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The nature of the training response; peripheral and central adaptations of one-legged exercise.

13 male subjects were studied and placed in 3 groups. Each group exercised one leg with sprint (S), or endurance (E) training and the other leg oppositely or not at all (NT). Oxygen uptake (Vo2), heart rate and blood lactate were measured for each leg separately and for both legs together during submaximal and maximal bicycle work before and after 4 weeks of training with 4-5 sessions per week. Muscle samples were obtained from the quadriceps muscle and assayed for succinate dehydrogenase (SDH) activity, and stained for myofibrillar ATPase. In addition, eight of the subjects performed after the training two-legged exercise at 70% Vo2 max for one hour. The measurements included muscle glycogen and lactate concentrations of the two legs as well as the blood flow and the a-v difference for O2, glucose and lactate.

Adaptation, Physiological

Foveal versus peripheral retinal responses: a new analysis for early diagnosis of multiple sclerosis.

Visual potentials evoked by brief flashes (VEPs) were recorded in 85 patients with MS, 30 healthy controls and 25 neurological patients without demyelinating diseases. In a group of 44 patients, diffuse field stimulation was used, resutling in 15 altered responses (34%). In a second group of 41 patients with superimposable characteristics including age, sex, diagnosis of MS (definite, probable and possible) and score on the Rose's scale, the separate responses of central and peripheral retina were analysed. A total of 30 abnormal VEPs were recognized (73%) with the following distribution: 16 foveal VEPs (78%), 4 peripheral responses (13%) and 26 centreperiphery latency differences (CPLD, 60%). Twenty subjects of Group A with normal or slightly altered full field VEPs were retested with both stimulating methods with the following result: 3 altered full field VEPs (15%) and 15 abnormal CPLD (75%). With diffuse field stimulation, the correlation between the VEP scores and the results of other examinations (visual, pyramidal, etc.) were insignficant; on the contrary, the CPLD was clearly correlated with the involvement of the visual and other systems in the fluctuating clinical course of MS.

Adolescent

Cellular immune response to peripheral nerve basic protein in idiopathic facial paralysis (Bell's palsy).

Lymphocytes from patients with Bell's palsy were shown to undergo significant stimulation when cultured in vitro in the presence of a purely neuritogenic basic protein (P1L) isolated from human peripheral nerve myelin. No sensitization was observed to other neural antigens, namely, another periperal nerve myelin basic protein (P2) and the central nerve myelin basic encephalitogenic protein (BE). A similar pattern of response was also demonstrated in patients with Guillain-Barré syndrome (GBS). Lymphocytes from patients suffering from other neuropathies or other diseases involving the face showed no response to any of these antigens. The specific in vitro response to P1L protein in Bell's palsy may suggest that an in vivo sensitization of lymphocytes to such self protein occurs in this condition, and that cell-mediated, probably post-infectious, autoimmune mechanisms may be an important factor in the pathogenesis of the paralysis. Thus, Bell's palsy is immunologically similar to GBS, or may even represent a mononeuritic variant of GBS. In view of these findings the administration of steroids to patients with Bell's palsy seems logical on the basis of their immunosuppressive action.

Adolescent

The adaptation of cochlear and brainstem auditory evoked potentials in humans.

The adaptation of the responses from the cochlear nerve and the auditory brainstem nuclei was studied using a burst of four clicks as the stimulus. Nine experimental conditions were obtained from three stimulus levels (60, 70 and 80 dB SL) and from three intervals between click in the burst (15, 24 and 32.5 msec). Six subjects were each tested three times for each of the experimental conditions and the techniques used and results obtained are summarized. Various models of the adaptation of the brainstem responses are proposed which predict different results. The results for the adaptation of the N1 response are basically in agreement with previous work, and the more central brainstem responses showed less adaptation than the peripheral responses. These findings may be explained by postulating different adaptation mechanisms for the peripheral and central responses. The 60dB stimulus level condition gave rise to more adaptation than the 80dB level, and this is in agreement with studies of low and high threshold reception systems reported elsewhere.

Adaptation, Physiological

Control of proliferation in mitogen responsive human peripheral blood lymphocytes: restimulation of cells stimulated by sodium periodate.

Human peripheral blood lymphocytes are stimulated to a greater extent by sodium periodate when cells are incubated in medium containing human serum than when incubated in medium with fetal calf serum. NaIO4 STIMULATION CAN BE REVERSED BY TREATMENT WITH SODIUM BOROHYDRIDE BUT CELLS ALREADY COMMITTED TO DIVISION ARE NOT AFFECTED BY BOROHYDRATE TREATMENT. Maximal commitment to DNA synthesis of a NaIO4 oxidized cell suspens-on occurs after about 28 hr of incubation in medium. The committal time after periodate stimulation is identical to that after stimulation with concanavalin A. Cells treated with periodate and then reduced with borohydride immediately after oxidation are refractory to further per-odate stimulation. Cells stimulated with periodate and then incubated for 6 hr before treatment with borohydride can be restimulated with periodate, indicating a turnover of membrane sites in the 6 hr period. Periodate-stimulated cells divide only once in response to the stimulation. The progeny of cells which were stimulated with periodate can be restimulated by treatment with either periodate or concanavalin A.

Animals

Primary in vitro antibody response from human peripheral blood lymphocytes.

A method for the induction of a primary in vitro antibody response from human peripheral blood lymphocytes is presented. Upon cultivation with trinitrophenyl conjugated polyacrylamide beads (TNP-PAA), an anti-TNP response can be obtained as indicated by the appearance of direct plaque-forming cells from day 5 of culture, with a reproducible peak on day 8. These plaques correspond to cells actively producing antibody of the IgM type, as shown by their inhibition by cycloheximide and by anti-human IgM serum, but not by anti-human Fc gamma serum. Their specificity for the TNP hapten can be demonstrated by the effector cell blockade phenomenon, with highly substituted TNP-human IgG. Although the anti-TNP response induced by TNP-PAA in mouse spleen cell cultures appears T independent the same response in human PBL may involve in addition the participation of T cells, since E-RFC depletion before culture led to a markedly decreased number of plaque-forming cells. A significant response could be obtained from the PBL of all of the 30 normal individuals tested. Importantly, the response was reproducible in its magnitude in the six individuals tested in at least three different experiments. Thus, the in vitro stimulation of human PBL by TNP-PAA can be proposed as a reliable test for the study of human B cell function in a specific primary antibody response.

Acrylamides

Inhibition of the mitogenic response of normal peripheral lymphocytes by extracts or supernatant fluids of a Herpesvirus saimiri lymphoid tumor cell line.

A Herpesvirus saimiri-infected marmoset lymphoid cell line (MLC-1) was examined for the presence of soluble factors which might affect lymphocyte functions and, therefore, relate to the pathogenesis of lymphoma in vivo. MLC-1 cells, cell extracts, and culture fluids were shown to reduce the spontaneous deoxyribonucleic acid (DNA) synthesis of normal peripheral blood lymphocytes and to completely inhibit their response to phytohemagglutinin (PHA). Suppression of PHA response was demonstrated against a variety of human and nonhuman primate species, with 90 to 95% inhibition occurring at dilutions of extract as great as 1:5,120. Inhibition of this type was also demonstrated using extracts of two of five other lymphoblastoid cell lines tested. Physical-chemical characteristics of the active factor(s) revealed a non-sedimentable, non-dialyzable, trypsin-resistant molecule, which was stable at 56 C for 30 min but inactivated at 80 C for 30 min. The factor(s) also exerted an effect on some but not all established lymphoblastoid cell lines, where DNA, ribonucleic acid, and protein synthesis were all inhibited, with DNA synthesis being the most affected (95% suppression). Cellular respiration was not affected by the presence of the factor(s), and the inhibition of DNA synthesis was reversible after 24 h. Purified human interferon did not reduce the PHA response of normal owl monkey peripheral blood lymphocytes and was less effective against an established lymphoblastoid cell line than the MLC-1 extract. Antiviral activity was also demonstrated in the preparations and may represent interferon, which these cells are known to produce at low levels.

Animals

Peripheral blood leucocyte response to coccidial infection: a comparison of the response in rats and chickens and its correlation with resistance to reinfection.

The peripheral blood leucocyte (PBL) response to infection with two species of the intestinal protozoan Eimeria shows a remarkably similar pattern in both rats and chickens. Like resistance to these parasites, the PBL response to reinfection is species-specific and it coincides with the inhibition of development of the parasite and with cellular infiltration of the lamina propria. In primary infections, the numbers of PBL increased biphasically and significant changes were found in the count of polymorphonuclear cells (PMN), lymphocytes, and large mononuclear cells (LMN). A consistent pattern of two increases in PMN, some lymphopenia, and two increases in LMN was found in rats and chickens. The response to secondary infections was more rapid and much briefer, particularly in chickens in which significant changes were detected within hours of infection and consisted of an almost equal increase in PMN and in lymphocytes. This secondary response occurred only in animals challenged with the homologous species. It was not evoked by challenge with a related species which develops in approximately the same area of the intestine.

Animals

Effect of falciparum malaria infection on the in vitro mitogen responses of spleen and peripheral blood lymphocytes from owl monkeys.

The response of spleen and peripheral blood lymphocytes (PBL) to mitogen stimulation with phytohemagglutinin (PHA), Concanavalin A (ConA), and pokeweed mitogen (PWM) was determined for owl monkeys (Aotus trivirgatus) experimentally infected with the Vietnam-Oak Knoll (FVO) and the Uganda-Palo Alto (FUP) strains of Plasmodium falciparum. PBL from Panamanian Aotus monkeys with less than 25% FVO infection responded normally to mitogen stimulation; however, increased parasitemia of 25--50% resulted in a significant suppression of ConA responsiveness. Colombian Aotus monkeys infected with the PUF strain also developed a suppression to ConA stimulation but with a lower parasitemia (10--25%). When the parasitemia became greater than 50% in these animals, PHA, ConA, and PWM responses were significantly decreased in cultures of PBL. Spleen cells from all acutely infected Aotus monkeys were suppressed to PHA and ConA, but not PWM stimulation. Changes in mitogen responsiveness of experimentally infected Aotus monkeys are similar to those reported for humans with acute falciparum malaria.

Animals

Cyclic appearance of antibody-producing cells in the peripheral blood in response to a chemically-defiend polyglycerophosphate antigen.

Cyclic production of serum antibody and of plaque-forming cells (PFC) of polyglycerophosphate (PGP) specificity was observed in the peripheral blood of rabbits following a single injection of antigen. Individual animals were examined at 4-day intervals up to 28 days post-injection. Direct and indirect PFC displayed initial peaks at 4 days post-injection with an 8-day lag between the first and second peaks and a 12-day lag between the second and third peaks. Serum IgM rose to a peak 4 days after the initial PFC peak and gradually dropped to baseline levels. Serum IgG rose sharply to a peak at 4 days following the initial PFC peak and generally remained at elevated levels for the duration of the experiment. Cycling of background sheep erythrocyte PFC was also observed, but cycles were out of phase with the PGP cycles and with each other.

Animals

Xenogenic response of human peripheral blood lymphocytes against murine cells in vitro.

Human peripheral blood lymphocytes (HPBL) were sensitized to mitomycin-treated murine spleen cells and mitomycin-treated mastocytoma P-815. A DNA proliferative response occurred to both cell types. The sensitized HPBL lysed chromium-51-labelled mastocytoma P-815 cells in a cell-mediated cytotoxicity assay (CMC). Evidence is presented that this human-murine xenogeneic system involves T cell response with specificity in CMC mainly toward H-2 antigens. DBA/2 splenocytes were superior to mastocytoma cells as sensitizers in the xenogeneic DNA proliferative assay.

Animals

Cellular cooperation in lymphocyte activation. II. Cooperative response of human peripheral T and B lymphocytes to rabbit anti-human beta 2-microglobulin.

In the present study we attempted to clarify the effects of anti-beta 2-microglobulin (a-beta 2m) on lymphocyte activation. Neither a-beta 2m IgG fraction nor F(ab')2 had a mitogenic effect on either highly purified T or B lymphocytes alone, while their mitogenic effect was observed when T and B lymphocytes were appropriately reconstituted. When T lymphocytes were reconstituted with mitomycin C (MMC) treated B lymphocytes, a negligible decrease in the response to a-beta 2m was observed compared to the response of an untreated mixture to a-beta 2m. On the other hand, when B lymphocytes were reconstituted with MMC-treated T lymphocytes, the response was markedly diminished. It was found, moreover, that the response of T lymphocytes separated by a semipermeable membrane from MMC-treated B lymphocytes was not enhanced, while a mixture of T and MMC-treated B lymphocytes in the same chamber showed a marked response. These results lead to the conclusion that the cells responding to a-beta 2m are mainly T lymphocytes whose response is strongly enhanced by B lymphocytes, and that for the mitogenic effect of a-beta 2m direct cell-to-cell interaction between T and B lymphocytes is necessary.

Animals

In vitro immune response of human peripheral lymphocytes. II. Properties and functions of concanavalin A-induced suppressor T cells.

Con A-stimulation of human peripheral T lymphocytes induced both suppressor and helper T cells. ConA-generated suppressor T cells inhibited PWM-induced IgG and IgM production in PBL. Lower concentrations of Con A (0.5 micrograms/ml) or shorter incubation periods (6 to 24 hr) induced mainly helper T cells, while higher concentrations of Con A (10 micrograms/ml) or longer incubation periods (at least 48 hr) induced suppressor T cells. Con A-generated suppressor T cells were sensitive to mitomycin treatment and exerted their suppressor function on the early phase of differentiation and/or proliferation of B cells but not on the final differentiation of B cells to Ig-producing cells. The identity of the MHC was not required for the expression of suppressor function. Suppressor T cells competed with helper T cells in PWM-induced Ig-production of PBL. This experimental system can be applied to estimate the regulatory function of T cells in several disease states.

B-Lymphocytes