosis.

Endemic cretinism was noted in alpine Europe as early as the 13th century. However, it was only in 1848 that a commission, sponsored by the King of Sardinia, first formally demonstrated its link to goiter. An important landmark was the publication of a report in 1871 describing several cases of nongoitrous hypothyroidism that were clearly distinguished from the endemic form of the disease, for which the author suggested the designation of "sporadic cretinism." Classification of the hypothyroid status was for a long time solely based on clinical observation. In the second half of the 20th century, the use of radionuclides (iodine radioisotope and technetium pertechnetate) allowed a more precise diagnosis and taxonomy into thyroid dysgenesis and dyshormonogenesis. This brief review summarizes the progress that has been achieved during the last 40 years in diagnosing the multiple variants of congenital hypothyroidism (CH). It becomes evident that while accurate diagnosis for CH is readily available, its exact etiology requires a precise molecular investigation as different genes are implicated in the differentiation, migration and growth of the thyroid gland.

Congenital Hypothyroidism↗
PubMed1995

Primary malignant lymphoma of the intestine: clinicopathologic and immunohistochemical studies of 39 cases.

Clinicopathologic and immunohistochemical features in 39 cases of primary intestinal non-Hodgkin's lymphoma (NHL) in Japanese patients were studied. Only resection materials in state IE and IIE-1 were included in this study because of the certainty that the intestine was the primary site of the lymphoma. The updated Kiel classification was used to classify NHL. Histologically, only two cases (5.1%) were follicular lymphomas, and the others were diffuse lymphomas. Twenty-eight patients (71.8%) had high-grade NHL and 11 (28.2%) had low-grade NHL. Twenty (71.4%) of the 28 high-grade NHL were centroblastic lymphomas, and 14 (70.0%) of these 20 cases of centroblastic lymphoma were the polymorphic variant. Ten (90.9%) of the 11 low-grade NHL were low-grade mucosa-associated lymphoid tissue (MALT) lymphomas. Macroscopically, 18 patients had polypoid masses, 17 ulcerative tumors and four had diffusely infiltrating NHL. Seven of the 10 low-grade MALT lymphomas were polypoid masses. Immunohistochemically, 35 lesions (89.7%) were of the B cell phenotype and three (7.7%) were of the T cell phenotype. In the remaining case, the cell lineage could not be determined. No lesions were considered to be of histiocytic origin. The 5 year survival rate for high-grade B cell lymphomas was poorer than for low-grade B cell lymphomas, and the present study indicated that the histological grade of the intestinal B cell lymphomas was a prognostically significant factor.

Adolescent↗
PubMed2006

[Post-cholecystectomy syndrome: the modern view of the problem].

The authors summarize and systematize literature data and their own observations concerning post-cholecystectomy syndrome (PCES), the reasons for and the mechanisms of its development, its clinical variants etc. The authors suggest the following PCES forms should be distinguished: functional ("egenuine") forms, which develop due to gall bladder removal and the loss of its functions, and organic ("conditional") PCES forms, which develop as a consequence ofaflawy surgery and/or preoperative complications of chronic calculous cholecystitis, which dominate in the postoperative clinical picture and are mistakenly considered cholecystectomy consequences. An original operational classification of PCES is adduced; possibilities provided by contemporary instrumental and laboratory techniques of differential diagnostics are considered; differential treatment and prophylaxis of PCES are described.

Diagnosis, Differential↗
PubMed1986

[Prospects and approaches to improving pathologo-anatomic services from the standpoint of the therapist].

The paper defines the morphologic basis of modern clinical medicine as one of the determining factors of its further development. Approaches to improvement of studies of the life-time biopsy specimens are discussed, as well as variants of cooperation between the pathoanatomists and clinical morphologists. The system of pathoanatomical reports, the work of treatment- and- control commissions and conferences on clinical anatomy are considered from the physician's point of view. Optimal measures should be taken to make the analysis of the physician's errors comprehensive and useful. Combined efforts are needed for the further improvement of the nomenclature, classification and terminologic characteristics of the diseases. Closer interactions between the pathoanatomists and therapists are suggested.

Biopsy↗
PubMed1981

[Primary centrocytic lymphoma of the skin: diagnosis, course and therapy (author's transl)].

A primary B-cell lymphoma of the skin is described, showing the clinical picture of a lymphadenosis cutis circumscripta. According to the Kiel classification, it has been classified as a centrocytic lymphoma (centrocytoma) belonging to the low-grade malignancy group. The centrocytoma is a newly defined type of lymphoma which is not identical with any earlier entity of lymphoreticular neoplasia. Although the centrocytoma is said to occur relatively often in the skin, the present case report seems to be the first clinical description of this variant. In our patient a solitary tumor of the face was found, which had slowly enlarged since 3 1/2 years. No lymph node and no systemic involvement were detectable. With a telecobalt-60 treatment up to a total of 40 Gy (= 4,000 rad) a complete involution could be achieved without recurrence 6 months after radiotherapy had been finished. In contrast to the centrocytoma of lymphonodal origin, the primary cutaneous type may obviously remain localized for a long time with low tendency to progression.

Female↗
PubMed1994

The pathology of low-grade adenosquamous carcinoma of the breast. An immunohistochemical study.

Low-grade adenosquamous carcinoma of the breast is a variant of metaplastic mammary carcinoma characterized by a locally invasive growth pattern and a low risk for metastases. In this study none of the carcinomas exhibited greater than 5 percent nuclear immunoreactivity for estrogen or progesterone receptors, and as a result they were classified as negative for these receptors. Reactivity for cathepsin D was found in 39 percent of the tumors, largely limited to areas of epidermoid differentiation. Membrane immunoreactivity for HER-2/neu oncogenes was present in glandular components of 46 percent of the carcinomas. Immunoreactivity for p53 (greater than 10 percent of nuclei) was present in 13 percent of the tumors, also in glandular elements. Six different patterns of coexpression of p53, HER-2/neu and cathepsin D were found, the most frequent being the following: HER-2/neu(+), p53(-), cathepsin D(-) (9 cases, 39%); cathepsin D(+), p53(-), HER-2/neu(-) (5 cases, 22%); and the three markers negative (5 cases, 22 percent). Coexpression of the two oncogenes was found in only one tumor which was also positive for cathepsin D. These results indicate that the expression of various immunohistochemical prognostic markers may be heterogeneous and that there may not be a specific pattern of marker coexpression within a carefully defined histologic subtype of mammary carcinoma. Furthermore, characteristics reported to be associated with an unfavorable prognosis (negative hormone receptors, presence of cathepsin D, and expression of oncogenes such as HER-2/neu) may be found in a substantial proportion of tumors that comprise this clinically and histologically low-grade variant of mammary carcinoma. This disassociation between expected prognosis based on expression of current prognostic markers and observed prognosis occurs in other forms of mammary carcinoma. Medullary carcinoma, when diagnosed on the basis of rigorously defined criteria, has an excellent prognosis despite the fact that these tumors are characterized by absence of estrogen and progesterone receptors and a high proliferative rate. The histological classification of mammary carcinomas is itself an important prognostic variable that may take precedence over selected biochemical markers.

Adult↗
PubMed1998

[Characteristics of spasm-induced vessels in patients with vasospastic angina and a history of syncope].

One hundred and eighty-seven consecutive patients with vasospastic angina and coronary spasm provoked by intracoronary injection of acetylcholine and/or ergonovine were treated from January 1991 to June 1997. Fifteen of these patients, 14 men and one woman (mean age of 63 years old), had a history of syncope. There were no significant differences in the distribution of induced spasm vessels, single spasm vs multiple spasms, variant angina pectoris and organic stenosis (< 75%) between patients with and without a history of syncope. There were no significant differences concerning the distribution of the sites of induced spasm in the circumflex artery and left anterior descending artery between the two groups. However, coronary spasm in the proximal portion of the right coronary artery (segment 1 or 2 according to the functional classification of American Heart Association) occurred more frequently in patients with a history of syncope [80.0% (12/15) vs 45.3% (78/172); p < 0.05]. Twelve of the 96 patients with coronary spasm in the proximal portion of the right coronary artery had a history of syncope, so these patients require careful management.

Acetylcholine↗
PubMed2001

Human immunodeficiency virus type 1 reverse-transcriptase and protease subtypes: classification, amino acid mutation patterns, and prevalence in a northern California clinic-based population.

Phylogenetic analysis of the reverse transcriptase (RT) and protease of 117 published complete human immunodeficiency virus (HIV) type 1 genome sequences demonstrated that these genes cluster into distinct subtypes. There was a slightly higher proportion of informative sites in the RT (40.4%) than in the protease (34.8%; P= .03). Although most variation between subtypes was due to synonymous nucleotide substitutions, several subtype-specific amino acid patterns were observed. In the protease, the subtype-specific variants included 7 positions associated with drug resistance. Variants at positions 10, 20, 36, and 82 were more common in non-B isolates, whereas variants at positions 63, 77, and 93 were more common in subtype B isolates. In the RT, the subtype-specific mutations did not include positions associated with anti-retroviral drug resistance. RT and protease sequences from 2246 HIV-infected persons in northern California were also examined: 99.4% of the sequences clustered with subtype B, whereas 0.6% clustered with subtype A, C, or D.

Amino Acid Sequence↗
PubMed1993

Molecular variation in trypanosomes.

Several species of the genus Trypanosoma cause parasitic diseases of considerable medical and veterinary importance throughout Africa, Asia and the Americas. These parasites exhibit considerable intra-species genetic diversity and variation, which has complicated their taxonomic classification. This diversity and variation can be defined at the level of both the genome and of individual genes. The nuclear genome shows considerable inter- and intra-species plasticity in terms of chromosome number and size (molecular karyotype). The mitochondrial (kDNA) genome also varies considerably between species, especially in terms of minicircle size and organization. There is also considerable intra-specific sequence diversity in minicircles and within the Variable Region of the maxicircle. Restriction enzyme analysis of this diversity has lead to the concept of 'schizodemes'. At the gene level, isoenzyme analysis has proven very useful for strain and isolate identification, with the classification into numerous 'zymodemes'. Considerable antigenic diversity has also been identified in T. cruzi and T. brucei, with the development of 'serodemes' in the latter. In addition to this inter-strain diversity, African trypanosomes (T. brucei, T. congolense, and T. vivax) exhibit the phenomenon of antigenic variation, where individual parasites are able to express any one of hundreds of different copies of the Variant Surface Glycoprotein gene at any particular time. The molecular mechanisms underlying antigenic variation are now understood in considerable detail. The implication of this molecular diversity and variation are discussed in terms of trypanosome taxonomy and disease control.

Animals↗
PubMed2004

Molecular characterization of uterine clear cell carcinoma.

Clinicopathological studies support a broad classification of endometrial carcinoma into two major types, designated as type I and type II, which correlate with their biological behavior. More recently, molecular studies have provided further insights into this classification scheme by elucidating the genetic events involved in the development and progression of endometrial carcinoma. Microsatellite instability and mutations in the PTEN gene have been widely associated with type I (endometrioid) endometrial carcinoma, while p53 mutations have been identified in the majority of type II endometrial carcinoma, of which uterine serous carcinoma is the prototype. Uterine clear cell carcinoma (UCC) is an uncommon variant of endometrial carcinoma, and clinicopathological studies have produced conflicting results regarding its biological behavior with 5-year survival ranging from 21 to 75%. The molecular characteristics of endometrioid and serous carcinoma have been studied extensively; however, there have been few molecular genetic studies of the clear cell subtype. In this study, we evaluated 16 UCCs (11 pure and 5 mixed) for mutations in the p53 gene, PTEN gene and for microsatellite instability. Although we found that these alterations were uncommon in pure clear cell carcinomas, all three were identified. In addition, two cases of mixed serous and clear cell carcinoma showed an identical mutation of the p53 gene in the histologically distinct components and one case of mixed clear cell and endometrioid carcinoma had identical mutations in the PTEN and p53 genes, and microsatellite instability in both components. Our data suggest that UCC represent a heterogeneous group of tumors that arise via different pathogenetic pathways. Additional molecular studies of pure clear cell carcinoma are required to further elucidate the genetic pathways involved in its development and progression.

Adenocarcinoma, Clear Cell↗
PubMed2006

Salivary mucoepidermoid carcinoma: revisited.

Mucoepidermoid carcinoma (MEC) is a malignant epithelial neoplasm composed of varying proportions of mucous, epidermoid, intermediate, columnar, and clear cells and often demonstrates prominent cystic growth. MEC is usually subclassified as low, intermediate, or high grade on the basis of its histologic features, including the presence of cystic spaces, cellular differentiation, proportion of mucous cells, growth pattern, type of invasion, and cytologic atypia. Because even low-grade neoplasms may metastasize, the term mucoepidermoid tumor is inappropriate. The 3-level grading approach to tumor classification has found general acceptance among pathologists; differences in biologic behavior can be demonstrated even though clinical stage has become a better prognosticator. However, in the case of MEC, no universal agreement exists regarding which histologic grading criteria are most the useful, and grading has varied. These issues have led to the investigation of more subjective systems. We describe these new schemes, the histologic variants of MEC, and the ancillary methods that allow for further stratification of patients with MEC, especially for patients with grade 2 tumors, which have a variable and unpredictable clinical course.

Carcinoma, Mucoepidermoid↗
PubMed1995

Sequence analysis of hepatitis C virus genotypes 1 to 5 reveals multiple novel subtypes in the Benelux countries.

Hepatitis C virus (HCV) isolates from a cohort of 315 patients from the Benelux countries (Belgium, The Netherlands, Luxembourg) were genotyped by means of reverse hybridization Inno-LiPA (line probe assay). Genotypes 1a, 1b, 2a, 2b, 3a, 4a and 5a were detected. From the cohort, isolates representing all types and those showing an aberrant LiPA pattern were further analysed by sequencing parts of the 5' UTR, core (nt 1 to 326; aa residues 1 to 108) and core/E1 (nt 477 to 924; aa residues 159 to 308) regions. Molecular evolutionary analysis of the core and core/E1 regions allowed discrimination between known and additional subtypes, especially within types 2 and 4. The core region is not suitable for classification of new subtypes because of the relatively high level of conservation. The core/E1 region displays a higher level of sequence variation and allows much more distinct discrimination between subtypes. Genotypes 2 and 4 are particularly heterogeneous, with at least 7 and 10 subtypes, respectively. In contrast to previous reports from Europe, HCV isolates from the cohort constituted a highly heterogeneous population of virus variants, especially within genotypes 2 and 4.

Belgium↗