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Biomedical subjects

R Hodes

Publications and source records attributed to R Hodes.

12 recordsLinked to original sources
PubMed1995

Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.

Costimulatory interactions between T and B lymphocytes are crucial for T cell activation and B cell proliferation and differentiation. We have compared the roles of CD40L and B7-2 in the initiation and maturation of humoral immunity by administering anti-CD40 ligand (L) or anti-B7-2 Ab during the early (days -1 to 3) or late (days 6-10) phases of primary responses to thymus-dependent (Td) and -independent (Ti) Ags. Germinal center (GC) formation in response to a Td Ag was inhibited completely by the early administration of anti-CD40L or anti-B7-2 Abs. Later in the response, established GCs remained sensitive to anti-CD40L but were resistant to treatment with anti-B7-2. However, Ig hypermutation was reduced dramatically in GCs of anti-B7-2-treated mice and humoral memory was impaired. Early administration of anti-CD40L reduced serum Ab levels to approximately 10% of controls, whereas early treatment with anti-B7-2 reduced Ab production by only 50%. Later treatments with either Ab had no effect on Ab production. Response to a type II Ti Ag was more resistant than Td responses to interruption of costimulatory interactions. Our findings suggest that the costimulatory roles of CD40:CD40L and B7-2:CD28/CTLA-4 differ in the GC; administration of anti-CD40L abrogates an established GC reaction, whereas Ab to B7-2 suppresses Ig hypermutation and entry into the B cell memory compartment. Once B cells have entered the differentiation pathway to Ab production, neither CD40L nor B7-2 is necessary for their continued differentiation and persistence.

Animals↗
PubMed1987

Secretory processes in lymphocyte function.

The secretion of immunoglobulin by plasma cells has been considered a classical example of the "non-regulated" pathway of protein secretion, in which newly synthesized protein is processed by the Golgi, packaged into small vesicles, and immediately secreted without intracellular storage. In the case of lymphokine secretion by T lymphocytes, it is generally not clear whether this non-regulated pathway is also being used, as opposed to the "regulated" pathway which has been proposed to operate in the cytotoxic lymphocyte mechanism. In this case, as in mast cells and endocrine cells, proteins are synthesized and then stored in cytoplasmic granules. The secretion is triggered (regulated) by a membrane receptor-ligand interaction, which for the cytotoxic lymphocytes is part of the target cell binding process. In cytotoxic T lymphocytes, this secretion process can be measured by following the appearance of a granule serine protease in the medium, and it has been shown to be triggered by target cells or by immobilized antibodies which bind the T cell receptor complex. In addition to cytotoxic lymphocytes, cloned T helper cells contain this serine protease in cytoplasmic granules with a low internal pH. Helper lymphocytes secrete this enzyme in response to (1) soluble antigen which has been processed by cells bearing the appropriate MHC antigens; (2) immobilized antibodies against the T cell receptor complex; (3) a combination of phorbol ester and calcium ionophore. Thus in both helper and cytotoxic lymphocytes, the regulated pathway of protein secretion clearly operates after triggering by the T cell antigen receptor.

Animals↗
PubMed1987

Structure and expression of class I MHC genes in the miniature swine.

The genome of the miniature swine, unlike other species, contains a relatively small class I MHC gene family, consisting of only seven members. This provides an excellent system in which to identify and characterize the regulatory mechanisms which operate to both coordinately and differentially regulate the expression of a multi-gene family. The structure of class I SLA genes, like other class I genes, consists of eight exons encoding a leader sequence, three extracytoplasmic domains, a transmembrane domain and intracytoplasmic domains. Despite the common structure, two sub-families of class I genes can be distinguished within the SLA family. One, containing the closely related PD1 and PD14 genes, encodes the classical transplantation antigens. Another contains the highly divergent PD6; the functions of the products of this subfamily, if any, are not known. The class I SLA genes share some common regulatory mechanisms, as evidenced by the fact that all three genes analyzed are transcribed in mouse L cells. Furthermore, interferon treatment of transfected mouse L cells enhances expression of all three genes. Both PD1 and PD6 are transcribed in vivo, where the highest levels of expression are observed in lymphoid tissues. Superimposed on the common patterns of class I gene expression are distinct ones, as evidenced by the findings that PD1 is preferentially expressed in B cells, whereas PD6 is preferentially expressed in T cells. These differences may reflect the extensive divergence of the 5' flanking sequences of these genes. Future studies will be aimed at elucidating the precise molecular interactions and mechanisms which give rise to the observed differential expression.

Animals↗
PubMed1985

Use of biofeedback training in treatment of Raynaud's disease and phenomenon.

To assess biofeedback training in Raynaud's, we retrospectively reviewed 23 patients' records. Eleven had Raynaud's disease and 12 had Raynaud's phenomenon; 9 had recurrent digital ulcers. Patients demonstrated lower baseline digital temperatures than controls (p less than or equal to 0.001), patients with Raynaud's and scleroderma manifesting the lowest. After biofeedback training all patients elevated baseline temperatures. Patients with scleroderma and systemic lupus erythematosus had the greatest elevations. Improvement, both subjective (57%) and ulcers (44%), persisted one year after treatment. Four of 7 patients were capable of elevating digital temperatures within 5 min, 18 months after their last training session. These findings support biofeedback training as beneficial therapy in Raynaud's.

Arthritis, Rheumatoid↗
PubMed1981

Strategies of arousal control: biofeedback, meditation, and motivation.

A series of four experiments assessed the effects of instructions to lower heart rate on heart rate change and general arousal reduction. Various conditions of biofeedback, cognitive load, incentive, knowledge of results, and the experimenter-subject relationship were tested. Experiment 1 compared physiological responses to the delivery of direct organ feedback (i.e., heart rate) with responses to electromyographic biofeedback from the frontalis muscle area and with responses to a nonfeedback tracking task. The results suggest that neither heart rate nor muscle tension feedback is an especially powerful method for achieving sustained reductions in heart rate. Furthermore, although some specificity of physiologic pattern is apparent, biofeedback is no more effective in lowering general activation level than simple instructions to relax accompanied by a general knowledge of results. The second experiment was designed to assess the role of cognitive load in arousal reduction. Heart rate biofeedback was compared with a procedure involving minimal external information processing--the secular meditation exercise of Wallace and Benson. The results indicated a clear superiority for the meditation strategy in effecting reductions in cardiac rate and lowering activation. However, in a third experiment, meditation subjects lowered heart rate much less than observed in the previous study, and this time the reduction did not exceed that achieved by feedback subjects. Subsequent analysis suggested that the quality of the subject-experimenter relationship (active-supportive vs. formal-distant) was a significant variable in accounting for outcome differences. The above hypothesis was supported by a fourth experiment. Under conditions of high subject-experimenter involvement, the superior meditation performance of Experiment 2 was reproduced; under low-involvement conditions the Experiment 3 result of no difference between training groups was obtained. The findings suggest that the effectiveness of any method for achieving relaxation (or physiological control) rests on a complex interaction between informational and motivational imperatives of the stimulus context and definable aspects of the interpersonal exchange between subject and experimenter. This research raises serious questions about the effectiveness of the usual biofeedback paradigm as an aid to arousal reduction and the cost efficiency of its applications in the clinical situation. Furthermore, these results demonstrate the great power in relaxation experiments of psychosocial and other moderator variables, and signal the practical difficulty of their control when these variables appear to be as potent in changing physiology as the primary training methods.

Arousal↗