Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A transient increase in extracellular calcium concentration causes a long-lasting enhancement of radiatum fibers evoked excitatory postsynaptic potential and population spike responses of CA1 pyramidal neurons which resembles long-term potentiation (LTP). The duration of this potentiation is much longer than described previously and is probably limited by the survival of the preparation itself (greater than 8 hr). Therefore, Ca-induced LTP can be used for the investigation of a postulated late phase of LTP. Ca effects were activity-independent, since the subsequently evoked responses were facilitated even when the presynaptic fibers were not concurrently stimulated during or immediately after superfusion with the high Ca medium. In contrast, if too frequent testing of the synaptic input was done during the high Ca pulse, a short lasting depression instead of potentiation was observed. A lower extracellular magnesium concentration in the standard medium (1.3 instead of 2.0 mM MgSO4) prevents the potentiation of the EPSP at least for the first few hours. Presumably, both tetanus- and Ca-induced LTP share some common mechanisms, since an additional tetanization after Ca induction was not followed by an additional LTP. Compared to the potentiation following tetanization, the Ca-induced LTP was, however, not accompanied by a potentiation of the EPSP/spike ratio within the range of the population spike threshold intensity.
 ...
PMID:Calcium-induced long-term potentiation in the hippocampal slice: characterization of the time course and conditions. 302 Dec 91

Patients with multiple myeloma are generally immunodeficient, with pronounced depression in primary antibody responses. We have attempted to delineate the reasons for the humoral immunodeficiency by analyzing the specificity repertoire of the surface immunoglobulin (Ig)-positive B cells in patients with multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS), in comparison with normal donors. B lymphocytes from 26 patients with multiple myeloma, 12 patients with MGUS, and 8 normal donors were transformed with Epstein-Barr virus (EBV) and cultured at limiting dilution for clonal analysis. The Ig secreted by each clone was analyzed for class and anti-tetanus toxoid (TT) specificity to determine the frequencies of IgM, IgG, anti-TT IgM, and anti-TT IgG antibody-secreting clones. Our objective was to establish whether the inability to mount humoral responses to common environmental pathogens was due to a lack of specific B cells or to inhibition of B-cell function. Our results indicate that the quantitative B-cell deficiency in patients was due to a nonrandom loss of selected sets of B cells. Although most patients had a reduced aggregate number of B cells, the number of TT-specific B cells was normal. There was, on average, a threefold increase in the proportion of the B-cell specificity repertoire devoted to recognition of TT. Forty-four percent of the patients with MGUS were also affected. In addition, the TT-specific B cells in multiple myeloma patients were severely compromised in their ability to secrete antibody or to differentiate to antibody-secreting cells in vivo. This arrest in differentiation appears to be extrinsic to the B cells, as they were fully able to secrete anti-TT antibody after transformation and culture in vitro. We postulate the existence of an autoimmune inhibitory network mediating the arrest in B-cell differentiation and the humoral immune deficiency.
 ...
PMID:Humoral immune deficiency in multiple myeloma patients due to compromised B-cell function. 302 34

The growth of Tetrahymena was influenced by both diphtheria and tetanus toxoids; depression occurred at a high and stimulation at a low concentration. Pretreatment with the stimulating concentration of diphtheria toxoid caused a lasting modification of growth rate and development of imprinting that resulted in an enhanced response of the cell at reexposure to the toxoid. Tetanus toxoid failed to induce either switch over of cell function or imprinting.
 ...
PMID:Effect of diphtheria and tetanus toxoids on the growth of, and imprinting developed in, Tetrahymena. 310 91

To evaluate the hypothesis that depressed neuromuscular transmission causes dithiobiuret (DTB)-induced muscle weakness in rats, the temporal development of impaired treadmill performance and deficits in the nerve-elicited muscle contractions were compared during daily treatment with the toxicant (DTB, 1 mg/kg/day X 6 days). Diminished treadmill test performance after 4 days of treatment marked the initial detection of impaired motor function. At this time fading (loss of tension during tetanus) of gastrocnemius contractions elicited in response to 100-Hz sciatic nerve stimulation occurred in DTB-treated rats but not in controls. After 5 and 6 days of treatment, treadmill failure became complete, tetanic fade worsened dramatically, and peak contractile tension measured during trains of nerve stimulation (10-250 Hz) decreased progressively. Appearing by Day 6 were marked body weight loss, dehydration, hypothermia, and a depression in serum concentrations of thyroid hormones. Total oxygen content of the blood was not reduced at any time during treatment, and serum concentrations of glucose, sodium, potassium, calcium, chloride, and phosphorus in DTB-treated rats on Day 6 were similar to those of control animals. Therefore, hypoxia, hypoglycemia, or a serum electrolyte imbalance do not initiate or modulate the neuromuscular toxicity. Light microscopic evaluation of liver, kidney, lung, thyroid, and other organs in intoxicated rats was unremarkable and in skeletal muscles and selected sites of brain, spinal cord, and sciatic nerve no morphologically significant lesions were observed. Even when DTB-intoxicated rats were maintained in a state of flaccid muscle weakness for 5 continuous days, peripheral nerve lesions proximal to the intramuscular nerves were not detected. Thus, depressed neuromuscular transmission appears to be the primary cause of the flaccid muscle weakness and no evidence was obtained that nonneural effects of DTB initiate or modulate this effect.
 ...
PMID:Temporal analysis of dithiobiuret neurotoxicity in rats and assessment of potential nonneural causes. 311 11

Brief repetitive trains of supramaximal nerve stimulation produce intermittent muscle activation and, in time, a progressive decline in force (i.e., neuromuscular fatigue) and depression of the electromyogram (EMG). These changes may include within-train reductions in EMG due to a failure of neuromuscular propagation. The aim of the present study was to investigate changes in EMG during a 360-second stimulus regimen designed to fatigue soleus and extensor digitorum longus muscles of anesthetized rats by activating the muscle with repetitive trains of 40 Hz stimuli. Measurements included peak force for each tetanus, variation of the within-train EMG (coefficient of variation for area), and magnitude of the first EMG waveform (area) of each train. Fatigue was characterized as the relative decline in force over the course of the test. The responses of the test muscles were categorized, based on an absolute scale of fatigability, into five groups: potentiated, nonfatigable, low fatigability, intermediate fatigability, and high fatigability. Fatigable muscles (low, intermediate, and high fatigability groups) demonstrated a decreased EMG magnitude and an increased EMG-area variation with repetitive activation. This increased variation, however, was nonmonotonically related to fatigability such that the least and most fatigable muscles had the smallest within-train EMG variation. We suggest that these data can be explained by considering the EMG (compound muscle action potential) as a stochastic process that represents a composite of single-fiber events (axonal to sarcolemmal transmission) with variable probabilities.
 ...
PMID:Fatigue-related changes in neuromuscular excitability of rat hindlimb muscles. 322 28

1. Adult soleus muscles were denervated and stimulated directly for 2-130 days with 'fast' (short pulse trains at 100 Hz) or 'slow' (continuously at 10 Hz, or long pulse trains at 15 Hz) stimulus patterns. 2. At the end of the period of stimulation isometric twitches and tetani and isotonic shortening velocities were measured. Frozen cross-sections were later examined with antibodies against myosin heavy chains specific for adult fast, adult slow and fetal myosin. 3. Isometric twitch duration (twitch time-to-peak and half-relaxation time) decreased during intermittent 100 Hz stimulation to values that were almost as fast as in the normal extensor digitorum longus (EDL) (95 and 94% transformation). The major part of the decrease occurred between 2 and 21 days after the onset of stimulation, and was accompanied by post-tetanic potentiation of the twitch, 'sag' in tension during an unfused tetanus, lower twitch/tetanus ratio and marked shifts to the right (higher frequencies) of the tension-frequency curve of the muscle. In contrast, during 10 or 15 Hz stimulation the isometric twitch duration remained slow, the twitch continued to show post-tetanic depression and absence of 'sag', while the twitch/tetanus ratio increased. 4. Denervation per se led to a slight increase and, then, after about a month, to a moderate and gradual decrease in twitch duration. The twitch/tetanus ratio increased markedly and post-tetanic depression became less pronounced or disappeared. Muscle weight and particularly tetanic tension were markedly reduced and these reductions were to a large extent counteracted by electrical stimulation. 5. Implantation of sham electrodes had no effect on twitch duration of denervated or innervated control muscles, but reduced tetanic tension in the innervated control muscles. 6. Maximum isotonic shortening velocity of the whole muscle (mm/s) increased during intermittent 100 Hz stimulation to a value as fast as in the normal EDL (110% transformation). Since the muscle fibres also increased in length (35%) maximum intrinsic shortening velocity (fibre lengths/s) was only incompletely transformed (55%). The increase in Vmax occurred between 7 and 14 days after the onset of stimulation. 7. All the fibres stimulated intermittently at 100 Hz were strongly labelled with anti-fast myosin and more than 90% were in addition weakly labelled by anti-slow myosin. Weak and variable labelling with anti-fast myosin was first detected 7 days after the onset of stimulation. In contrast, essentially all the fibres stimulated at 10 or 15 Hz showed no binding of anti-fast but strong binding of anti-slow myosin.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Slow-to-fast transformation of denervated soleus muscles by chronic high-frequency stimulation in the rat. 323 51

1. The effects of 2,3-butanedione monoxime (BDM, 0.2-10 mmol/l) have been examined at different temperatures on calcium transients (measured with aequorin) and isometric force in intact bundles of fibres from soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles of the rat and on Ca2+-activated isometric force of mechanically skinned soleus and EDL fibres. Ca2+ release and uptake by the sarcoplasmic reticulum has also been investigated directly on skinned EDL fibres at 1 mmol/l BDM at 23 degrees C. 2. BDM bound calcium with low affinity (KCaBDMapp = 55.9 +/- 4.3 M-1 at 22 degrees C, pH 7.10, ionic strength approximately 155 mmol/l) and did not affect the kinetics and quantum yield of the Ca2+-induced aequorin luminescence. 3. BDM reversibly reduced both force- and Ca2+-dependent aequorin light during the twitch and tetanus of all intact-muscle preparations in a dose-related manner. Twitch responses of soleus fibres were more sensitive to BDM than were EDL fibres. Higher concentrations of BDM were needed to abolish the tetanic force response than the twitch response in both muscle types. 4. The initial rate of rise and the decay rate constants of twitches in both soleus and EDL muscles were increased in the presence of BDM. Accordingly, a higher frequency of stimulation was required to produce fusion of the tetanus. This phenomenon could be explained by the reduced magnitude of the Ca2+ transient. 5. BDM reduced maximal Ca2+-activated force development in mechanically skinned soleus and EDL muscle fibres in a dose-dependent fashion. This depression of force was less sensitive to BDM than were the light transients in intact fibres. Furthermore, BDM affected EDL skinned fibres to a greater extent than soleus skinned fibres, in contrast with its effects on intact fibres. 6. At concentrations of BDM greater than 2.5 mmol/l, BDM significantly decreased the sensitivity of the contractile apparatus to calcium. The relative force-pCa (= -log [Ca2+]) curves for both soleus and EDL skinned fibres were shifted to the right (i.e. to higher calcium concentrations) in a dose-related manner. 7. BDM (10 mmol/l) slowed maximal Ca2+-activated force development of skinned preparations of both fibre types at all temperatures investigated (4-24 degrees C). 8. BDM reduced stiffness in skinned preparations maximally activated by calcium in proportion to the reduction in the isometric force response. BDM also inhibited rigor force of all fibres but only if it was present before the onset of rigor.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effects of 2,3-butanedione monoxime on the contractile activation properties of fast- and slow-twitch rat muscle fibres. 325 25

We have investigated the mechanisms by which topical corticosteroids modulate cutaneous immune reactions in man. Volunteers applied clobetasone butyrate 0.05% (Eumovate; EV), betamethasone valerate 0.1% (Betnovate; BV), clobetasol propionate 0.05% (Dermovate; DV), and control vehicles twice daily to forearm skin for 7 days. Steroid therapy significantly decreased the number of HLA-DR/T6 (CD1a) positive Langerhans cells (LCs) per mm2 in suction blister-derived epidermal sheets, expressed as a mean percentage of controls, as follows: EV 69.2%; BV 67.3%; DV 37.8%. LC antigen presenting capacity was determined in the allogeneic and autologous epidermal cell-lymphocyte reactions. The LC-dependent allostimulatory capacity of epidermal cells, expressed as a mean percentage of controls, was also significantly reduced by steroid therapy: EV 45.1%; BV 41.9%; DV 23.4%. Following therapy with clobetasol propionate 0.05%, the capacity of epidermal cells to present tetanus toxoid to, and to augment concanavalin A mediated lymphocyte stimulation of, autologous lymphocytes was reduced to 33.6% and 19.7% respectively of controls. Depression of epidermal cell allostimulatory capacity was not the result of a steroid-induced decrease in the production of epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1 by keratinocytes, since it could not be reversed by addition of exogenous interleukin 1. Indomethacin, added to block any potential prostaglandin synthesis during the culture period, did not restore the allostimulatory capacity of epidermal cells from steroid-treated sites. Addition of epidermal cells from DV-treated sites depressed the capacity of control epidermal cells to stimulate lymphocytes in the allogeneic epidermal-lymphocyte reaction. Our results demonstrate that the anti-inflammatory action of topical corticosteroids in man is associated not only with a reduction in the number of HLA-DR/T6 positive LCs, but also with a marked decrease in Langerhans cell-dependent T lymphocyte activation. The effects of the different steroids on both of these parameters correlated with their potency as determined in the standard occlusive vasoconstrictor assay. Topical corticosteroids are widely used for the treatment of inflammatory skin disorders, and inhibit not only the elicitation phase, but also the induction phase, of allergic contact dermatitis reactions.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effects of topical corticosteroid therapy on Langerhans cell antigen presenting function in human skin. 328 68

Normal human peritoneal macrophages show a restricted capacity to differentiate into inflammatory macrophages in vivo. We now report that these cells are unable to cap and internalize HLA-DR, as compared to endometriosis, and other macrophages. Immunoelectron microscopy indicated that lack of modulation was not due to the presence of preclustered antigenic sites. Northern blot analysis demonstrated transcripts for HLA.DR, c-fms, and c-fos, indicating that the surface defects were not likely to be associated with a general depression of transcriptional activity. There was no correlation between the mobility of class II molecules and the ability to present antigen as determined by autologous lymphocyte responses to tetanus toxoid. The inability of normal peritoneal macrophages to modulate class II antigens may represent a normal and more general environmental alteration required to permit peritoneal cells a scavenging function without developing the deleterious effects leading to a peritoneal inflammatory response.
 ...
PMID:Normal human peritoneal macrophages are unable to cap and internalize class II antigens. 340 27

During the onset of activation in isolated frog muscle fibres the development of the force-velocity (T-V) relation was determined by imposing single and double ramp releases. The experiments were performed at 3.5-6 degrees C or 19-22 degrees C and at a starting sarcomere length of about 2.25 micron. A velocity- and time-dependent shortening deactivation was shown to exist during the development of contraction. It was found that, early during the tetanus rise, at submaximal levels of activation, the values of T (the steady force exerted by the muscle fibres at any velocity of shortening V lower than V0) were significantly affected by previous conditioning shortening. Conditioning shortening at lower speeds led to potentiation of T and, at higher speeds, to depression. Both these effects were independent of the amount of shortening and, in addition, were not present at the tetanus plateau. At each given time or isometric tension throughout the tetanus rise the values of T. normalized for those determined at the same velocities at the tetanus plateau, were found to be inversely correlated with the actual velocities of shortening. The slope of this relation (a measure of the velocity-dependent shortening deactivation) decreased exponentially with time, attaining, in six fibres at low temperature, 10% of its initial value within 26-73 ms. The results may be explained in terms of a cross-bridge model of contraction by assuming that the rate of development of activation is controlled by the rate of release of the Ca2+ as well as by the velocity at which the muscle fibres are allowed to shorten and in turn by the actual number of attached cross-bridges.
 ...
PMID:A velocity-dependent shortening depression in the development of the force-velocity relation in frog muscle fibres. 349 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>