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J D Burton

Publications and source records attributed to J D Burton.

At least 19 recordsLinked to original sources

Cytokine induction in HTLV-I associated myelopathy and adult T-cell leukemia: alternate molecular mechanisms underlying retroviral pathogenesis.

The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing a variety of host cellular genes including many of the cytokines responsible for immune regulation and osteoclast activation. This derangement in cytokine expression may contribute to the panoply of disease states associated with HTLV-I infection such as the adult T-cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). We wished to determine if there was a correlation between the expression of an array of cytokines and the diverse clinical manifestations of ATL and HAM/TSP. Utilizing the techniques of specific mRNA amplification by the polymerase chain reaction (PCR) as well as Northern blotting, we analyzed the ex vivo mRNA expression of gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and transforming growth factor-beta 1 (TGF-beta 1) in the peripheral blood of HAM/TSP and ATL patients as well as asymptomatic seropositive carriers. IFN-gamma, TNF-alpha, and IL-1 beta transcripts were up-regulated in patients with HAM/TSP and seropositive carriers when compared to their levels in ATL and normal controls. In contrast, the ATL patients constitutively expressed higher levels of TGF-beta 1 mRNA than HAM/TSP and seropositive carriers. In addition, TNF-alpha and IL-1 beta serum levels were elevated in HAM/TSP, but not in ATL patients nor seropositive carriers. However, the circulating leukemic cells from ATL patients secreted increased levels of TGF-beta 1 protein into the culture medium than T-cells derived from HAM/TSP patients. Collectively these results suggest that induction of IFN-gamma, TNF-alpha, and IL-1 beta in HAM/TSP may initiate an inflammatory cascade with subsequent events leading to immune mediated destruction of the central nervous system in these patients. Expression of osteoclast activators such as TNF-alpha and IL-1 beta is not associated with hypercalcemia in ATL. Finally, impaired cellular and humoral immune responses present in ATL, but not in HAM/TSP, may be related to elevated levels of TGF-beta 1 produced by the leukemic cells. These differences in retroviral-induced host cytokine expression in ATL and HAM/TSP suggest alternate roles in disease pathogenesis.

Adult

Human B lymphocytes express the p75 component of the interleukin 2 receptor.

The nature of the interleukin 2 (IL-2) receptor on purified human B lymphocytes was examined. Both normal and malignant cells showed evidence of a 70-75,000 mol. wt (p75) IL-2 binding molecule as assessed by 125I-labeled IL-2 binding and receptor cross-linking. On normal, Tac-negative B lymphocytes the estimated number of p75 binding sites was 1100 per cell and the dissociation constant (Kd) was 1.7 nM. Consistent with this, cross-linking experiments demonstrated the presence of an IL-2 binding molecule of 70-75,000 mol. wt. Purified B cells from patients with hairy cell leukemia and chronic lymphocytic leukemia (CLL) also expressed the p75 IL-2 binding molecule. In the HCL samples, a small number of high-affinity IL-2 binding sites were detected (27-90) while the majority of binding sites (2100-10,800) were typical of low-affinity p55 Tac binding. IL-2 added to the purified normal and CLL B lymphocytes led to the induction of p55 Tac expression and the generation of high-affinity IL-2 receptors. This response to IL-2 was equivalent to the response observed when normal B lymphocytes were stimulated by Staphylococcus aureus Cowan I.

Antigens, CD

Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy.

A state of T-cell activation, reflected by a marked degree of spontaneous proliferation in vitro, exists among patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) but not in those with retroviral-induced adult T-cell leukemia (ATL). We wished to define the mechanism by which the immune activation of circulating cells from HAM/TSP is driven, thus gaining insight into the pathogenesis of this HTLV-I-associated disease. By using a modification of the polymerase chain reaction, we compared the levels of interleukin 2 (IL-2) and IL-2 receptor alpha chain (IL-2R alpha) mRNA expression to the transcription of the HTLV-I transactivator gene, pX, in peripheral blood mononuclear cells of HAM/TSP and ATL patients as well as seropositive carriers. Up-regulation of IL-2 and IL-2R alpha transcripts was detected in HAM/TSP and seropositive carriers that paralleled the coordinate mRNA expression of the pX transactivator. In addition, IL-2 and soluble IL-2R alpha serum levels in HAM/TSP and seropositive carriers were elevated. Despite markedly elevated levels of soluble IL-2R alpha in ATL, transcripts for IL-2 and pX were not demonstrable in the circulating cells. Finally, the marked degree of in vitro spontaneous proliferation present in HAM/TSP was profoundly inhibited by specific anti-IL-2R or anti-IL-2 blocking antibodies. Collectively, these results suggest that immune activation in HAM/TSP, in contrast to ATL, is virally driven by the transactivation and coordinate expression of IL-2 and IL-2R alpha. This deregulated autocrine process may contribute to the evolution of inflammatory nervous system damage in HAM/TSP.

Base Sequence

Dominant mutations causing alterations in acetyl-coenzyme A carboxylase confer tolerance to cyclohexanedione and aryloxyphenoxypropionate herbicides in maize.

A partially dominant mutation exhibiting increased tolerance to cyclohexanedione and aryloxyphenoxypropionate herbicides was isolated by exposing susceptible maize (Zea mays) tissue cultures to increasingly inhibitory concentrations of sethoxydim (a cyclohexanedione). The selected tissue culture (S2) was greater than 40-fold more tolerant to sethoxydim and 20-fold more tolerant to haloxyfop (an aryloxyphenoxypropionate) than the nonselected wild-type tissue culture. Regenerated S2 plants were heterozygous for the mutant allele and exhibited a high-level, but not complete, tolerance to both herbicides. Homozygous mutant families derived by self-pollinating the regenerated S2 plants exhibited no injury after treatment with 0.8 kg of sethoxydim per ha, which was greater than 16-fold the rate lethal to wild-type plants. Acetyl-coenzyme A carboxylase (ACCase; EC 6.4.1.2) is the target enzyme of cyclohexanedione and aryloxyphenoxypropionate herbicides. ACCase activities of the nonselected wild-type and homozygous mutant seedlings were similar in the absence of herbicide. ACCase activity from homozygous tolerant plants required greater than 100-fold more sethoxydim and 16-fold more haloxyfop for 50% inhibition than ACCase from wild-type plants. These results indicate that tolerance to sethoxydim and haloxyfop is controlled by a partially dominant nuclear mutation encoding a herbicide-insensitive alteration in maize ACCase.

Acetyl-CoA Carboxylase

Malignant chronic lymphocytic leukemia B cells elaborate soluble factors that down-regulate T cell and NK function.

To determine if the frequently observed T cell and natural killer dysfunction in B-chronic lymphocytic leukemia might be related to the presence of large numbers of malignant B cells, we studied the effects of secretory or shed products of CLL B cells on normal (control) T cell and NK function. The cell-free supernatants from CLL B cells cultured from 24 to 48 hr inhibited a variety of T cell functions including: PHA-induced proliferation, PHA-stimulated entry of T cells into the cell cycle, and PHA-induced production of interleukin-2. In addition, B-CLL supernatants diminished control NK activity. Purified control B cells and other malignant cell lines produced little or no inhibitory activity toward these T cell or NK functions. The sera from these same B-CLL patients diminished PHA-induced interleukin-2 production by control T cells. Initial molecular characterization of the inhibitory factor(s) revealed it to be of low molecular weight (less than 5000 daltons) with loss of functional activity after treatment with neuraminidase. This suggested that this substance might be either a ganglioside or glycoprotein whose inhibitory activity depends on the presence of a sialic acid moiety. If CLL B cells are capable of secreting or shedding immunosuppressive factor(s), then alteration of this property may result in a more normal immune system for these patients.

B-Lymphocytes

Inhibition of plant acetyl-coenzyme A carboxylase by the herbicides sethoxydim and haloxyfop.

Incorporation of [14C]acetate or [14C]pyruvate into fatty acids in isolated corn seedling chloroplasts was inhibited 90% or greater by 10 microM sethoxydim or 1 microM haloxyfop. At these concentrations, neither sethoxydim nor haloxyfop inhibited [14C]acetate incorporation into fatty acids in isolated pea chloroplasts. Sethoxydim (10 microM) and haloxyfop (1 microM) did not inhibit incorporation of [14C]malonyl-CoA into fatty acids in cell free extracts from corn tissue cultures. Acetyl coenzyme A carboxylase (EC 6.4.1.2) from corn seedling chloroplasts was inhibited by both sethoxydim and haloxyfop, with I50 values of 2.9 and 0.5 microM, respectively. This enzyme in pea was not inhibited by 10 microM sethoxydim or 1 microM haloxyfop.

Acetyl-CoA Carboxylase

AIDS and sudden death.

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Acquired Immunodeficiency Syndrome

Physico-chemical limitations in experimental investigations.

An element or compound in a natural water system is usually distributed between a variety of physico-chemical forms, both dissolved and particulate. The distribution is determined by the properties of the ion or molecule in question and by a number of major variables, including ionic strength, the nature and concentrations of major dissolved elements, particulate matter and organic complexing material, pH and the electron activity (pE); it may thus vary widely between different environments. The design of experiments to study sublethal effects of pollutants in sea water ideally requires that the test medium is closely matched to the environment for which information is needed, with respect to the ranges of concentration and activity, and the chemical speciation, of the pollutant and of any other constituents which may influence its effects. This in turn requires either that the pollutant can be added in the appropriate forms, implying a knowledge of the existing speciation, or that the added material rapidly exchanges with the forms already present. The implications of these requirements are most apparent for those pollutants that show complex chemical behaviour in sea water. This account concentrates on metals of toxicological significance. Consideration of particulate associations, redox speciation, and complex formation in the dissolved state with inorganic and organic ligands, suggests that physicochemical factors limit the usefulness, in terms of environmental predictions, of experimental studies of biological effects of metals, both inherently and through inadequate knowledge of environmental speciation and the mechanisms and rates of interconversion between species. Of particular importance are non-equilibrium features in speciation, such as the presence of thermodynamically unstable oxidation states and of kinetically non-labile associations. Interpretation of the nature of these associations is complicated by the presence of colloidal and organic macromolecular material in dissolved fractions as conventionally defined. While the chemical behaviour of some substances in sea water is considerably less complicated than that of the trace metals, there is a need with all types of pollutants for greater attention to physico-chemical factors in both the design and interpretation of experiments to investigate biological effects.

Chemical Phenomena

The spectrum of eosinophilic infiltration of the gastrointestinal tract and its relationship to other disorders of angiitis and granulomatosis.

Six cases of eosinophilic infiltration of the gastrointestinal tract were studied. Three cases were of the diffuse infiltrative variety (eosinophilic enteritis, two cases; eosinophilic peritonitis, one case), and three cases were of the circumscribed variety (so-called inflammatory fibroid polyp). Two of the infiltrative lesions showed necrotizing granulomas identical to those described by Churg and Strauss; one of the two also showed active vasculitis. One circumscribed lesion occurred in a patient with polyarteritis nodosa. Necrotizing eosinophilic granulomas were also noted in this lesion. Our observations suggest that the two forms of eosinophilic infiltration of the gastrointestinal tract are parts of a disease spectrum. Supporting evidence in the literature is presented. The relationship of this group of eosinophilic lesions to the hypereosinophilic syndrome, allergic granulomatosis and angiitis of Churg and Strauss, and polyarteritis nodosa is discussed.

Adult

The physics of the cranial cavity, hydrocephalus and normal pressure hydrocephalus: mechanical interpretation and mathematical model.

It is intended for this research, to provide some basis for the understanding of the rational mechanics of the cranial content. There are many interesting and controversial facts derived from the experimental and clinical-pathological observations of hydrocephalus and increased intracranial pressure. For instance, in some patients a moderate increase of intracranial pressure is accompanied by hydrocephalus and mental changes, while in others, with high intracranial pressure, the ventricles and mental functions remain unaltered. What then is the parameter that changes the size of the ventricles and impairs brain function? It is shown how the transmission of intraventricular pressure throughout the brain parenchyma creates a stress distribution that varies in magnitude; how during the production, maintenance, and reversal of hydrocephalus, and normal pressure hydrocephalus the stress is distributed throughout the brain; and how in the presence of a sudden increase of intracranial pressure nature has arranged additional mechanisms for protecting the brain. It is important to recognize that some aspects of intracranial physiopathology can be explained through classical concepts of physics, prior to attempting to interpret such processes solely in terms of biological or auto-regulatory phenomena.

Adult

A histochemical method of differentiating lower gastrointestinal tract mucin from other mucins in primary or metastatic tumours.

Epithelial mucins of the normal terminal ileum, caecum, colon, and rectum of man are unique in that they alone exhibit staining following the periodate-borohydride/KOH/PAS technique. Application of this technique enables one to differentiate those mucin-producting metastases arising from adenocarcinoma of the lower gastrointestinal tract from those arising elsewhere, and may occasionally be useful in determining the site of the primary tumour when it is in doubt. Furthermore, it was found to be especially useful in distinguishing between primary adenocarcinoma of the lung and metastases in the lung from adenocarcinoma of the lower gastrointestinal tract.

Adenocarcinoma