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Biomedical subjects

A Seth

Publications and source records attributed to A Seth.

At least 181 records · Page 10Linked to original sources
PubMed1988

Impaired autoreactive T cell-induced T cell-T cell interaction in aged mice.

Self-Ia-reactive (autoreactive) L3T4+ T cell clones have been shown earlier to stimulate the proliferation of syngeneic naive L3T4+ T cells and initiate a T cell-T cell (T-T) interaction leading to the generation of immunoregulatory circuits. Since aging has been shown to be associated with a decline of the immune responsiveness, age-related alterations in the T-T interaction was investigated in the present study. Using several I-Ed-specific autoreactive T cell clones isolated from 2- to 3-month-old (young) DBA/2 mice as stimulators, it was observed that L3T4+ T cells from 22- to 24-month-old (aged) DBA/2 mice, failed to demonstrate a significant response to the autoreactive T cells. In contrast, L3T4+ T cells from young mice responded strongly to the autoreactive T cell clones. The deficient T-T cell interaction in aged mice correlated with an impaired syngeneic mixed lymphocyte reaction in these mice, thereby suggesting that aging induces a defect both in the autoreactive T cells and in T cells which react with the autoreactive T cells. When exogenous recombinant interleukin 2 (rIL-2), recombinant interleukin 4 (rIL-4), or a combination of these was added to the interaction, it was observed that rIL-4 but not rIL-2 enhanced the T-T interaction in young mice. However, rIL-4 or a combination of rIL-2 and rIL-4 failed to correct the defective T-T interaction in aged mice. Since the T cell network is believed to play an important role in the maintenance of normal immune system homeostasis, the present study suggests that age-related alterations in T and B cell functions and increased susceptibility to autoimmune diseases with age may result from a defect in the T cell network regulation.

Aging↗
PubMed1988

Expression of the J11d marker on peripheral T lymphocytes of MRL-lpr/lpr mice.

MRL-lpr/lpr (lpr) mice spontaneously develop massive lymphadenopathy resulting from the expansion of a unique population of Thy-1+ cells which are CD4- and CD8- (double negative) and the nature of which is not clear. The antibody J11d has been shown to define a differentiation Ag found on immature thymocytes but not on mature and functional peripheral CD4+ or CD8+ T cells. To analyze the possible relationship between the lpr double-negative T cells and the thymocytes, we investigated the simultaneous expression of J11d and Thy 1 Ag on the double-negative lpr lymph node cells by using two-color immunofluorescent staining technique. We observed that lpr mice at 3 to 4 weeks of age, before the onset of lymphadenopathy, did not have significant numbers (less than 4%) of J11d+ T cells in the periphery, similar to the number found in the control MRL +/+ mice. However, with increasing age of approximately 8 to 10 weeks and coinciding with the appearance of lymphadenopathy, a significant number (approximately 35%) of J11d+ Thy-1+ cells started appearing in the periphery of lpr mice and was maintained until the mice died at 20 to 24 weeks of age. The J11d+ T cells belonged to the abnormal double-negative T cell pool, inasmuch as J11d+ CD4+ or J11d+ CD8+ cells were absent in the lymph nodes of 20-wk-old lpr mice. Furthermore, 20-wk-old lpr mice demonstrated increased numbers (approximately 41%) of double-negative T cells in the thymus, a significant proportion of which were J11d+. In contrast, the 20-wk-old +/+ mice or 4-wk-old lpr mice had only 4% double-negative T cells in the thymus. The present study suggests that a significant number of peripheral double-negative T cells of lpr mice bear the immature thymic differentiation Ag J11d. The possibility that the accumulation of double-negative T cells results from abnormal peripheralization of double-negative J11d+ thymocytes, before complete differentiation into CD4+ or CD8+ T cells, is discussed.

Aging↗
PubMed1988

Bacterial expression and characterization of nine polypeptides encoded by segments of the envelope gene of human immunodeficiency virus.

Nine envelope (Env) polypeptides, encoding different regions of HIV gp120 and gp41 Env proteins, and accounting for approx. 96% of the entire Env precursor glycoprotein complex (gp160) were expressed in Escherichia coli at levels ranging from approx. 2 to 20% of total cellular protein. The recombinant polypeptides were produced either as hybrid products fused to the cII gene fragment of the lambda vector or in an unfused form without interfering cII products. Partially purified protein fractions of each polypeptide were characterized serologically by Western-blot analysis against a panel of well characterized human immunodeficiency virus (HIV)-positive human reference sera. Most of the Env polypeptides were highly immunoreactive with anti-gp120/gp41 antibodies present in the sera of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related diseases, but the patterns of reactivity were different. These results demonstrate that some of the antigenic determinants residing on the viral gp160 complex are retained on the surfaces of the recombinant Env polypeptides, and suggest that these sites are differentially immunogenic. These results are therefore interpreted in the context of an ongoing process towards using bacterially expressed HIV Env polypeptides to help define biological and structural epitopes to aid in the development of more sensitive diagnostic and therapeutic reagents in the fight against AIDS.

Cloning, Molecular↗
PubMed1988

Chemotherapy of mice bearing syngeneic tumors with 1,3-bis (2-chloroethyl)-1-nitrosourea is effective only in normal, but not in irradiated or nude, mice: role of L3T4+ (CD4+) and Lyt-2+ (CD8+) T cells.

We earlier demonstrated that treatment of C57BL/6 mice bearing a syngeneic tumor, LSA, with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resulted in over 90% survival of the mice, and 100% of the cured mice rejected secondary rechallenge with the homologous tumor but not with a heterologous syngeneic tumor such as EL-4. In the present study we investigated whether the host's immune system was also essential for successful chemotherapy with BCNU. It was observed that BCNU treatment was effective only in normal tumor-bearing mice (100% survival) but not in irradiated or nude tumor-bearing mice (0% survival), thereby suggesting that the immune system, particularly the T cells, was essential for effective treatment with BCNU. Since BCNU-cured mice lack demonstrable T suppressor (Ts) cells, these mice were next used as a model to investigate the phenotype of the T cells mediating tumor rejection. It was observed that L3T4+ (CD4+) or Lyt-2+ (CD8+) T cells from BCNU-cured mice could provide significant protection (80 and 40% survival, respectively) in irradiated or nude mice but not in normal mice. It was also observed that BCNU-cured LSA mice elicited tumor-specific delayed-type hypersensitivity (DTH) reaction, while, normal mice or LSA tumor-bearing mice failed to elicit DTH reaction. Also, only L3T4+ but not Lyt-2+ T cells from BCNU-cured mice when adoptively transferred into nude mice could elicit a DTH reaction. The present study suggests that for effective chemotherapy against a syngeneic tumor, with a tumoricidal drug such as BCNU, the presence of L3T4+ and Lyt-2+ T cells in the host is essential.

Animals↗
PubMed1988

Chronic weight loss in lean and obese rats with a brain-enhanced chemical delivery system for estradiol.

Studies were undertaken to determine the effects on body weight and food intake of a chemical delivery system which preferentially delivers estradiol (E2) to the brain and there serves as a source for the sustained release of the steroid. We injected intravenously various doses of this estradiol-chemical delivery system (E2-CDS), E2-valerate (E2-VAL) or the dimethyl sulfoxide (DMSO) vehicle to young lean male rats and monitored body weight and 24 hr food intake for 39 days postinjection. E2-VAL caused a transient reduction in food intake and body weight gain. By contrast, a single injection of E2-CDS caused a chronic, dose-dependent reduction in the rate of body weight gain. In these lean rats, the duration of reduced body weight gain was not correlated with the observed transient reduction in food intake. In aged, obese male rats, E2-CDS caused a marked and chronic dose-dependent reduction in body weight. In contrast to lean rats, E2-CDS caused a long-term reduction in food intake in obese rats. To evaluate the importance of the E2-CDS-induced reduction in food intake in the observed persistent weight loss in obese rats, E2-CDS was administered to a group of obese rats and a second group which received the DMSO vehicle was pair-fed an equivalent amount of food daily. The resulting weight loss in both groups was equivalent. These results show that the enhanced delivery of E2 to the brain with the E2-CDS causes sustained reduction in the rate of body weight gain in lean rats and persistent weight loss in obese animals.

Animals↗
PubMed1988

Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases.

The proteins encoded by the human TPR-MET oncogene (p 65tpr-met) and the human MET protooncogene (p140met) have been identified. The p65tpr-met and p140met, as well as a truncated TPR-MET product expressed in Escherichia coli, p50met, are autophosphorylated in vitro on tyrosine residues. Using the immunocomplex kinase assay, p140met activity was detected in various human tumor epithelial cell lines. In vivo, p65tpr-met is phosphorylated on both serine and tyrosine residues, while p140met is phosphorylated on serine and threonine. p140met is labeled by cell-surface iodination procedures, suggesting that it is a receptor-like transmembrane protein-tyrosine kinase.

Cell Line↗
PubMed1988

Coronary angioplasty in unstable angina and stable angina: a comparison of success and complications.

One hundred and five patients with unstable angina and 175 with chronic stable angina were treated by primary percutaneous transluminal coronary angioplasty. Patients with unstable angina had had symptoms for a shorter time and were more likely to have angiographically complex lesions and lesions less than 10 mm in length than patients with chronic stable angina. Other baseline variables were not significantly different in the two groups. The overall primary success rate was similar in both groups (87% v 86%). Nine of the 14 unsuccessful procedures in those with unstable angina and nine of the 24 unsuccessful procedures in those with stable angina were the result of acute occlusion. These results led to a 9% frequency of procedure related myocardial infarction in patients with unstable angina and a 5% rate in those with stable angina (NS). The procedure related infarct rate tended to be higher in patients with unstable angina who had coronary angioplasty soon after an episode of unstable angina (mean 10 days) than in those in whom it was delayed (mean 35 days) (12% v 3%) (NS). In patients with unstable angina who had had a previous myocardial infarction procedure related infarction was significantly more common (18%) than in patients with no previous myocardial infarction (3%). The difference between those with and without previous infarction was also significant in patients with stable angina (10% v 3%).

Angina Pectoris↗
PubMed1988

The role of v-mos in transformation, oncogenicity, and metastatic potential of mink lung cells.

A cloned line of S + L- mink lung cells (A clone), which exhibited a flat morphology, was superinfected with a novel dual-tropic virus (E1BX-MuLV) showing a broad host range and a B-tropism. These cells gave rise to transformed cells with two phenotypes: those which were still anchorage-dependent (AD), and those which readily detached spontaneously from the substratum and grew in suspension. A clone of these AD cells (B clone) was isolated and compared with a clone of the anchorage-independent suspension-cultured (AISC) cells (C clone). While the C clone exhibited a high oncogenicity and ability to metastasize in nude mice, the A and B clones were not tumorigenic. The integrated v-mos was greatly amplified in the C clone, and moderately increased in the B clone as compared with the A clone. The amounts of v-mos mRNA expressed by B and C clones paralleled those of v-mos sequence in their chromosomal DNA, whereas there was no detectable v-mos mRNA in the A clone. Thus, conversion of S + L- mink cells from an AD growth to an AISC phenotype accompanied by manifestation of oncogenicity and metastatic potential in nude mice is associated with amplification of integrated v-mos gene and its enhanced expression. Furthermore, a revertant (D clone) showing AD phenotype was derived from the C clone by selective growth in ouabain. This revertant exhibited a markedly decreased oncogenicity in nude mice, although the copy numbers of integrated v-mos gene and its mRNA did not differ from those of the parent C clone. While more p37mos protein was found in the C than in the D clone, it was not detectable in the A and B clone. The amounts of helper virus-related mRNA and infectious E1BX-MuLV were markedly higher in the B than in the C and D clones. It is concluded that v-mos gene amplification and overexpression is necessary for these cells to exhibit oncogenicity, but other factors associated with ouabain-resistance can modify or suppress its oncogenicity despite the v-mos amplification and mRNA overexpression.

Animals↗
PubMed1988

Management of unstable angina soon after myocardial infarction.

The recurrence of angina soon after myocardial infarction is not uncommon and represents areas of viable myocardium at risk from infarct extension and thus a worse prognosis. A better understanding of the pathogenesis of acute ischaemic syndromes and developments in interventional cardiology in the past decade have helped us rationalize our approach to this high-risk subset and achieve maximal myocardial salvage with its short- and long-term benefits.

Adrenergic beta-Antagonists↗
PubMed1988

Success and complication rates of coronary angioplasty in patients with and without previous myocardial infarction.

The primary success rate and incidence of major complications have been retrospectively assessed in a consecutive series of 224 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) in one centre. The patients have been divided into three groups; those with angina and no previous myocardial infarction (Group 1; N = 130), those with angina and a previous transmural myocardial infarction (TMI) (Group 2; N = 59), and those with angina and a previous non-transmural myocardial infarction (NTMI) (Group 3; N = 26). The three groups were well matched for age, gender and angiographic severity of stenosis. The primary success rate in Group 1 was 90% compared to 64% in Group 2. The success rate in Group 3 lay in between at 77%. The lower success rates in Groups 2 and 3 were mainly due to an increase in the frequency of major complications. Acute coronary occlusion occurred in seven patients in Group 1, nine patients in Group 2 and four patients in Group 3. In all these patients in Groups 2 and 3 the outcome of acute occlusion was a procedure-related clinical myocardial infarction despite immediate re-angioplasty and/or emergency coronary artery bypass grafting whereas only four patients in Group 1 sustained an acute infarct. In this series of patients undergoing coronary angioplasty for symptom limiting angina, previous myocardial infarction appears to be a risk factor for a lower success rate mainly due to an increase in the frequency and severity of major complications.

Adult↗
PubMed1988

Study of the bioequivalence of three oral formulations of ibopamine in healthy volunteers.

Ibopamine (SK & F 100168-A), a new chemical entity, is capable of eliciting positive inotropic effects accompanied by vasodilating, diuretic and saliuretic activity after oral administration. The relative bioavailability and bioequivalence of 3 oral presentations of Ibopamine was examined after a single oral dose. Thirty healthy subjects (15 males and 15 females) received the 3 formulations at one-week intervals according to "single-blind assayer" latin-square crossover design. Two tablets of 100 mg ibopamine (SIMES formulations), 2 tablets of 100 mg ibopamine (UK formulation) and 1 tablet of 200 mg ibopamine (US-Tiltab formulation) were used. In a 4th occasion, all volunteers received again the 200 mg-tablet of the US-Tiltab formulation in order to assess the intra-individual variability of its oral bioavailability. Free epinine plasma levels were measured before and 10, 20, 30, 45, 60, 90, 105 min and 2, 2.5, 3, 4, 6, 8 and 24 h after each oral administration. Free epinine was assayed by HPLC/electrochemical detection method. The amount of drug absorbed as measured by the area under the curve, AUC0-8 h, and the rate of absorption, as measured by Cmax and tmax, were compared by examining the symmetric 95% confidence intervals. If the symmetric 95% confidence interval with respect to AUC is between 80% and 120%, two formulations are considered bioequivalent.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Characterization and localization of the products of the human homologs of the v-ets oncogene.

The avian erythroblastosis virus, E26, an acute leukemia virus, contains a transforming gene composed of two cellular components, v-myb and v-ets. The v-ets related sequences of man and other mammals consist of two transcriptionally active genes, ets-1 and ets-2, located on separate chromosomes. By contrast, both of these genes are contiguous in birds, are located on the same chromosome, and are coordinately transcribed. The human ets-1 and ets-2 gene products were identified by means of antibodies directed against the ets-1 and ets-2 encoded products. A 51 kD protein has been identified as the ets-1 gene product, and a 56 kD protein as the ets-2 gene product. Cellular fractionation studies indicated that the ets-1 protein is located in the cytoplasm and the ets-2 protein is nuclear. By comparison, the chicken ets protein, which contains both the ets-1 and ets-2 domains, distributes equally between the cytoplasm and nucleus. The differential compartmentalization of the ets gene products and their non-coordinate expression suggest that these proteins have different biological functions.

Cell Compartmentation↗
PubMed1987

The 3'-orf protein of human immunodeficiency virus shows structural homology with the phosphorylation domain of human interleukin-2 receptor and the ATP-binding site of the protein kinase family.

The primary amino acid sequence within a stretch of 25 residues (positions 91-116) of the middle portion of the 3'-orf protein (p27(3')-orf) of the human immunodeficiency virus (HIV) shares structural homology with a highly charged region within the intracytoplasmic phosphorylation domain of human interleukin-2 receptor (IL-2R) and the ATP-binding site of the catalytic subunit of cAMP-dependent protein kinase (cAMP-PK) and other members of the protein kinase family. Comparison of the predicted secondary structure within this region of p27(3')-orf with the phosphorylation domain of human IL-2R and the ATP-binding region of the phospho-kinase family of protein suggests that the 3'-orf protein could serve homologous function(s).

Adenosine Triphosphate↗
PubMed1987

Nucleoside triphosphate-dependent DNA-binding properties of mos protein.

We have previously shown that the mos gene product, p40mos, produced in Escherichia coli binds ATP and has ATPase activity. In the present study, we investigated the DNA-binding properties of p40mos and two mos deletion mutant proteins. Nitrocellulose blot protein-DNA binding assays showed that p40mos binds DNA in the presence of Mg2+-ATP and certain other nucleoside triphosphates. Ninety percent of the p40mos-bound DNA is dissociated if the complex is washed in the presence of 1 M NaCl or in the absence of ATP. p40mos-DNA binding is not observed in the presence of AMP or the nonhydrolyzable ATP analog adenosine 5'-[beta, gamma-methylene]-triphosphate; however, in the presence of ADP, p40mos binds DNA at 20% of the level that is observed with ATP. An N-terminal-deletion mutant protein, p19mos, has no DNA-binding activity, whereas a C-terminal-deletion mutant protein, p25mos, does. p25mos contains the ATP-binding domain, binds DNA in the presence of either ADP or ATP, and shows 5% and 45% binding (relative to that in the presence of ATP) in the presence of AMP and adenosine 5'-[beta, gamma-methylene]triphosphate, respectively. These results suggest that the N-terminal domain of p40mos is responsible for nucleoside triphosphate-mediated DNA binding. We also observed differential histone-DNA binding in the presence and absence of ATP.

Adenosine Triphosphate↗
PubMed1987

Identification of the human papillomavirus type 6b L1 open reading frame protein in condylomas and corresponding antibodies in human sera.

Genital warts (condylomata acuminata) are among the most frequent sexually transmitted infections. Human papillomavirus type 6 (HPV-6), which is etiologically related to a majority of these lesions, has not been propagated in tissue culture. We generated two forms of HPV-6 viral antigens: a chemically synthesized oligopeptide (referred to as the C-terminal synthetic peptide) corresponding to residues 482 to 495 of the 500-amino-acid-long L1 open reading frame (ORF), and a bacterially expressed 54-kilodalton (kDa) fusion protein containing the N-terminal 13 amino acids encoded by the lambda bacteriophage cII gene followed by one vector-insert junctional residue and 462 amino acids of the L1 ORF sequence (residues 39 to 500). The cII-L1 fusion protein was specifically recognized by an antipeptide serum directed against the N-terminal 13 amino acids derived from the cII gene, an antiserum raised against the C-terminal synthetic peptide, and a genus-specific serum prepared by immunization with disrupted viral capsids. The 54-kDa fusion protein was purified, and the sequence of its first 36 amino acids was determined and found to be as predicted by the DNA sequence. Both the genus-specific anticapsid serum and the antiserum raised against the fusion protein identified authentic L1 ORF proteins in HPV-1-induced (58 kDa) and HPV-6/11-induced (56 kDa) papillomas. The synthetic peptide antiserum recognized the 56- to 58-kDa protein in HPV-6-induced warts, but not in HPV-1- or HPV-11-infected specimens. Using the fusion protein as antigen in immunoassays, we were able to detect the corresponding antibodies in human sera.

Antibodies, Viral↗
PubMed1986

Analysis of the transforming potential of the human homolog of mos.

The human homolog, c-moshu, of the mouse cellular mos proto-oncogene (c-mosmu) transforms NIH 3T3 cells at low efficiency. Furthermore, the c-moshu-induced foci are less distinct, and transformed cells contain a high level of human mos protein. The transforming activity of hybrid mos genes derived from human and mouse sequences reveals three domains within the coding region, as well as a negative regulatory sequence upstream from the c-moshu ORF that reduces its transforming efficiency. The mos C-terminal region, however, which contains the src-kinase homology domain, appears to have the greatest influence on transforming efficiency. The low transforming efficiency of c-moshu may provide a selective advantage to the host, but it also may indicate a reduced or modified function of mos in humans.

Animals↗
PubMed1986

High-level expression vectors to synthesize unfused proteins in Escherichia coli.

A new class of plasmid vectors (pANK-12, pANH-1, and pPL2) for synthesizing unfused proteins was constructed by inserting synthetic linkers at the NdeI site (CATATG) of plasmid pJL6, which contains the lambda cII gene initiator codon. These expression vectors contain the lambda pL promoter, the cII ribosome-binding site, cII start codon and unique restriction sites (KpnI, Asp718, HpaI, BamHI) downstream from the initiator ATG for expression of unfused proteins. The main advantage of these vectors is that any DNA fragment with an open reading frame that does not possess a start and/or a stop codon can be directed to overproduce protein in an unfused form.

Cloning, Molecular↗