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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At the beginning of this conference, Dr Ford asked whether or not Hodgkin's disease was a malignancy. Most physicians would agree that, regardless of whether this question can be answered on a molecular level, Hodgkin's disease certainly behaves like a malignancy, and clinically fits criteria necessary to call it one. It grows without control locally, comprising vital organs. It 'metastasizes', infiltrates organs, and causes organ dysfunction. Patients afflicted with the disease have a shortened life span without proper therapy, as demonstrated by DeVita in his original publication describing the benefits of MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone) (DeVita et al., 1970). However, it can progress very slowly, with 50 per cent of untreated patients with stage III or IV disease dead at one year, but 10 to 15 per cent alive at five years. Therefore, in its clinical behaviour, Hodgkin's disease certainly qualifies as a malignant disorder, despite the fact that we do not have the molecular means of calling it one.
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PMID:Prognostic factors in decision-making in the clinical management of Hodgkin's disease. 304 83

1. Na currents and fluctuations of Na currents were studied under voltage clamp in the same myelinated nerve fibres of Rana esculenta at 13 degrees C. The results were used to test several kinetic models for the gating process of Na channels.2. Long voltage pulses, depolarizing the membrane by 16-48 mV from a hyperpolarizing holding level of - 28 mV, were applied in 4 sec intervals. The d.c. and a.c. components of the membrane current were recorded during the last 328 msec of the 473 msec pulses. For each depolarization, ninety-six trials were made with the node in Ringer solution and, again, after adding 300 nm-tetrodotoxin (TTX) in that solution.3. The TTX-sensitive d.c. component declined during the 328 msec records by 14-51% of its time average. The a.c. component was corrected for this trend by subtracting the first from the second of each pair of subsequent records. The TTX-sensitive part of its variance declined, on the average, in parallel to the current, as if the open probability rather than the conductance of the individual Na channels was reduced by a slow process.4. Single-channel conductances, gamma, were calculated on the assumption that Na channels have only one non-zero conductance and were corrected for the limited band width (5 kHz) of the a.c. records. Values of gamma increased slightly (< 30% from 16 to 40 mV), and averaged 8.85 +/- 0.7 pS (s.e. of mean, seventeen measurements on ten fibres). This small degree of change in gamma suggests that deviations from the all-or-none gating are very small.5. Power spectral densities of the fluctuations between 3 Hz and 5 kHz were calculated from the trend-free a.c. records and corrected for the TTX-insensitive noise component. Control calculations showed that the only effect of the nonstationarity in the Na current was to enhance the low-frequency points of such spectra by less than 10%. The spectra revealed at least two Lorentzian components with cut-off frequencies in the range expected from the activation and inactivation kinetics. The low-frequency component became dominant as depolarization was increased.6. Na currents recorded during brief (< 40 msec) depolarizations were analysed in terms of various all-or-none gating models, in which inactivation either was independent of activation (Hodgkin-Huxley (HH) model) or could occur only from the partly or fully activated states (coupled models). The transient Na currents were reproduced by all models.7. With the parameters from such fits, the fluctuation spectra expected for each model were calculated. The predictions differed in the fraction, r(h), of the variance contributed by the slow (inactivation) fluctuations; r(h) was larger in the coupled models than in the HH model.8. The experimental spectra were divided into two spectral components to yield empirical values for r(h). We used as templates the spectral curves derived for the fast and for the slow fluctuations of the HH model. The empirical r(h) values were one (48 mV) to four (16 mV) times larger than those expected for the HH model. They were also larger than the theoretical r(h) of the coupled models at the small depolarizations, but became equal or smaller than those at the largest depolarization. Direct comparison of the measured and theoretical spectra revealed the same discrepancies.9. We conclude that all of the simple gating models considered in this paper are inconsistent with the fluctuation measurements, the coupled models giving slightly smaller deviations than the model with independent activation and inactivation.
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PMID:Conductance fluctuations from the inactivation process of sodium channels in myelinated nerve fibres. 626 98

The power spectrum of current fluctuations and the complex admittance of squid axon were determined in the frequency range 12.5 to 5,000 Hx during membrane voltage clamps to the same potentials in the same axon during internal perfusion with cesium. The complex admittance was determined rapidly and with high resolution by a fast Fourier transform computation of the current response, acquired after a steady state was attained, to a synthesized signal with predetermined spectral characteristics superposed as a continuous, repetitive, small perturbation on step voltage clamps. Linear conduction parameters were estimated directly from admittance data by fitting an admittance model, derived from the linearized Hodgkin-Huxley equations modified by replacing the membrane capacitance with a "constant-phase-angle" capacitance, to the data. The constant phase angle obtained was approximately 80 degrees. At depolarizations the phase of the admittance was 180 degrees, and the real part of the impedance locus was in the left-half complex plane for frequencies below 1 kHz, which indicates a steady-state negative Na conductance. The fits also yielded estimates of the natural frequencies of Na "activation" and "inactivation" processes. By fitting Na-current noise spectra with a double Lorentzian function, a lower and an upper corner frequency were obtained; these were compared with the two natural frequencies determined from admittance analysis at the corresponding potentials. The frequencies from fluctuation analyses ranged from 1.0 to 10.3 times higher than those from linear (admittance) analysis. This discrepancy is consistent with the concept that the fluctuations reflect a nonlinear rate process that cannot be fully characterized by linear perturbation analysis. Comparison of the real part of the admittance and the current noise spectrum shows that the Nyquist relation, which generally applies to equilibrium conductors, does not hold for the Na process in squid axon. The Na-channel conductance, gamma Na, was found to increase monotonically from 0.1 to 4.8 pS for depolarizations up to 50 mV from a holding potential of -60 mV, with no indication of a maximum value.
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PMID:Fluctuation and linear analysis of Na-current kinetics in squid axon. 662 70

The authors report the results obtained in the necropsic study of nine cases of the so-called acute, visceral form of Hodgkin's disease (HD). Most of the patients (six men and three women, ranging from 42 to 74 years of age) lacked peripheral lymphadenopathies and had fever, weight loss, abnormality of hepatic function, and pancytopenia. Mixed cellularity was diagnosed in two, diffuse fibrosis in four, and reticular subtype of lymphocyte depletion in three cases. Despite the predominant infradiaphragmatic involvement, supradiaphragmatic lymph nodes were involved in six and tonsils in three cases. Spleen and bone marrow were involved in eight cases and the liver was involved in seven cases. In four cases there were also lesions in other extralymphoid organs. The involvement of the bone marrow was widespread and showed concurrent myelofibrosis and/or other signs of hematopoietic disturbance. There was a close relationship between the presence of vascular invasion (seven cases) and the extent of HD spread. It is concluded that despite its peculiarity, this form of HD fits the classic model of unicentric origin, lymphogenic contiguous spread, and hematogeneous dissemination, and should not be identified with any particular histologic type of HD.
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PMID:Hodgkin's disease with predominant infradiaphragmatic involvement and massive invasion of the bone marrow. A necropsic study of nine cases. 662 7

A semiautomated electronic system has been employed for sizing nuclear area and for evaluating nuclear form factors in non-Hodgkin's lymphomas with the purpose to correlate these parameters with survival and histotype. By mathematical models for best fits correlating the dependent variables with the survival has been demonstrated that an inverse correlation corresponding to a negative exponential function exists between mean nuclear area and survival. It has also been shown that the nuclear form is less irregular (i.e. more similar to an ellipse) when the mean nuclear area ranges from 12.5 to 20 mu2 and from 30 to 37.5 mu2 than when it ranges from 20 to 30 mu2. Lymphomas of low-grade malignancy are characterized by a mean nuclear area which is significantly lower than that of lymphomas of high-grade malignancy. The authors believe that morphometrical analysis of the nuclear area and of the form factors may eliminate subjectivity and give reproducible data to be used in both classification and prognosis of lymphomas.
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PMID:A morphometric semiautomated method for analyzing cell nuclei in lymph node sections from non-Hodgkin's lymphomas. Significance of data. 668 63

The maximum potential displacement that gives a linear K conductance response was determined to be 1 mV (rms) from a voltage-clamp analysis of TTX treated axons. For perturbations below this amplitude the K conductance kinetics are indistinguishable from a first-order rate process. Linearity and order of kinetics were assessed by four types of measurements: (i) the shape of the onset of the potassium current (sigmoidal vs. exponential); (ii) the symmetry of small hyperpolarizing and depolarizing pulses, (iii) wide band admittance, and (iv) harmonic analysis. The simplest interpretation of the results is that the small-signal linear response arises from a first-order gating mechanism, whereas the large-signal conventional voltage-clamp pulse of tens of millivolts evokes nonlinear phenomena. The small-signal results are consistent with the Hodgkin-Huxley description or any other nonlinear model which fits the large signal data and produces a linear first-order response for small perturbations.
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PMID:Small-signal analysis of K+ conduction in squid axons. 740 Nov 67

1. Neurons of the nodose ganglia provide the sole connection between many types of visceral sensory inputs and the central nervous system. Electrophysiological studies of isolated nodose neurons provide a practical means of measuring individual cell membrane currents and assessing their putative contributions to the overall response properties of the neuron and its terminations. Here, we present a comprehensive mathematical model of an isolated nodose sensory neuron that is based upon numerical fits to quantitative voltage- and current-clamp data recorded in our laboratory. Model development was accomplished using an iterative process of electrophysiological recordings, nonlinear parameter estimation, and computer simulation. This work is part of an integrative effort aimed at identifying and characterizing the fundamental ionic mechanisms participating in the afferent neuronal limb of the baroreceptor reflex. 2. The neuronal model consists of two parts: a Hodgkin-Huxley-type membrane model coupled to a lumped fluid compartment model that describes Ca2+ ion concentration dynamics within the intracellular and external perineuronal media. Calcium buffering via a calmodulin-type buffer is provided within the intracellular compartment. 3. The complete model accurately reproduces whole-cell voltage-clamp recordings of the major ion channel currents observed in enzymatically dispersed nodose sensory neurons. Specifically, two Na+ currents exhibiting fast (INaf) and slow tetrodotoxin (TTX)-insensitive (INas) kinetics; low- and high-threshold Ca2+ currents exhibiting transient (ICa,t) and long-lasting (ICa,n) dynamics, respectively; and outward K+ currents consisting of a delayed-rectifier current (IK), a transient outward current (I(t)) and a Ca(2+)-activated K+ current (IK,Ca). 4. Whole-cell current-clamp recordings of somatic action-potential dynamics were performed on enzymatically dispersed nodose neurons using the perforated patch-clamp technique. Stimulus protocols consisted of both short (< or = 2.0 ms) and long (> or = 200 ms) duration current pulses over a wide range of membrane holding potentials. These studies clearly revealed two populations of nodose neurons, often termed A- and C-type cells, which exhibit markedly different action-potential signatures and stimulus response properties. 5. Using a single set of equations, the model accurately reproduces the electrical behavior of both A- and C-type nodose neurons in response to a wide variety of stimulus conditions and membrane holding potentials. The structure of the model, as well as the majority of its parameters are the same for both A- and C-type implementations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A- and C-type rat nodose sensory neurons: model interpretations of dynamic discharge characteristics. 752 13

Ara-CMP-Stearate (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate, YNK 01, Fosteabine) is the orally applicable prodrug of cytosine-arabinoside (Ara-C). During a phase I study in patients with advanced low-grade non-Hodgkin lymphomas or acute myeloid leukemia, the pharmacokinetic parameters of Ara-CMP-Stearate (kindly provided by ASTA Medica, Frankfurt, Germany) were determined by HPLC analysis. Seventy-two hours after a first starting dose which served for the determination of baseline pharmacokinetic parameters, Ara-CMP-Stearate was administered over 14 days by daily oral application. Ara-CMP-Stearate was started at a dose of 100 mg/day and was escalated in subsequent patients to 200 mg/day and 300 mg/day. Plasma and urine concentrations of Ara-CMP-Stearate, Ara-C and Ara-U were measured during the initial treatment phase and within 72 h after the end of the 14-day treatment cycle. So far six patients have been treated with 100 mg/day, three with 200 mg/day and another six with 300 mg/day. One patient was treated consecutively with 100 mg, 300 mg and 600 mg. Fitting the results of the plasma concentration measurements of Ara-CMP-Stearate to a one-compartment model, the following pharmacokinetic parameters were obtained (average and variation coefficient VC). Ara-CMP-Stearate dose-independent parameters: lag time = 1.04 h (0.57); tmax = 5.72 h (0.30); t1/2 = 9.4 h (0.36). Dose-dependent parameters: at 100 mg: AUC = 1099 ng/h/ml (0.31); concentration(max) = 53.8 ng/ml (0.28); at 200 mg: AUC = 2753 ng/h/ml (0.32); concentration(max) = 154.8 ng/ml (0.46); at 300 mg: AUC = 2940 ng/h/ml (0.66); concentration(max) = 160.0 ng/ml (0.59). The long lag time and late tmax can be explained by resorption in the distal part of the small intestine. No Ara-CMP-Stearate was detected in urine samples (limit of detection = 500 pg/ml). Pharmacokinetic parameters of Ara-C following Ara-CMP-Stearate application showed the following characteristics: t1/2 = 24.3 h (0.39); AUC (100 mg) = 262 ng/h/ml (0.93); AUC (200 mg) = 502 ng/h/ml (0.87); AUC (300 mg) = 898 ng/h/ml (1.07). Since Ara-CMP-Stearate causes intravascular hemolysis after intravenous administration, it was not possible to determine its bioavailability by comparing the AUC after oral and i.v. application. Instead, the renal elimination of Ara-U, as the main metabolite of Ara-C was measured during the first 72-h period and after the last application.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetics of Ara-CMP-Stearate (YNK01): phase I study of the oral Ara-C derivative. 759 74

A quantitative analysis of the time- and voltage-dependent kinetics of the Guard Cell Anion Channel (GCAC1) current in guard cell protoplasts from Vicia faba was analyzed using the whole-cell patch clamp technique. The voltage-dependent steady-state activation of GCAC1 current followed a Boltzmann distribution. For the corresponding steady-state value of the activation variable a power of two was derived which yielded suitable fits of the time course of voltage-dependent current activation. The GCAC1 mediated chloride current could successfully be described in terms of the Hodgkin-Huxley equations commonly evoked for the Na channel in nerve. After step depolarizations from a potential in the range of the resting potential to potentials above the equilibrium potential for chloride an activation and also an inactivation could be described. The gating of both processes exhibited an inverse relationship on the polarity of the applied step potentials in the order of milliseconds. Deactivating tail currents decline exponentially. The presented analysis contributes to the understanding of the rising phase of the observed action potentials in guard cells of V. faba. Evidence is presented that the voltage-dependent kinetic properties of the GCAC1 current are different from those properties described for the excitable anion currents in the plasmalemma of Chara corallina (Beilby & Coster, 1979a).
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PMID:Hodgkin-Huxley analysis of a GCAC1 anion channel in the plasma membrane of guard cells. 856 42

Markov kinetic models were used to synthesize a complete description of synaptic transmission, including opening of voltage-dependent channels in the presynaptic terminal, release of neurotransmitter, gating of postsynaptic receptors, and activation of second-messenger systems. These kinetic schemes provide a more general framework for modeling ion channels than the Hodgkin-Huxley formalism, supporting a continuous spectrum of descriptions ranging from the very simple and computationally efficient to the highly complex and biophysically precise. Examples are given of simple kinetic schemes based on fits to experimental data that capture the essential properties of voltage-gated, synaptic and neuromodulatory currents. The Markov formalism allows the dynamics of ionic currents to be considered naturally in the larger context of biochemical signal transduction. This framework can facilitate the integration of a wide range of experimental data and promote consistent theoretical analysis of neural mechanisms from molecular interactions to network computations.
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PMID:Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. 879 31


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