Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Delta variant”

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 559 records · Page 31Linked to original sources
PubMed1998

Abrogation of mitochondrial cytochrome c release and caspase-3 activation in acquired multidrug resistance.

Acquired multidrug resistance to anti-cancer agents has been associated with overexpression of the P-glycoprotein and other members of the ATP-binding cassette superfamily. The present studies demonstrate that SCC-25 cells selected for resistance to the alkylating agent cisplatin (CDDP) overexpress the anti-apoptotic Bcl-xL protein. In contrast to parental cells, the SCC-25/CDDP-resistant variant failed to exhibit activation of caspase-3, cleavage of protein kinase C delta, and other characteristics of apoptosis in response to CDDP. Similar results were obtained when SCC-25/CDDP cells were exposed to the structurally and functionally unrelated antimetabolite 1-beta-D-arabinofuranosyl-cytosine (ara-C). Other cells selected for resistance to doxorubicin or vincristine also exhibited overexpression of Bcl-xL and failed to respond to CDDP and ara-C with activation of caspase-3. The results further demonstrate that multidrug-resistant cells exhibit a block in the release of mitochondrial cytochrome c into the cytosol and that this effect is dependent on overexpression of Bcl-xL. The demonstration that lysates from the resistant cells respond to the addition of cytochrome c with activation of caspase-3 confirms that the block in apoptosis is because of inhibition of mitochondrial cytochrome c release. These findings demonstrate that cells respond to diverse classes of anti-cancer drugs with overexpression of Bcl-xL and that this response represents another mechanism of acquired multidrug resistance.

Antineoplastic Agents↗
PubMed1998

Carbapenems as inhibitors of OXA-13, a novel, integron-encoded beta-lactamase in Pseudomonas aeruginosa.

A clinical Pseudomonas aeruginosa strain, PAe391, was found to be resistant to a number of antibiotics including ticarcillin, piperacillin, cefsulodin and amikacin, and a disk diffusion assay showed evidence of pronounced synergy between imipenem and various beta-lactam antibiotics. Cloning and nucleotide sequence analysis revealed the dicistronic arrangement of an aac(6')-Ib variant and a novel blaOXA-type gene between the intI and qacE delta 1 genes typical of integrons, in PAe391, this integron was apparently chromosome-borne. The beta-lactamase, named OXA-13, displayed nine amino acid changes with respect to OXA-10:I in position 10 of OXA-10 to T (I10T), G20S, D55N, N73S, T107S, Y174F, E229G, S245N and E259A, OXA-13 (pIapp = 8.0) showed poor catalytic activity against penicillins as well as cephalosporins, but was efficient in hydrolysing some penicillinase-resistant beta-lactams, such as cefotaxime and aztreonam. It was efficiently inhibited by imipenem (KIapp = 11 nM), and formed a stable complex. While the KIapp value of meropenem was similar (16 nM), the corresponding complex was less stable.

Anti-Bacterial Agents↗
PubMed1995

Inhibition of pulmonary metastases and tumor cell invasion in experimental tumors by sodium D-glucaro-delta-lactam (ND2001).

Sodium D-glucaro-delta-lactam (ND2001) inhibited spontaneous pulmonary metastases of the highly metastatic B16 melanoma variant with a maximal inhibition rate of 99.5%, and 6 of 7 animals remained metastasis-free. Likewise, ND2001 inhibited the spontaneous pulmonary metastases of both Lewis lung carcinoma (3LL) with a rate of 98.0% (3 of 5 animals remaining metastasis-free) and rat KDH-8 liver carcinoma with a rate of 82.5% (3 of 7 animals remaining metastasis-free), although it was unable to inhibit the metastases of mouse BMT-11 fibrosarcoma and rat SST-2 breast carcinoma. Pretreatment with ND2001 in vitro inhibited the pulmonary metastases of the B16 variant and 3LL cells, which indicates direct action upon the cancer cells. When the invasive activity of cancer cells was measured by the Boyden chamber method, the number of invading B16 variant or 3LL cells was reduced with maximal inhibition rates of 93.0% or 89.9%, respectively, but pretreatment with ND2001 failed to reduce the invasive activity of BMT-11 or SST-2 cells. ND2001 showed neither cytocidal nor antitumor activity. These results suggest that ND2001 inhibited pulmonary metastases at the invasive step into the basement membrane by directly changing some property of the tumor cells.

Animals↗
PubMed1979

Haemoglobin Lepore trait: haematological and structural studies on the Italian population.

Haematological data on 59 heterozygotes for haemoglobin (Hb) Lepore and 10 double heterozygotes for Hb Lepore and beta thalassaemia from 36 Italian families are reported. The red cell indices are defined and compared with those of groups of non-thalassaemic and beta thalassaemic subjects of comparable number, age and sex distribution. The relative level of each haemoglobin fraction and the absolute production of single polypeptide chains are calculated in order to compare the expression of the non-alpha chain genes in Hb Lepore trait and beta thalassaemia. Structural studies demonstrate that the haemoglobin Lepore is of the Boston type (delta 87 beta 116) in all subjects, confirming that this type of fusion variant is probably the only one which occurs in Mediterranean populations. The distribution and incidence of the Lepore haemoglobinopathy are discussed.

Adult↗
PubMed1982

Hemoglobin Parchman: double crossover within a single human gene.

Structural analysis of a new variant hemoglobin revealed tryptic peptides with the amino acid composition of normal delta-globin, except for two internal peptides, which had the compositions of normal beta-globin. The most likely explanation for these findings is that a double, nonhomologous crossover between the delta-and beta-globin genes had occurred.

Amino Acid Sequence↗
PubMed2004

Expression of estrogen receptors alpha and beta in human osteoblasts: identification of exon-2 deletion variant of estrogen receptor beta in postmenopausal women.

BACKGROUND: Postmenopausal osteoporosis is associated with estrogen deficiency. Estrogens have effects on bone metabolism, which are mediated by estrogen receptors (ERs). If estrogen responsiveness is related to the ER expression level, ER expression in postmenopausal women should be different from previous studies using osteoblast lineage. We investigated the expression of variant isoforms of ER messenger ribonucleic acid (mRNA) in osteoblasts (OB) from postmenopausal women and a human osteosarcoma cell line, MG 63. METHODS: Osteoblast cultures were prepared from the upper femur of postmenopausal patients or MG 63. For OB cultures at 5, 10, 15, 20, and 25 days, the expressions of ERalpha and beta mRNA were examined using reverse transcriptase-polymerase chain reaction. RESULTS: In MG 63, ERbeta mRNA was constantly and highly expressed during the 25-day culture, whereas ERalpha mRNA was barely detected. In the primary OB cells, both ERalpha and beta mRNA were transcribed during the 25-day culture, but expression of ERalpha mRNA was much stronger than that of ERbeta mRNA. A splice variant form of ERbeta mRNA that was missing the entire exon 2 (ERbeta delta 2) was detected and heterogeneously expressed in OB cultures from 16 postmenopausal women. CONCLUSION: Differential expressions of these ER isoforms suggest that they may have different functions or that they interact with each other during bone metabolism. The different ratio of ERbeta to ERbeta delta 2 mRNA or ERalpha to ERbeta mRNA expressions in osteoblast cultures may be related to different bone conditions. Whether the presence of ERbeta delta 2 in postmenopausal women influences the biological properties of bone needs to be determined.

Bone Neoplasms↗
PubMed1990

Association of the human CD3-zeta chain with the alpha beta-T cell receptor/CD3 complex. Clues from a T cell variant with a mutated T cell receptor-alpha chain.

The TCR for Ag, on the majority of human T cells, is a disulfide-linked heterodimer composed of TCR-alpha and -beta chains noncovalently associated with the monomorphic CD3 complex composed of the CD3-gamma, -delta, -epsilon, and -zeta chains. The interactions involved in the assembly of the various components of this multimeric protein complex are not fully understood. In this report, a variant of the human leukemic T cell line Jurkat that synthesized all of the known components of the TCR/CD3 complex but fails to express the TCR/CD3 complex at the cell surface is further characterized. This variant, J79, has a mutated TCR-alpha chain that does not affect the assembly of the pentameric form (TCR-alpha beta-CD3-gamma delta epsilon) of the TCR/CD3 complex but inhibits the assembly of the CD3-zeta homodimer with the rest of the complex (TCR-alpha beta-CD3-gamma delta epsilon----TCR-alpha beta-CD3-gamma delta epsilon zeta 2). Transfecting a wild-type TCR-alpha gene into J79 reconstituted expression of a complete functionally competent TCR/CD3 complex at the cell surface. The results indicate that the TCR-alpha chain plays a crucial role in the assembly of the CD3-zeta homodimer with the pentameric form of the TCR/CD3 complex.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Structural alterations of chromosome 2 in Leishmania major as evidence for diploidy, including spontaneous amplification of the mini-exon array.

We have utilized pulsed field electrophoresis to characterize several karyotypic alterations in Leishmania major. Promastigotes of the LT252 line contain three small chromosomes, of 300, 350 and 385 kb. Quantitative densitometry of ethidium bromide-stained gels suggest that these chromosomes are present in equal levels (2:2:2). Two derivatives of this line, one appearing spontaneously (LT252 delta) and one obtained following selection with methotrexate (11-MTXR20), exhibit altered levels of these chromosomes, in the ratio of 2:1:3, respectively. The variant pattern in both lines is due to an increase in size of chromosome 2, yielding a new chromosome similar in size to chromosome 3. The enlarged chromosome 2 of the LT252 delta line is a result of amplification of the mini-exon gene array normally located on this chromosome, which increases from about 93 to 150 copies of the 0.44-kb mini-exon tandem repeat, as shown by quantitative hybridization and sizing of the mini-exon array. In contrast, the increased size of chromosome 2 within the methotrexate-resistant mutant 11-MTXR20 is not due to mini-exon amplification. In both variant lines, there are equal levels of the wild-type and enlarged chromosome 2, and the wild-type chromosome 2 is now present at 50% of the level of chromosome 1. These and other data suggest that Leishmania is diploid for chromosomes bearing housekeeping genes such as the mini-exon locus.

Animals↗
PubMed1991

Expression and function of a variant T cell receptor complex lacking CD3-gamma.

A T cell line termed DIL2 has been derived from an infant with a polyclonal T cell receptor (TCR)/CD3 cell surface expression defect. Indirect immunofluorescence showed that the expression of certain TCR/CD3 epitopes (like those detected by WT31 and BMA031 monoclonals) was strongly reduced (around five-fold) on DIL2, whereas other epitopes (like those detected by SP34 and Leu4) were only around two-fold lower than in normal T cell lines. Specific immunoprecipitates of surface-radioiodinated DIL2 cells contained TCR-alpha, TCR-beta, CD3-delta, CD3-epsilon and TCR-zeta chains, but lacked CD3-gamma. This structural TCR/CD3 variant was, however, capable of transducing certain activation signals, since normal proliferation and a low but significant calcium flux was observed in DIL2 cells after engagement with specific antibodies. Our data suggest that a functional TCR/CD3 complex can be expressed on the surface of T cells in the absence of CD3-gamma.

Antibodies, Monoclonal↗
PubMed1981

The gamma chain heterogeneity of fetal hemoglobin in black beta-thalassemia and HPFH heterozygotes.

High pressure liquid chromatography (HPLC) was applied to the HbF isolated from blood of numerous black patients with beta-thalassemia trait or homozygosity, G gamma-delta beta-thalassemia trait, G gamma A-gamma HPFH heterozygosity, or the G gamma-[delta+ beta+]-HPFH condition. The method allowed an accurate evaluation of the relative quantities of three types of gamma-chain (G gamma, A gamma I, A gamma T) in the fetal hemoglobins. The results have shown the following. (A) The incidence of the A gamma T-chain in beta-thal heterozygotes and G gamma A gamma-HPFH heterozygotes is about the same as has been observed in black newborn; about one of five blacks are heterozygous for this A gamma-chain variant. The A gamma T-chain was not detected in the nine G gamma-delta beta-thal heterozygotes nor in the eight G gamma-[delta+ beta+]-HPFH heterozygotes. (B) In most cases, the A gamma T-chain was produced by the A gamma gene in trans to the beta-thal or HPFH determinant. The contribution by the gamma-chain genes in trans to the beta-thal or HPFH determinant is about 15% of the total gamma-chain production in both conditions. (C) Three black beta-thal heterozygotes (and five additional relatives) had the A gamma T gene in cis to the beta-thal determinant. Four of these patients had a low levels of G gamma-chain (the "adult" level), and the contribution by the A gamma gene in cis to the beta-thal determinant was about three times that of the A gamma gene in trans. The four additional patients, all members of one family, had a high level of G gamma-chain (the "newborn" level), and the contribution of the A gamma gene in cis was half of that seen in the previously mentioned four patients while that of the A gamma gene in trans was essentially the same. These limited data suggest that the genetic anomaly causing high high G gamma levels in adult beta-thal heterozygotes is linked to the beta-thal determinant and that one of its primary effects is a decreased synthetic expression of the A gamma gene in cis to the beta-thal determinant.

Adolescent↗
PubMed2026

Correlation assessment of SARS-CoV-2 variants and their subvariants present in clinical and wastewater samples in Oregon, USA (February 7, 2021 - February 26, 2022) using the Freyja bioinformatics approach.

BACKGROUND: Wastewater surveillance is a valuable tool for monitoring SARS-CoV-2 at the community level. As the virus diversified into many variants and subvariants that share overlapping mutations, resolving them accurately from wastewater becomes a key bioinformatic challenge. OBJECTIVES AND AIMS: This study evaluated two distinct bioinformatic approaches, multilocus sequence typing (MLST) and Freyja, for identifying SARS-CoV-2 variants and subvariants in Oregon wastewater samples collected from February 2021 to February 2022. METHODS: The MLST approach identified SARS-CoV-2 variants using unique mutations curated from clinical samples. In contrast, the Freyja approach resolved variant and subvariant abundances using genome wide mutation profiles weighted by sequencing depth. In this study, the variant and subvariants relative abundances produced by both approaches were compared against those observed in clinical surveillance data. RESULTS: Both approaches identified SARS-CoV-2 variants at relative abundances that agreed closely with those observed in clinical surveillance data. However, only the Freyja approach identified over 200 Delta subvariants, divided into three clades (21A, 21I and 21J) and two levels (Level 1 and 2) based on Pango subvariants. Delta subvariants showed strong agreement at Level 1 subvariants (rs = 0.892-0.944), while agreement at Level 2 subvariants was inconsistent (rs = 0.324-0.903). CONCLUSIONS: The Freyja approach provided enhanced resolution of SARS-CoV-2 variants and subvariants in wastewater, at abundances that agreed with clinical surveillance. This added resolution is a critical advantage for public health surveillance as SARS-CoV-2 continues to evolve and share mutations across variants and subvariants.

Oregon↗
PubMed2005

Hepatitis C virus genotype distribution in China: predominance of closely related subtype 1b isolates and existence of new genotype 6 variants.

To determine hepatitis C virus (HCV) genotype distribution in China, a total of 148 HCV RNA positive serum samples were collected from nine geographic areas and subjected to RT-PCR followed by direct DNA sequencing and phylogenetic analysis of the core, E1, and NS5B regions. HCV was genotyped in 139 (93.9%) samples. Among them subtype 1b was the most predominant [66% (92/139)] followed by 2a [14% (19/139)]. Of 92 subtype 1b isolates, 35 (38%) and 30 (33%) formed two clusters, designated groups A and B. Group A was prevalent throughout China, while group B was predominant in the central and southern regions. In three cities in the Pearl River Delta, subtype 6a replaced 2a as the second most predominant subtype, and in Kunming (southwest) multiple HCV genotypes/subtypes were present. New variants of HCV genotype 6 were discovered in three samples from Kunming and one in Guangzhou in the Pearl River Delta.

China↗
PubMed1994

Expression of two variants of the human mu opioid receptor mRNA in SK-N-SH cells and human brain.

A partial mu opioid receptor gene was isolated from a human genomic library using a mouse delta opioid receptor cDNA as a probe. Using information from this genomic clone and the published human mu receptor, MOR1, a cDNA was isolated from SK-N-SH mRNA that codes for a variant of the MOR1 mRNA, MOR1A. The presence of MOR1A is also shown in human brain using RT-PCR. MOR1A differs from MOR1 in that the 3' terminal intron has not been removed. An in-frame termination codon is found four amino acids after the 5' consensus splice site, making MOR1A eight amino acids shorter than MOR1. Both receptors show similar ligand binding and coupling to cAMP in CHO-K1 cells. The C-terminal differences between MOR1 and MOR1A could have effects on receptor coupling or receptor transport and localization.

Alternative Splicing↗
PubMed2005

An efficient method to express and refold a truncated human procaspase-9: a caspase with activity toward Glu-X bonds.

A truncated form of human procaspase-9 missing the first 111 amino acids, and a variety of mutants derived therefrom, have been expressed in Escherichia coli inclusion bodies. Upon refolding to active enzymes, Delta(1-111) procaspase-9 and mutants were recovered at purity greater than 95% and with a final yield of 20-35 mg/L cell culture. Our active procaspase-9 retains its pro-segment, while undergoing major auto processing at Asp315 and a minor (20%) cleavage at Glu306. This unusual cleavage at a Glu-X bond also took place in the D315E mutant, and we describe herein the inhibitor Z-VAE-fmk that shows enhanced inactivation of procaspase-9 over caspases-3. The bond at Asp330, not processed by procaspase-9, is cleaved by caspase-3 and the resulting procaspase-9 variant, missing the 316-330 bridge, is six times as active as the non-mutated Delta(1-111) proenzyme. A deletion mutant lacking residues 316-330 underwent auto activation by cleavage at Asp315-Ala331 bond. Moreover, substitution of Glu306 by an Asp residue in this mutant led to rapid removal of the peptide spanning Ser307 to Asp330, and resulted in an enzyme that was 7.6 times as active as the non-mutated Delta(1-111) procaspase-9. Finally, replacing both Asp315 and Glu306 with Ala generated a procaspase-9 mutant incapable of auto processing. This single chain procaspase-9 was fully as active as the non-mutated Delta(1-111) enzyme processed at Asp315 or Glu306. Our demonstration that unprocessed procaspase-9 mutants are active as proteases with caspase-type specificity suggests that the role of procaspase-9 in cascade activation of executioner caspases might, in some circumstances, be carried out alone and without association of the apoptosome.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

Kinetic analysis of the interaction between protein A domain variants and human Fc using plasmon resonance detection.

A real-time biospecific interaction analysis (BIA) was performed to study the specific interaction between the Fc portion of human immunoglobulin G1 (Fc1) and a one domain analogue (designated Z) of staphylococcal protein A, in monovalent (Z) and divalent (ZZ) forms, and five different single amino acid substituted Z variants (L17D, N28A, F30A, I31A, K35A). Experimental BIA data were used to calculate association rate constants (kon), dissociation rate constants (koff) and affinity constants (Kaff). The divalent form (ZZ) showed a higher affinity for Fc1 mainly because of a slower off rate. Out of the five mutant Z proteins, four (L17D, N28A, I31A, K35A) showed a decreased affinity to Fc1 compared to the parent Z molecule. Surprisingly, two (L17D, I31A) of these four had the major effect of a decreased binding energy as a lowered kon while the other two (N28A, K35A) mutant proteins showed an increased koff as the major kinetic difference from Z in their binding to Fc1. For five of the six different Z variants, as well as for the ZZ molecule, calculated Kaff and calculated differences in binding free energies relative to the parent Z molecule (delta delta G), are in good agreement with the corresponding values obtained in a competitive displacement assay using radioactively labeled Z as a tracer (Cedergren et al., (1993) Prot. Eng. 6, 441-448). However, the I31A variant, with a measured kon that was more than three orders of magnitude lower than that of Z in the BIA assay, showed a significantly weaker affinity to Fc1 when calculated from the BIA data compared to the competitive displacement assay. The discrepancy between these two methods for Z(I31A) is discussed as well as possible explanations for the unexpected large effect of lowered kon for two of the mutant Z proteins.

Amino Acid Sequence↗
PubMed1993

High-resolution mapping of the HyHEL-10 epitope of chicken lysozyme by site-directed mutagenesis.

The complex formed between hen egg white lysozyme (HEL) and the monoclonal antibody HyHEL-10 Fab fragment has an interface composed of van der Waals interactions, hydrogen bonds, and a single ion pair. The antibody overlaps part of the active site cleft. Putative critical residues within the epitope region of HEL, identified from the x-ray crystallographic structure of the complex, were replaced by site-directed mutagenesis to probe their relative importance in determining affinity of the antibody for HEL. Twenty single mutations of HEL at three contact residues (Arg-21HEL, Asp-101HEL, and Gly-102HEL) and at a partially buried residue (Asn-19HEL) in the epitope were made, and the effects on the free energies of dissociation were measured. A correlation between increased amino acid side-chain volume and reduced affinity for HELs with mutations at position 101 was observed. The D101GHEL mutant is bound to HyHEL-10 as tightly as wild-type enzyme, but the delta delta Gdissoc is increased by about 2.2 kcal (9.2 kJ)/mol for the larger residues in this position. HEL variants with lysine or histidine replacements for arginine at position 21 are bound 1.4-2.7 times more tightly than those with neutral or negatively charged amino acids in this position. These exhibit 1/40 the affinity for HyHEL-10 Fab compared with wild type. There is no side-chain volume correlation with delta delta Gdissoc at position 21. Although Gly-102HEL and Asn-19HEL are in the epitope, replacements at these positions have no effect on the affinity of HEL for the antibody.

Amino Acid Sequence↗
PubMed2002

Chemokine receptor gene polymorphisms and risk of human T lymphotropic virus type I infection in Jamaica.

Polymorphisms of some chemokine receptor genes and their ligands are associated with susceptibility and progression of human immunodeficiency virus infection. This study assessed whether these variants are also responsible for susceptibility to infection with human T lymphotropic virus (HTLV) type I. Frequencies of CCR5-Delta 32, CCR2-64I, and SDF-1-3'A genotype among 116 HTLV-I-positive and 126 HTLV-I-negative persons of African descent in Jamaica were 1.0%, 14.9%, and 5.4%, respectively. The association of HTLV-I infection with the most common variant, CCR2-64I, was examined in 532 subjects. Thirteen (5.4%) of 241 HTLV-I-negative subjects were homozygous for CCR2-64I, versus 3 (1.0%) of 291 HTLV-I-positive subjects (P=.005). Among HTLV-I carriers, provirus load and antibody titer were not significantly different in persons with CCR2-+/64I or CCR2-+/+. These findings suggest that CCR2-64I, or alleles in linkage disequilibrium with it, may affect the risk of HTLV-I infection in a recessive manner.

Chemokine CXCL12↗
PubMed1995

Rearrangement and expression of the human psi C lambda 6 gene segment results in a surface Ig receptor with a truncated light chain constant region.

The constant region of the human Ig lambda locus consists of seven tandemly organized J-C gene segments. Although it has been established that the J-C lambda 1, J-C lambda 2, J-C lambda 3, and J-C lambda 7 gene segments are functional, and code for the four distinct Ig lambda isotypes found in human serum, the J-C lambda 4, J-C lambda 5, and J-C lambda 6 gene segments are generally considered to be pseudogenes. Although one example of a functional J-C lambda 6 gene segment has been documented, in the majority of cases, J-C lambda 6 is rendered nonfunctional by virtue of a single duplication of four nucleotides, creating a premature translational arrest. We show here that rearrangements to the J-C lambda 6 gene segment do occur, and that such a rearrangement encodes an Ig lambda protein that lacks the terminal end of the constant region. We also show that this truncated protein is expressed on the surface with the IgH chain, creating an unusual surface Ig (sIg) receptor (sIg delta CL). Cells that express this receptor on the surface do so at significantly reduced levels compared with clonally related variants, which express sIg receptors with conventional Ig lambda L chains. However, the effects of sIg cross-linking on tyrosine phosphorylation and surface expression of the CD25 and CD71 Ags are similar in cells that express conventional sIg receptors and in those that express sIg delta CL receptors, suggesting that the latter could possibly function as an Ag receptor.

Amino Acid Sequence↗