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H Griffin

Publications and source records attributed to H Griffin.

35 records · Page 2Linked to original sources
PubMed1992

Restoration of the LFA-3 adhesion pathway in Burkitt's lymphoma cells using an LFA-3 recombinant vaccinia virus: consequences for T cell recognition.

Conjugate formation between cytotoxic T lymphocytes (CTL) and target B cells, as observed in vitro, is mediated by interactions between adhesion molecules on the two cell surfaces rather than involving immune recognition through the T cell receptor. It is still not clear to what extent such adhesive contacts facilitate the process of immune recognition and target cell lysis. However, work on the Epstein-Barr virus (EBV)-associated malignancy Burkitt's lymphoma (BL) has suggested that down-regulation of one particular adhesion molecule, the lymphocyte function-associated antigen LFA-3, on the tumor cell surface is a key factor in allowing these target cells to escape EBV-specific T cell surveillance. To examine this directly, we used a cDNA for the full-length transmembrane form of LFA-3 to construct a recombinant vaccinia virus (Vacc-LFA 3), which is capable of restoring surface LFA-3 in adhesion molecule-negative BL cell lines to levels as high as seen in EBV-transformed lymphoblastoid cell lines (LCL); biochemical studies confirmed expression of the authentic N-glycosylated protein. The recombinant vaccinia-encoded LFA-3 was functional as an adhesion molecule since BL cells acutely infected with Vacc-LFA-3 then acquired the ability to form conjugates with activated T cells in vitro. However, there was no clear dependence upon LFA-3 when such BL cell lines were tested as targets for cytotoxic T lymphocytes (CTL). Firstly, LFA-3- BL cells could be killed by allospecific CTL recognizing HLA class I alloantigens, in some cases as efficiently as the corresponding LCL. In other cases where lysis was slightly below that of the LCL, Vacc-LFA-3 infection of the BL cells increased lysis up to, but never beyond, LCL values. Secondly, we studied the sensitivity of BL to EBV-specific HLA class I-restricted CTL using a BL target line which was LFA-3- but which expressed the same spectrum of EBV target proteins as an LCL. This line was not recognized by appropriately HLA-matched effectors, even after restoration of LFA-3 expression. We conclude that the LFA-3 status of BL cells influences their conjugate forming ability in in vitro assays but not necessarily their sensitivity to immune T cell-mediated cytolysis.

Antigens, Surface↗
PubMed1992

Immune escape by Epstein-Barr virus (EBV) carrying Burkitt's lymphoma: in vitro reconstitution of sensitivity to EBV-specific cytotoxic T cells.

Epstein-Barr virus (EBV) positive Burkitt's lymphoma (BL) cells are markedly less sensitive to EBV-specific cytotoxic T cell (CTL) recognition than EBV-transformed lymphoblastoid cell lines of normal B cell origin. Three features of the BL cell phenotype might contribute to this reduced susceptibility: (i) low expression of cell adhesion molecules, (ii) low expression of HLA class I and selective down-regulation of particular alleles, and (iii) down-regulation of all transformation-associated EBV antigens except EBV-encoded nuclear antigen (EBNA)-1. This study assesses the individual importance of each of these features for immune escape. For this purpose the WW1-BL cell line was used which expresses all the known transformation-associated EBV antigens (EBNA-1 to -6 and latent membrane protein-1 and -2) but which is negative for HLA A11 and for the adhesion molecule leukocyte function associated antigen-3 (LFA-3). Using recombinant vectors, these deficiencies have been sequentially corrected and the cells have been tested for sensitivity to EBV (B95.8 strain)-induced CTL preparations recognizing epitope(s) of EBNA-4 in the context of HLA A11. Expression of HLA A11 alone or in combination with LFA-3 did not sensitize WW1-BL cells to these effectors. Lysis was only achieved when HLA A11 was co-expressed with the B95.8 virus-encoded EBNA-4 protein, and in these circumstances sensitization did not require LFA-3. These results indicate that reconstitution of the relevant HLA-EBV epitope target complex on the cell membrane is sufficient to render BL cells sensitive to virus-specific cytolysis. The requirement for EBNA-4 reconstitution to achieve lysis of the WW1-BL/A11 transfectant suggested that the resident WW1 virus-encoded EBNA-4 protein did not contain the relevant target epitope for HLA A11-restricted recognition. This was confirmed by transferring the WW1 virus isolate into another A11-positive B cell background.

Antigens, CD↗
PubMed1992

T cell recognition of Epstein-Barr virus associated lymphomas.

Epstein-Barr virus, a lymphotropic herpesvirus of humans, has potent B cell growth transforming activity yet persists in the lymphoid tissues of most individuals as a lifelong asymptomatic infection. Virus induced B cell growth transformation in vitro is associated with the expression of a limited set of viral genes encoding six nuclear antigens (EBNA 1, 2, 3A, 3B, 3C and LP) and two latent membrane proteins (LMP 1, 2). Healthy virus carriers possess strong EBV specific CTL memory that can be reactivated in vitro. Here, we summarize experiments in which the antigenic specificities of these HLA class I restricted memory CTL responses have been mapped in a range of individuals with different HLA backgrounds. Of the known EBV latent proteins, EBNA 3A, 3B and 3C are frequently the dominant targets for such responses, but examples of responses directed against epitopes of EBNA 2, EBNA-LP or the LMP have been identified; by contrast, CTL responses against epitopes of EBNA 1 have not been observed. Epstein-Barr virus is associated with at least three malignancies of lymphoid origin--immunoblastic lymphomas of the immunosuppressed, endemic Burkitt's lymphoma and a subset of Hodgkin's disease. The immunoblastic lymphomas express the complete spectrum of EBV coded latent proteins and a cellular phenotype similar to that of in vitro transformed B lymphoblastoid cell lines; accordingly, they remain sensitive to EBV specific CTL recognition. Endemic BL cells are not recognized by such CTL, and at least three consistent features of this tumour could contribute to immune escape: (a) allele specific downregulation of HLA class I antigen expression, (b) absence/low expression of cellular adhesion molecules and (c) restriction of EBV latent protein expression to EBNA 1 only. The relative importance of these three features of the BL cell phenotype with regard to sensitivity to CTL recognition is re-interpreted in the light of recent results. Finally, the pattern of virus latent protein expression in EBV positive Hodgkin's disease is described, and the possibility of EBV specific CTL control against this tumour is discussed.

Antigens, Viral↗
PubMed1991

Changes in plasma lipoprotein metabolism in chicks in response to polychlorinated biphenyls (PCBs).

The results of the present study strongly suggest that the hypertriglyceridaemia in chicks treated with Aroclor 1254 is a result of reduction in VLDL clearance rather than an increase in rate of VLDL secretion. The decrease in post-heparin LPL activity responsible for reduced VLDL clearance may be mediated by cytokines produced by chronic activation of the immune system.

3-Hydroxybutyric Acid↗
PubMed1991

Balance and cognitive impairment in two epileptic patients before and after vagal nerve stimulation.

Balance and cognition were assessed in two patients with uncontrolled complex partial seizures. The patients were on anticonvulsant medications and were treated with left vagal stimulation. Balance and cognition were assessed before and after vagal stimulation, and the results were compared with age matched controls and older patients with Parkinson's disease. Severe impairments of function were found in the epileptic patients, and such negative effects of medication make vagal stimulation a potentially practical alternative treatment for uncontrolled epilepsy.

Adult↗
PubMed1989

Nutrient influences on rat intestinal phenytoin uptake.

The intestinal uptake of phenytoin was studied as a function of concentration, intestinal region, coperfused glucose, and calcium chloride in rat intestinal perfusions and everted intestinal rings. Steady-state intestinal membrane permeabilities were obtained in an in situ perfusion system and initial rates of intestinal tissue uptake were obtained in an in vitro everted ring system as rate of absorption parameters. Steady-state membrane permeabilities were independent of phenytoin perfusion concentration and decreased from duodenum to ileum. Coperfusion of glucose increased, and high calcium chloride concentrations decreased phenytoin permeabilities. While phenytoin uptake in the in vitro ring system was also concentration-independent and depressed by high calcium concentrations, regional variations and glucose enhancement were not observed. Thus, drug-nutrient interactions involved in intestinal absorption from phenytoin solutions are a function of the isolation procedure.

Animals↗
PubMed1989

Plasma lipoprotein metabolism in lean and in fat chickens produced by divergent selection for plasma very low density lipoprotein concentration.

Plasma lipoprotein metabolism was studied in vivo in two lines of chickens produced by selection for high and low plasma very low density lipoprotein (VLDL) concentration. Rates of VLDL secretion were measured by determining the rate of accumulation of triglyceride in the plasma after intravenous injection of anti-lipoprotein lipase antibody. The clearance of VLDL-triglyceride and its uptake into liver and adipose tissue was examined using radioactively labeled VLDL synthesized in vivo. The rate of VLDL secretion was about threefold higher in the high-VLDL line as compared to the leaner, low VLDL-line (6.7 vs 2.1 mumol VLDL triglyceride/h per ml of plasma). The clearance of VLDL from the circulation of the low VLDL line was much faster than that of the high VLDL line (t1/2 of 3.7 and 13.6 min, respectively). The proportion of administered radiolabel taken up by the abdominal fat pad was substantially greater in the fat line than in the lean line (11.9 vs 4.8%, respectively). Lipoprotein lipase activities in leg muscle and heart were consistently greater in the low-VLDL line and beta-hydroxybutyrate concentrations in the plasma of the low-VLDL line were significantly greater than those in the high-VLDL line (0.86 vs 0.48 mumol/ml). The results show that the approximately tenfold difference in plasma VLDL concentration between lines is primarily due to markedly different rates of hepatic VLDL production and that selection has made a major effect on partitioning of VLDL triglyceride between adipose and other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1986

Does vitellogenin inhibit lipoprotein lipase in the laying hen?

Vitellogenin isolated from laying-hen plasma strongly inhibited chicken adipose-tissue lipoprotein lipase in vitro, but inhibition was reduced or prevented by Ca2+ and Mg2+ ions and by partial dephosphorylation. Plasma from blood collected from laying hens using EDTA as anticoagulant was a potent inhibitor of lipoprotein lipase, but serum from laying hen blood caused inhibition only when dilute or after addition of EDTA. Heparin reduced or abolished the inhibition of lipoprotein lipase by plasma, serum and purified vitellogenin. The results suggest that inhibition of lipoprotein lipase by vitellogenin requires the presence of charged phosphate groups on vitellogenin and an unoccupied heparin-binding site on the enzyme. Neither condition is likely to occur in the laying hen in vivo.

Adipose Tissue↗
PubMed1986

Cisplatin administered as a continuous 5-day infusion: plasma platinum levels and urine platinum excretion.

Total and filterable platinum in plasma were monitored for seven courses (five patients, 25 mg/m2/day) using continuous 5-day infusions and one 30-minute infusion at a similar dose level (120 mg/m2). Maximum filterable (non-protein-bound) platinum levels (0.1-0.3 mg/L) for the extended infusions were ten to 40 times lower than that for the short-term infusion (4.0 mg/L). Filterable drug exposure as measured by the area under the [Pt]filterable-time curve is greater for the extended infusions (9.6 mg X hr/L) than that for the short-term infusion (4.8 mg X hr/L). Renal excretion of cisplatin (% of dose excreted/24-hour period after the beginning of the infusion) was measured for four courses of continuous 5-day infusions and for the 30-minute infusion. Urine excretion rates were lower for the continuous infusion (5%-8% of dose/24-hour period during the infusion) compared to the short-term infusion (33% of dose/24-hour period after the beginning of the 30-minute infusion).

Cisplatin↗
PubMed1984

Effects of diethyldithiocarbamate and nickel chloride on glutathione and trace metal concentrations in rat liver.

Concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG) and 4 trace metals (Ni, Cu, Mn, Zn) were measured in livers from rats treated with sodium diethyldithiocarbamate (DDC, 0.67 or 1.33 mmol/kg, i.m.) and NiCl2 (0.25 or 0.50 mmol/kg, s.c.), singly or in combination. In rats treated with DDC or NiCl2, singly, hepatic GSH was diminished at 4 h and returned to control levels (or slightly above) at 17 h. In rats that received DDC plus NiCl2, hepatic GSH was not diminished at 4 h after increased 1.4-1.8-fold at 17 h. Hepatic GSSG was diminished at 4 h after NiCl2 treatment and returned to control values at 17 h; hepatic GSSG did not differ from control values at 4 h or 17 h after treatment with DDC, alone or combined with NiCl2. Hepatic Ni was below the detection limit (approximately 20 nmol/g) in control and DDC-treated rats; hepatic Ni was increased to 53 +/- 26 (S.D.) nmol/g at 17 h after treatment with NiCl2 alone, and was increased 6-fold (308 +/- 63 nmol/g) in rats that received Ni plus DDC. Under the same conditions, hepatic Zn was increased 33% or 41%, respectively, in rats that received NiCl2 or DDC, singly, and was not further increased by combined treatment; hepatic Cu and Mn concentrations were unaffected by NiCl2 or DDC, singly, but were diminished in rats that received NiCl2 and DDC. This study suggests: (a) that increased hepatic uptake of Ni is largely responsible for the synergistic induction of heme oxygenase activity in rats treated with NiCl2 and DDC; and (b) that increased hepatic uptake of Zn contributes to the induction of hepatic metallothionein by NiCl2 and DDC.

Animals↗
PubMed1982

Hydrolysis of plasma triacylglycerol-rich lipoproteins from immature and laying hens (Gallus domesticus) by lipoprotein lipase in vitro.

Very-low-density (VLD) lipoproteins and portomicrons were isolated from the plasma of immature and laying hens and their size, lipid composition and susceptibility to hydrolysis by lipoprotein lipase were compared. In agreement with other studies, VLD lipoproteins from laying hens were found to be smaller and have a different lipid composition than VLD lipoproteins from immature hens. Portomicrons from immature and laying hens had mean diameters of about 150 nm and similar lipid compositions. Hydrolysis of VLD lipoproteins from immature hens, and portomicrons from immature and laying hens, proceeded rapidly until at least 40% of the substrate had been used. In contrast only 1--15% of laying-hen VLD-lipoprotein triacylglycerol was readily hydrolysis occurred slowly. The limited susceptibility of laying-hen VLD lipoproteins appeared to be due to their low content of lipoprotein lipase activator apoprotein, which occurred despite an abundance of activator in the high-density lipoproteins of laying-hen plasma. The results provide further evidence that the liver of the laying hen synthesizes specialized lipoproteins. Their limited susceptibility to hydrolysis by lipoprotein lipase is probably a major factor in ensuring transport of lipid to yolk rather than to other tissues. The form of transport of dietary lipid, however, is similar in immature and laying hens.

Age Factors↗
PubMedDate not supplied

A community hospital's effort to expedite treatment for patients with chest pain.

OBJECTIVE: The purpose of this study was to determine treatment times at a community hospital that does not receive prehospital electrocardiogram (ECG) transmission and to determine the effect of time to first hospital ECG on overall door-to-drug time. DESIGN: Descriptive. SETTING: 238-bed Regional Medical Center in Burlington, North Carolina. SAMPLE: One hundred four patients with a final diagnosis of acute myocardial infarction were included in this 16-month study. RESULTS: A median door-to-ECG time of 5 minutes was within the American College of Cardiology/American Heart Association recommendation of 10 minutes. Shorter treatment times to obtain the first ECG and initiate thrombolytic therapy were associated with younger patients and those arriving by ambulance. CONCLUSIONS: While efficiency in obtaining a first hospital ECG on patients with suspected acute myocardial infarctions was achieved, this did not result in low door-to-drug times. Further streamlining of protocol and the exploration of prehospital initiatives may result in a significant reduction in door-to-drug times.

Chest Pain↗