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)

1. All essential attributes of the amyloidosis in aged persons ("senile amyloidosis") correspond to the condition which in younger individuals develops after infections, particularly following tuberculosis and lymphogranulomatosis, as so-called secondary amyloid degeneration, and also manifests many features of the so-called primary amyloidosis, not connected with infections. 2. Amyloid depositions in the brain, cardiac muscle, and in pancreatic islets (the "senile amyloidotic triad") dominate the morbid anatomic aspect. However, we know no organ or tissue which necessarily remains spared. The number of involved organs and tissues, in general, increases with the progressive aging of the patients. In those persons living long enough, amyloidosis affects every individual and probably all organs and tissues. 3. Contrary to the so-called secondary amyloidosis, in many cases of senile amyloidosis the spleen, liver and kidney remain intact. 4. In the so-called Alzheimers disease, in which both clinically and pathoanatomically a particularly destructive cerebral amyloidosis in relatively young persons prevails, just as in the common senile dementia of aged persons, the brain condition is associated with a systemic amyloid degeneration of many other organs. 5. Several cerebral and cardiac lesions due to amyloid accumulations can probably be diagnosed electrographically. Thus, through these already known morbid anatomical observations we have the promise of an essential enrichment of diagnostic perspectives. 6. In general, the etiologic manifoldness of amyloidosis presently seems to be incomparable. Infections, ionizing radiation, traumatic lesions in human pathology, the introduction of chemically definable substances, infections, and stress consequent to social burdening, proved effective in spontaneous and experimental amyloid degeneration of animals. 7. The demonstration of a tuberculous infection with the help of postmortem radiographs, as well as with the employment of histologic and microbiologic procedures to provide the evidence of acid fast bacilli in calcified remnants of pulmonary foci, proved to be eminently successful methods in the exploration of causes of senile tuberculosis and amyloidosis: Tuberculosis, after its invasion of the organism in early childhood, with its toxic and immunobiologic influences, holds it under its spell for an entire, even very long life and can be considered the most frequent cause of senile amyloidosis. 8. Chromosomal disturbances, with their hereditary manifestations, or, as in cases of mongoloid idiocy, associated with individual deformations, may present as amyloidoses. 9. Amyloid deposits in human pathology may develop by the transformation of normal structures, like cartilage, osteoid tissue, vascular elastic fibers, and also from scar hyalin and from fibrin. 10. We observed the disappearance of cerebral and cardiac amyloid accumulations producing typical defects. 11. Amyloidosis represents one of the most frequent spontaneous diseases of animals...
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PMID:[Amyloidosis as a manifestation and origin of presenile and senile degeneration]. 13 66

The inward sodium current in cardiac muscle is difficult to study by voltage clamp methods, so various indirect experimental measures have been used to obtain insight into its characteristics. These methods depend on the relationship between maximal upstroke velocity of the action potential (Vmax) and the sodium current (INa), usually defined in terms of the Hodgkin-Huxley model. These relationships were explored using an adaptation of this model to cardiac Purkinje fibers. In general Vmax corresponded to INa, and it could be used to determine the relationship of membrane potential to GNa, and h infinity. The results, however, depended on the method of stimulation of the action potential, and an optimal stimulation method was determined. A commonly used experimental technique called "membrane responsiveness" was shown to distort seriously the properties of steady-state gating inactivation that is supposed to measure. Estimation of the changes in maximal sodium conductance, such as those produced by tetrodotoxin (TTX), would be accurately measured. Some experimental results have indicated a voltage-dependent effect of TTX. Characteristics of the measures of TTX effect under those conditions were illustrated. In summary, calculations with a model of the cardiac Purkinje fiber action potential provide insight into the accuracy of certain experimental methods using maximal upstroke velocity as a measure of INa, and cast doubt on other experimental methods, such as membrane responsiveness.
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PMID:The relation of Vmax to INa, GNa, and h infinity in a model of the cardiac Purkinje fiber. 26 97

1. The three-micro-electrode voltage clamp method (Adrian, Chandler & Hodgkin, 1970) was adapted for the study of regenerative inward currents in cardiac muscle. The adequacy of measurements of slow inward current in cardiac Purkinje fibres was assessed. 2. Membrane current density is reported simultaneously by total applied current (IT), along with a longitudinal voltage difference signal (delta V), recorded between two intracellular micro-electrodes. 3. Non-linear cable calculations show that delta V is a more faithful measure of membrane current density than IT as peak inward current increases. Quantitative agreement between delta V and IT only occurs when both signals report the membrane characteristics that would be obtained with an ideal longitudinal space clamp. 4. Agreement between delta V and IT is thus a useful criterion for satisfactory experimental measurements which we applied to the slow inward current. This component was elicited by depolarizing steps from a holding potential near =45 mV in the presence of tetrodotoxin. The IT signal was compared directly with delta V/R, where R is an effective longitudinal resistance that was experimentally determined. 5. delta V/R and IT showed very good agreement in both peak amplitude and time course at all potentials studied. 6. Radial non-uniformity during the measured peak slow inward current was estimated by calculations assuming clefts 200 A wide with a uniform distribution of ionic channels. The calculated voltage span from surface to centre was always less than 5 mV, and the measured I-V characteristics showed little distortion. 7. In another check, I-V characteristics and slow response membrane action potentials were compared. The measured peak current showed good agreement with the product (total preparation capacitance) x (rate of rise). 8. The experimental and theoretical analysis suggest that the measurements of slow inward current are a good approximation to genuine membrane properties.
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PMID:Three-micro-electrode voltage clamp experiments in calf cardiac Purkinje fibres: is slow inward current adequately measured? 46 51

1. The effect of adrenaline on the Ca-dependent slow inward current, Is, of mammalian cardiac muscle has been investigated by the voltage-clamp method. The mechanism of the increase in the conductance, gs, was analysed on the basis of a kinetic scheme (Hodgkin & Huxley, 1952) applicable to this system. 2. The rate constants alphad and betad, of activation of gs were not influenced by adrenaline, although the limiting conductance, gs, was greatly increased. 3. Reduction of [Ca]o from 1-8 to 0-2 mM decreased the amplitude of inward tail currents when gs was fully activated; however, the relative decrease of the current amplitude was the same with and without adrenaline. The reversal potential, ER, of Is was not changed by the drug. This indicates that the catecholamine has no influence on the selectivity of these conductance channels. 4. An increase in the number of functional conductance channels by adrenaline is discussed as a possible mechanism for the increase in Gs.
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PMID:The regulation of the calcium conductance of cardiac muscle by adrenaline. 83 56

Using spleen cells from athymic nude mice grafted with Ichikawa tumour, we have generated the monoclonal antibody IND.64, which detects a proliferation-associated nuclear antigen. Immunoblotting analysis with IND.64 showed a double band with apparent molecular weights of 395 and 345 kD. In normal human tissues, the antigen detected by IND.64 was expressed only by the nuclei of proliferating cells, such as germinal centre cells of reactive lymph nodes, cortical thymocytes, the basal layer of the skin, and proliferative compartments of the stomach, small intestine, and colon. IND.64 did not react with cells known to be non-proliferative or to show only a low turnover, such as cells of the kidney, liver, smooth muscle, cardiac muscle, and brain. The expression of this antigen during the cell cycle was determined using two approaches: IND.64 immunostaining of synchronized adult bovine aortic endothelial cells and flow cytometric analysis of double-labelled PHA-stimulated peripheral mononuclear blood leucocytes with a DNA marker and IND.64. The antigen recognized by IND.64 was found to appear in the late G1 phase, and persisted in phases S, G2, and M, but was absent in the G0 and early G1 phases. IND.64 was further investigated in different tumour types to evaluate the correlation between the percentage of IND.64-positive cells (IND.64 index) and the histological grade. In non-Hodgkin's lymphomas, an excellent correlation was found between the percentage of IND.64-positive cells and the cytomorphological grade. In nodular sclerosis and mixed cellularity Hodgkin's disease, a high number of Reed-Sternberg cells were positive with IND.64. The non-lymphoid neoplasms investigated showed a variable percentage of positive cells. IND.64 appears to be a promising tissue marker to complement the evaluation of prognosis in human cancer.
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PMID:Production of a monoclonal antibody (IND.64) identifying a cell cycle-associated antigen using spleen cells from nude mice bearing Ichikawa tumour. 146 May 36

The influence of interstitial or extracellular potentials on propagation usually has been ignored, often through assuming these potentials to be insignificantly different from zero, presumably because both measurements and calculations become much more complex when interstitial interactions are included. This study arose primarily from an interest in cardiac muscle, where it has been well established that substantial interstitial potentials occur in tightly packed structures, e.g., tens of millivolts within the ventricular wall. We analyzed the electrophysiological interaction between two adjacent unmyelinated fibers within a restricted extracellular space. Numerical evaluations made use of two linked core-conductor models and Hodgkin-Huxley membrane properties. Changes in transmembrane potentials induced in the second fiber ranged from nonexistent with large intervening volumes to large enough to initiate excitation when fibers were coupled by interstitial currents through a small interstitial space. With equal interstitial and intracellular longitudinal conductivities and close coupling, the interaction was large enough (induced Vm approximately 20 mV peak-to-peak) that action potentials from one fiber initiated excitation in the other, for the 40-microns radius evaluated. With close coupling but no change in structure, propagation velocity in the first fiber varied from 1.66 mm/ms (when both fibers were simultaneously stimulated) to 2.84 mm/ms (when the second fiber remained passive). Although normal propagation through interstitial interaction is unlikely, the magnitudes of the electrotonic interactions were large and may have a substantial modulating effect on function.
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PMID:Electrophysiological interaction through the interstitial space between adjacent unmyelinated parallel fibers. 160 78

A theoretical model is presented for the early currents in the voltage clamp of cardiac muscle using the single sucrose gap technique. The preparation is represented by a single one-dimensional active cable with modified Hodgkin-Huxley membrane and the interent imperfections in the technique are also included, e.g., leakage through the sucrose gap and resistance in series with the membrane in the test compartment. The stability of the control system was found to depend on the position of the control point with respect to the sucrose gap border. Computed currents for a stable system closely resembled those in the literature and those from a near-ideal system (e.g., squid axon.) The potential immediately across the membrane, however (not including potential drops across the series resistance external to the membrane), was found to be essentially uncontrolled and the "current-voltage" relationship was shown to be almost independent of membrane properties.
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PMID:Voltage clamp of cardiac muscle. A theoretical analysis of early currents in the single sucrose gap. 464 23

1. The membrane currents in Purkinje fibres under voltage clamp conditions have been investigated in the range of potentials at which the action potential plateau occurs. The results show that in this range slow outward current changes occur which are quite distinct from the potassium current activated in the pace-maker range of potentials.2. The time course of current change in response to step voltage changes is non-exponential. At each potential the current changes may be analysed in terms of the sum of two exponential changes and this property has been used to dissect the currents into two components, i(x1) and i(x2), both of which have been found to obey kinetics of the Hodgkin-Huxley type.3. The first component, i(x1), is activated with a time constant of about 0.5 sec at the plateau. At more positive and more negative potentials the time constants are shorter. The steady-state degree of activation varies from 0 at about -50 mV to about 1 at +20 mV. The instantaneous current-voltage relation is an inward-going rectifier but shows no detectable negative slope. In normal Tyrode solution ([K](0) = 4 mM) the reversal potential is about -85 mV.4. The second component, i(x2), is activated extremely slowly and the time constant at the plateau is about 4 sec. The steady-state activation curve varies from 0 at about -40 mV to 1 at about +20 mV. The instantaneous current-voltage relation is nearly linear. The reversal potential occurs between -50 and -20 mV in different preparations.5. It is suggested that these currents are carried largely by K ions, but that some other ions (e.g. Na) also contribute so that the reversal potentials are positive to E(K).6. The relation of these results to previous work on delayed rectification in cardiac muscle is discussed.
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PMID:Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres. 576 44

The validity of a Hodgkin-Huxley type voltage-dependent inactivation of slow inward Ca current (Isi) was tested in frog heart using a computer simulation. The time course of Isi was calculated during the development of a frog atrial action potential (AP). With a time constant of inactivation (tauf) of 55 ms at a membrane potential (Em) of -15 mV, the variation of Isi was biphasic: after a transient increase followed by a decrease to zero, Isi partially "reactivated" (at the beginning of the AP repolarization phase) and then fully deactivated. The "reactivation" phase of Isi developed whether tauf was an increasing, decreasing, U-shaped, or bell-shaped function of Em. The addition of an independent and slower process responsible for the recovery from inactivation only partly suppressed the "reactivation" phase. However, until now there was no experimental evidence supporting such a biphasic variation of Isi during AP repolarization. Thus our results indicate that the Hodgkin-Huxley type model of the voltage-dependence of Isi-inactivation process may not correctly represent the actual behavior of frog cardiac muscle.
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PMID:Slow inward Ca current in frog heart: theoretical evidence against a voltage-dependent inactivation. 629 80

The voltage and time-dependence of the tetrodotoxin sensitive, fast sodium current in cardiac muscle is described with the Hodgkin-Huxley formalism using two microelectrode, voltage-clamp data obtained by Ebihara et al. (1980, J. Gen. Physiol., 75:437) from small spherical clusters of tissue-cultured 11-d-old embryonic heart cells. The data chosen from that study for quantitative analysis was obtained at 37 degrees C and in standard tissue-culture medium; it was not smoothed, and the capacitive transient was sufficiently brief to make its removal unnecessary. The sodium current, INa, is considered to be given by the following equation: INa = gNa m3h(V - VNa), where gNa is a constant (23 mS), VNa is the sodium equilibrium potential (29 mV), and m and h are independent, first order, dimensionless variables, which can vary between 0 and 1, as defined by the following differential equations, dm/dt = alpha m(1 - m) - beta mm and dh/dt = alpha h(1 - h) - beta hh, where the rate coefficients, alpha m = [0.32 x (V + 47.13)]/[1 - exp(V + 47.13)] and beta m = 0.08 x exp (-V/11). For potentials more positive than -40 mV, alpha h = 0 and beta h = 1/0.13 (exp [(V + 10.66)/ - 11.1] + 1), and for potentials more negative than -40 mV, alpha h = 0.135 x exp [(-80 - V)/6.8] and beta h = 3.56 x exp (0.079V) + 3.1 x 10(5) exp (0.35V). These functions of potential are similar to those of the squid at 15 degrees C, except that their magnitudes are larger (faster). Using these model equations the membrane current in a membrane patch with and without a series resistance was simulated. For the value of series resistance estimated for the preparation from which the analyzed data were obtained, the effects of series resistance on the shape and magnitude of the inward transient current were found to be minimal. It was concluded that their should be no large errors in the data, even in the absence of complete series resistance compensation.
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PMID:Fast sodium current in cardiac muscle. A quantitative description. 726 Mar 1


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