Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+ inward currents evoked by membrane depolarization have been studied by the intracellular dialysis technique in the somatic membrane of isolated dorsal root ganglion neurones of new-born rats. In about 20% of the investigated cells a hump has been detected on the descending branch of the current-voltage curve, indicating the presence of two populations of Ca2+ channels differing in their potential-dependent characteristics. An initial less regular component of the Ca2+ current was activated at membrane potentials from -75 to -70 mV. Its amplitude reached 0.2-0.9 nA at 14.6 mM-extracellular Ca2+. The activation kinetics of this component could be approximated by the Hodgkin-Huxley equation using the square of the m variable. tau m varied in the range from 8 to 1 ms at potentials between -60 and -25 mV ('fast' Ca2+ current). The second component of the Ca2+ current was activated at membrane depolarizations to between -55 and -50 mV. It could be recorded in all cells investigated and reached a maximum value of 1-7 nA at the same extracellular Ca2+ concentration. This component decreased rapidly during cell dialysis with saline solutions. The decrease could be slowed down by cooling and accelerated by warming the extracellular solution. Intracellular introduction of 3',5'-cAMP together with ATP and Mg2+ not only prevented the decrease but often restored the maximal current amplitude to its initial level. The activation kinetics of this component could also be approximated by a square function, tau m being in the range 16-2.5 ms at membrane potentials between -20 and +3 mV ('slow' Ca2+ current). The fast Ca2+ current inactivated exponentially at sustained depolarizations in a potential-dependent manner, tau h varying from 76 to 35 ms at potentials between -50 and -30 mV. The inactivation of the slow Ca2+ current studied in double-pulse experiments was current-dependent and developed very slowly (time constant of several hundreds of milliseconds). It slowed down even more at low temperature or after substitution of Ba2+ for Ca2+ in the extracellular solution. Both currents could also be carried by Ba2+ and Sr2+, although the ion-selecting properties of the two types of channels showed quantitative differences. Specific blockers of Ca2+ channels (Co2+, Mn2+, Cd2+, Ni2+ or verapamil) exerted similar effects on them. The existence of metabolically dependent and metabolically independent Ca2+ channels in the neuronal membrane and their possible functional role are discussed.
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PMID:Two types of calcium channels in the somatic membrane of new-born rat dorsal root ganglion neurones. 258 15

The effect of hypercalcemia on T wave morphology, polarity, and amplitude was studied in 14 patients with a primary diagnosis of malignant lymphoma (8 patients), adult T-cell leukemia (5 patients), and Hodgkin's disease (1 patient). Hypercalcemia was severe to extreme in 11 (14.9-22.8 mg/dl), moderate in 1 (13.4 mg/dl), and mild in 2 (11.8 and 12.2 mg/dl) patients. Ten of the 11 patients (91%) with severe hypercalcemia showed inverted, biphasic, and notched T waves, mainly in the chest leads. Notched T waves were observed in all 10 of these patients in anterior to lateral, mid to lateral, or lateral chest leads. Biphasic and/or inverted T waves in anterior or anterior to midchest leads were present in 4 of these 10 patients who had extreme hypercalcemia (greater than 16 mg/dl). Changes in T wave morphology were not observed in moderate or mild hypercalcemia. T wave amplitude showed significant inverse correlation with serum calcium (T mV vs Ca, r = -0.60, p less than 0.001; T/R ratio vs Ca, r = -0.68, p less than 0.001; n = 35). Decrease in T wave amplitude was marked in severe hypercalcemia (p less than 0.0001) and moderate hypercalcemia, but there was no change in mild hypercalcemia. Changes in T wave morphology, polarity, and amplitude either appeared with development of hypercalcemia or disappeared with normalization of serum calcium level. It was concluded that in addition to shortening the QT interval, severe to extreme hypercalcemia can cause development of inverted, biphasic, or notched T wave with a marked decrease in amplitude of T waves.
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PMID:Changes in T wave morphology during hypercalcemia and its relation to the severity of hypercalcemia. 270 29

We studied a nine-year-old boy with severe, recurrent infections. The patient was exposed in utero to azathioprine and prednisone. He had autoimmune hemolytic anemia, bronchiectasis, and Hodgkin's disease. The patient's circulating lymphocytes were normal in number and phenotype, but stimulation of the T-cell receptor by antigens, mitogens, and monoclonal antibodies failed to induce interleukin-2-receptor expression, interleukin-2 synthesis, or lymphocyte proliferation. The early biochemical events necessary to initiate lymphocyte activation--accumulation of the second messenger diacylglycerol, activation of the enzyme protein kinase C, and elevation of the free intracellular calcium concentration--failed to occur in this patient's lymphocytes. The defect in the lymphocyte could be corrected in vitro by two agents that bypass the receptor-mediated signal mechanism (the diacylglycerol analogue phorbol and the calcium ionophore ionomycin). Further studies localized the defect in signal transduction to the interaction between cell-surface receptors and the guanine nucleotide-binding protein. We conclude that this patient's immunodeficiency was caused by a defective coupling of surface receptors to signal-transducing proteins in his T lymphocytes, resulting in failure of lymphocyte activation.
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PMID:An immunodeficiency characterized by defective signal transduction in T lymphocytes. 278 45

Currents were generated by depolarizing pulses in voltage-clamped, dissociated neurons from the CA1 region of adult guinea pig hippocampus in solutions containing 1 microm tetrodotoxin. When the extracellular potassium concentration was 100 mM, the currents reversed at -8.1 +/- 1.6 mV (n = 5), close to the calculated potassium equilibrium potential of -7 mV. The currents were depressed by 30 mM tetraethylammonium in the extracellular solution but were unaffected by 4-aminopyridine at concentrations of 0.5 or 1 mM. It was concluded that the currents were depolarization-activated potassium currents. Instantaneous current-voltage curves were nonlinear but could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. Conductance-voltage curves could be described by a Boltzmann-type equation: the average maximum conductance was 65.2 +/- 15.7 nS (n = 9) and the potential at which gK was half-maximal was -4.8 +/- 3.9 mV (mean +/- 1 SEM, n = 10). The relationship between the null potential and the extracellular potassium concentration was nonlinear and could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. The rising phase of potassium currents and the decay of tail currents could be fitted with exponentials with single time constants that varied with membrane potential. Potassium currents inactivated to a steady level with a time constant of approximately 450 ms that did not vary with potential. The currents were depressed by substituting cobalt or cadmium for extracellular calcium but similar effects were not obtained by substituting magnesium for calcium.
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PMID:Potassium current activated by depolarization of dissociated neurons from adult guinea pig hippocampus. 284 59

1. Instantaneous current-voltage (I-V) relations were measured from tail currents with 10 mM-external calcium at 20 degrees C. The I-V relations had a lower potential dependence than predicted by the Goldman-Hodgkin-Katz constant-field equation. Previously proposed symmetric two-site three-barrier (2S3B) rate theory models were able to account for the I-V relations reasonably well. 2. Reversal of the current flow through the calcium channels was recorded using 10 mM-barium internally and 20 mM-barium externally. The channels appeared to rectify at positive potentials, a property not consistent with symmetric rate theory models. 3. Externally applied cadmium ions blocked the calcium channels through at least two sites. One high-affinity blocking site was located within the membrane electric field and had a dissociation constant of around 16 microM at O mV. Cadmium block at this site was relieved with hyperpolarization with a voltage dependence equivalent to a divalent cation moving through about 75% of the membrane electric field. 4. A low-affinity potential-independent blocking site also appeared to be present, having a dissociation constant of around 106 microM. 5. Cadmium had significant effects on the tail current kinetics at potentials close to 0 mV, presumably due to slow unblocking events. The rate at which cadmium ions left the calcium channel free to conduct was estimated to be about 3300 s-1 at +10 mV.
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PMID:Permeation of barium and cadmium through slowly inactivating calcium channels in cat sensory neurones. 285 42

In a physiological medium the resting membrane potential of synaptosomes from guinea-pig cerebral cortex, estimated from rhodamine 6G fluorescence measurements, was nearly -50mV. This agreed with calculations using the Goldman-Hodgkin-Katz equation. With external [Ca2+] less than or equal to 3 mM veratridine depolarisation (to -30 mV) was accompanied by increases in intrasynaptosomal free calcium concentrations (monitored by entrapped quin2) and parallel increases in total acetylcholine release. With external [Ca2+] greater than 3 mM both intrasynaptosomal free calcium concentrations and transmitter release were paradoxically reduced, providing further evidence for a close correlation between the two events. To support an explanation of these findings based on divalent cation screening of membrane surface charge (increasing the voltage gradient within the membrane and closing voltage-inactivated channels) surface potential measurements were made on synaptic lipid liposomes by using a fluorescent surface-bound pH indicator. These experiments provided evidence for the presence of screenable surface charge on synaptosomes, and it was further shown in depolarised synaptosomes themselves that total external [Ca2+ + Mg2+], and not [Ca2+] alone, set the observed peak in intrasynaptosomal free calcium.
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PMID:External calcium, intrasynaptosomal free calcium and neurotransmitter release. 286 83

Fifteen patients with lymphoma and hypercalcemia (greater than or equal to 11.0 mg/dL) were identified by screening the serum chemistry profile obtained from patients upon admission to the Los Angeles County/USC Medical Center. Seven of the 15 (47%) possessed a frankly elevated serum concentration of 1,25-dihydroxyvitamin D [1,25-(OH)2-D]. An additional patient with severe hypercalcemia (16.2 mg/dL) had a serum 1,25-(OH)2-D concentration in the midnormal range, not a suppressed value. To examine the potential existence of hypercalciuria in absence of overt hypercalcemia, prospective screening of 23 normocalcemic patients with lymphoma was undertaken. Four of the 23 patients (17%) had increased fractional urinary calcium excretion rates (0.35 +/- 0.3 mg calcium/100 mL glomerular filtrate [GF], mean +/- SE; normal, less than 0.16 mg/100 mL GF); two of the hypercalciuric patients had a frankly elevated serum 1,25-(OH)2-D concentration. Of the 19 hypercalcemic/hypercalciuric lymphoma patients identified, none had an elevated serum immunoreactive parathyroid hormone concentration. Fourteen of the 19 hypercalcemic/hypercalciuric patients (74%) suffered from B-cell neoplasms, three had Hodgkin's lymphoma, and two had adult T-cell leukemia/lymphoma. All hypercalcemic/hypercalciuric patients had widespread disease (stage III or IV). Six patients, four with hypercalcemia and two with hypercalciuria, had acquired immunodeficiency syndrome (AIDS). These data suggest that the deregulated synthesis of a 1,25-(OH)2-D-like metabolite is a common cause of hypercalcemia and hypercalciuria in patients with lymphoma including patients with AIDS-associated tumors.
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PMID:Vitamin D metabolite-mediated hypercalcemia and hypercalciuria patients with AIDS- and non-AIDS-associated lymphoma. 291 Mar 61

Disorders of the basal ganglia and the extrapyramidal motor system exhibit an imbalance of neurotransmitter concentrations in affected neurons. For three synapses with dopamine, acetylcholine, and gamma-amino butyric acid (GABA), mathematical models of synaptic transmission are developed. To describe the kinetics of transmitter substances, compartment analysis is used. Membrane potential behaviour is described by the Hodgkin-Huxley equations with an additional equation accounting for a presynaptic calcium current mediating transmitter release. At the postsynaptic site, activated receptor molecules control the activity of ion channels, eliciting either inhibitory or excitatory postsynaptic potentials. A simple model of the feedback loop connecting the caudate nucleus and the substantia nigra is simulated on a digital computer using the simulation language ACSL. A comparison of the control case with a model of Parkinson's disease shows a shift of eigenvalues towards zero in the diseased state.
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PMID:A computer model of neuronal pathways in the basal ganglia. 301 86

We have examined the Ca2+ content and pathways of Ca2+ transport in frog rod outer segments using the Ca2+-indicating dye arsenazo III. The experiments employed suspensions of outer segments of truncated, but physiologically functional, frog rods (OS-IS), intact isolated outer segments (intact OS), and leaky outer segments (leaky OS with a plasma membrane leaky to small solutes, but with sealed disk membranes). We observed the following. Intact OS or OS-IS isolated and purified in Percoll-Ringer's solution contained an average of 2.2 mM total Ca2+, while leaky OS contained 2.0 mM total Ca2+. This suggests that most of the Ca2+ in OS-IS is contained inside OS disks. Phosphodiesterase inhibitors increased the Ca2+ content to approximately 4.2 mM in intact OS or OS-IS, whereas the Ca2+ content of leaky OS was not altered. Na-Ca exchange was the dominant pathway for Ca2+ efflux in both intact and leaky OS/OS-IS. The rate of Na-Ca exchange in intact OS/OS-IS was half-maximal between 30 and 50 mM Na+; at 50 mM Na+, this amounted to 5.8 X 10(7) Ca2+/OS X s or 0.05 mM total Ca2+/s. This is much larger than the Ca2+ component of the dark current. Other alkali cations could not replace Na+ in Na-Ca exchange in either OS-IS or leaky OS. They inhibited the rate of Na-Ca exchange (K greater than or equal to Rb greater than Cs greater than or equal to Li greater than TMA) and, as the inhibition became greater, a delay developed in the onset of Na-Ca exchange. The inhibition of Na-Ca exchange by alkali cations correlates with the prolonged duration of the photoresponse induced by these cations (Hodgkin, A. L., P. A. McNaughton, and B. J. Nunn. 1985. Journal of Physiology. 358:447-468). In addition to Na-Ca exchange, disk membranes in leaky OS showed a second pathway of Ca2+ transport activated by cyclic GMP (cGMP). The cGMP-activated pathway required the presence of alkali cations and had a maximal rate of 9.7 X 10(6) Ca2+/OS X s. cGMP caused the release of only 30% of the total Ca2+ from leaky OS. The rate of Na-Ca exchange in leaky OS amounted to 1.9 X 10(7) Ca2+/OS X s.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Na+- and cGMP-induced Ca2+ fluxes in frog rod photoreceptors. 303 Nov 99

Cyclic nucleotide phosphodiesterase (PDE) activities were studied in peripheral blood monocyte-depleted lymphocytes and enriched T-lymphocyte suspensions from thirteen patients with previously untreated Hodgkin's disease (HD) and fourteen age and sex matched healthy volunteers. Monocyte-depleted lymphocytes from HD patients showed PDE-activities which were two times higher than in their normal counterpart cells. The mean cAMP-PDE activity present in enriched HD T-lymphocyte suspensions was four times higher than in control T-lymphocytes, and the mean cGMP-PDE associated with HD T-lymphocytes was three times higher than in the controls. The hydrolytic activities present in both monocyte-depleted and T-lymphocyte enriched cells suspensions remained unchanged in absence or in the presence of calmodulin and calcium. Since depressed cAMP and cGMP resting levels have been observed in HD lymphocytes and lymphocyte subpopulations, our results suggest that the elevated PDE activities are, at least in part, responsible for the alterations in lymphocyte cyclic nucleotide levels.
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PMID:Cyclic AMP and cyclic GMP phosphodiesterase activities in Hodgkin's disease lymphocytes. 304 Jun 9


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