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At least 37 records · Page 2Linked to original sources
PubMed1997

Tumor-specific expression of alternatively spliced estrogen receptor messenger ribonucleic acid variants in human pituitary adenomas.

The well documented mitogenic and hormone regulatory effects of estrogen (E2) on pituitary cells are mediated via its nuclear receptor (ER), a cellular homolog of v-erbA oncogene. ER isoforms generated by alternative exon splicing, termed ER variants delta 2ER to delta 7ER, have been identified in breast cancer and have been postulated to have important pathogenetic and clinical implications in tumorigenesis and/or development of hormone resistance. Because pituitary tumors, particularly prolactinomas, are known to be E2-dependent, we investigated alternatively spliced ER variant messenger ribonucleic acid expression in 40 human pituitary tumors of various phenotypes and normal pituitary tissues, using reverse transcription-PCR and Southern blot analyses. Nine of 11 prolactinomas readily expressed multiple ER variants (delta 2ER, delta 4ER, 5ER, and delta 7ER), whereas 6 of 11 tumors showed faint expression of delta 3ER. Four of 7 glycoprotein hormone-producing tumors that synthesized FSH beta expressed delta 2ER, delta 5ER, and delta 7ER. In 9 GH- and 10 ACTH-secreting tumors examined, the expression of normal and variant ER was restricted to tumors that also exhibited scattered PRL immunoreactivity. Variant and normal ER were not found in three null cell tumors (oncocytomas) that showed negative immunoreactivity for all pituitary hormones or their subunits. In contrast, only delta 4ER and delta 7ER were uniformly detected in normal pituitaries. delta 6ER was not detected in any normal or neoplastic pituitary specimen studied. We conclude that multiple alternatively spliced ER variants are coexpressed with normal ER in a tumor phenotype-specific manner. In addition, ER variants delta 2ER and delta 5ER were found to be tumor specific. Future functional studies will be required to determine whether coexpression of multiple ER variants along with normal ER confers a pathophysiological role in pituitary hormone regulation and/or tumor cell proliferation.

Adenoma↗
PubMed1994

Failure of the splicing variant p65 delta of the NF-kappa B subunit p65 to transform fibroblasts.

A naturally occurring splice variant of the p65 subunit of the inducible transcription factor NK-kappa B, called p65 delta, has recently been reported to transform rat-1 fibroblasts in transfection experiments. Criteria for transformation included focus formation, growth in soft agar and tumor formation in athymic mice. In the present study we provide evidence that p65 delta cannot transform either rat-1 or rat-2 cells although p65 delta was efficiently expressed and showed all transcriptional activities reported previously. Eleven rat-1 fibroblasts cells lines selected for stably overexpressing p65 delta also showed neither focus formation nor anchorage-independent growth in soft agar. No transformation of primary rat fibroblasts was evident when p65 delta was cotransfected with either ras or myc oncogenes, whereas a combination of the two oncogenes caused focus formation. We submit that the transforming potential of p65 delta is highly conditional and presumably restricted to a particular subclone of rat-1 cells.

Animals↗
PubMed2002

Hb A2-Monreale [delta146(HC3)His-->Arg], a novel delta chain variant detected in west Sicily.

We report a novel mutation, Hb A2-Monreale [delta146(HC3)His-->Arg], detected by cation exchange high performance liquid chromatography in a family from West Sicily. The mutation is due to a CAT-->CGT substitution at codon 146 of the delta-globin gene. The two carriers had reduced levels of normal Hb A2 (1.1%), but comparable levels (0.9%) of the Hb A2 variant. Most likely the new variant has the same characteristics as Hb Cochin-Port Royal [beta146(HC3)His-->Arg], that is stable but has a 75% reduction of the Bohr effect. The finding of the new variant increases the genotype heterogeneity of the delta-globin gene in the Mediterranean area, and is relevant to the study and prevention of Cooley's Anemia.

Adult↗
PubMed1989

Hb A2-Wrens or alpha 2 delta 2 98(FG5) Val----Met, an unstable delta chain variant identified by sequence analysis of amplified DNA.

Data are reported for an 85-year-old black make who had an HPFH condition on one chromosome and a suspected 'delta-thalassemia' on the other. Sequence analysis of amplified DNA of an appropriate segment of the delta-globin gene identified a GTG to ATG mutation for codon 98 and thus a Val----Met replacement in the delta chain. This abnormality was confirmed by hybridization of amplified DNA with 32P-labeled synthetic probes and by the amino-acid composition of the isolated tryptic peptide delta T-11. Thus, the 'delta-thalassemia' is caused by the presence of an Hb A2 variant that is considered to be unstable to a similar extent as is Hb Köln, its beta chain counterpart.

Aged↗
PubMed1982

Hb A2-Canada or alpha 2 delta 2 99(G1) Asp replaced by Asn, a newly discovered delta chain variant with increased oxygen affinity occurring in cis to beta-thalassemia.

An Indian family is described in which the father has a delta chain abnormal hemoglobin which is the result of a mutation of the delta gene in cis to a beta-thalassemia heterozygosity. The abnormality concerns a substitution of the Asp residue in position 99 (G1) by an Asn residue. A similar substitution has been found in the beta chain of Hb Kempsey (alpha 2 beta 2 99 Asp replaced by Asn). The observed abnormality results in a greatly increased oxygen affinity of this newly discovered Hb A2 variant.

Adolescent↗
PubMed1986

The use of monoclonal antibodies to quantify the levels of sialoglycoproteins alpha and delta and variant sialoglycoproteins in human erythrocyte membranes.

By using radioiodinated monoclonal antibodies we have estimated that there are about 600 000 copies of sialoglycoprotein alpha (synonym glycophorin A) and 80 000 copies of sialoglycoprotein delta (synonym glycophorin B) per normal human erythrocyte. Erythrocytes expressing the product of only one alpha gene contain about 300 000 copies of alpha/cell. Two erythrocyte types containing alpha-delta hybrid molecules were studied. Those with heterozygous expression of the (alpha-delta)Mi.V gene contain about 100 000 alpha-delta copies per cell, whereas those with heterozygous expression of the En(UK) gene contain about 80 000 alpha-delta copies/cell. Erythrocyte types containing delta-alpha hybrid molecules were also studied. About 200 000 copies of (delta-alpha)Dantu were measured in cells with heterozygous expression of the (delta-alpha)Dantu gene (donor M.P.), whereas about 315 000 copies of the putative (delta-alpha)Dantu hybrid were found on the erythrocytes of donor J.O. [which also have heterozygous expression of the putative (delta-alpha)Dantu gene]. The erythrocytes of donor M.P. have normal levels of alpha, whereas those of donor J.O. have only about half-normal levels. It is proposed that the hybrid sialoglycoprotein of donor J.O. is of alpha-delta-alpha composition [(alpha-delta-alpha)Dantu] rather than delta-alpha and results from a double cross-over analogous to that which gives rise to haemoglobin Parchman.

Antibodies, Monoclonal↗
PubMed1985

Hemoglobin A2 Honai (alpha 2 delta 2(90)(F6)Glu----Val): a new delta chain variant.

A new slow-moving variant of hemoglobin(Hb) A2, designated as Hb A2 Honai, was found to have an amino acid substitution of valine for glutamic acid at position 90(F6) in the delta chain. Hb A2 Honai comprised 0.84% of total hemoglobin. Hb A2 and Hb A were estimated to be 1.30% and 97.85%, respectively. Hb A2 Honai was observed in 4 members of a family in 3 generations. No hematologic abnormalities were associated with Hb A2 Honai.

Aged↗
PubMed1966

Hemoglobin Sphakiá: a delta-chain variant of hemoglobin A2 from Crete.

A new variant of the normal minor component Hb A(2) has been detected in a family that lives in Sphakiá, Crete. Chemical studies of this abnormal hemoglobin, designated Hb A(2) delta Sphakiá, indicates a substitution of the histidyl residue number two of the delta-chain by an arginyl residue.

Adult↗
PubMed2025

Unveiling the Dynamics of SARS-CoV-2 Gamma and Delta Waves in Paraná, Brazil - Delta Displacing a Persistent Gamma Through Alternative Routes of Dispersal.

The Gamma and Delta variants of concern (VOCs) of SARS-CoV-2 drove the second and third wave in Brazil and significantly intensified the number of cases and deaths. In this study, we investigate the timeline and origins of the Gamma and Delta variants using a spatiotemporal analysis based on 1508 genomes collected between March and September 2021 from health administrative regions in Paraná state, Brazil. Our findings indicate that community transmission of Gamma-P.1 began in late 2020, with substantial contributions from the Northeast and North regions. In contrast, our analysis of the Delta-AY.101 genomes underscored the crucial role of Paraná in national-level transmission dynamics beginning in late March 2021. At a local level, the movement estimates inferred from the monophyletic clades showed that the Curitiba health region was the primary source for Gamma-P.1, with a substantial contribution from Londrina. This health-region also emerged as an important hub for Delta-AY.101. Our phylogeographical GLM analysis demonstrates that air travel fluxes and population size at the origin of locations were the strongest predictors of shaping SARS-CoV-2 dispersal dynamics within Paraná. In addition, viral load analysis suggests that Gamma-P.1 and Delta-AY.101 may have maintained a similarly high transmissibility potential throughout the evaluated months, providing insights into the prolonged co-circulation dynamics. Our study underscores the relevance of understanding SARS-CoV-2 introductions and regional circulation contributions at the country level to enhance public health preparedness and strengthen local surveillance programs.

Brazil↗
PubMed2023

Phylogeny and evolution of SARS-CoV-2 during Delta and Omicron variant waves in India.

SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2↗
PubMed2006

Expression of Delta DNMT3B variants and its association with promoter methylation of p16 and RASSF1A in primary non-small cell lung cancer.

Despite the role of DNMT3B in de novo DNA methylation, a correlation between DNMT3B expression and promoter DNA methylation has not being established in tumors. We recently reported DeltaDNMT3B, a subfamily of DNMT3B, with seven variants, as the predominant expression forms in non-small cell lung cancer (NSCLC). We hypothesized that expression of the DeltaDNMT3B variants plays a role in promoter methylation formation during lung tumorigenesis. Expression of seven DeltaDNMT3B variants was measured in 119 NSCLCs and the corresponding normal lungs using reverse transcription-PCR. The expression patterns of DeltaDNMT3B variants were analyzed with the status of p16 and RASSF1A promoter methylation in the tumors as well as in patients' clinical variables, including outcomes. Expression of DeltaDNMT3B variants was detected in 94 of 119 (80%) tumors but in only 22 (18%) of the corresponding normal lungs (P < 0.0001). DeltaDNMT3B1, DeltaDNMT3B2, and DeltaDNMT3B4 were the most frequently detected transcripts in the tumors (62%, 76%, and 46%, respectively). The expression of DeltaDNMT3B variants was associated with p16 and RASSF1A promoter methylation in the tumors, but the strongest association was between DeltaDNMT3B4 and RASSF1A. Forty-two of 46 (91%) tumors with RASSF1A promoter methylation expressed DeltaDNMT3B4 compared with only 13 of 73 (18%) tumors without the promoter methylation (P < 0.0001). Strong associations were also observed between expression of the variants in the tumors and in patients' clinical outcomes. Expression of DeltaDNMT3B variants is common in NSCLC and may play an important role in the development of promoter methylation.

Adult↗
PubMed2001

Existence of variant gamma delta T cells in Crohn's disease.

BACKGROUND AND OBJECTIVES: gamma delta T cell populations are well-known for their unique distribution (e.g. intra-epithelial lymphocytes). Though their ligands play a major role in the immune response they have remained largely obscure. To shed light on this issue, we have analyzed in this study the complementarity determining region (CDR) 3 of the T cell receptor (TCR) V delta 2 chains. This provides an insight into the antigenic immune response in the intestinal mucosa in sickness and health. METHODOLOGY: Total RNA was extracted from surgically resected intestinal mucosa of patients with Crohn's disease (CD) and controls. TCR V delta 2 cDNA was PCR-amplified using V delta 2 sense primer and C delta antisense primer. The PCR products were then subcloned in pUC18 plasmid. From each sample, 20 subclones were randomly selected and subjected to nucleotide sequence analysis. RESULTS: Sequence analysis revealed that the CDR3 sequences of the TCR V delta 2 chains were unique to each individual. The evidence also showed a significant restriction of the junctional diversity of the TCR V delta 2 chains while no such restriction was found for CD. CONCLUSIONS: The marked complexity of the TCR V delta 2 junctional sequences and the oligoclonality of the TCR V delta 2 genes in the control subjects are indicative of a positive selection and expansion of specific T cells in the normal, healthy condition. In CD patients, however, the expression of distinct, non-overlapping TCR V delta 2 clonotypes can be found, suggesting polyclonal activation of gamma delta T cells in the diseased colon of CD patients. These findings have led us to conclude that accumulation of multiple gamma delta T cell clonotypes may be involved in the pathogenesis of CD.

Crohn Disease↗