Search PubMed⌕ Search

Biomedical subjects

T L Moore

Publications and source records attributed to T L Moore.

At least 73 records · Page 4Linked to original sources
PubMed1990

The in vitro effects of methotrexate on peripheral blood mononuclear cells. Modulation by methyl donors and spermidine.

The mode of action of low-dose methotrexate (MTX) in rheumatoid arthritis (RA) is unclear. The effects of MTX are mediated primarily through inhibition of dihydrofolate reductase, resulting in a dose-dependent inhibition of purine and pyrimidine synthesis. Other folate-dependent metabolic pathways might be secondarily affected. One such pathway is the regeneration of methionine from homocysteine, with subsequent formation of the methyl donor S-adenosylmethionine (SAM) and polyamines, which are important in cell-mediated immune reactions. To assess whether MTX inhibits SAM and polyamine synthesis in lymphocytes, pokeweed mitogen-stimulated mononuclear cells from healthy donors were incubated with MTX. This resulted in decreased proliferation and IgG, IgM, and IgM rheumatoid factor synthesis. However, addition of folinic acid, methionine, SAM, or spermidine resulted in reversal of the MTX-mediated inhibition. These data suggest that MTX inhibits the folate-dependent pathway of methionine regeneration, thereby inhibiting SAM and polyamine synthesis. Since RA lymphocytes have increased concentrations of polyamines, the beneficial effects of MTX in RA may be related to its potential ability to reduce polyamine synthesis.

Antibody-Producing Cells↗
PubMed1990

Neuronal type N calcium channels mediate norepinephrine release in isolated rabbit pulmonary artery.

Several types of voltage sensitive calcium channels (VSCC) including types N and Ln are present in varying degrees in neurons from different locations and they appear to differ from the Lm type VSCC on muscle cells. Omega conotoxin blocks N and Ln channels but not Lm channels. Verapamil blocks Ln and Lm but not N channels. The purpose of this study was to determine whether N or Ln channels mediate norepinephrine (NE) release in isolated rings of rabbit pulmonary artery. The release of endogenous NE from intramural sympathetic neurons was evoked by field electrical stimulation (ES) of the tissues. Conotoxin (10(-6) M) had no effect on contractions of rabbit pulmonary artery induced by 40 mM K+ or exogenous NE (10(-9)-10(-5) M) but significantly depressed the response to ES (21V, 0.5 msec pulse duration) at all stimulation frequencies (1-20Hz). Thus, the effects of conotoxin are restricted to the N and/or Ln calcium channels on neurons in this issue. Verapamil (5 x 10(-6) M) depressed 40 mM K(+)-induced contractions by 86 +/- 2% as well as contractions induced by endogenous (ES at 1-20 Hz) and exogenous NE (10(-9)-10(-5) M). Moreover, for contractions of equal magnitude, verapamil depressed the response to endogenous (ES) and exogenous NE to the same degree. Had Ln channels mediated NE release in the tissue, verapamil should have had a greater effect on ES-induced contractions because ES activates both pre- and post-junctional calcium channels whereas exogenous NE activates only post-junctional channels on smooth muscle cells. Thus, it appears that N-type calcium channels mediate NE release in rabbit pulmonary artery.

Animals↗
PubMed1990

Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter.

The function of c-Myb protein was revealed by transfecting an expression vector containing the entire c-Myb protein-coding sequence into the murine CTLL-2 T-cell line. Expressions of high levels of c-Myb protein did not alter the expression of several T-cell markers, c-fos mRNA expression, responses to interleukin-2, and growth characteristics of these cells. Interestingly, expression of the c-myc gene was drastically increased in this clone. Further, the c-myb expression plasmid, but not a frameshift mutant of c-myb, enhanced the expression of a hybrid construct of c-myc promoter linked to a reporter gene by 8- to 14-fold. These results demonstrate a role of c-Myb protein in c-myc gene expression.

Animals↗
PubMed1990

Prediction of total intake of dry matter and net energy in a lactation.

Daily records on DM intake, net energy intake, and milk yield from 191 Holstein cows in six herds were used to study the differences in accuracy and precision among different methods of estimating total DM intake during a lactation. In using cumulative measures of intake from partial lactations to predict total intake, accuracy reached 85% at 100 d postpartum. Measurements of intake taken around midlactation gave better predictions of total intake than those taken during other periods of lactation. Methods were evaluated for estimating total feed intake during a lactation based on data collected intermittently and separated by either equal or unequal intervals throughout the lactation. The average percentage of bias across all sampling schemes was 6% or less of actual intake. Six of the seven sampling schemes using only 10 d of intake information throughout the lactation had correlations with actual intake of .97 or higher. For equally spaced methods, both accuracy and precision of estimation increased with increased frequency of sampling. For unequally spaced methods, accuracy increased with sampling frequency after 150 d in milk. Total milk production was used to predict feed intake during a lactation. Milk yield alone accounted for 37 and 33% of the variation of total intake using actual and estimated yields, respectively.

Animals↗
PubMed1989

A beta-adrenergic agonist modulates DR alpha gene transcription via enhanced cAMP levels in a glioblastoma multiforme line.

In this study we have examined the ability of the beta-adrenergic agonist isoproterenol (ISO) to alter the expression of the human MHC class II Ag, DR, on a glioblastoma multiforme cell line. We have determined that ISO induces an increase in both DR alpha-specific RNA and protein. This induction is most likely due to the increase in cAMP levels elicited by the agonist, based on the direct measurements of cAMP levels and the ability of DBcAMP and the adenylate cyclase activator, forskolin to mimic the effects of isoproterenol. Blocking of the induction was achieved with the beta-antagonist, propranolol, but not with the alpha-antagonist phentolamine, indicating that this is a beta-adrenergic receptor-mediated phenomenon. Finally this induction is transcriptionally regulated as determined by nuclear run-on experiments. Future studies will center on identifying DNA regions of the DR alpha-chain gene which are important in this regulation.

Bucladesine↗
PubMed1989

Cross-reactive antiidiotypic antibodies against human rheumatoid factors from patients with juvenile rheumatoid arthritis.

We prepared antiidiotypic (anti-Id) antibody to 2 polyclonal IgM rheumatoid factors (IgM-RF) and 2 polyclonal "hidden" IgM-RF. The anti-Id antibodies were isolated by chromatography on Sepharose 4B, to which was bound rabbit anti-human IgG Fc fragments. F(ab')2 fragments from the anti-Id antibodies were generated by pepsin digestion and isolated by gel filtration. The anti-Id antibodies directed against RF from 4 patients with juvenile rheumatoid arthritis (JRA) were tested by an inhibition hemolytic assay for cross-reactivity with IgM-RF from 4 adult patients with rheumatoid arthritis, 6 patients with JRA, and 13 JRA patients with hidden RF. The 4 anti-Id antibodies had variable cross-reactivity with the isolated adult RA RF, JRA RF, and JRA hidden RF. Similar results were obtained by a direct-binding enzyme-linked immunosorbent assay for the anti-Id antibodies. The broad pattern of cross-reactivity was apparently unrelated to a particular amino acid sequence, but was associated with the antigen-binding site of IgM-RF. These results suggest the possibility that the anti-Id antibodies prepared against isolated RF obtained from JRA patients bear the "internal image" of antigen; that is, the Fc region of human IgG. These anti-Id antibodies may be generated in JRA patients and may possess specific immunomodulatory properties.

Animals↗
PubMed1989

Heart disease in systemic sclerosis.

Primary cardiovascular manifestations of SSc include pericardial disease, myocardial disease, conduction abnormalities, and cardiac arrhythmias. Significant cardiac abnormalities are present in more than half of SSc patients at autopsy. As the frequency of subclinical cardiac involvement is now appreciated and noninvasive cardiac diagnostic modalities continue to improve, the ability to detect early asymptomatic involvement in SSc has improved. Two-dimensional echocardiography, radionucleotide imaging, and ambulatory ECG allow recurrent serial testing with virtually no morbidity. The current treatment of cardiac involvement in SSc is emperic and primarily directed at symptomatology. Large prospective randomized trials are needed to determine if preventive therapy is effective. With the advent of new immunological and cardiotropic agents and a better understanding of the primary disease process, our ability to alter the pathogenesis and final outcome of cardiac involvement in SSc should improve.

Arrhythmias, Cardiac↗
PubMed1989

Class II box consensus sequences in the HLA-DR alpha gene: transcriptional function and interaction with nuclear proteins.

The promoter regions of class II major histocompatibility complex genes contain two highly conserved sequences, the X and Y boxes, which may be involved in the control of class II gene expression. In this study, we correlate in vivo functional assays for cis-acting regulatory elements in the HLA-DR alpha gene with in vitro binding assays for trans-acting regulatory proteins. Mutagenesis and transient transfection analyses indicated that both the X and Y boxes were important for HLA-DR alpha promoter function in a B lymphoblastoid cell line. Although specific nuclear protein interactions with the X consensus sequence were not apparent, the Y box, which contained an inverted CCAAT sequence, did bind specifically to at least one nuclear protein. This Y box-binding protein was present in nuclear extracts of all cell types examined, including human B and T cells and HeLa cells. The molecular mass of the protein, as determined by photoactivated protein-DNA cross-linking, was approximately 40 to 50 kilodaltons. Mutagenesis of the Y box that decreased protein binding also decreased promoter activity, implying that protein binding to this DNA sequence is important for DR alpha promoter function.

Base Sequence↗
PubMed1989

Antibody to streptococcal cell wall peptidoglycan-polysaccharide polymers in sera of patients with juvenile rheumatoid arthritis but absent in isolated immune complexes.

Sera of 88 children with juvenile rheumatoid arthritis (JRA) (10 seropositive, polyarticular onset, 29 seronegative, polyarticular onset, 32 pauciarticular onset, and 17 systemic onset) were evaluated for the presence of serum antibodies to streptococcal cell wall peptidoglycan-polysaccharide polymers (PG-PSP). Immune complexes (IC) isolated by the antihuman IgM (HIgM) affinity column method were also evaluated for the presence of antibodies to PG-PSP. Forty-one of 88 patients with JRA (7 of 10 seropositive, polyarticular onset, 11 of 29 seronegative, polyarticular onset, 16 of 32 pauciarticular onset, and 7 of 17 systemic onset) showed elevated levels of antibodies to PG-PSP in their sera. IgM rheumatoid factors (RF) were demonstrated in 70/88 isolated IC fractions of patients with JRA and IgG RF in 7; however, none of the patients demonstrated the presence of antibodies to PG-PSP in their isolated IC fractions from the anti-HIgM affinity column. These data indicate that antibodies are produced to PG-PSP in all JRA onset types, but they are not constituents of isolated IC by the anti-HIgM affinity column method.

Antibodies, Bacterial↗
PubMed1989

Antinuclear antibody in juvenile rheumatoid arthritis sera reacts with 50-40 kDa antigen(s) found in HeLa nuclear extracts.

To identify whether sera containing antinuclear antibody (ANA) from patients with juvenile rheumatoid arthritis (JRA) recognize a common antigen, extracts of HeLa nuclei were prepared by incubating the nuclei with buffers of sequentially increasing salt concentrations (0.1 M, 0.3 M, and 0.5 M NaCl). Western blot analysis using sera from 82 patients with JRA revealed that 63% of ANA positive JRA sera reacted with 2 bands (50-40 kDa) in the 0.3 M extract whereas only 14% of ANA negative JRA sera had antibody to these bands. Antibody to the 50-40 kDa antigen(s) strongly correlated with the presence of ANA by immunofluorescence and was found in 70% of patients with iritis; however, it did not correlate with disease subgroup or disease activity.

Antibodies, Antinuclear↗
PubMed1989

Antibodies to iris and retina detected in sera from patients with juvenile rheumatoid arthritis with iridocyclitis by indirect immunofluorescence studies on human eye tissue.

Sera from 12 patients with juvenile rheumatoid arthritis (JRA) with active iridocyclitis were incubated with frozen, sectioned, whole human eye tissue. Antibodies were detected using fluorescein conjugated goat F(ab')2 antibody to human IgG by immunofluorescent microscopy. Immunofluorescence was determined on tissue from the iris, retina, and 3 portions of the ciliary body. Sera of patients with JRA with iridocyclitis were compared to sera from patients with JRA with and without antinuclear antibodies (ANA) and healthy children. An increased frequency of antibody to the human iris was seen with sera of patients with JRA with iridocyclitis compared to healthy children's sera. A higher frequency of antibody was also noted to human retina in sera of patients with JRA with iridocyclitis compared to patients without ANA and healthy children. No increased frequency of antibody was detected to ciliary body. Sera of 7 patients with JRA with iridocyclitis were also compared during a time of inactive eye disease to a time of active disease. No difference in binding to eye tissue was detected at times of inactive disease compared to controls. Our results demonstrate the presence of antibody to iris and retina by immunofluorescence in the sera of patients with JRA with iridocyclitis.

Antibodies, Antinuclear↗
PubMed1989

Dorsal duct sphincterotomy is effective long-term treatment of acute pancreatitis associated with pancreas divisum.

Nonbiliary, nonalcoholic pancreatic inflammatory disease was investigated by biochemical investigation, ultrasonography, endoscopic retrograde cholangiopancreatography, and secretin tests. Twenty-five consecutive cases were followed up for 12 months to 10 years after treatment of disease associated with pancreas divisum, diagnosed by endoscopic retrograde cholangiopancreatography. Thirteen patients had no recurrence of acute pancreatitis after dorsal duct sphincterotomy alone, during long-term follow-up (mean, 54 months); one patient had recurrent pancreatitis during 33 months after failed sphincterotomy. Eight patients had variable results 12 months to 8 years (mean, 49 months) after dorsal duct sphincterotomy for pancreatic pain syndrome (without amylase elevation), three were pain free, and one had recurrent pancreatitis. For 10 years after dorsal duct sphincterotomy for chronic pancreatitis, one patient had no pain relief; after subtotal pancreatectomy and pancreaticojejunostomy of the dorsal duct, both for chronic pancreatitis, one patient each was pain free and normoglycemic after 54 and 12 months, respectively. Dorsal duct sphincterotomy alone is successful in achieving long-term freedom from recurrence of acute pancreatitis associated with pancreas divisum. Pancreatic pain syndrome is not consistently improved by dorsal duct sphincterotomy. Chronic pancreatitis associated with pancreas divisum should be treated by resection or drainage procedures, not by dorsal duct sphincterotomy.

Acute Disease↗
PubMed1988

Complement fixing immune complexes containing antinuclear antibodies in patients with systemic lupus erythematosus.

Immune complexes (IC) in the sera of patients with systemic lupus erythematosus (SLE) were isolated using goat antihuman C3 and rabbit antihuman Clq immunoabsorbent columns. The sera from 12 patients with SLE were sequentially eluted from the columns with veronal buffer, 0.02 M EDTA, 0.5 M NaCl, and 1 M propionic acid. The isolated IC were analyzed for antinuclear antibodies (ANA) with an HEp-2 cell substrate. ANA were detected in 6 patients' eluates from the EDTA fractions and 2 patients' propionic acid fraction by the antihuman Clq column method. ANA were noted in 7 patients' isolates from antihuman C3 column, 6 EDTA fractions, and 2 patients' propionic acid fractions. The ANA showed speckled patterns in 6 patients and a diffuse pattern in 1. Our studies demonstrate complement fixing IC containing ANA can be detected in the sera of patients with SLE by isolation with the antihuman Clq and antihuman C3 columns.

Antibodies, Antinuclear↗
PubMed1988

Enzyme linked (ELISA) immunoabsorbent assay for the detection of hidden 19S IgM rheumatoid factors in juvenile rheumatoid arthritis.

Determination of hidden IgM rheumatoid factors (RF) in juvenile rheumatoid arthritis (JRA) offers advantages for diagnosis and in following disease activity. Sera from 30 patients with JRA were assayed for RF by latex fixation test (LFT), sensitized sheep cell agglutination test (SCAT), nephelometry, and by ELISA. IgM containing fractions were prepared by chromatography and assayed for hidden RF by the hemolytic method and ELISA. Ten patients were seropositive by LFT. All of them gave positive tests on the serum for RF with the SCAT, nephelometry, and ELISA, and on the IgM containing fractions by the hemolytic assay and ELISA. Seventeen patients seronegative by LFT were positive for hidden RF by the hemolytic test and ELISA on the IgM containing fraction. When unfractionated serum was used, 15 were positive by ELISA. Three patients were seronegative and also negative for hidden RF by the hemolytic assay and ELISA. Thus, only 2 of 30 patients had discordant results between the hemolytic assay on the IgM containing fraction and the ELISA on the serum. Our results indicate the ELISA on the serum in conjunction with the LFT offers a simple, rapid, alternative test for hidden 19S IgM RF in JRA patients.

Agglutination Tests↗