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Biomedical subjects

J C Reed

Publications and source records attributed to J C Reed.

At least 523 records · Page 29Linked to original sources
PubMed1985

Functional properties of the 50 kd protein associated with the E-receptor on human T lymphocytes: suppression of IL 2 production by anti-p50 monoclonal antibodies.

Monoclonal antibody 9.6 is specific for a 50 kd T cell surface protein (p50) associated with the sheep erythrocyte (E)-receptor on human T lymphocytes. This antibody interferes with many T cell functions. We have examined the effect of antibody 9.6 on lymphocyte proliferation and interleukin 2 (IL 2) production triggered by mitogens, soluble antigens, and alloantigens to elucidate the mechanism(s) of its immunosuppressive action. At concentrations as low as 50 ng/ml, 9.6 suppressed lymphocyte proliferation and the elaboration of IL 2 by T cells stimulated by PHA, alloantigens, or low concentrations of the phorbol ester TPA (less than or equal to ng/ml). Furthermore, in cultures stimulated by a combination of PHA plus TPA, 9.6 did not inhibit the acquisition of IL 2 receptors but inhibited proliferation and IL 2 production. Immunoaffinity-purified IL 2 completely restored lymphocyte proliferation in cultures inhibited by 9.6. Studies of kinetics of inhibition by 9.6 showed that this antibody inhibited lymphocyte proliferation induced by PHA, alloantigen, and PPD even when added at 24, 48, and 72 hr, respectively, after the initiation of these cultures, suggesting that 9.6 does not block lectin binding or antigen recognition by T cells and that it can inhibit lymphocyte proliferation even after cells have undergone one or more rounds of cell division. A dose-response analysis of lymphocyte proliferation induced by PHA or by TPA demonstrated that the degree of inhibition by 9.6 decreased with increasing concentrations of these mitogens. Antibody 9.6 did not inhibit lymphocyte response induced by optimal concentrations of PHA (50 to 100 micrograms/ml; PHA-M) but inhibited proliferation of maximally induced lymphocytes by using a synergistic combination of low concentrations of PHA (5 micrograms/ml, PHA-M) plus TPA (1 ng/ml). Taken together, these findings indicate that 1) 9.6 inhibits lymphocyte proliferation by affecting IL 2 production, 2) 9.6 does not inhibit the acquisition of 9.6 receptors induced by a synergistic combination of PHA plus TPA, and 3) p50 molecules may be involved in multiple pathways of T cell activation.

Antibodies, Monoclonal↗
PubMed1985

Stimulation and inhibition of human T cell subsets by wheat germ agglutinin.

Wheat germ agglutinin (WGA), a tetravalent lectin, has both stimulatory and inhibitory effects on human T lymphocytes. It has been suggested that these actions are related and that WGA selectively stimulates a suppressive subset of T cells. We studied the ability of WGA to stimulate and inhibit subpopulations of human peripheral blood mononuclear cells (PBMC) known to have helper or suppressor activity. Fresh human PBMC were depleted of either T4+ or T8+ cells by using antibody-mediated complement lysis. The resultant cell populations were stimulated with WGA, and the proliferative response was assessed by [3H]thymidine incorporation, IL 2 receptor expression, the ability to elaborate IL 2 in culture supernatants, and the susceptibility to inhibition by the monoclonal antibody anti-Tac. Similar experiments with cells from a WGA-responsive continuous T cell culture were also performed. WGA inhibited phytohemagglutinin (PHA)-induced proliferation of PBMC depleted of either T4+ or T8+ cells. WGA also inhibited PBMC that had been depleted of adherent cells and Ia+ cells and then induced to proliferate with a combination of TPA and PHA. Our findings indicate that WGA induces IL 2-dependent proliferation in a small proportion of both T4+ and T8+ lymphocytes. We also provide evidence that the inhibitory activity of WGA is not mediated by a T4+, T8+, or Ia+ cell, suggesting that WGA acts directly on the proliferating cell rather than selectively stimulating a suppressive subpopulation.

Dose-Response Relationship, Immunologic↗
PubMed1985

Effect of wheat germ agglutinin on the interleukin pathway of human T lymphocyte activation.

Wheat germ agglutinin (WGA) inhibits proliferation of human peripheral blood mononuclear cells (PBMC) induced by mitogens and antigens. We investigated the mechanism by which WGA inhibits PHA-induced human lymphocyte proliferation with regard to the interleukin pathway. Our data revealed that although PBMC-proliferation was markedly suppressed by WGA, levels of IL 2 activity in WGA-inhibited cultures were not reduced, but instead were increased, suggesting failure to utilize IL 2. Furthermore, the addition of exogenous IL 2 failed to overcome the suppression. Consistent with these observations, culturing PBMC with PHA plus WGA markedly decreased the number of high-affinity IL 2 receptor per cell, as determined by binding of purified [3H]IL 2, relative to cultures containing PHA alone. WGA immobilized on support beads bound detergent-solubilized IL 2 receptors from PHA-activated T cells, but did not bind human IL 2. However, WGA did not competitively block the binding of [3H]IL 2 to PHA-induced lymphoblasts. These results suggest that WGA inhibits lymphocyte proliferation by binding to and decreasing the number of high-affinity IL 2 receptors displayed on T cells, without impairing IL 2 production.

Cells, Cultured↗
PubMed1985

Monoclonal antibody OKT11A inhibits and recombinant interleukin 2 (IL 2) augments expression of IL 2 receptors at a pretranslational level.

The expression of receptors for interleukin 2 (IL 2) represents a critical event regulating the growth of normal T lymphocytes. We investigated the effects of the inhibitory monoclonal antibody OKT11A (anti-sheep erythrocyte receptor) and of purified recombinant IL 2 (rIL 2) on the expression of IL 2 receptors by activated T cells at both the protein and the mRNA levels. Adding OKT11A antibody (0.5 microgram/ml) to phytohemagglutinin (PHA)-stimulated cultures of human peripheral blood mononuclear cells (PBMC) markedly suppressed cellular proliferation (assessed by [3H]thymidine incorporation) and IL 2 receptor expression (determined by immunofluorescence assay by using the anti-IL 2-receptor antibody, anti-Tac). Northern blot analysis performed with the use of a cDNA probe specific for the human IL 2 receptor gene demonstrated that OKT11A antibody also decreased the accumulation of IL 2 receptor mRNA induced by PHA in PBMC. Purified rIL 2 (10 U/ml) alone had little effect on the expression of IL 2 receptors in unstimulated PBMC cultures. In combination with PHA or with PHA plus OKT11A, however, rIL 2 augmented both the expression of IL 2 receptor protein on PBMC and the accumulation of IL 2 receptor mRNA in PBMC. Adding anti-Tac antibody to PBMC cultures to block the interaction of IL 2 with its receptor diminished the accumulation of IL 2 receptor mRNA induced by PHA. Taken together, these data demonstrate that OKT11A antibody inhibits and IL 2 augments expression of IL 2 receptors on PHA-stimulated T cells, at least in part, at a pretranslational level.

Adjuvants, Immunologic↗
PubMed1984

Unusual radiologic manifestations of bronchogenic cyst.

We have presented four cases of bronchogenic cyst, emphasizing the uncommon radiologic manifestations, including air trapping and/or lobulated contour. Two of the cysts were in the lung parenchyma, one in the left hilum adherent to the left lower lobe bronchus, and one in the posterior mediastinum. Recognition of the unusual radiologic features aids in establishing an appropriate differential diagnosis and directing subsequent evaluation.

Adult↗
PubMed1984

Interleukins and inhibitors in human lymphocyte regulation.

It seems clear, from studies in many laboratories, that both IL-1 and IL-2 play an important role in lymphocyte activation and are thus significant in the initiation and amplification of an optimal immune response. These conclusions have been extended to human lymphocytes, and preliminary data with macrophages and T-cells from alveolar spaces suggest that the interleukins are also important in vivo. A number of details remain to be worked out concerning these complex cellular and humoral interactions involved in triggering the immune response, and the increasing availability of purified reagents should help to speed the clarification of remaining issues. To date, much less work has been done with inhibitory factors produced by macrophages and lymphocytes than with the stimulatory interleukins. The preliminary studies by our laboratory and by others suggest that some suppressive agents may act through interference with the IL-1-IL-2 pathway and that others may be interleukin independent. Such investigations are only beginning, however, and much more investigation is needed to dissect in detail the mechanisms by which immunologically nonspecific inhibitory factors may contribute to the regulation of early steps in the immune response.

Antibodies, Monoclonal↗
PubMed1981

Blockade of frontocortical-brain stem pathway prevents ventricular fibrillation of ischemic heart.

The hypothesis tested was that functional blockade of a pathway known to travel from the frontal cortex through the posterior hypothalamus to the brain stem might prevent the occurrence of ventricular fibrillation (VF) in the ischemic heart of conscious stressed pigs. The hypothesis was based on previous findings that 1) psychological stress is a necessary factor for the initiation of VF in the ischemic heart of conscious pigs, 2) the frontal cortex and its related thalamic gating mechanism, uniquely show neuroelectric responses to stressful stimuli, and 3) direct electric stimulation of either the frontal cortex, posterior hypothalamus, or fields of Forel will produce ventricular arrhythmias and myocardial necrosis. In the present study it was found that cryogenic blockade of the forebrain, posterior hypothalamus, or fields of Forel prevents or delays VF after left anterior descending coronary artery occlusion in conscious stressed pigs (P less than 0.01). Blockade of control structures adjacent to these loci in another group of pigs had no effect on VF latency. Neither heart rate nor electroencephalographic changes could explain the differences between the groups. The results show that blockade of the frontocortical-brain stem pathway prevents the lethal consequences of myocardial ischemia in stressed animals.

Animals↗
PubMed1981

Metastatic melanoma in the thorax: report of 130 patients.

Early detection of metastatic melanoma has become more important as newer and more effective therapeutic regimens are used. Between 1970 and 1980, 1,600 patients were treated at one institution for malignant melanoma. Of these, 260 (16.3%) developed thoracic metastasis. Satisfactory chest radiographs were available for analysis in 130 of 260 patients. The patterns of the intrathoracic metastasis include multiple pulmonary nodules (52 patients), solitary nodule (26), miliary pattern (two), mediastinal and/or hilar adenopathy (nine), pleural effusion (three), lytic bony lesions (one), extra-pleural mass (one), and combined lesions (36). Both the staging of melanoma and the radiographic pattern of thoracic metastasis seemed to prognosticate the survival rate of these patients. Miliary metastasis and bone destruction implied a grave prognosis. Patients with a solitary lung nodule had the best survival experience. Immunotherapy, chemotherapy, and surgery of selected distal metastases significantly improved the survival of most of these patients.

Adolescent↗
PubMed1981

Nevus leiomyomatosus systematicus.

Leiomyomas of the skin are classified as pilar, genital, or angioleiomyoma depending on the site of origin. Pilar leiomyomas are the most common form, and usually multiple tumors are found in a single patient. An unusual variant of multiple pilar leiomyoma is nevus leiomyomatosus systematicus, a descriptive term used when tumors are wide-spread and patterned, suggesting a nevoid condition. Many of the large pilar tumors are painful and require surgical excision for relief of symptoms.

Adult↗
PubMed1978

Neural tumors of the thorax: subject review from the AFIP.

160 tumors of neural origin occurring in the thorax were analyzed. The major histological features of schwannoma, neurofibroma, neuroblastoma, ganglioneuroblastoma, ganglioneuroma, and paraganglioma are described. Radiological analysis emphasized shape and location. Calcification was relatively uncommon but may be specific. The comparatively low figures on incidence of rib and vertebral abnormalities might be increased by special studies, including vertebral tomography. Evidence of local spread such as pleura-based nodules and pleural effusion constitutes evidence of malignancy. Age may be the most important clinical parameter for distinguishing between histological types.

Adolescent↗