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Biomedical subjects

A Arnold

Publications and source records attributed to A Arnold.

At least 181 records · Page 10Linked to original sources
PubMed1987

Effect of chloroquine on intestinal lipid metabolism.

Most studies that have quantitated recovery of infused lipid in the intestinal mucosa and mesenteric lymph have only been able to recapture 50-75%. One possibility is that the missing lipid enters a triacylglycerol (TG) storage pool in the enterocyte and is hydrolyzed by lysosomal lipase, and the free fatty acid released is transported by the portal vein. This postulate was tested by comparing glyceryl trioleate (TO)-infused rats pretreated with the lysosomotropic drug, chloroquine (6.3 mg.kg-1.h-1) with saline controls. Chloroquine increased mucosal TG from 94 +/- 6 to 128 +/- 8 mumol. Additionally, the specific activity of the mucosal TG relative to the infused [3H]TO was reduced in the treated rats. The mucosal TG increase was not due to impaired TG output, which remained the same as controls. We conclude that the TG in the acid lipase-sensitive pool derives most of its glyceride-glycerol from endogenous sources. Furthermore, the increment in mucosal TG caused by chloroquine is not enough to explain the majority of the acyl groups unaccounted for in the mucosa and lymph after a TG infusion. For these a direct passage of acyl groups through the enterocyte is postulated.

Animals↗
PubMed1987

Evaluation of immunotoxicity in a subchronic feeding study of triphenyl phosphate.

Triphenyl phosphate (TPP), a potential food contaminant, was fed to weanling Spartan Sprague-Dawley rats at dose levels of 0, 0.25, 0.5, 0.75, and 1.0% for 120 days. The immunotoxicity evaluation, planned as a minimum testing model in a subchronic study design as well as to provide information on TPP, was performed along with the routine testing of a separate group of animals. Traditional measures were made of growth and food consumption, total protein analysis, electrophoretic analyses of serum proteins, lymphoid organ weights in relation to growth, and histopathology, with expanded immunohistochemical evaluation of B- and T- lymphocyte regions in spleen, thymus, and lymph nodes, using immunoperoxidase staining. Assessment was made of the humoral response to a T-lymphocyte-dependent antigen, sheep red blood cells, and was begun at midterm of the feeding period for the primary response followed by secondary and tertiary booster immunizations at 3-week intervals. The kinetics of the responses were measured by hemolysin assay of relative antibody titers at days 3, 4, 5, and 6 postinjection. No significant effects on the responses were noted for either sex at any of the dose levels tested. The only effects noted were a decreased rate of growth at high levels of TPP and increases in the levels of alpha- and beta-globulins suggestive of increased hepatic activity.

Animals↗
PubMed1987

Teratogenic potential of triphenyl phosphate in Sprague-Dawley (Spartan) rats.

Male and female Sprague-Dawley (Spartan) rats were fed dietary levels of 0, 0.25, 0.50, 0.75 or 1.00% triphenyl phosphate (TPP) from 4 weeks post weaning for 91 days, through mating and gestation. At these dietary levels, the daily intake of TPP during pregnancy was 0, 166, 341, 516 and 690 mg/kg body weight, respectively. TPP exposure had no toxic effects on mothers or offspring at these dosages. The types of developmental anomalies were similar in both treated and control animals. No significant increases in the incidence of anomalies were seen in the treated groups as compared to control values. TPP was not teratogenic in Sprague-Dawley rats at the levels tested.

Animals↗
PubMed1986

CTP:phosphocholine cytidylyltransferase in intestinal mucosa.

CTP:phosphocholine cytidylyltransferase is thought to be a rate-limiting enzyme in phosphatidylcholine synthesis. This enzyme has not been well studied in intestine. We found that activity was greater in the non-lipid stimulated state (cytosolic form of the enzyme) than any previous tissue investigated (2.7 nM/min per mg protein). On addition of lysophosphatidylethanolamine, the enzyme only increased in activity 2.4-fold which is less than any previously reported tissue on lipid stimulation. As compared to liver, the enzyme was resistant to inhibition by chlorpromazine (gut, 100% activity remaining at 80 microM; 14% in liver). Tetracaine and propranolol were found to be impotent as inhibitors of the intestinal enzyme. Octanol-water partitioning showed that both chlorpromazine and tetracaine were hydrophobic, propranolol was not. pKa studies demonstrated that at the reaction pH, chlorpromazine would be uncharged. Physiologic experiments in which de novo phosphatidylcholine synthesis was either stimulated by bile duct fistulization and triacylglycerol infusion or suppressed by including phosphatidylcholine in a lipid infusion demonstrated that the enzyme (cytosolic enzyme) responded by decreasing Vmax but that the Km remained the same. In sum, these studies suggest that CTP:phosphocholine cytidylyltransferase in intestine is unique as compared to other tissues and that its response to a physiological stimulus is counter to that which would be adaptive.

Animals↗
PubMed1986

Coronary angioplasty of the unstable angina related vessel in patients with multivessel disease.

This study is a retrospective analysis of the efficacy of percutaneous transluminal coronary angioplasty of the ischaemia-related vessel in patients with unstable angina. Forty-three patients had multivessel disease with dilatation of the ischaemia-related vessel only (group I; partial revascularization) while 111 patients had single vessel disease only (group II; total revascularization). The initial success rate in both groups was identical (88 versus 88%). The need for emergency coronary artery bypass surgery was similar in the two groups (group I 12% versus group II 9%; NS). The total post PTCA myocardial infarction rate (despite urgent CABG) was also similar in the two groups (group I 9% versus group II 10%; NS). The results of electrocardiographic exercise testing and Thallium-201 scintigraphy provide objective evidence for incomplete revascularization in group I. The maximum workload achieved was lower, and the frequency of exercise induced angina, ST-segment depression and reversible perfusion defect was higher than in group II. Moreover, at 6 months follow-up the recurrence rate of angina pectoris rate was higher in group I than in group II (29% versus 16% P less than 0.05). It is concluded that dilatation of the ischaemia related vessel only in patients with unstable angina and multivessel disease is as effective in the management of the acute phase of unstable angina as is dilatation of the ischaemia related vessel in patients with single vessel disease. However, due to only partial revascularization the recurrence rate of angina pectoris is higher.

Adult↗
PubMed1986

Steady-state kinetic analysis of triacylglycerol delivery into mesenteric lymph.

The output of triacylglycerol in chylomicrons can be increased 60% by prefeeding rats with a 20% fat diet or 110% by including phosphatidylcholine in a lipid infusion. The present study was designed to determine whether the increment was due to an expansion of the chylomicron triacylglycerol precursor pool or an increase in its fractional turnover rate. A steady-state kinetic model was established in rats receiving 135 mumol glyceryl trioleate/h. The decay in specific activity of triacylglycerol after removal of radiolabeled glyceryl trioleate from the duodenal infusate was followed for 4 h and analyzed by the SAAM 23 program. It was found that the fractional turnover rate of the chylomicron precursor pool remained the same in each experimental condition. However, the pool was found to expand in direct proportion to the chylomicron triacylglycerol output. Functionally the infused [3H]glyceride-glycerol and tri[14C]oleate behaved the same in lymph chylomicrons and was 90% of infusate specific activity. In summary, these data suggest that increases in chylomicron triacylglycerol output are dependent on the size of the mucosal precursor pool and the monoacylglycerol acyltransferase synthetic pathway for its triacylglycerol.

Animals↗
PubMed1985

Immunological consequence of renal transplantation and immunosuppression. I. Alterations in human natural killer-cell activity.

The role and activity of natural killer (NK) cells following renal transplantation remain unknown. To monitor NK activity, a 51Cr release of K-562 targets in prednisone- and azathioprine-treated patients receiving renal allografts was utilized. In 18 patients in whom NK activity was measured prior to and after transplantation, a significant diminution in NK activity within 3 weeks following transplantation was demonstrated compared to pretransplant values (34.71 vs 12.20%, respectively; P less than 0.001). In 11 subjects who had NK activity assayed at various intervals after transplantation but not prior to allografting, mean NK values were markedly lower (mean, 14.2%) than those of normal volunteers or patients maintained on hemodialysis (P less than 0.001). The latter two control groups demonstrated no difference (P = NS) in mean NK activity (39.46 vs 35.82%, respectively). In 5 of the 29 patients evaluated with good long-term graft function (mean, 2.7 years), restitution of normal NK activity was demonstrated. In two patients with bacterial infections, NK activity increased from 39.29 to 51.7% and from 13.54 to 20.00%. After infection, these values were 35.3% in the former and 3.39% in the latter. Viral infection did not appear to affect NK activity significantly. NK activity was increased in only one of seven patients with documented rejection episodes. In three of such patients, NK activity declined significantly following pulse methylprednisolone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Factors influencing triacylglycerol delivery into mesenteric lymph.

The transport of triacylglycerol (TG) in mesenteric lymph was studied in rats with duodenal and mesenteric lymphatic cannulas with or without bile fistulas. Rats were infused with 135 mumol glycerol trioleate (TO) for 4 h, followed by 5 h of NaCl infusion. Rats with intact fistulas prefed 20% corn oil had nearly twice the maximum output of TG in lymph as controls. Decay from peak values was zero order for controls and indeterminate for rats prefed corn oil. In rats with bile fistulas, less TG was transported in lymph than in those in which 2 mM phosphatidylcholine (PC) was added to the infusate. The decay from maximum values was zero order for controls and first order for rats infused with PC and TO. Recovery of infused [3H]glycerol trioleate in controls was 43% and increased to 68% on inclusion of PC in the infusate. We conclude that in chow-fed rats lymph TG delivery rates were well below infusion rates, suggesting alternate TG transport routes, TG transport was improved by supplementing the infusate with PC or prefeeding with 20% TG in chow, and PC may be limiting in TG transport in rats with bile fistulas.

Animals↗
PubMed1985

NIH conference. Molecular genetic analysis of human lymphoid neoplasms. Immunoglobulin genes and the c-myc oncogene.

Immunoglobulin genes responsible for individual antibodies are organized as discontinuous DNA segments in their germline form. As an uncommitted stem cell develops into an antibody-synthesizing plasma cell, rearrangements of these immunoglobulin gene segments serve to activate the genes and to generate the virtually unlimited capacity to synthesize antibodies that recognize potential antigens. The analysis of immunoglobulin gene structure and arrangement has been of immense value in the study of human lymphoid neoplasms. Recombinant DNA technology involving analysis of immunoglobulin gene arrangement has been used to classify neoplasms of previously uncertain lineage, aid in the diagnosis of neoplasms of the B-cell series, and define the state of differentiation of neoplastic B-cell precursors. Furthermore, the demonstration of translocation of a particular transforming gene, the c-myc oncogene, into the immunoglobulin gene locus in Burkitt's lymphoma has provided a major insight into the cause of malignant transformation of these lymphoid cells.

Alleles↗
PubMed1985

Human B lymphoblastoid cell lines provide an interleukin 1-like signal for mitogen-treated T lymphocytes via direct cell contact.

The B lymphoblastoid cell lines (B-LCL) 8392, SB, 1788, and Daudi provide accessory cell activity for mitogen-treated T cells, whereas the T lines MOLT-4, 8402, CEM, and HSB do not provide this function. Direct cell contact is required for the accessory cell activity, and active lymphocyte growth factors could not be detected in the supernatants of the B-LCL. The B-LCL also present alloantigens to responding T cells, and this response is independent of additional accessory cells. The target for the B-LCL is the responding T cell itself, rather than a minor contaminating population of endogenous accessory cells. This conclusion is based on the finding that, under culture conditions in which T cells do not proliferate in response to PHA, accessory cell activity of the B-LCL is maintained. Paraformaldehyde- or glutaraldehyde-treated B-LCL retain their accessory cell activity at levels of these agents that completely eliminate metabolic activity of the B-LCL, as determined by incorporation of leucine, thymidine, and uridine into macromolecules. This treatment eliminates alloantigen presentation by the B-LCL. T cells treated with IO-4 or with monoclonal anti-T3 antibodies fail to respond to highly purified IL 1, and respond minimally to supra-optimal concentrations of IL 2. Nevertheless, these cells respond maximally to the accessory cell activity of the B-LCL. The IO-4 treated cells or cells exposed to anti-T3 also proliferate in response to TPA. Together, our data suggest that the B-LCL provide an IL 1-like signal for mitogen-treated T cells via direct cell contact, in the absence of detectable soluble IL 1.

Antigen-Presenting Cells↗
PubMed1984

Mitogenic properties of neuraminidase and galactose oxidase-treated lymphoblastoid cells and plasma membranes for peripheral blood lymphocytes.

Generation of aldehydes on terminal D-galactose or N-acetyl-D-galactosamine residues of cell surface glycoproteins by treatment with neuraminidase and galactose oxidase (NAGO) renders some types of cells mitogenic for T lymphocytes. The cell surface molecules required for the presentation of mitogenic signals by NAGO-treated cells are unknown. We tested the mitogenic properties of NAGO-treated lymphoblastoid cell lines (LCL) and subcellular fractions as an initial step in the isolation and characterization of cell surface molecules required for stimulation. We report here that the NAGO-LCL of B cell lineage were potent stimulators, whereas the NAGO-LCL of T cell lineage were weaker and more variable stimulators of lymphocyte proliferation. T-LCL that were stimulatory in indirect stimulation did not induce a mixed lymphocyte response, whereas the B-LCL were positive in both assays. Aldehyde-bearing plasma membrane-enriched subcellular fractions, depleted of nuclear, cytosolic, and mitochondrial components, were mitogenic, and the stimulatory activity was dose dependent. The ability to induce mitogenesis was abrogated by reduction of cell surface aldehyde groups. The results indicate that lymphocyte activation, induced by NAGO-treated stimulatory cells, is a plasma membrane-associated event and does not require the metabolic activity of intact cells. Furthermore, the aldehyde moiety is required but not sufficient for presentation of mitogenic signals. The LCL provide a suitable and reproducible source for isolation and characterization of stimulatory cell surface structures.

Aldehydes↗
PubMed1983

Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms.

Immunoglobulin genes in their germ-line form are separated DNA subsegments that must be joined by means of recombinations during B-cell development. Individual immunoglobulin-gene rearrangements are specific for a given B cell and its progeny. We show that the detection of such gene rearrangements by Southern hybridization provides a sensitive marker for both clonality and B-cell lineage within lymphoid tissues lacking expression of definitive surface phenotypes. We have used these genetic markers in three ways: to establish a diagnosis of lymphoma in a neoplastic disorder of uncertain cell type, to show that some lymphomas that were previously classified as being of T-cell type in fact contain monoclonal B cells, and to detect clonal B-cell populations within lymphomatous tissues of uncertain immunotype and within an atypical lymphofollicular hyperplasia having no other clonal surface markers. These sensitive and unique indicators of clonality located directly at the DNA level are capable of providing insights into the cellular origin, early detection, and natural history of neoplasia.

B-Lymphocytes↗
PubMed1983

Lymphoid blast crises of chronic myelogenous leukemia represent stages in the development of B-cell precursors.

The origin and stage of differentiation of the blast-crisis cells in chronic myelogenous leukemia have remained uncertain. Because immunoglobulin heavy-chain and light-chain genes must undergo a DNA rearrangement during B-cell development but rarely do so in human non-B-cell lineages, we examined these genes in 18 episodes of chronic myelogenous leukemia. In eight of nine episodes of lymphoid blast crisis, heavy-chain genes were rearranged, and in three, rearrangements in light-chain genes were also present. In contrast, cells from chronic myeloid, myeloid blast, and erythroid-like phases retained germ-like immunoglobulin genes. The observed phenotypic markers and gene configurations revealed that most lymphoid blast crises represent stages of development of B-cell precursors. In two separate episodes of lymphoid crisis, cells from a single patient possessed identical heavy-chain but different light-chain-gene configurations. Thus, the precursor cells that monoclonally expand to produce a lymphoid crisis are capable of immunoglobulin-gene rearrangements and represent discrete steps in early B-cell maturation.

Antigens, Surface↗